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The costs and cost-effectiveness of tuberculosis control

Vassall, A.

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The Costs and Cost-effectiveness of Tuberculosis Control

Anna Vassall

Tuberculosis is a leading cause of ill-health and death in low and middle income coun-tries. Tuberculosis control is essential for achieving the Millennium Development Goalsrelating to health by 2015. However, despite efforts made to expand tuberculosis controlover the past decades, tuberculosis remains a serious global health problem. This bookaims to assist the expansion of tuberculosis control by adding to the evidence on thecost-effectiveness of different tuberculosis control strategies. It presents research fromfive countries: Egypt, Ethiopia, Syria, Peru and Ukraine. It examines the implementation of the World Health Organization recommended strategy, Directly Observed TreatmentStrategy (dots). New technologies currently being developed to tackle drug resistanceare also assessed. Emphasis throughout is placed on the importance of health systemsand the costs for patients accessing treatment. This book is essential reading for anyoneinterested in economic aspects of tuberculosis control.

Anna Vassall is a leading advisor to several international organizations and govern-ments in the area of health economics. Her specific focus is on strengthening healthsector planning and investments in low and middle income countries, by supportingthe generation and use of economic evidence.

UvA Dissertation

Faculty of Economics and Business

9 789056 295950

Anna Vassall The Costs and Cost-effectiveness of Tuberculosis Control

AUP-Vassall:AUP/Buijn 10-09-2009 15:30 Pagina 1

The costs and cost-effectiveness of tuberculosis control

The publication of this book was made possible by a contribution from KNCV

Tuberculosefonds, The Hague.

Lay-out: The DocWorkers, Almere

Cover design: Rene Staelenberg, Amsterdam

Cover illustration: BMB MottMacDonald

ISBN 978 90 5629 595 0

e-ISBN 978 90 4851 146 4

NUR 883

© A. Vassall / Vossiuspers UvA – Amsterdam University Press, 2009

All rights reserved. Without limiting the rights under copyright reserved above,

no part of this book may be reproduced, stored in or introduced into a retrie-

val system, or transmitted, in any form or by any means (electronic, mechani-

cal, photocopying, recording or otherwise) without the written permission of

both the copyright owner and the author of the book.

The costs and cost-effectivenessof tuberculosis control

Academisch Proefschrift

ter verkrijging van de graad van doctor

aan de Universiteit van Amsterdam

op gezag van de Rector Magnificus

prof. dr. D.C. van den Boom

ten overstaan van een door het college voor promoties

ingestelde commissie,

in het openbaar te verdedigen in de Agnietenkapel

op donderdag 29 oktober 2009, te 10.00 uur

door

Anna Vassall

geboren te Kingston upon Thames, Verenigd Koninkrijk

Promotor: Prof. dr. J. Van der Gaag

Co-promotor: Prof. dr. M.W. Borgdorff

Overige leden: Prof.dr. F.F.H. Rutten

Prof.dr. T. Rinke de Wit

Prof. dr. P.A. Kager

Prof.dr. M.P. Pradhan

Prof. dr. J. van der Velden

Prof.dr. A.P. Hardon

Faculteit: Economie en Bedrijfskunde

The research in this thesis was made possible with support from the EuropeanCommunity, the Royal Tropical Institute and the World Health Organisation.My special thanks are extended to all my colleagues and friends who supportedme during this thesis. My special thanks goes to my family, in particular myhusband Jan-Paul Wagenaar.

Contents

Chapter 1 – General Introduction 9

Chapter 2 – Cost-effectiveness of different treatment strategies for

tuberculosis in Egypt and Syria 23

Chapter 3 – Reforming tuberculosis control in Ukraine; results of pilot

projects and implications for the national scale-up of DOTS 37

Chapter 4 – Cost effectiveness analysis of introducing rapid, alternative

methods to identify multidrug-resistant tuberculosis in

middle income countries 55

Chapter 5 – The patient costs of accessing collaborative TB/HIV

interventions in Ethiopia 73

Chapter 6 – Estimating the resource needs of scaling-up HIV/AIDS and

tuberculosis interventions in sub-Saharan Africa: a systematic

review for national policy makers and planners 87

Chapter 7 – General discussion and conclusion 113

Chapter 8 – Summary/Samenvatting 121

List of Abbreviations

AIDS Acquired Immune Deficiency Syndrome

ART Anti-Retroviral Therapy

ARV Anti-Retroviral

CC Carer Cost

CMH Commission for Macro-economics and Health

CO Cotrimoxazole

CPT Cotrimoxazole Preventative Therapy

CXR Chest X-Ray

DALY Disability Adjusted Life Year

DC Direct Cost

DLJ Direct Lowenstein Jensen

DOT Directly Observed Therapy

DOTS Directly Observed Treatment Strategy

DST Drug Susceptibility Testing

E Ethambathol

EC European Community

EU European Union

FMOH Federal Ministry of Health

GHS General Health Service Staff

H Isoniazid

HAART Highly Active Anti-Retroviral Therapy

IC Indirect Cost

IDLJ Indirect Lowenstein Jensen

IEC Information, Education and Communication

INH Isoniazid

IPT Isoniazid Preventative Therapy

MBB Marginal Budgeting for Bottlenecks

MDG Millenium Development Goal

MDR-TB Multi-drug Resistant Tuberculosis

MMR Mass Miniature Radiography

NA Not applicable

NTP National Tuberculosis Programme

OI Opportunistic Infection

PCF Passive Case Finding

PHC Primary Health Care

PHCU Primary Health Care Unit

PTB Pulmonary Tuberculosis

R Rifampicin

S Streptomycin

SC Specialised Clinics

SM+ Smear Positive

SM- Smear Negative

TB Tuberculosis

TC Transport Cost

VCT Voluntary Counselling and Testing

WDR World Development Report

WHO World Health Organisation

8 The costs and cost-effectiveness of tuberculosis control

Chapter 1

General Introduction

INTRODUCTION

Tuberculosis (TB) is a principal cause of mortality and morbidity among the

adult population of low income countries. The Commission on

Macroeconomics and Health (CMH) reports that TB contributes substantially

to the avoidable mortality of the world’s poorest. The World Health

Organisation (WHO) recommended strategy for TB control is known as

DOTS (Directly Observed Treatment, short-course).1 DOTS is based upon the

premise that the early detection and effective treatment of TB cases reduces

both the current burden of TB and the spread of the disease. This strategy has

been proven to be highly effective and cost-effective in low income settings (1).

However, today DOTS is only available to around half the world’s population

and thus there remains a considerable mountain to climb to ensure global

access to effective TB treatment. In March 2000, governments from around the

world formalised the accelerated expansion of DOTS in the Amsterdam

Declaration to Stop TB. The Global Stop TB partnership2 has built on this

commitment and developed a plan of action, the Global Plan for TB Control.

This was further updated to the Global Plan II for 2006-2015, in line with the

Millennium Development Goals. A central aim of the plan is to ensure that by

2015 70% of notified TB cases globally will have access to DOTS.

The pursuit of global access to DOTS faces significant challenges as the TB epi-

demic is constantly evolving. If TB control is to be successful, DOTS will need

to be adapted and extended to face these challenges. The foremost challenge

faced is co-infection between TB and HIV/AIDS. This is rapidly increasing the

severity of the TB epidemic, particularly in Sub-Saharan Africa. In addition,

the emergence of multi-drug resistance TB (MDR-TB) threatens to limit the

effectiveness of TB treatment for current and future generations. Finally, TB

control faces a significant challenge in trying to reach the poorest of the poor,

a group that is highly susceptible to TB. Although these challenges are consid-

erable, there are opportunities ahead. Developments in health systems and new

diagnostic tools, drugs and vaccines all have an important contribution to

make to the effectiveness of TB control in the future.

Improving the evidence base on the economic and financial aspects of TB con-

trol can contribute towards TB control in the following ways:

Firstly, economic analysis can be used to justify domestic and international

investment in TB control. If TB control is to meet the challenges it faces it will

require both innovative approaches and increased resources. Economic analysis

provides policy-makers and planners with a clear framework to justify invest-

ment in TB control compared to investment in other areas. In particular, it can

be used to justify the use of public finances for TB control by assessing market

failure and identifying efficiency gains.


Secondly, economic analysis can assist policy makers and planners identify the

interventions that best achieve TB control objectives, given the available

resources, by comparing the cost-effectiveness of different interventions. It is

particularly useful in low income countries where the burden of TB is the high-

est, but resource constraints most severe. Economic analysis also has a role to

play in the development of the extensions to DOTS required to meet the chal-

lenges of HIV/AIDS, MDR-TB and poverty. Through the assessment of the

potential markets and cost-effectiveness of new prevention, diagnostic and

treatment technologies, economic analysis can support investment in the devel-

opment of new technologies to control TB.

Thirdly, financial and economic analyses have a role to play in supporting TB

policy makers, planners and managers identify, plan and channel financial

resources to and within TB control programmes. Economic analysis provides a

framework to examine the resource gaps which exist, estimate the resource

requirements of filling them and to develop the most efficient ways to finance

them. The development and use of improved tools for the estimating resource

requirements and the financial planning of TB control are essential to support

the successful implementation of TB control programmes.

This thesis aims to contribute towards this effort by improving the evidence

base on the costs and cost-effectiveness of a variety of TB control

interventions.

BACKGROUND AND LITERATURE REVIEW

This section summarises the evidence on the costs and cost-effectiveness of TB

control interventions available prior to conducting this thesis.3 It begins by

looking at the cost-effectiveness of TB Control and DOTS generally and the

evidence base for their comparative cost-effectiveness in low income countries.

This summary contains a detailed examination of the evidence establishing the

cost-effectiveness of different elements of DOTS compared to their alternatives.

It first examines the cost-effectiveness of different methods of case detection

and evidence of the relative cost-effectiveness of passive approaches. It moves

on to look at the cost-effectiveness of different ways of diagnosing TB and in

particular the evidence that established the cost-effectiveness of smear micro-

scopy. Finally, evidence of the cost-effectiveness of short course standardised

therapy and improving treatment compliance are examined. The last part of

this summary looks at the cost-effectiveness of extensions/ new additions to

DOTS, including evidence on the treatment of MDR-TB and interventions to

reduce TB related to HIV.

General Introduction 11

Directly Observed Treatment Strategy (DOTS)

The World Development Report 1993 (WDR 1993) identifies the detection and

treatment of TB as one of the most cost-effective health interventions. It esti-

mates that the cost per DALY of treating a smear positive case of TB is $1-3

(1993 prices) and therefore recommends its inclusion in the essential package

of health care for both low and middle-income countries. In addition, it is esti-

mated that the cost of diagnosis and treatment of smear negative TB is likely

to be in the range of $5 to $20 per DALY (2), still a comparatively cost-effective

intervention. The main source of data for the estimates used in the WDR 1993

is a study of the cost-effectiveness of TB control conducted in Malawi,

Tanzania and Mozambique in 1991 (3). This study clearly demonstrates that in

all three countries TB control is a cost-effective intervention. One of the main

reasons for this finding is that, although TB treatment is often thought to be a

curative intervention, its main benefit is preventative and therefore compares

favorably against most other interventions, despite the relative expense and

long course of treatment.

There are several studies that focus on measuring the gains in cost-effectiveness

made from moving from existing systems of TB control to DOTS. This type of

study often supports the re-orientation of substantial TB infrastructure away

from hospitalisation towards integrated ambulatory care. A study from South

Africa (4) finds that cure rates rose substantially when TB treatment was pro-

vided through twice weekly ambulatory care with a 2-3 week initial stay in hos-

pital, compared to hospitalisation for the whole course of treatment, making it

substantially more cost-effective. Furthermore a study from Uganda, also shows

that the cost-effectiveness of TB control is likely to increase as patients are

moved from hospitalised care to ambulatory DOT(5).

In recent years, this issue has become increasing relevant in middle income set-

tings, where a TB control infrastructure is well established, but TB remains a

threat. Cost-effectiveness studies can demonstrate the economic gains of adopt-

ing DOTS to policy makers who may be reluctant to apply evidence solely

from low-income settings. For example, studies from Russia show that moving

from a TB control strategy based on active case detection and individual hospi-

talised treatment to one based on passive case finding and ambulatory short

course therapy significantly improves cost-effectiveness (6,7). Nevertheless

more examples are still required to demonstrate that DOTS is cost-effective in

middle-income countries.

Elements of DOTS

Whilst the DOTS strategy overall is seen as being cost-effective, different ele-

ments of the strategy have also been subjected to economic evaluation, in order

to inform its design.


Case detectionThe WHO recommends passive case detection, that is, case finding among

symptomatic patients self-reporting to health services. The alternative, active

case detection, involves screening populations using chest X-ray, or by survey-

ing respiratory symptoms. There are no recent cost-effectiveness studies in

low-income countries. However, one of the studies from Russia, which has a

history of using active case detection, shows that it is less cost-effective (7).

The cost of a case detected through active methods is estimated to be up to

five or six times the cost of a passively detected case. In addition the conclu-

sion that passive finding is more cost-effective than active case finding is intui-

tive, given the widespread experience that improvements in diagnostic services

lead to substantial increases in the notification of TB cases, but have a consid-

erably lower cost than providing screening detection. Sputum–positive TB is

highly symptomatic and surveys show that high proportions of patients seek

care relatively quickly if high quality and low cost diagnostic and treatment ser-

vices are available. In addition, clinical TB develops quicker than the shortest

possible screening intervals, and therefore screening does not always detect

cases before they become infectious.

The finding that passive case detection is more cost-effective than active

screening does not mean that active screening should not be provided. It only

implies that passive screening should be established first. In some circum-

stances active screening for TB may still be cost-effective compared to other

health interventions. At the current time, case detection methods are coming

under renewed scrutiny as, despite the fact that some countries have good

laboratory services, high DOTS coverage and cure rates, many of them still

have low case detection rates. In these circumstances, where capacity has been

developed to provide effective passive case detection, it may be cost-effective to

pursue active case detection (8). The evidence supporting this is currently

based on modeling and is controversial given the high costs of screening and

the fact that there are no studies that demonstrate either the cost or effective-

ness of active case detection in a field setting in low-income countries.

However, these models suggest that active screening may be cost-effective as an

extension to DOTS for population groups where TB incidence is suspected to

be high. For example, the screening of contacts, prison populations, popula-

tions with high levels of HIV/AIDS and populations with suspected high rates

of MDR-TB may be considered for screening.

As an intermediate approach to boost case detection, information, education

and communication (IEC) is considered as an integral part of DOTS. In coun-

tries, which have low case detection rates together with high cure rates, signifi-

cant investment in IEC may also be highly cost-effective. IEC can take many

forms, from a doctor providing a patient with appropriate information on how

TB is transmitted, to mass media campaigns. However, there are no studies

either on the overall cost effectiveness of IEC for TB or the cost-effectiveness of


different methods. Unfortunately, it is also difficult to make estimates of cost-

effectiveness based on IEC from other areas of health, as there is little evidence

on the cost-effectiveness of IEC generally. This is because the effects of IEC

have proven difficult to measure and attribute.

Finally, case detection rates can potentially be improved through collaboration

with the private sector. However, so far there have been no studies in this area

and little is known about the cost-effectiveness of public/private collaboration

in TB control.

Diagnosis by smear microscopyThe WHO recommended method of diagnosis of pulmonary TB is smear

microscopy. Sputum positive TB may also be diagnosed by a culture test.

However, basic calculations suggest that smear microscopy is more cost-effec-

tive and less costly than culture (9). The effectiveness of microscopy is high

and it requires less sophisticated and costly laboratory resources than culture

testing. In addition, diagnosis is significantly faster and therefore reduces the

time that the patient remains untreated and infectious. It is currently recom-

mended that three consecutive sputum examinations are required for a smear

test. There is some evidence that the third test may have a high incremental

cost and therefore some argue that a policy of examining two samples should

be considered in resource poor settings (10). This may be most applicable for

populations with a high level of HIV infection, where laboratories may be

over-burdened.

For TB suspects who cannot be diagnosed by smear microscopy, X-rays are the

most commonly used method to identify suspect cases. However, although

most cases of TB will show abnormalities on an X-ray4 (high sensitivity),

abnormalities may also be due to a variety of other conditions (low positive

predictive value). Sputum culture tests therefore also required to diagnose

smear negative TB. There is no data on the comparative cost-effectiveness of

X-ray and culture testing compared to culture testing alone. Finally, new diag-

nostic tools, such as the PCR test, are being developed which may be faster

than normal culture testing and can be used for all TB cases. There are studies

showing potential gains in cost-effectiveness from these technologies, however,

it remains to be seen if they are feasible (11).

Short Course TherapyStandardised short course regimens are an important element of DOTS. TB

Programmes using short course therapies have consistently achieved higher

cure rates than those relying on longer therapies. Short course therapies are

more effective for two reasons: one, they are more efficacious; and two, com-

pliance is higher. Importantly, short course therapies also reduce relapse rates

and therefore multi-drug resistance. There is strong and consistent evidence

that short course therapies are also more cost-effective. Several studies (7, 12,


13) find that although the short regimens are more expensive, the reduced

length of treatment means that the overall cost to both the health service and

the patient is lower.

Compliance – ObservationEvidence demonstrating that it is unnecessary to hospitalise TB patients for

long periods to prevent transmission was established in the 1960’s, however

many countries still treat TB on an inpatient basis. In addition as new short

course treatments present few side effects, delivering treatment on an ambula-

tory basis through primary health services or the community is now feasible.5

However, ambulatory treatment is only effective if the level of compliance

achieved is high. In the past, most ambulatory programmes relying on the self-

administration of treatment failed to achieve high cure rates. The WHO there-

fore now recommends a policy of direct observation (DOT). In practice, direct

observation means that patients should be observed taking their drugs for at

least for the initial phase of treatment, (usually the first two months of treat-

ment). This requires the close monitoring and follow-up of patients.

Countries applying DOT have achieved high cure rates with ambulatory treat-

ment. However, there is some debate over whether these high rates are due to

DOT or other elements of the DOTS strategy, such as the supervision of provi-

ders and improvements in programme management. This is important from

an economic perspective, as the costs of DOT can be high, particularly in cir-

cumstances where health services are operating at full capacity and the inci-

dence of TB is high. At the time of writing the debate on observation has not

reached its conclusion. Some argue that multiple components might account

for the success of DOTS and that focusing on direct observation as a key factor

in the promotion of adherence is inappropriate. There is only one study exam-

ining the cost-effectiveness of DOT (14). It finds that self-administration is

more cost-effective than supervision by health workers or family members.

This paper has however, been strongly criticised, arguing that there is abundant

evidence of the success of DOT from many countries, where high cure rates

have been achieved. Compared to this, in the study none of the methods of

observation examined had high cure rates, indicating that the DOT was not

being correctly implemented (15).

Two additional points should be noted. Firstly, the definition of observation is

variable. Observation in its widest sense means treatment that is not self-admi-

nistered. In fact there are a variety of ways in which treatment can be consid-

ered as observed. Family and community members can play an important role

in observation and this may be significantly more cost-effective than self-

administration or health service observation (16, 17). Secondly, the studies to

date have not examined the effects of observation on the incidence of MDR

TB. A high treatment completion rate does not indicate whether the treatment

was taken in a correct manner, which has consequences for MDR TB. This


however, is difficult to assess as MDR relapses may not reveal themselves until

after treatment has been completed.

Another strategy to improve compliance is to provide patient incentives. Many

successful TB programmes provide incentives or enablers to patients to com-

plete treatment. These incentives come in several forms, such as: subsidised

patient transportation, food packages, payments to the employers of patients,

and monetary payments to the patient (18). The review referred to several

unpublished studies examining whether these incentives provide added value

and increase treatment completion; most are based in the US or Canada. Most

of these studies (14 out of 17) show that incentives do improve programme

performance. There are two studies that examine patient incentives in develop-

ing countries, one in Haiti and one in Bangladesh. Both find that groups

receiving incentives are more likely complete treatment. However neither study,

looks at the incremental cost-effectiveness of incentives.

Incentives to ProvidersMany TB Programmes face severe human resource constraints, not just in the

absolute lack of staff, but also high rates of turnover and low motivation. In

recent years there has therefore been a renewed interest in providing incentives

to TB providers. Literature on the impact of incentive payments for staff in TB

control is extremely limited, despite the widespread use of TB related incen-

tives. The same review of all the studies identifies fifteen provider incentive

schemes (18). Eight of the schemes use monetary incentives, with the remain-

der providing food, transportation or fuel. Incentives are given for different

behaviours, cures, visits or referrals. There are two unpublished studies exam-

ining provider incentives in low-income countries. The first is from

Bangladesh where incentive payments are made to community health workers

and the second describes the national TB programme in China where incen-

tives are provided to village doctors. Both schemes make payments at different

points in diagnosis and treatment. Both studies show that the introduction of

incentives was associated with increases in detection and completion. However,

as with patient incentives no study was done of the incremental cost-effective-

ness of the schemes.

The studies also raise several concerns about incentive schemes. Financial sus-

tainability of schemes is a key concern, as external financing is responsible for

financing in a large proportion of schemes. Secondly, there is also concern that

schemes need sufficient monitoring to prevent misuse. In some instances the

payment was formalised through a contract, however there is little known

about the best form of contract and mechanism for contract monitoring.


Diagnosis and treatment of MDR-TB (DOTS-plus)

The main strategy to combat MDR-TB is DOTS. By ensuring that treatment is

observed and consists of a combination of at least three different drugs, MDR-

TB can be prevented. However, where outbreaks occur and MDR–TB is already

prevalent, it may be necessary to include the treatment of MDR-TB as an

extension to DOTS. Initial estimates of the cost of treating one patient in

developed countries are in the tens of thousands of dollars. However, over the

last few years there has been a considerable international effort to obtain con-

cessional prices for MDR-TB drugs, and initial estimates of cost for low and

middle countries are considerably lower than those in developed countries.

The first study of the cost-effectiveness of the treatment of MDR-TB, from

Peru (19) estimates the cost of treating one patient to be $2381, with the drugs

cost estimated to be $824. It also estimates the cost per DALY to be somewhere

between $200 and $300. This is well under $550 per DALY, the criteria estab-

lished by the WDR 1993 for inclusion in essential packages in middle-income

countries. Unlike the wealth of information on the different elements of

DOTS, there are currently no strategies examining the cost-effectiveness of dif-

ferent elements of DOTS-plus. In particular little attention has been focused

on the cost-effectiveness of case detection and the diagnosis of MDR-TB.

Collaborative TB HIV/AIDS Interventions

One of the most significant threats to TB control is the HIV/AIDS epidemic.

Although DOTS remains the recommended strategy for TB control in high

endemic HIV/AIDS environments, ways to adapt and integrate DOTS with

HIV/AIDS strategies are currently being explored. Three interventions for those

with living with HIV may also impact the TB epidemic: preventative therapy;

HAART; and interventions which reduce the incidence of HIV.

Several studies show that the mass use of preventive therapy in developing

countries is not likely to be as cost-effective as treating TB, as infection levels

in the population are high and progression to TB is infrequent. In 1986, a

study in Eastern Europe estimated that mass use of preventive therapy costs

$7112 per case prevented, (over $550 per DALY in 2000 prices), using the most

cost-effective regimen of 24 weeks (20). However, as HIV positive patients

have a relatively high risk of developing active TB from infection, the possibi-

lity of providing preventive therapy routinely to HIV positive patients and

family members of those with TB has been re-examined in the last few years.6

Although preventive therapy is efficacious, as with TB treatment, the effective-

ness of the therapy depends primarily on whether a patient is prepared to com-

ply with therapy, in this case for an illness that they do not yet have.

In one of the first studies modeling the potential benefits of preventive therapy,

it was estimated that providing preventive therapy in South Africa would result


in a net saving of around $1million over 8 years (21). This finding is supported

by a study from Uganda (22). It finds that preventive therapy does not result

in a reduction in future health service cost, if only the direct costs of HIV

patients are examined. However, if social costs and the prevention of secondary

cases are also included then preventive therapy will result in net savings. A

study in Zambia (23) also supports this finding, and estimates a net cost if

only direct costs are included, but significant net savings if lost patient income

is taken into account. Excluding indirect and secondary benefits savings, the

Ugandan study estimates the cost per DALY of preventive therapy at some-

where between $150 and $350. The reason for this relatively high figure is the

assumption that TB preventative therapy will only have a small effect on the

life expectancy of an HIV positive patient (8.37 years instead of 7.79 years) and

the relatively low compliance rate.

Where TB is so strongly associated with HIV/AIDS, HIV/AIDS prevention can

also be considered as intervention that controls TB. However, it is likely that

reductions in HIV incidence will take several years before they impact TB inci-

dence, although in the long term it still may prove to be cost-effective way of

controlling TB. There is currently a debate over whether HAART should be

seen as an effective TB control intervention. The application of HAART has

been shown to reduce the incidence of TB in HIV/AIDS cases (2). However

this effect may be temporary. In addition, the current body of economic evi-

dence raises questions about the comparative cost-effectiveness and affordabil-

ity of HAART (24). However, as the evidence base in this area very weak there

needs to be a considerable amount further economic and operational research

in this area before firm conclusions can be made.

In recent years the WHO has begun to work to develop a TB/HIV strategy,

drawing on this evidence, for those countries significantly affected by HIV.

Research is needed to establish cost-effectiveness of the package in a variety of

settings.

ConclusionThis literature review summaries the evidence base on the cost-effectiveness of

TB control strategies. Although the broad cost-effectiveness of DOTS has been

established, it highlights several areas that still require further investigation,

these include: the examination of the cost-effectiveness of re-structuring health

services in middle income countries to provide DOTS; examination of new

strategies for case detection, examination of new strategies/ tools to combat the

growing threat of MDR-TB and assessing the cost-effectiveness of the integra-

tion of TB/HIV services. This thesis aims to support this broad effort, firstly by

adding to the evidence base by estimating costs and cost-effectiveness of differ-

ent TB control strategies, and secondly by examining ways in which to apply

these results to estimate the total resource requirements of implementing TB

control.


THE STUDY PROJECT GOALS AND OBJECTIVES

This thesis reports on a variety of studies exploring different elements of the

TB control strategy. It focuses primarily on estimating the costs and cost-effec-

tiveness of the implementation of DOTS, diagnostic strategies for MDR-TB,

and expanding TB/HIV services, and the use of these results by decision

makers.

Overall Goal

The ultimate goal of this thesis is to contribute towards improved case detec-

tion and control of TB, the development of local research capacity, and the use

by TB policy makers and practitioners of economic analysis.

Objective

The main objective of this thesis is to assess the costs and cost-effectiveness of

selected new TB control strategies in low and middle income countries and

methodologies for applying these to decision making.

Specific Objectives

The specific objectives of this thesis are:

L To assess the cost-effectiveness of re-structuring TB control to DOTS in

middle income countries: Egypt, Syria and Ukraine

L To assess the cost-effectiveness of adopting new technologies to tackle

MDR-TB

L To assess the costs to the patient of integrated TB/HIV services

L To assess the methodologies used to estimate the costs of TB control (and

HIV interventions) in low income countries

THE STRUCTURE OF THE THESIS

Chapter Two examines the cost-effectiveness of DOTs compared to other treat-

ment strategies in Egypt and Syria. This chapter reports on the results of a

study conducted half way through DOTS implementation in these two coun-

tries. Chapter Three examines the cost-effectiveness of DOTS compared to

other treatment strategies in Ukraine. This chapter reports on the results of

pilot projects and discusses the implications for national scale-up of DOTS.

Chapter Four focuses on diagnostic technologies for MDR-TB. It reports on

the results of an economic evaluation conducted as part of a clinical trial in

Peru. Chapter Five presents the results of a study into the patient costs before

and during the use of TB/HIV services. This study was part of a broader cost-

ing study into the costs of TB/HIV services in low income countries. Chapter


Six review the methods used to estimate the costs of TB and HIV interventions

in sub-Saharan Africa. This review aims to inform national policy makers and

planners on the use of costing studies in their medium term financial plans.

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role of active case-finding. International Journal of Tuberculosis and Lung Disease. 1998, 2(9),

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(3): 246-251.

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Lung Disease. 1998 2(3): 235-241.

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Akksilp S. Cost-effectiveness analysis of three short-course anti-tuberculosis programmes com-


pared with a standard regimen in Thailand. Journal of Clinical Epidemiology. 1993; 46 (7):

631-6

14. Khan MA. Walley JD, Witter SN, Imran A, Safdar N.Costs and cost-effectiveness of different

DOT strategies for the treatment of tuberculosis in Pakistan. Health Policy and Planning; 17

(2): 178-186. Oxford University Press 2002

15. Freiden. Lancet 2006, Mar 18; 367 (9514):878-9

16. Floyd, K; Wilkinson D; Gilks CF. Community-based, Directly Observed Therapy for

Tuberculosis: an economic analysis. Corporate Communication Division of the Medical

Research Council. Feb 1997.

17. Islam A, wkai, S, Ishikawa N, Chowdury AMR, Vaughan JP. Cost-effectiveness of community

health workers in tuberculosis control in Bangladesh. Bulletin of the World Health

Organisation 2002, 80 (6).

18. Beith A, Eichler R, Sanderson J, Weil D. Can incentives and enablers improve the performance

of Tuberculosis Control Programmes? Analytical Framework, Catalogue of Experiences and

Literature Review. Stop TB Partnership 2001. Working Draft

19. Suarez PG, Floyd K, Portocarrero J, Alarcon E, Rapiti E, Ramos G, Bonilla C, Sabogal I,

Aranda I, Dye C, Raviglione M, Espinal MA. Feasibility and cost-effectiveness of standardised

second-line drug treatment for chronic tuberculosis patients; a national cohort study in Peru.

Lancet 2002; 359: 1980-89.

20. Snider DE, Caras J, Koplan JP. Preventative therapy with Isoniazid. JAMA 1986 Vol 255, No12

21. Masobe P, Lee T, Price M. Izoniazid prophylactic therapy for tuberculosis in HIV-sero-positive

patients – a least cost analysis. SAMJ Vol 85 No 2 Feb 1995.

22. Bell JC, Rose DN, Sacks HS. Tuberculosis preventive therapy for HIV-infected people in sub-

Saharan Africa is cost-effective. AIDS 1999, 13: 1549-1556

23. Foster S, Godfrey–Fausett P, Porter J. Modelling the economic benefits of tuberculosis preven-

tive therapy for people with HIV: the example of Zambia. AIDS 1997, 11: 919-925.

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NOTES

1 This is now called WHO’s (new) stop-TB strategy (Raviglione et al, Lancet 2006;367:952-5),

however as this thesis was started before this change, this is referred to as DOTS throughout

the thesis.

2 A partnership of international organisations committed to and active in TB control. This

includes the WHO, World Bank and Unicef, NGO’s, and MOHs.

3 The discussion section of this thesis updates this section in the light of the studies presented

and those conducted by others on the same topics during the timeframe of this thesis.

4 Although this is less likely for HIV patients.

5 See above.

6 Also the length of time of preventive therapy, and whether to use a single drug.



Chapter 2

Cost-effectiveness ofdifferent treatment strategiesfor tuberculosis in Egypt andSyria

A Vassall

S Bagdadi

H Bashour

H Zaher

P Van Maaren

SUMMARY

We calculated the costs and effectiveness of alternative ways of implementing TB con-

trol in Egypt and Syria, in order to illustrate the factors influencing the cost-effective-

ness of TB treatment in middle-income countries. We compared the costs and cure rates

in Egypt and Syria of the World Health Organisation recommended directly observed

treatment strategy (DOTS) and alternative strategies. Cost includes costs to both the

health services and to the patient. In Egypt and Syria, the cost-effectiveness of DOTS

implemented through the primary health care (PHC) system is $258 and $243 per

patient cured respectively. This compares to a cost per patient cured of $297 (Egypt)

and $693 (Syria) for alternative strategies implemented through specialist clinics. In

Egypt, when DOTS is implemented through specialist chest clinics it costs $585 per

patient cured. Hospitalisation costs $1490, $1621 or $1699 per patient cured depending

on treatment delivery in the continuation phase. This study demonstrates that the move

towards DOTS integrated at the PHC level has substantially improved the effectiveness

of TB treatment in Egypt and Syria, without increasing costs. An analysis of the different

costs and effectiveness of the variety of TB treatment strategies has enabled the

National Tuberculosis Programmes in both countries to expand DOTS in a way that

takes into account resource scarcity and local health system constraints.

INTRODUCTION

Tuberculosis (TB) is an increasing public health problem, presently accounting

for 3% of global mortality (1). The World Health Organisation (WHO)

recommends a TB Control strategy of directly observed treatment, short course

(DOTS). This entails the use of short course regimens of effective drug combi-

nations, direct supervision of treatment for at least the first two months, and

evaluation of treatment for each patient. DOTS as a broad TB Control strategy

also includes drugs supply, monitoring and case detection based on micro-

scopy. DOT, rather than DOTS refers to observed treatment alone.

The two main aspects of DOT that substantially determine cost and are therefore

likely to influence cost-effectiveness are: one, where treatment is delivered; and

two, the number of visits or level of observation. Generally, TB treatment is

delivered either on fully ambulatory basis or with an initial stay in hospital, fol-

lowed by ambulatory care. Ambulatory care can be integrated or delivered

through specialist centres, with varying degrees of observation. Most studies to

date have found that ambulatory TB treatment, even with a high frequency of

observation, is less costly to health service (2-16) and to the patient than treat-

ment involving an initial stay in hospital. The broad DOTS strategy, through a

combination of observation and improved management has shown its potential

to be highly effective in ambulatory settings. It has therefore been assumed that

for countries moving from a strategy of hospitalised or specialist care to a strat-

egy of ambulatory based DOTS, improvements in both costs and effectiveness

can be made. Additional gains may also be made through integration with other

general health services, from economics of scope.

As a preparation to implementing DOTS, several studies have estimated the

costs of DOTS (4,7,8,9). These have found that despite the number of visits,

the cost of ambulatory based DOTS is still likely to remain below the previous

alternative of hospitalisation or specialised care. However, to date there is little

known about whether these low costs can be achieved at scale and the costs in

middle country settings.

This study sets out to verify these models by measuring the costs and effective-

ness of TB treatment before and after the move to ambulatory DOTS in two

middle income countries. Before the early nineties TB treatment was delivered

through hospitals in Egypt. In Syria, TB treatment was delivered through a net-

work of specialist TB centres on an ambulatory basis. Both countries achieved

a 50-60% cure rate. In the mid-nineties both countries decided to adopt the

DOTS strategy and to integrate TB diagnosis and treatment in the network of

Primary Health Care (PHC) centres. We present here the costs and effective-

ness of integrated DOTS compared to the previous TB control strategy. By

making this comparison, this study illustrates the relationship between differ-

ent delivery strategies and cost-effectiveness of TB control.

Cost-effectiveness of different treatment strategies for tuberculosis 25

METHODS

We used data collected by the National Tuberculosis Programmes (NTP’s) in

Egypt and Syria. At the time of the study both countries were halfway through

their implementation of DOTS integrated at the PHC level. This provided the

opportunity to compare the effectiveness of the large scale implementation of

PHC DOTS to the previous strategies at the same point in time.

The study compares several different treatment strategies, these are summarised

in Table 1. In Egypt, in addition to strengthened programme management,

DOTS is based on a treatment strategy of two months of EHRZ followed by

four months of HR. Treatment is observed daily in the initial phase and weekly

in the continuation phase. In the main, treatment is delivered through the

Primary Health Care (PHC) system. However, where the PHC system is con-

sidered inadequate, treatment can also be provided in chest clinics located in

each district or the initial phase can be provided in hospital. The previous

Non-DOT treatment strategy consists of two months EHRZ followed by either

six or ten months of HE. The initial phase can either be self administered or

supervised in hospital. The continuation phase is self administered, with treat-

ment being provided on a monthly basis. In Syria, DOT (2 EHRZ/4HR) is

delivered through the PHC system. Non-DOT treatment (also 2 EHRZ/4HR)

is self-administered, with treatment being provided on a monthly basis. It is

delivered through a network of specialised TB Centres.

We estimated health service costs by collecting expenditure data from sampled

facilities in both DOTS and Non-DOTS areas. It is common in costing studies

to use stratified sampling techniques. The sampling of facilities had two stages:

the first stage selected provinces of Egypt and Syria; the second stage selected

facilities within them. Provinces were selected to obtain a representative mix of

geographical and population conditions. Within provinces, the selection of

facilities was based on population density and utilisation. Clinics with no cur-

rent TB cases were excluded from the sample.

We calculated the average incremental cost of diagnosis and treatment per

patient. Health service costs were divided into two types, fixed and variable.

Fixed costs are those costs which do not vary when the level of output rises,

variable costs are those which do. The relevant cost with which to compare

cost-effectiveness is average additional (incremental) cost per patient of each

strategy (17-19). The incremental cost associated with TB treatment, is the

sum of the fixed costs whose primary purpose is TB treatment and the variable

costs of TB treatment. If there is no spare capacity in the existing health system

and all the resources required to treat TB are additional, then the incremental

and total costs of TB treatment will be equal. If the resources used for TB treat-

ment can be found from spare capacity in the existing health system, then

incremental costs will be less than total costs.


It was assumed that the PHC system had sufficient spare capacity in terms of

fixed costs to absorb DOT. We therefore excluded these items from our incre-

mental cost calculations, as their primary purpose was not TB. This assump-

tion was based on the fact that TB treatment is not a substantial proportion of

PHC activity (most PHC centers seeing on average 5 TB patients a year). This

assumption was verified during the costing interviews. The PHC staff inter-

viewed felt that no extra staffing, buildings and equipment were required to

add DOT to their existing activities. The main costs items included are there-

fore supervision, training, supplies and drugs. As this assumption is unlikely to

apply in countries where the burden of TB is higher or the PHC system more

stretched, a sensitivity analysis was conducted using average PHC costs. All

costs are shown in US$ 1999 and the exchange rate was 3.4 Egyptian Pounds =

$1 and 46 Syrian Pounds = $1.

We defined TB treatment as the process from diagnosis of TB to confirmation

of cure or the treatment ending. It therefore included the costs of the labora-

tory or X-ray used to diagnose and confirm TB, all chemotherapy, and the

costs of confirming cure. The basic cost items were similar for all facilities and

included capital and recurrent costs. Capital costs included building, equip-

ment, furniture and vehicles, but excluded land. Recurrent costs included sal-

aries, drugs, supplies, utilities. The overhead costs of training and supervision

were also included. Technical support by external agencies was excluded, as

these were not required for the normal running of activities. Where resources

were provided free to the health service, their cost was estimated using market

prices and added to expenditure to estimate total cost. Some cost items in

facilities were shared between TB and non-TB activities. We allocated costs to

TB on the basis of usage or activity rates. We allocated labour costs using time

estimated from interviews with staff. The methodology for allocating overhead

and shared costs in hospitals is the standard "step-down" methodology as

described in Drummond et al (17).

In order to measure the cost-effectiveness from a societal perspective, we

included the costs of different strategies to the patient and their families in

addition to health service costs. We included all monetary costs, including pay-

ments for treatment, payments for travel and miscellaneous expenses. We also

included the opportunity cost of time spent traveling to and receiving treat-

ment. We valued the opportunity cost of patient time by using a low-middle

national income average in Egypt, and the responses of patients in Syria. Due

to time limitations we did not estimate the monetary cost of hospitalisation in

Egypt. However, as hospital time costs were expected to be significantly higher

than the time costs of ambulatory care, it was anticipated that this would not

affect the comparison of results. We included the costs to the patient and per-

sons accompanying the patient to receive treatment.


We measured patient costs using a facility based survey and a stratified sample

of patients beginning TB treatment in the second half of 1998. The sample was

representative in terms of age, sex and area of residence. In both countries we

selected patients from the sampled facilities and interviewed patients at the

point of receiving treatment. In Syria, we interviewed a total of 135 patients

from 595 total cases beginning treatment nationally. In Egypt, we interviewed

150 patients from an estimated total of 2500 beginning treatment nationally.

The two countries used slightly different methods to collect patient costs, as

data collection tools were designed taking into account patient privacy consid-

erations. However, as the objective of the study is to make comparisons within

countries, these differences did not affect the end result. In Syria, the monetary

cost includes the complementary expenditure made in the private sector.

We measured the direct benefits that accrue as a result of treatment, to the

patient or the health services. We chose cure rate as our primary measure of

effectiveness. This is equivalent to the WHO measure of patients successfully

treated. The cure rate is defined as the proportion of those patients whose cure

was confirmed by sputum examination and found to be negative for TB bacilli

and those who complete a full treatment regimen. Data on cure rates for

nationally and for sampled facilities was obtained from NTP records.

Cure rate captures the direct health benefits of TB treatment, but not the non-

health benefits or indirect benefits to others. However, higher cure rates will

result in less transmission of TB and a lower requirement for second-line treat-

ment and less multi-drug resistance (MDR). The benefits from reduced trans-

mission are significant and can represent up to 82% of health benefits from

treatment (3) Although we did not have sufficient information to model trans-

mission for Egypt and Syria, we did make an estimate of the potential savings

to the health service of the different treatment strategies, using an international

model in Murray et al (3). An estimate of 7 cases prevented over 18.5 years per

case cured was used. Future costs were discounted at a rate of 3%. Our esti-

mate does not include the cost savings from reduced MDR or second-line

treatment. We did not estimate the direct and indirect benefits of preventing

chronic TB cases or investigate other possible benefits of the DOTS strategy

such as increases in the proportion of pulmonary positive in comparison to

pulmonary negative and extra-pulmonary tuberculosis. Cost effectiveness was

calculated by dividing total incremental cost by cases cured, to arrive at an

average incremental cost per case cured.

Three sensitivity analyses were conducted. The first tested the impact of the

allocation of salaries cost to TB and non-TB activities. This was necessary as

salaries expenditure is a significant proportion of cost and there is always some

uncertainty about the accuracy of responses from staff interviewed about how

they spend their time, (although all responses were cross checked with supervi-

sors and patient records). The salaries costs were halved for the chest clinics


and hospitals in Egypt as the cost-effectiveness ratios were found to be reason-

ably close to those at the PHC level. The test was unnecessary for the Syrian

results as all activities in the clinics relate to TB and staff therefore were not

required to estimate the proportion of time allocated to TB. A second sensitiv-

ity analysis examined the different impact of sampled and national cure rates

on the cost-effectiveness ranking for Egypt, as these differed considerably, (see

Table 4), indicating that we may have chosen under-performing DOTS areas

and over-performing non-DOTS areas. The third sensitivity analysis tested the

cost-effectiveness ranking if average rather than incremental costs were used

for the PHC level, as this assumption, although reflecting the reality, may not

apply should the PHC service becomes fully utilised.

Table 1 – Alternative Strategies

TB Diagnosis and Treatment Strategy Regimen Initial PhaseFrequency

ContinuationPhaseFrequency

SYRIADOTS through the PHC system 2EHRZ/4HR Daily WeeklyNon-DOTS through TB centres 2EHRZ/4HR Monthly MonthlyEGYPTDOTS through the PHC system 2EHRZ/4HR Daily WeeklyDOTS through specialist centres 2EHRZ/4HR Daily WeeklyDOTSHospitalised initial phaseCont. Through specialist centres

2EHRZ/4HR Daily Weekly

DOTSHospitalised initial phaseCont. Through PHC

2EHRZ/4HR Daily Weekly

Non-DOTSAll through specialist centres

2EHRZ/10HE Monthly Monthly

Non-DOTSHospitalised initial phaseCont. Phase through specialist centres

2EHRZ/6HE Daily Monthly

S = Streptomycin; H = Isoniazid; Z = Pyrazinamide; R = Rifampicin; E = Ethambutol

RESULTS

Health service costs per case treatedThe average incremental health service costs per case treated for each strategy

are shown in Table 2. DOTS implemented through the PHC network is the

cheapest strategy in Syria, costing under $200 per case treated. In Syria, Non-

DOTS, (no strengthened supervision, training and programme management,

short course self administered therapy) is considerably more expensive at

around $350. The main explanation for this difference is the considerable dif-

ference in diagnosis cost, not treatment costs. The move towards integration of

TB treatment at the PHC level has meant that general diagnostic facilities are


used to diagnose TB. The previous specialist clinics had relatively few TB

patients for the investment in diagnostic services. Treatment costs do not

change because although observation involves increased numbers of visits the

average cost per visit is lower.

Table 2 – Average Incremental Health Service Cost (US$) per case treated

TB Diagnosis and TreatmentStrategy

Health Service Costs Total

Diagnosis/Confirmationof cure

TreatmentInitial PhaseTreatment

TreatmentContinuationPhase

SYRIADOTS/ PHC 49 115* 19* 183Non-DOTS/ SC 223 92 38 353

EGYPTDOTS/ PHC 27 86* 51* 164DOTS/SC 26 219 102 347DOTS/ Hospital/ SC 105 774 102 981DOTS/Hospital/ PHC 105 774 58 937Non-DOTS/SC 46 73 47 166Non-DOTS/ Hospital/ SC 123 774 47 944

SC- specialist clinic* The difference in costs of PHC DOTS in Egypt and Syria is primarily explained by differingdrugs costs in each of the countries

In Egypt, DOTS integrated through the PHC system is the lowest cost option,

at $164 per patient treated. This compares to the near equivalent cost of $166

for standard therapy, self administered therapy delivered through specialised

clinic. This is similar to the situation in Syria, whereby the lower average cost

of the PHC level compensates for the increased level of observation. DOTS is

implemented through specialist clinics is considerably more expensive than

Non-DOTS at around $350. Treatment with the initial phase in hospital is the

considerably more expensive than the ambulatory options costing $900-$1000

per case treated.

In both countries supervision and management costs also do not differ sub-

stantially between the DOTS and Non-DOTS areas. This is likely to be because,

although DOTS may increase supervision and management, this is integrated

in district management. In the non-DOTS area, visits and training, although

less frequent, cost more, as they often involved central level TB specific staff.

Patient costs per case treatedPatient costs are shown in Table 3 and display a similar pattern to health ser-

vice costs. In both countries, patient costs are equivalent in areas where DOTS

is implemented through the PHC system and areas where Non-DOTS is imple-

mented through the specialist clinics. For DOT delivered through the PHC sys-


tem the patient has to make small costs often, for self-administered therapy

through the specialist clinics the patient has to make large costs, but these are

relatively infrequent. When short course therapy is observed and delivered

through specialist clinics the cost to the patient increases as this requires fre-

quent and high cost visits. Hospitalisation is the most expensive option for the

patient. It consumes comparatively large amounts of patients time which has a

high opportunity cost in terms of income forgone.

Table 3 – Patient Costs (US$) per case treated

TB Treatment Strategy Time costs2 Monetary3 Total

SyriaDOTS/ PHC 23 18 41Non-DOTS/SC1 23 19 42

EgyptDOTS/ PHC 19 3 22DOTS/SC 69 5 74DOTS /Hospital/SC 240 2 242DOTS/Hospitalised/ PHC 229 1 230Non-DOTS/SC 19 2 21Non-DOTS/ Hospital/SC 232 1 233

1. SC-Specialised clinics2. Time converted into dollars using patient responses (Syria) and low-middle income average

(Egypt).3. Monetary costs are all costs where payment was made by the patient, includes travel fares,

drugs costs etc.

Treatment OutcomeTreatment outcomes both nationally and for the study sample are shown in

Table 4. In the study sample TB treatment in DOTS clinics is found to be

more effective than the Non-DOTS. DOTS achieves a cure rates of 92% in

Syria and 72% in Egypt, (the national picture for DOTS is 88% in Syria and

83% in Egypt). Non-DOTS clinics in both countries achieve cure rates of

between 60-70%. As stated in the methodology, it must be noted that specific

conclusions about observed short course treatment (DOT) cannot be drawn

from this comparison, as DOTS includes improved management.

In Egypt, where DOT patients are hospitalised there is no increase effectiveness

on a national basis. Effectiveness seems to be primarily determined by the

strategy used in the continuous phase, with DOTS being more successful than

Non-DOTS. However, in our sample from Non-DOTS areas, we found a high

cure rate for hospitalisation followed by self-administration. This is due to the

influence of one large hospital that was achieving exceptional results.


Table 4 – Treatment Outcome - % Cases cured national/ sampled

TB Treatment Strategies Cure Rate1 - Sampled Facilities Cure Rate - National

SyriaDOTS/ PHC 92% 88%Non-DOTS/SC 57% 68%EgyptDOTS/ PHC 72% 83%DOTS/ SC 72% 83%DOTS/ Hospital/ SC 72% 83%DOTS/ Hospital/ PHC 72% 83%Non-DOTS/ SC 63% 64%Non-DOTS/ Hospital/ SC 79% 64%

1. Cure rate = % of patients cure confirmed and those completing treatment whose cure wasnot confirmed.

Cost EffectivenessWe combined average incremental costs with sampled cure rates to arrive at an

average incremental cost per case cured. The results are shown in Table 5. In

both Egypt and Syria, the most cost-effective strategy is DOTS implemented

through the PHC system. DOTS implemented through the PHC system

improves effectiveness without increasing the cost either to the health service

or the patient compared to the other strategies in Egypt and Syria.

Comparing treatment delivery through specialist clinics, however, reveals that

DOTS is less cost-effective than non-DOTS at this level. In this case, improve-

ments in effectiveness are only gained at an increased cost to the health service

and to the patient. In this circumstance, where strategies are more expensive,

but more effective, the essential question facing decision-makers is whether

curing extra patients is worth the additional cost. In Egypt, we estimated that

the additional cost of curing one extra patient, if specialist clinics adopt a

DOTS strategy compared to non-DOTS, is $2605.

Table 5 – Cost per Patient Cured (US$)

TB Treatment Strategies Total Cost percase treated(a)

Cost percase cured

Future costsavings percase treated(present value) (b)

Net savingsper casetreated(present value) (b-a)

SyriaDOTS/ PHC 224 243 1853 1629Non-DOTS/ SC 395 693 1052 657

EgyptDOTS/ PHC 186 258 683 497DOTS/ SC 421 585 683 262Non-DOTS/ SC 187 297 600 413DOTS/ Hospital/ SC 1223 1699 683 (540)Non-DOTS/ Hospital/SC 1177 1490 755 (422)DOTS/ Hospital/ PHC 1167 1621 683 (484)


Table 5 also shows the calculation for reduction in future cost savings. Using

the model described above, our estimates of future savings show that all the

ambulatory strategies result in savings, whereas the strategies involving hospita-

lisation in the initial phase result in a net cost. The greatest savings in both

countries are from a strategy of DOTS delivered through the PHC system. For

every $1 dollar spent DOTS delivered through the PHC system saves $7.

Sensitivity AnalysisThe results of the sensitivity analyses can be seen in Table 6. The first sensitiv-

ity analysis halving the salary cost at the chest clinic results in a changing of

cost-effectiveness ranking. Non-DOTS provided at the chest clinic level in

Egypt becomes the most cost-effective option, with a cost per case cured of

$241. However, taking into account the future prevention of cases, it is likely

that over the long term PHC DOTS remains the option as it will still generate

the highest net savings due to its higher effectiveness. The second sensitivity

test using national cure rates in Egypt increases the cost-effectiveness of the

DOTS alternatives, with cost per patient cured with DOTS implemented at the

PHC level costing $224 instead of $258. Therefore the ranking of the alterna-

tives did not change. The third test found that using average costs instead of

average incremental costs for PHC activities decreases their cost-effectiveness.

In Egypt, the cost per patient cured rises to $292, and in Syria to $420.

However, despite this increase there is no change in the ranking of alternatives.

However, it must be noted that in Egypt the cost-effectiveness of DOTS at the

PHC level and self-administration at the chest clinic level ($297) come very

close to each other.

Table 6 – Sensitivity Analysis

TB Treatment Strategies Cost percasecured

Cost percase cured(halving salariescost at clinics –

Egypt)

Cost percase cured(Nationalcure rates)

Cost percase cured(Average costsat PHC level)

SyriaDOTS/ PHC 243 NA 381 420Non-DOTS/ SC 693 NA 695 NA

EgyptDOTS/ PHC 258 NA 224 292DOTS/ SC 585 414 507 NANon-DOTS/ SC 297 241 292 NADOTS/ Hospital/ SC 1699 NA 1473 NANon-DOTS/ Hospital/SC 1490 NA 1403 NADOTS/ Hospital/ PHC 1621 NA 1839 NA


DISCUSSION

The results of this study demonstrate that DOTS implemented through the

PHC system is the most cost-effective strategy in Egypt and Syria. It increases

effectiveness without increasing costs compared to the previous TB strategies

in both countries. A continued move towards DOTS implemented through the

PHC level to improve the cost-effectiveness of TB control.

Most of the gains on the cost are made from integration. Integrating DOTS in

the PHC system reduces health service costs. This finding applies whether aver-

age or average incremental costs are used. This also applies to the costs of

supervision which did not increase as TB programme management was inte-

grated in district management systems. Despite the increased number of visits,

average patient costs are also lower for DOT at the PHC level than less frequent

observation at specialist clinics and hospitals. The patient gains as services are

brought closer to home.

On the effectiveness side, the gains are likely to come from DOT are not

adversely affected by integration. Both in our sample and nationally, DOT has

achieved a substantially higher cure rate than previous hospitalized and self-

administered treatment in both Egypt and Syria. However, we cannot make

any conclusions about whether the increased effectiveness associated with DOT

is due to higher rates of observation or improved programme management

resulting in improvements in service quality. It is unlikely that patient costs

were a factor as they remained similar in DOTS and Non-DOTS settings. In

Egypt, however, a reduction in the length of treatment may also be a factor as

implementing DOTS involves a change from standard to short course therapy.

The comparison between DOTS and Non-DOTS at the chest clinic level in

Egypt, demonstrates the cost increase associated DOTS where integration at

the PHC does not take place. Where DOTS is delivered through specialist

clinics it was found to be less cost-effective than self-administration. Moving

from monthly visits to DOTS, increases the number of visits five fold (approxi-

mately from 10 visits to 50), and therefore also increases incremental average

cost five fold. By comparison, cure rates are only increased by 20%. In these

circumstances, although DOTS increases effectiveness, it increases costs by a

greater proportion, and reduces the overall cost-effectiveness of TB treatment.

In part as a result of these findings, both countries have continued with their

expansion of DOTS nationally. In addition, the programmes have refined their

health systems approach to deliver DOTS. In Egypt, delivery of DOTS through

the chest clinics is being reduced to minimum, and is only permitted where

the PHC system is not functioning. In addition, further studies have been com-

missioned to evaluate the efficiency and management of specialist chest clinics.

These studies will assess whether the resource management in clinics can be


improved and therefore average costs reduced. In Syria, the role of the TB cen-

tres is also being re-examined. It is expected that average cost per visit at these

clinics are likely to rise further, as the number of TB patients reduces.

Consideration is therefore been given to expanding their remit to chest diseases

more generally.

Finally, the results of this study are being used by the Egyptian TB programme

to encourage hospital managers, insurance organisations and clinicians to

adhere to the standard protocols, and therefore only to accept hospital admis-

sion for the more serious TB cases. If hospital admission can be reduced sub-

stantial savings should be generated to the health service, insurance

organisations and patients.

CONCLUSION

This study illustrates that the move towards DOTS integrated at the PHC level

has substantially improved the effectiveness of TB treatment in Egypt and

Syria, without substantially increasing costs. This verifies previous models pre-

dicting that countries moving away from hospital based or self administered

specialized clinic based treatment to PHC based DOTS are likely to see

improvements in the cost-effectiveness of TB control. On the cost side most of

the gains come from moving to integrated ambulatory care. On the effective-

ness side gains are likely to come from DOT and improved programme man-

agement. This study cannot make any conclusions about observation or any

other specific aspect of DOTS per se. This cost-effectiveness analysis has been

successfully used by both NTPs to continue to expand DOTS in a way that

takes into account resource scarcity and local health systems.

REFERENCES

1. World Health Organisation. The World Health Report 2000 Health Systems: Improving

Performance. WHO; 2000.

2. Kamolratanakul P, Chunhaswasdikul B, Jittinandana A, Tangcharoensathien V, Udomrati N,

Akksilp S. Cost-effectiveness Analysis of three Short-course Anti-Tuberculosis programmes

compared with a standard regimen in Thailand, Journal of Clinical Epidemiology 1993; 46 (7):

631-636.

3. Murray CJL, DeJonghe E, Chum HJ, Nyangulu DS, Salomao A, Styblo. Cost effectiveness of

chemotherapy for pulmonary tuberculosis in three sub-Saharan African countries. The Lancet

1991 Nov 23; 338.

4. Floyd K, Wilkinson D, Gilks CF. Community-based, Directly Observed Therapy for

Tuberculosis: An economic analysis. Corporate Communication Division of the Medical

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5. Burman WJ, Dalton CB, Cohn DL, Butler JRG, Reves RR. A Cost-effectiveness Analysis of

Directly Observed Therapy vs Self-administered Therapy for Treatment of Tuberculosis, Chest

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6. Moore RD, Chaulk P, Griffiths R, Cavalcante S, Chaisson RE.. Cost-Effectiveness of Directly

Observed Versus Self-Administered Therapy for Tuberculosis. American Journal of Respiratory

and Critical Care Medicine 1996; 154: 1013-1019.

7. Milgliori GB, Khomenko AG, Punga VV, Ambrosetti M, Danilova I, Ribka LN et al. Cost-effec-

tiveness analysis of tuberculosis control policies in Ivanovo oblast, Russian Federation. Bulletin

of the World Health Organisation 1998; 76 (5): 475-483.

8. Saunderson PR. An economic evaluation of alternative programme designs for tuberculosis

control in rural Uganda. Soc.Sci.Med; 40 (9): 1203-1212.

9. Kriegel AV. Comparison between a DOTS strategy and the traditional strategy of TB treatment

in Uzbekistan. Medecins Sans Frontieres Holland.

10. Sawert H, Kongsin S, Payanandana V, Akarasewi P, Nunn PP, Raviglione MC. Cost and benefits

of improving tuberculosis control: the case of Thailand. Social Science Medicine 1997; 44(12):

1805-1816.

11. Chunhaswasdikul B, Kamalratanakul P, Jittinandana A, Tangcharoensathien V, Kuptawintu S,

Pantumabamrung P. Anti-Tuberculosis Programs in Thailand: A cost analysis. Southern Asian

Journal of Tropical Medicine and Public Health 1992; 23 (2).

12. Barnum HN. Cost savings from alternative treatments for tuberculosis. Soc Sci Med 1986; 23

(9): 847-850.

13. Joesoef MR, Remington PL, Tjiptoherijanto P. Epidemiological Model and Cost-Effectiveness

Analysis of Tuberculosis Treatment Programmes in Indonesia. International Journal of

Epidemiology 1989; 18(1).

14. Fryatt RJ. Review of published cost-effectiveness studies on tuberculosis treatment pro-

grammes. Int J Tuberc Lung Dis 1997; 1(2):101-109.

15. Murray, CJL. Social, economic and operational Research on Tuberculosis: Recent Studies and

some Priority Questions. Bull Int Union Tuberc Lung Dis 1991; 66.

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tries. AWorld Bank Book. Oxford Medical Publications; 1993.

17. Drummond MF, O’Brien B, Stoddart GL, Torrance GW. Methods for the Economic Evaluation

of Health Care Programmes. 2nd ed. Oxford Medical Publications; 1997.

18. Floyd K. Generic protocols for cost en cost-effectiveness analysis of tuberculosis diagnosis and

treatment services. WHO; 1999.

19. Sawert, H. Cost Analysis and Cost Containment in Tuberculosis Control Programmes; The

case of Malawi. WHO; 1996.

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Republic of Egypt. Partnership for Health Reform, Health Policy Support Programme.

Technical Report 25. PHR; 1998.


Chapter 3

Reforming tuberculosis controlin Ukraine; results of pilotprojects and implications for thenational scale-up of DOTS

A Vassall

Y Chechulin

I Raykhert

N Osalenko

MJ van der Werf

S Svetlichnaya

A Kovalyova

LV Turchenko

E Hasker

К Miskinis

J Veen

R Zaleskis

Health Policy and Planning 2009 Jan; 24(1): 55-62

SUMMARY

The period of economic transition has had severe consequences for health and health

systems in Ukraine. The tuberculosis (TB) situation illustrates this. The World Health

Organization (WHO) recommended strategy for TB, Directly Observed Treatment Strategy

(DOTS), has the potential to provide real improvements in TB services, forming the basis

of the response to the growing epidemic. In 2002, Ukraine financially supported by

USAID and the European Community (EC) began to introduce DOTS through pilot pro-

jects in Mariupol and Kyiv City. The aim of this study is to assess the feasibility, effec-

tiveness, health service cost, patient cost, and cost-effectiveness of these pilots, in

order to inform the national scale-up of DOTS.

The study finds that DOTS is feasible and has the potential to be both effective and

cost-effective in Ukraine. Following this study, Ukraine adopted DOTS as a national TB

control strategy in 2005. However, the pilots also found that there are several evidence

related concerns and perverse economic incentives to both providers and patients that

will need to be addressed if national scale-up is to be successful. These include con-

cerns related to the treatment of MDR-TB, economic benefits to some patients to remain

hospitalized, and payments to providers and health facilities that support current prac-

tices. These will need to be addressed if Ukraine is to develop an effective response to

its emerging TB epidemic.

INTRODUCTION

The period of economic transition in the Ukraine and other ex-Soviet coun-

tries has had severe consequences for tuberculosis (TB) control. TB control ser-

vices have faced several major challenges. Firstly, TB control services

experienced a severe reduction in funding. Secondly, the population became

substantially poorer. Thirdly, social security benefits for TB patients (disability

pension, job security) have disappeared. Lastly, there has been a concurrent

spread of the HIV/AIDS-epidemic, bringing with it more dually infected TB

cases (Drobniewski and Nikolayevsky 2005, Hamers and Downs 2003). As a

result of these factors, tuberculosis case notification rates in Ukraine have more

than doubled since the collapse of the Soviet Union, from 32 per 100,000 in

1990 to 80.9 per 100,000 in 2004. The incidence of Multi-Drug Resistant TB

(MDR-TB) has also risen (Dye and Espinal 2002).

Although it is difficult to attribute the extent to which the epidemic has been

affected by different factors, it is clear that the health system has failed to

respond (Coker and Atun 2004). The system for controlling TB in Ukraine was

established in the time of the Soviet Union. Although general health services

have the ability to diagnose TB, many cases are detected through mass screen-

ing of the population by fluorography. TB services are vertically organised and

highly centralised. General health services have no major role in treating TB

patients. TB patients typically undergo lengthy, non-standardised treatments,

in specialised TB hospitals. The infrastructure of these specialised services has

deteriorated and staff morale has been substantially weakened by low salaries

and reduced professional status. It is argued that a combination of administra-

tive inertia, professional beliefs about communicable disease control and scep-

ticism about the evidence base for Directly Observed Treatment Strategy,

(DOTS) (World Health Organisation 1999) have prevented the adoption of

internationally accepted best practice (Coker and Atun 2004).

Since 2002, the World Health Organisation (WHO), USAID, the European

Union (EU) and KNCV Tuberculosis Foundation have worked together imple-

menting pilot projects introducing DOTS. The aim of these pilots has been a)

gradual reorientation of TB detection to passive screening using microscopy;

b) standardization of treatment regimens; c) increased use of ambulatory treat-

ment; d) increased involvement of general health services in case detection and

treatment. The aim of this paper is to report and assess the feasibility, effective-

ness, and cost-effectiveness of these pilots and to inform the national level to

scale-up DOTS.

Reforming tuberculosis control in Ukraine 39

METHODS

Setting

Two pilot projects were established in Mariupol and Kyiv City. Mariupol city

has a population of half a million people. In 2003 the case notification rate

was 87 per 100,000 and 445 new cases of TB were newly registered. Kyiv city

has a population of 2.64 million. In 2001 the case notification rate was 40.5

per 100,000 and 1,056 TB cases were newly registered.

Alternative TB Control Strategies

A summary of the existing and piloted DOTS based TB control strategies is

presented in Table 1. These differ from each other in several respects. Firstly,

Ukraine has traditionally relied on mass fluorography screening to detect TB

cases. In contrast the pilot projects introduced passive case detection using

sputum smear microscopy through general health services. Secondly, TB

patients in Ukraine were previously treated using individualized treatment.

This treatment required patients to stay between six months to two years in

hospital (averaging in the pilot sites around eight months). Treatment in both

sites continued until the radiological closure of cavities and patients could be

monitored as outpatients for up to ten years. In contrast, the pilot projects

introduced short standardized treatment regimens. These shorter regimens

consisted of two phases, an intensive phase and a continuation phase. The

intensive phase used four drugs (H,R,Z and E or S)7 for at least two months,

followed by four month continuation phase, using two drugs (H and R).

During the intensive phase, patients were treated as inpatients in a TB hospital.

During the continuation phase patients could opt for ambulatory treatment,

provided under direct observation (DOT) from TB dispensaries, polyclinics, or

Red Cross facilities. A social support scheme for TB patients was set up to sup-

port adherence to treatment. The Red Cross provided basic food rations to all

ambulatory patients every fortnight. Treatment success was monitored by spu-

tum smear conversion, but also by culture and chest X-ray.8

Assessment of Feasibility

The progress of the pilot projects was recorded using WHO and EC’s TACIS

reporting system. Using a logical framework approach, this monitors progress

against project results and project milestones. Key results included: general

health services staff (GHS) able to correctly identify and manage suspects and

to administer treatment on an ambulatory basis; WHO recommended treat-

ment schemes implemented; passive case finding (PCF) improved through pro-

moting health seeking behaviour of the community; and policy developed and

implemented to ensure adherence to treatment. Reasons for success or failure

were identified and analysed by all stakeholders in quarterly periods through-


out the project. Final outcomes were reported, presented and evaluated at the

end of each project.

Table 1 – TB Control Strategies

Area Year Case Detection Diagnosis and Treatment

Mariupol 2001 Mass screening by fluorography Long course hospitalized treat-ment (9-12 months), plus follow-up in outpatients (6 months)

2003 Passive case detection bymicroscopy

Shorter course hospitalizedtreatment (2-3 months), plus fol-low-up in outpatients (4 months)

Kyiv City 2003 Mass screening by fluorography Long course hospitalized treat-ment (9-12 months), plus follow-up in outpatients (6 months)

2004 Passive case detection bymicroscopy

Short course hospitalized (2-3month) and ambulatory treat-ment in a polyclinic (4 months)

Estimating Effectiveness

Effectiveness was measured using a number of metrics, including measures of

the effectiveness of case detection, measures of treatment success and measures

of health outcome as outline in the WHO guidelines (WHO 1997). Ideally,

comparing the effectiveness of two TB control strategies should be done

through a randomized controlled trial. However, this was not possible, as the

projects were primarily aimed at demonstrating the feasibility of DOTS, not as

a controlled trial of its effectiveness. Therefore the method used to assess effec-

tiveness was a before and after approach.

Data on the effectiveness of mass screening by fluorography was collected ret-

rospectively, from the existing case notification system. Data on smear micro-

scopy was collected using a recording and reporting system established during

the pilot projects based on WHO guidelines (WHO 1997). Effectiveness of

treatment was measured using WHO defined treatment success of new smear

positive TB cases (WHO 1997). Treatment success could be measured in

Mariupol, however in Kyiv it was not possible to measure outcomes at the end

of treatment. This was only possible at the point of two months, due to the

length of available funding. Effectiveness of the previous system of treatment

was measured retrospectively using medical records. An algorithm to obtain

comparable indicators of treatment success was developed using test results

and patient events to determine cure or treatment completion at eight months,

(the time horizon for DOTS) for all bacteriologically confirmed TB cases. It

was not possible to exclude non-pulmonary respiratory TB from this effort.

However, these cases are unlikely to have bacteriological confirmation, so out-

comes for respiratory and pulmonary TB are regarded as broadly comparable.9


It was also not possible to exclude patients who were culture positive but smear

negative in the old reporting system. These patients are also likely to have bet-

ter treatment outcomes than those who are smear positive as they have a less

severe form of the disease.

Finally, deaths averted and Disability Adjusted Life Years (DALYs) gained were

estimated using international life expectancies in accordance with WHO guide-

lines (Tan-Torres Edejer and Balthussen 2003). These estimates were based on

treatment outcome at eight months. They did not include the DALYs gained

from reductions in transmission.

Estimation of Health Service Costs

Health Service costs were estimated using an ‘ingredients approach’. This

method measures the quantities of all resources used and prices/values them to

arrive at cost (Tan-Torres Edejer and Balthussen 2003). An exception was made

for overhead costs for both inpatient and outpatient days. These were esti-

mated using standard methods, collecting overhead expenditure data and allo-

cating to TB control activities using the step-down method (Drummond

1997). Data was sourced from one TB hospital in Mariupol and four TB hospi-

tals in Kyiv City, ranging in size from 100-400 beds. Data was also collected

from six GHS polyclinics. Polyclinics were selected using stratified sampling,

dependant on area and utilization, from 60 polyclinics in Kyiv City.

Fluorography costs were estimated using expenditure data from the Central TB

Services. We attributed all expenditure on fluorography to TB services.

Although fluorography may detect a variety of other lung diseases, in Ukraine

it is primarily funded on the basis of its role in detecting TB cases.

The average cost of diagnosis and treatment was calculated by using the aver-

age number of outpatient visits, inpatients bed-days, drug costs and diagnostic

costs for different types of patients (Floyd 2002). Activity data was sourced ret-

rospectively from hospital and TB services medical records and patient records

databases.

Estimating Patient Costs

Data on patient costs was collected in 2004 from Kyiv and Mariupol using a

structured questionnaire. The questionnaire was also used for a study on health

care seeking behaviour (Van der Werf and Chechulin 2006). Data was collected

on direct and indirect costs of both patients and care-givers. Information for

each patient was gathered from medical records and by face-to-face interview.

All patients >15 years of age who consented to participate and were diagnosed

with pulmonary TB less than four months before the interview (to reduce

recall bias) were eligible for inclusion in the study. Patients not speaking

Ukrainian or Russian, patients with a chronic underlying pulmonary condition


and patients who were seriously ill were excluded from the study. The number

of TB patients selected per facility was proportional to the number of new

patients admitted to the facility in 2002. To estimate the cost of ambulatory

care, we interviewed patients attending Red Cross sites in Kyiv City, as insuffi-

cient numbers of patients were being treated in general health services at the

time. The data were entered in Microsoft Access in duplicate by two different

persons and the two files were compared to identify typing errors. Analysis was

conducted using SPSS.

For all local costs we an exchange rate of 5.31 UAH to 1 US$ (International

Monetary Fund). Costs are presented in exchange rate US$ constant prices

2003. We used a discount rate of 5% when annuitising capital costs (Walker

2002). When comparing costs between time periods we used a 5% deflator.

Assessment of Cost-effectiveness

Cost effectiveness was assessed using standard methods and taking a societal

perspective (Floyd K 2002, Drummond and O’Brien 1997). A sensitivity analy-

sis was conducted on impact on our results of changing several variables.

These included activity levels (i.e. number of outpatient visits, inpatient bed-

days) to assess the effects of uncertainty surrounding retrospective data collec-

tion; and effectiveness to assess the effects of uncertainty surrounding the qual-

ity of medical records. All spreadsheets on costs, effectiveness and cost-

effectiveness estimates are available from the corresponding author.

RESULTS

Feasibility

The pilot projects were partially successful in achieving their results. The pro-

jects successfully provided the resources, systems and training to establish a

functioning DOTS-based TB control system. Smear microscopy was introduced

in GHS, standardized treatment regimens were provided, and patients had

(and used) the option to receive the continuation phase of treatment on an

ambulatory basis.

However, the pilots were not fully able to replace the existing system with

DOTS. Fluorography screening continued during both pilot projects. It was

only at the end of the pilot project in Mariupol that restricting the use of fluor-

ography screening to high risk groups was adopted. In Kyiv, TB specialists

agreed to the WHO recommended schemes as the minimum requirement, but

felt it necessary to retain the flexibility to treat certain patients in an individua-

lized way. TB doctors were therefore allowed to continue treatment for longer

if they felt this was necessary. A further compromise was reached in Kyiv

whereby DST testing was then carried out on all new TB cases. Once the result


was known, in case of drug resistance a new treatment regimen with second

line anti-TB drugs was initiated. This individualized treatment had to be

approved by the ‘Central Physician Consultation Committee’, a committee of

TB specialists that met on a weekly basis and evaluated all newly registered TB

cases. Finally, neither pilot projects managed to reduce the level of follow-up

treatment (post eight months) even in cases that had a confirmed cure.

Effectiveness

Both projects were successful in demonstrating improvements in TB treatment

effectiveness. Table 2 shows effectiveness of TB treatment before and during

the pilot projects. In Mariupol, treatment success rate increased rapidly

between 2001 and 2003, with the introduction of the short course WHO regi-

men. Failures and death rates fell, but the most dramatic change was a reduc-

tion in the numbers of treatment interrupted. In Kyiv, data for the first cohort

of patients was not available at the end of the pilot project. Initial sputum

results after two months showed 63% of patients converting to negative.

There was a 43% treatment success rate in the old system, suggesting that

improvements were made.

Table 2 – Effectiveness of Diagnosis and Treatment, WHO treatment outcomeclassification

Treatment Outcome Mariupol Kyiv

2001 2003 2001 2003

Failure 18% 14% 11% Sputumconversionat twomonths63%

Treatment interrupted 18% 8% 30%Died 5% 3% 14%Transfer out 1% 1% 2%Treatment success 58% 74% 43%

Health Service Costs

Both projects also demonstrated a reduction in costs. Table 3 shows the health

service costs for each alternative for each city. In Kyiv, the average health ser-

vice cost of treating and diagnosing a case of smear positive TB in the old sys-

tem was $1141 and in Mariupol $951. This is slightly lower than the costs

found in Russia (Migliori and Khomenko 1998, Jacobs and Clowes 2002). By

comparison, the cost of diagnosis and treatment during the projects was found

to be substantially lower, at $663 for Mariupol and $589 for Kyiv. The reduc-

tion in cost is primarily due to the shortened length of inpatient stay. Drugs

costs were not substantially reduced in Mariupol remaining at around $90-100

per patient. Moving to internationally purchased WHO regimens would

further reduce costs to around $20. It should however be noted that outpatient


visit costs in the polyclinics were found to be higher than at hospital. This is

because polyclinic capacity was underutilized and may change as more cases

are treated on an ambulatory basis.

Table 3 – Average Health Service Costs to Diagnose and Treat a New Case of SmearPositive Pulmonary Tuberculosis (SM+PTB) (US$ 2003)

Mariupol

Activity Unit Cost Quantity Total Cost

2001 2003 2001 2003

Inpatient Bed-day 3.56 225 139 801.00 494.84Outpatient Visit hospital 0.34 56 43 19.04 14.62Smear Microscopy 0.94 10 10 9.40 9.40Culture 3.62 0 6 0.00 21.72X-ray 4.17 4 4 16.68 16.68DST Culture 3.54 0 2 0.00 12.53Drugs 105.00 93.00

Average health service cost to diagnose and treat a newcase of Sm+ PTB(2003$)

951 663

Kyiv City

Activity Unit Cost Quantity Total

2003 2004 2003 2004

Inpatient Bed-day 5.85 166 64.5 971.10 377.33Outpatient visit hospital 0.57 14 4 7.98 2.28Outpatient visit polyclinic 3.02 0 50 0.00 151.00Smear Microscopy 0.75 12 9 9.00 6.75X-ray 6.03 6 4 36.18 24.12Culture 1.89 12 8 22.68 15.12DST Culture 2.08 2 1.1 4.16 2.29Drugs 89.62 20.00

Average health service cost to diagnose and treat a newcase of SM+PTB (2003$)

1141 599

Patient Costs

The impact of the pilot projects on patient costs was mixed. In Kyiv and

Mariupol, 156 and 58 new smear positive TB (Sm+PTB) cases being treated as

inpatients and 51 and 50 outpatients were interviewed respectively. An addi-

tional 36 polyclinic patients receiving outpatient care from Red Cross facilities

were also interviewed in Kyiv. Tables 4 and 5 show the results. Where the cost

is indicated as negative, this means that patients benefited from treatment, as

the social benefits they received outweighed the costs. In Mariupol, on average,

patients receiving TB treatment in both 2001 and 2003 benefited economically.


In Kyiv, on average, inpatients treated in 2003 incurred a cost, despite the

social benefits available, as both patients and caregivers experience substantial

income losses. This is because most patients in Kyiv are salaried employees,

with only 19.5% of patients jobless (Van der Werf and Chechulin 2006). If

social benefits are excluded (as transfer payments) then costs for patients fell in

Mariupol, but increased in Kyiv.

Table 4 – Average Patient Costs Pre-treatment and during Diagnosis and Treatmentfor a New Case of Smear Positive Pulmonary TB in Mariupol (US$ 2003)

Unit cost Quantity Total

2001 2003 2001 2003

Pre-treatment costs(n=58) Days from symptom to TB diagnosis 0.27 31 31 8.37 8.37

Direct Costs during Diagnosis and Treatment(n=58) Inpatient bed-days 0.02 225 139 4.5 2.78(n=50) Outpatient visit hospital 0.01 56 43 0.56 0.43

Indirect costs during Diagnosis and Treatment(n=58) Inpatient treatment days 0.06 232 146 13.92 8.76(n=50) Outpatient treatment days -1.43 151 126 -215.93 -180.13

Care givers costs during Diagnosis and Treatment(n=58) Inpatient treatment days 0.00 232 139 0.00 0.00(n=50) Outpatient treatment days 0.00 151 126 0.00 0.00

Average Costs including Social Benefits -188.58 -159.79

Social Benefits during Diagnosis and Treatment(n=58) Inpatient bed-days 0.22 225 139 49.5 30.58(n=50) Outpatient treatment days 1.48 152 126 224.96 186.48

Average Costs excluding social benefits 85.88 57.27


Table 5 – Average Patient Costs Pre-treatment and during Diagnosis and Treatmentfor a New Case of Smear Positive Pulmonary TB in Kyiv (US$ 2003)

Unit cost Quantity Total

2001 2003 2001 2003

Pre-treatment costs(n=156) Days from symptom to TB diagnosis 0.77 48 48 36.96 36.96

Direct Costs during Diagnosis and Treatment(n=156) Inpatient bed-days 0.36 166 64.5 59.76 23.22(n=51) Outpatient visit hospital 0.02 14 4 0.28 0.08(n=36) Outpatient visit polyclinic 1.51 0 50 0 75.5

Indirect costs during Diagnosis and Treatment(n=156) Inpatient treatment days 0.61 173 71.5 105.53 43.62(n=51) Outpatient treatment days hospital -0.21 0 0 0 0(n=36) Outpatient treatment days polyclinic -3.22 0 121 0 -389.62

Care givers costs during Diagnosis and Treatment(n=156) Inpatient treatment days 0.65 173 71.5 112.45 46.48(n=51) Outpatient treatment days hospital 0.63 0 0 0 0(n=36) Outpatient treatment days polyclinic 0.00 0 121 0 0

Average Cost, including social benefits 314.98 -163.76

Social benefits during Diagnosis and Treatment(n=156) Inpatient treatment days 0.23 173 71.5 39.79 16.45(n=51) Outpatient treatment days hospital 0.21 0 0 0 0(n=36) Outpatient treatment days polyclinic 4.93 0 121 0 596.53

Average Cost, excluding social benefits 354.77 449.22

Cost-effectiveness

Both projects demonstrated improvements in cost-effectiveness. Table 6 and 7

present the results on cost-effectiveness. Our findings show that cost of detect-

ing one case of TB using mass screening is between $5713-10,229 per case

detected. By comparison it costs between $188-247 to detect a patient using

passive case detection. The cost-effectiveness of diagnosis and treatment

improved in both settings between 2001 and 2003. In Mariupol the cost per

case cured fell from $2729 to $1333, more than a fifty percent reduction. In

Kyiv the fall was equally dramatic, with falls from $6504 to $2414 (assuming a

63% eventual cure rate).10 The cost per DALY for the new method ranges from

$55 to $100. Our sensitivity analysis showed that these results are robust after

adjusting for reasonable ranges of activity rates and effectiveness.


Table 6 – Average Cost per New Case of Smear Positive Case of Pulmonary TB (SM+PTB) Detected (US$ 2003)

Location Method of casefinding

Unit cost percase screened

Number of casesscreened to detectone case of Sm+PTB

Cost perSM+ case ofPTB detected

Mariupol Active Case Detectionusing Fluorographyscreening

4.90 1166 5713

Passive Case Detectionusing Microscopy

3.50 70.6 247

Kyiv City Active Case Detection usingFluorography screening

3.67 2787 10229

Passive Case Detection usingMicroscopy

3.96 47.5 188

Table 7 – Cost-Effectiveness of Diagnosis and Treatment of Smear PositivePulmonary TB (SM+ PTB) (US$ 2003)

Mariupol Kyiv

2001 2003 2001 2003

Average Health Service Costs toDiagnosis and Treat SM+ PTB (2003$)

951 663 1141 599

Average Patient Costs (excluding socialbenefits) (2003$)

86 57 355 449

Average Costs to Diagnose and TreatCase of Sm+ PTB (2003$)

1037 720 1496 1048

Success rate58% 74% 43% 63%

(Sputumconversionat twomonths)

Average Cost per Sm+ PTB Case Cured(2003$)*

2729 1333 6504 2437

Average Cost per Death Averted (2003$)* 3034 1482 7227 2708Average Cost per DALY (2003$)* 117 55 268 100

* Excluding transmission effects, with an assumption 20% self cure, assumption 90% of thosecured would otherwise die

DISCUSSION

The pilot projects demonstrate that DOTS is potentially effective and cost-

effective in Ukraine. This mirrors findings from other evaluations of DOTS

pilots from the ex-Soviet Union (Migliori and Khomenko 1998, Jacobs and

Clowes 2002). The improvement in cost-effectiveness is due to a number of


factors. Firstly, fluorography has a substantial cost and may not be as effective

as passive case detection using microscopy. In Kyiv city, with a population of

2.64 million, almost half of the population is screened by fluorography every

year. To detect one case, more than 2,500 people needed to be screened.

Despite this substantial effort, in the year 2000, only 30% of all new cases were

detected through fluorography. However, fluorography consumes around 50%

of the total budget available for TB control.

Secondly, the introduction of standardized treatment regimens substantially

reduces costs, without a significant impact on effectiveness. In 2000, the esti-

mated budget requirement for TB drugs for new patients (WHO category I)

for Kyiv City was $207,659. Yet the total number of new TB cases diagnosed

annually is around 1,000 and a full course of the WHO recommended category

I treatment regimen can be purchased for as little as $ 20 through international

non-profit suppliers. The Mariupol pilot found that despite relatively high fail-

ure rates and the threat from MDR-TB, standardized short course regimens are

effective for the majority of TB patients. Finally, the pilots demonstrated that

ambulatory treatment is potentially feasible, less costly and does not reduce the

effectiveness of treatment. In Mariupol ambulatory treatment substantially

improved adherence to treatment and therefore its effectiveness.

These pilots were primarily designed as implementation pilots and therefore

our analysis of cost-effectiveness has several limitations. Firstly, the weakness of

a ‘before and after’ design is clearly illustrated by the increase in patient costs

after DOTS in Kyiv. This increase is primarily explained by the high incomes

of the group of patients opting for ambulatory care. A further example is the

difference between the definition of patients (i.e. the definition of respiratory

TB and inclusion of smear negative TB) when comparing treatment effective-

ness between the pilots and the old system. In addition, as fluorography con-

tinued throughout the project period, it is likely that the effectiveness of

passive detection through microscopy is also underestimated. However, despite

these weaknesses, all these factors bias our analysis of cost-effectiveness towards

the old system, and therefore our central finding that the pilots were more

cost-effective remains robust. Lastly, it should be noted that our analysis only

shows results from pilots over a short period. Particularly in the case of results

from Kyiv, our results are only suggestive regarding treatment success.

Despite these weaknesses, the pilots demonstrate the potential effectiveness and

cost-effectiveness of DOTS in Ukraine. However, they did not manage to fully

introduce DOTS and replace the ex-Soviet approach. Considerable effort may

still be required before DOTS can be implemented as a national TB control

strategy. A number of issues need to be tackled. Firstly, there remains consid-

erable concern among TB specialist that some high risk groups will not be

identified by passive case detection, and therefore resistance to removing mass

screening remains. A solution would be to retain screening for high risk


groups. Further study is therefore recommended to better identify which

groups are at a high risk of TB in Ukraine.

Secondly the use of microscopy as a fast, easy and cheap method to identify

infectious cases was only reluctantly accepted. It was seen as an old methodol-

ogy, not relevant for the needs of Ukraine. Yet it allows early segregation of

infectious patients and therefore is important in the reduction of nosocomial

transmission and prevention of occupational risk of infection for the staff. It

usefulness in this role needs to be further stressed in the Ukrainian adapted

WHO guidelines.

Lastly, there is still some way to go in convincing TB specialists that standar-

dized treatment should replace individualized treatment in a context where

there is a threat from MDR-TB. The pilot projects improved the process for

providing individual treatment, but did not remove it. Treatment failure rate

in the Mariupol pilot remained high at 14%, and was of considerable concern

to TB specialists. In Kyiv, TB specialists were only prepared to accept DOTS on

the basis that DST would be carried out on all positive cases beginning treat-

ment. Knowledge is scarce on the threat of man-made resistance by prescrib-

ing insufficient doses or too few combinations of effective drugs. Further

studies are therefore recommended to further investigate the best method for

addressing the problem of treatment failures within the Ukraine. A clear policy

for the identification and treatment of MDR-TB needs to be established, that

adequately addresses Ukrainian TB specialists concerns about the spread of the

disease.

When the project started TB specialists were collecting and aggregating a

wealth of data, but they were not analysing the results in order to remedy

weaknesses. Historically weaknesses were hidden to avoid punishment by the

administration. In the pilot sites the administration was change oriented, and

the systematic analysis of effectiveness did create ‘advocates’ for the broad

DOTS strategy. This in some part led to the adoption of DOTS as a national

TB control strategy in 2005. However, even if the remaining evidence gaps are

addressed our analysis of costs also shows that there are significant economic

dis-incentives that may affect the scale-up of DOTS in Ukraine.

The introduction of DOTS affects both patients and providers economically.

On the patient side, hospital admissions can fulfill a social purpose for some

patients (Atun and Samyshkin 2005). This is particularly the case with the

homeless, where TB hospitals provide beds and social support. However, con-

trary to widespread belief that high numbers of TB patients are homeless in

Ukraine, this study found that only 5.3% of pulmonary TB patients in Kyiv are

homeless. The patient costs survey shows that the majority of patients in fact

incur substantial costs with hospitalization. It is probable that this high oppor-

tunity cost of inpatient care is a major factor for defaulting. When the results


of this study were presented to hospital managers and TB clinicians, most

recognized this as the primary reason given for defaulting, reporting that most

defaulters were those with higher incomes, who left hospital as soon as they

felt well. In addition, the pilot in Kyiv demonstrates that for the minority of

patients who benefit from hospitalization, some of these social benefits can be

successfully delivered through an outpatient/community based approach, sup-

porting adherence. It therefore is feasible for TB services to link with other ser-

vices to ensure that the minority who are in need of substantial economic

support get the help they need. A hospital bed is unlikely to be the cheapest

way of providing much needed accommodation.

The reduction in hospitalization resulting from increasing ambulatory treat-

ment will have a significant impact the funding of TB control providers. The

short time frame of the project meant that the thorny issue of TB hospital

down-sizing was not addressed. In fact the additional resources provided

through pilot projects may mask any reductions in hospital incomes resulting

from reductions in inpatient care. This issue will become apparent in a

national scale up. At present, there is a substantial economic incentive to

maintain long length of stays as hospitals in Ukraine are paid according to the

number of beds and norms for resource usage. Given the limited number of

TB patients, hospitals need to keep patients in their beds in order to maintain

the number of beds when reviews are made, and therefore maximize revenue.

This provides a dis-incentive to down-size the number of hospital beds.

Moving to a payment system where hospitals are paid a fixed fee per case

would provide an incentive to treat patients in the lowest cost way, but this

would need to be carefully introduced. Safeguards would need to be made to

ensure that an adequate quality of care was provided and that no perverse

incentives occur to over-diagnose cases. In addition, policy makers must

develop a transparent pathway for down-sizing TB hospitals that includes ade-

quate compensation for the staff currently working in these hospitals. In

Ukraine the average age of TB clinicians in Kyiv is over retirement age.

However, state pensions have been substantially reduced, removing any eco-

nomic incentive to retire.

Attention also needs to be given to incentives provided to general health ser-

vices. National scale-up will not be achieved if there is a disincentive to general

practitioners to provide TB treatment. There is little known about the level of

informal payments in Ukraine. However, anecdotal evidence suggests that they

are significant. The patient cost study only found low levels of informal pay-

ments to TB doctors. This supports the argument that newly trained doctors

are reluctant to specialize in communicable diseases due to the low level of

informal income associated with these diseases. Ensuring adequate payments to

general practitioners providing ‘free’ TB services may therefore also facilitate

reform.


CONCLUSION

This study shows that the DOTS can improve TB control in Ukraine. This will

enable Ukraine to combat the TB epidemic in a sustainable way. The DOTS

based approach is likely to both substantially increase the effectiveness of TB

control and reduce the costs of TB diagnosis and treatment to the health ser-

vice and the patient. However, in order to realise these gains, health systems

planners now need to find ways of addressing both the evidence based con-

cerns of Ukrainian TB physicians, and economic incentives both to the users

and providers. These aspects need to be included in the overall strategy for

expanding DOTS in Ukraine.

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IM, Coker RJ. Barriers to sustainable tuberculosis control in the Russian Federation health sys-

tem. Bullentin of the World Health Organisation. March 2003, 83(3) 217-223.

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Melentsiev A, Marchenko G, Zakharova S, Atun R. Tuberculosis control in Samara Oblast,

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and TB rates in Odessa and the Ukraine. Int J STD AIDS. 2005 May;16(5):374-8.

9. Drummond MF, O,Brien B, Stoddart GL, Torrance GW. Methods for the Economic Evaluation

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Africa. BMJ Vol 315 1407-1411. (29 Nov) 1997

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12. Hamers FF, Downs AM, 2003. HIV in central and eastern Europe. Lancet 361: 1035-44.


13. Jacobs B, Clowes C, Wares F, Polivakho V, Lyagoshina T, Permitin G, Banatvala N. Cost-effec-

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14. Kamolratanakul P, Chuhnaswasdikul B, Jittinandana A, Tangcharoensathien V, Udomrai N,

Akksilp S. Cost-effectiveness analysis of three short-course anti-tuberculosis programmes com-

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15. Migliori GB, Khomenko AG, Punga VV, Ambrosetti M, Danilova I, Ribka LN, Grzemska M,

Sawert H, Raviglione MC. Cost-effectiveness analysis of tuberculosis control policies in

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18. Tan-Torres Edejer T, Baltussen R, Adam T, Hutubessy R, Acharya A, Evans DB, Murray CJL.

Making Choices in Health: WHO Guide to Cost-effectiveness Analysis. Geneva, World Health

Organisation 2003

19. Van der Werf MJ, Chechulin Y, Yegorova OB, Marcinul T, Stopolyanskiy A, Voloschuk V,

Zlobinec M, Vassall A, Veen J, Hasker E, Turchenko LV. Health care seeking behaviour for TB

symptoms in Kyiv City, Ukraine. Int J Tuberc Lung Dis. 2006; 10(4): 390-395

20. Vassall A, Bagdadi S, Bashour H, Zaher, H, Van Maaren P Cost-effectiveness of directly

observed treatment for tuberculosis in Egypt and Syria. International Journal of Tuberculosis

and Lung Disease. 2002 Dec; 6(12): 1083-90.

21. Vassall A, Chechulin Y, Raykhert I, Turchenko LV, Hasker E, Miskinis K, Veen J. The social

costs of tuberculosis treatment in the Ukraine. Awaiting publication.

22. Walker D, Kumaranayake L. Allowing for differential timing in cost analyses: discounting and

annualisation. Health Policy and Planning; 17 (1):112-118

23. World Bank. Ukraine at a Glance. Washington, World Bank, 2005

24. World Health Organisation. Treatment of Tuberculosis: Guidelines for National Programmes.

WHO/TB/97.220. Geneva, World Health Organisation. 1997

25. World Health Organisation. What is DOTS? A Guide to understanding the WHO-recom-

mended TB Control Strategy known as DOTS. WHO/CDS/CPC/TB/99.270. Geneva, World

Health Organisation,1999.

26. World Health Organisation/Stop TB. Global Plan to Stop Tuberculosis. World Health

Organisation. WHO/CDS/STB/2001.16

53Reforming tuberculosis control in Ukraine 53

NOTES

7 H=Isoniazid; R=Rifampicin; Z=Pyrazinamid; E=Ethambutol; S=Streptomycin

8 Fluorography is a small sized photograph of a fluorescent image of the chest used for screening

purposes (Mass Miniature Radiography, MMR), while a chest X-ray (CXR) is a projecttion

radiograph of the chest made for diagnostic purposes.

9 The FSU used definitions of respiratory and non-respiratory TB, defining basically intrathora-

cal and extrathoracal localisation of the disease. The WHO classification uses pulmonary and

extrapulmonary TB, defining disease in organs that have an open connection with the upper

airways (lungs, bronchial tree) and that in other organs.

10 The cure rate may be higher if there is a late conversion. On the otherhand it is usually lower

because of default in the continuation phase.


Chapter 4

Cost effectiveness analysis ofintroducing rapid, alternativemethods to identify multidrug-resistant tuberculosis in middleincome countries

C Acuna-Villaorduna

A Vassall

G Henostroza

C Seas

H Guerra

L Vasquez

N Morcillo

J Saravia

R O’Brien

M Perkins

J Cunningham

L Llanos-Zavalaga

E Gotuzzo

Clinical Infectious Diseases. 2008 Aug 15; 47(4): 487-95

SUMMARY

Background: Resistance to commonly used anti-tuberculosis (TB) drugs is emerging

worldwide. Conventional drug susceptibility tests (DST) are slow and demanding.

Alternative, rapid DST methods would permit the early detection of drug resistance and

in turn arrest TB transmission.

Methods: A cost-effectiveness analysis of five DST methods was performed in the con-

text of a clinical trial comparing rapid and conventional DST methods. The methods

under investigation were: direct phage replication assay (FASTPlaque-Response TB);

direct amplification and reverse hybridization of the rpoB gene (INNO-LiPA Rif TB); indir-

ect colorimetric MIC (MTT), and direct proportion method on Löwenstein-Jensen (DLJ).

These were compared with the widely used, indirect proportion method on Löwenstein-

Jensen (IDLJ).

Results: All alternative DST methods were found to be cost-effective compared to other

health interventions. DST methods also generate substantial costs savings in high MDR-

TB prevalence settings. Excluding benefits of transmission, DLJ was the most cost-effec-

tive alternative DST method for patient groups with a MDR-TB prevalence of 2%, 5%,

20% and 50% ($94, $36, $8 and $2 per DALY respectively).

Conclusion: Alternative, rapid methods for DST are cost-effective and should be consid-

ered for use by National Tuberculosis Programs in middle income countries settings.

INTRODUCTION

Resistance to commonly used anti-tuberculosis drugs is emerging worldwide.1-3

National Tuberculosis Control Programs (NTPs) require effective strategies to

rapidly detect and treat patients infected with resistant organisms. Guidelines

on multi-drug resistant tuberculosis (MDR-TB) treatment and affordable drugs

are now available.4-9 However, consensus on the best strategy for detecting

MDR-TB in resource-poor settings remains elusive. Conventional drug suscept-

ibility testing (DST) methods are slow and cumbersome.10-11 This limits their

availability and allows the transmission of MDR-TB to proceed unchecked.12-15

In contrast, alternative, rapid methods for assessing in vitro antibiotic suscept-

ibility would permit the prompt detection and treatment of MDR-TB.

The indirect proportion method on Lowenstein Jensen media (IDLJ) is the

most widely used DST method. However it takes 8 to 12 weeks to yield results

in good circumstances and up to 6 months in field conditions. Morbidity,

mortality and transmission of resistant strains during this period are critical

concerns. Recently, a number of alternative methods for DST have been devel-

oped, including colorimetric indicators for early detection of bacterial growth,

molecular methods to detect resistance-associated mutations, and phage repli-

cation assays. Several studies have evaluated the performance of these methods

with promising results.16-25 However, there are no studies estimating the cost

and cost-effectiveness of implementing DST methods in low or middle income

settings. The question of whether DST methods are affordable and cost-effec-

tive in the context of the severe resource constraints faced by developing coun-

tries therefore remains unanswered.

Peru is a middle-income country26 with an incidence of pulmonary TB of 178

per 100,000 inhabitants. Currently, MDR-TB testing is limited to the IDLJ

method for those with high risk for MDR-TB and those failing treatment at

five months.27 Recently, several alternative methods for detecting MDR-TB

have been evaluated in a large trial. These included: the commercially available

line probe assay Inno Lipa (Innogenetics, Belgium) that detects mutations in

the RpoB “hot spot” gene region, responsible for more than 90% of rifampicin

resistance;16-17 a phage-based assay (FAST PlaqueResponse Test, Biotech UK)

that detects live M. tuberculosis in a plaque assay on a lawn of rapidly growing

detector cells;18-19 a non commercial colorimetric method using tetrazolium

salt 3-(4,5-dimethylthiazolyl-2)-2,5-diphenyltetrazolium bromide (MTT, ICN

Biomedicals Inc.), a general indicator of cellular growth and viability whose

oxidized yellow form becomes purple upon reduction to formazan by the

dehydrogenases of live bacterial cells20-22 and the direct proportion method in

Lowenstein Jensen medium (DLJ), whereby sputum is inoculated directly on LJ

slants with and without antibiotics after being decontaminated and diagnosis is

based on the proportion of mycobacteria growing in a drug-containing LJ slant

in comparison with the growth of the strain in a drug-free slant.25

Cost effectiveness of methods to diagnose MDR-TB 57

We report here on costs and cost-effectiveness of introducing these methods in

Peru for patient groups with different prevalences of MDR-TB. Our results can

be used by other NTPs in middle income country settings to help assess

whether alternative DST methods could rationally be adopted, and to estimate

the financial impact of doing so.

METHODS

Data on the cost and performance of DST methods was collected from a phase

III clinical trial, conducted in Lima Norte. This region, one of five health juris-

dictions in Lima, has a population of 3,3 million inhabitants. MDR-TB preva-

lence among new smear positive patients is 2% and among treatment failures

is 50%.27 From May 2004 to September 2005, all adults newly diagnosed with

smear positive pulmonary tuberculosis from all 37 health care centers in Lima

Norte were identified. After obtaining informed consent, at least 1 sample con-

taining 5 ml of sputum was obtained for each patient and sent for decontami-

nation and DST (3 samples had previously been taken to establish smear

positive TB). IDLJ, Inno Lipa, MTT and DLJ were performed in the National

Institute of Health laboratory, Lima. FAST Plaque-Response was performed at

Alexander von Humboldt Tropical Medicine Institute laboratory, Lima.

Cost and cost-effectiveness estimates were calculated for patient groups with

2%, 5%, 20%, and 50% MDR-TB prevalence. These rates correspond to those

most commonly found on global surveillance of tuberculosis drug resistance by

WHO.28 Costs and health outcomes for each method were calculated compared

to a ‘do-nothing’ state where MDR-TB treatment is provided, but DST is not

available. In this state, clinical diagnosis of MDR-TB is made based on failure

of first line treatment failure. It was assumed that patients failing first line

treatment would be switched to a standardized MDR-TB regimen at five

months and that 2% of patients would die while waiting for MDR-TB treat-

ment. In contrast, it was assumed that a patient with DST results is switched to

MDR-TB treatment within 7 days. Patient pathways for DST and for clinically

defined MDR-TB are shown in Figure 1.

The first step in our analysis was to calculate average cost per case detected for

each DST method. This cost includes: the unit costs of tests; cost savings from

shortened first line treatment resulting from increased diagnostic speed; and,

the costs of mistakenly treating false positives. The cost of false positives was

calculated assuming that these patients would receive a full course of MDR-TB

treatment.

Unit test costs for each DST method were measured using standard meth-

ods.29,30 Costs were calculated for each test using a health services perspective.

Costs were measured for IDLJ and all alternative DST methods when used to


determine rifampicin resistance, and where appropriate for rifampicin and iso-

niazid resistance (MDR-TB). All costs were measured from the time of sputum

collection until the time of test result. We included all indirect (overhead) and

direct inputs (including buildings, equipment, training, transportation, sup-

plies, salaries and utilities). Test costs were calculated using the ‘ingredients’

approach. This multiplies the quantity of inputs used by their price. There

were two exceptions: the cost for sputum collection which was taken from

Suarez;31 and overhead and quality control costs, which were calculated by allo-

cating total expenditures to each test based staff time (for example manage-

ment/ supervision costs), or where relevant building space (for example

utilities costs).

The quantity of inputs used (e.g. staff time, supplies) was measured by a mix-

ture of observation and recording by laboratory technicians. This was done at

the mid-point of the trial. Quantities were based on 20 observations per test

method, and was verified by examining protocols, expenditure and laboratory

records. This measurement did not include staff time in between tests, the

wastage of supplies and unused equipment capacity. Data on these were col-

lected through a mixture of observation, interviews and laboratory records

examination. Costs were then calculated assuming 80% usage of staff and

equipment, and 5% wastage of medical supplies. Costs of contamination and

invalid tests were also included.

Costs are presented using international prices (US$2004). Prices of inputs vary

considerably by country and there are no standard international prices available

for many laboratory supplies. We sourced prices from catalogues and websites,

reviewed by the WHO. Cost of delivering goods to Lima was included. Local

prices were converted to international dollars using an exchange rate of 3.5

soles to the dollar.

The second step was to estimate the average cost per case detected, including

the future cost savings associated with reduced transmission of MDR-TB from

improved diagnostic speed. Estimates of the period of infectiousness assume

that DST testing would occur at 0 months for all patient groups, patients

would remain infectious for the first two months of treatment, and that false

negatives would remain infectious for the entire period. The model presented

in Bailey32 was used to estimate the probability of infection and secondary

cases averted during the period of infectiousness. This model excludes further

(tertiary) cases generated by secondary cases. Cost savings were calculated by

multiplying the number of secondary cases by MDR-TB treatment costs. These

future savings were discounted at an annual rate of 3%, as recommended by

the Panel on Cost-Effectiveness in Health and Medicine.33-34

The third step was to estimate the average cost per Disability Adjusted Life

Year (DALY) for each test. Estimates of health outcome and DALY’s were based


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on the deaths averted from early case detection and the corresponding reduced

transmission. For those treated, no direct health benefit was assumed from

starting treatment early as evidence of this is scanty. Deaths averted from sec-

ondary cases were calculated assuming that 30% remain untreated, in line with

national case detection rates. Age at onset of MDR-TB, treatment cure rates

and life expectancy were sourced from trial, NTP data and international life

tables. As with cost savings from reduced transmission, DALYs calculated

exclude the benefits from preventing further tertiary cases generated by second-

ary cases.

Data analysis was conducted using Excel. A full list of assumptions, variables

and their source is presented in table 1. It should be noted that although IDLJ

is widely used as gold standard for DST in developing countries, there is little

evidence to support this. Therefore the cost-effectiveness of IDLJ was calculated

assuming 98% specificity and sensitivity. A spreadsheet containing all estimates

and data analysis can be obtained from the authors.

Table 1 – List of assumptions used in cost-effectiveness analysis

Variable Case base estimate Source

Variables related to costsCost of MDR-TB treatment $ 2895† 31Daily cost of SCC (intensive phase) $ 0,91667 27Daily cost of SCC (continuation phase) $ 0,16667 27Number of days of intensive phase 60 27Number of days of continuation phase 120 27Wastage of buildings, equipments andstaff

20% Observation, records

Wastage of medical supplies 5% Observation, recordsExchange rate from soles to int'l dollars 3,5 WHO choice websiteDiscount rate 3% 33-34Length of time to change for first line toMDR-TB treatment once diagnosed

7 days NTP data

Variables related to effectiveness

Sensitivity Rif only/ MDR-TBFastPlaque-Response 93,6/92,8 Clinical trialInnoLipa 92,5/92,8 Clinical trialDLJ 93,5/93,5 Clinical trialMTT 84,3/83,5 Clinical trialIDLJ 98/98 Assumption

Specificity Rif only/ MDR-TBFastPlaque Response 96,8/95,3 Clinical trialInnoLipa 99,3/98,1 Clinical trialDLJ 99,0/98,5 Clinical trialMTT 99,2/97,8 Clinical trialIDLJ 98/98 Assumption


Variable Case base estimate Source

Speed of Diagnosis and rates of contamination/indeterminate resultsFastPlaque Response 2 days and 24,6% Clinical trialInnoLipa 2 days and 0,7% Clinical trialDLJ 40 days and 6,1% Clinical trialMTT 35 days and 8,9% Clinical trialIDLJ 70 days and 6,4% Clinical trial

Variable related to impact of diagnosis on transmissionRate of infected patients that developactive MDR-TB after 2 years.

8% 47

Probability of infection after exposure to apatient with MDR-TB�

elog odds /1+ elog odds* 29

Average number of close contacts perpatient

6 Clinical trial

Average number of contact hours per dayof household contacts

8 Assumption

Death rate per month for patients withMDR-TB on first line treatment.

2% Assumption

Length of time that MDR-TB patientremains on first line treatment withoutdiagnosis

5 months Clinical trial

Cure rate among MDR-TB patients treatedwith second line standardized treatment

50% 32

Variables related to calculation of DALYSAverage age of illness 31 Clinical trialLife expectancy 70 Census dataDiscount rates for assessing costs andhealth gain in the future

3% 33-34

� This model estimates the probability of being infected with tuberculosis after having contactwith a smear positive patient for a specific amount of time. We assumed that 8% of infectedpeople will develop active tuberculosis in the future.Log odds were calculated assuming that the hypothetical contact was exposed 8 hours dailyto a 30 year old patient with smear positive pulmonary TB with cavitations in the CXR

Sensitivity analysis was performed to test the robustness of our results. Results

were subjected to a one-way, two-way and multi-way analysis. The effect of

changes in prices (+/- 10%), sensitivities, specificities (+/- 2%) and our effi-

ciency assumptions (+/- 5%) were amongst the variables tested. Finally, we

ran a Monte Carlo simulation involving 10 000 iterations for most variables in

our model, including the sensitivities and specificities of tests, period of infec-

tiousness, wastage, self cure rate, hours of daily contact, number of contacts

per patient, percentage of latent TB patients who develop active TB. We used

@Risk software (version 3.5) to determine means and upper and lower bounds

(5th and 95th centiles) of the main output of interests (average cost per DALY

gained).


RESULTS

During the study period, 1120 patients with smear positive pulmonary tuber-

culosis were enrolled. Out of these 278 were excluded, 35 because of inability

to produce sputum and 243 because the sample obtained was later found to be

smear-negative. 842 patients were confirmed as cases of smear-positive and cul-

ture-positive pulmonary tuberculosis. DST results were available for IDLJ in

804 (95,4%) specimens, for FastPlaque-Response in 607 (72,1%), for InnoLipa

in 797 (94,7%), for DLJ in 739 (87,8%) and for MTT in 799 (94.9%).

FastPlaque-Response displayed a high level of contamination and indetermi-

nate results. Table 1 shows diagnostic performances, speed of diagnosis and

contamination rates.

Unit costs for each DST method are presented in Table 2. The unit cost for all

tests, aside from InnoLipa, is between $25-42. DLJ has the lowest unit cost

($30.5 for MDR-TB). InnoLipa has the highest unit cost ($111.7 for MDR-

TB). Medical supplies (i.e. kit costs) are the major determinant of cost for the

commercial tests. The non-commercial tests (DLJ, IDLJ and MTT) are more

time intensive and therefore had a high proportion of overhead and capital

costs. Staff costs are high for Innolipa and FastPlaque-Response due to the

time and expertise required. Unit costs for MDR-TB tests are slightly higher

than those for rifampicin resistance.

The cost of testing 1000 patients and the average cost per case detected foreach DST method, excluding transmission savings, are presented in Table 3.DLJ had the lowest cost per case detected for all prevalence patient groups($3913, $1522, $326 and $87 per MDR-TB case detected respectively). IDLJranked second ($4886, $1950, $433 and $129 respectively) and MTT third($6146, $2399, $525 and $151).

Table 4 presents the cost of testing 1000 patients and average cost per case

detected for each DST method, including savings from future transmission. All

tests are cost-saving in patient groups with over a 20% MDR-TB prevalence.

For the 50% prevalence patient group, all methods generate near equivalent

savings (approximately $700 saved per MDR-TB case detected). DLJ is the low-

est cost option for 2% and 5% prevalence group ($3031 and $640 per case

detected). IDLJ was the second lowest option ($4111 and $1159 per case

detected).

Table 5 presents average cost per DALY for each DST method. Including cost

savings from reduced transmission, DLJ has the lowest cost per DALY gained

at 2% prevalence of MDR-TB ($41 per DALY gained) and MTT is the second

lowest ($95 per DALY gained). One way sensitivity analysis showed that our

results were robust for all of variables tested. The confidence intervals gener-

ated by the Monte Carlo analysis show a significant degree of uncertainty that


will affect the cost-effectiveness ranking of different DST methods, particularly

for patient groups with a high MDR-TB prevalence.

DISCUSSION

MDR-TB testing is not routinely performed in developing countries, raising

concern about the transmission of resistant strains from unidentified cases.

Our study demonstrates that MDR-TB testing among patients with smear-

positive TB, using IDLJ or other methods is cost-effective, even in settings with

moderate prevalence of drug resistance.

All the DST methods studied are cost-effective when the average cost per DALY

(excluding transmission effects) is compared to a benchmark of Gross National

Income. For example, the cost-effectiveness of using the least cost-effective

alternative, FastPlaque Response in settings with 2% of MDR-TB prevalence

($272 per DALY gained) compares favourably to providing antiretroviral ther-

apy to TB patients coinfected with HIV35 ($462 per DALY gained) or providing

individualized treatment for MDR-TB patients not responding to standardized

second-line therapy31 ($368 per DALY gained). Strikingly, introducing an inex-

pensive and moderately rapid method like MTT for high prevalence popula-

tions has cost-effectiveness comparable to implementing DOTS strategy in

developing countries36 ($12 vs. $15.3 per DALY gained).

Our calculation of cost-effectiveness underestimates both the health benefits

and cost savings from early diagnosis. We assumed no benefit from timely

treatment, nor benefits from reduced transmission from secondary cases.

However, all testing methods yielded cost savings compared to clinically

defined drug resistance in high prevalence settings. DST methods generate sub-

stantial savings in diagnostic time, which translates into substantial cost savings

once transmission is considered, even in a model that only includes household

contacts and secondary cases. MDR-TB treatment costs substantially impact

our estimates of treatment savings. Treatment and hospitalization costs are

comparatively low in Peru ($2895 for MDR-TB and $75 for first line treat-

ment).31 Thus, the costs savings associated with reductions of transmission

from rapid diagnosis may be higher in other settings, particularly where ambu-

latory care is not well established.37

Due to high levels of uncertainty found by the Monte Carlo analysis and taking

into account that our data is generated from a single clinical trial, our study is

only suggestive on the relative cost-effectiveness ranking of different tests.

Nevertheless we found that test costs and costs of false positives significantly

affect the cost-effectiveness of DST. DLJ perform well in both aspects and

therefore emerge as the most cost-effective DST methods in our study. For

groups with higher MDR-TB prevalence the speed of diagnosis becomes more


Table2–UnitCo

stpe

rTest*

Test

Spu

tum

Colle

ction

Decon

tamination

Prep

aration

ofLowen

stein

Jens

en

Testing

Averag

ecost

per

patien

tOverhea

dCa

pital

Staff

Med

ical

supp

lies

Sub-

total

Contam

ination

Adjustmen

tSub

-total

Rifampcin

resistan

cede

tection

Indirect

LJ5.7

11.4

4.3

4.0

6.3

3.5

0.5

14.3

1.3

15.5

37.0

FastPlaq

ueRe

spon

se5.7

11.4

0.0

3.2

1.6

6.2

8.4

19.4

4.8

24.2

41.3

Inno

Lipa

5.7

11.4

0.0

2.5

1.5

5.5

84.5

94.0

0.7

94.6

111.8

DirectLJ

5.7

11.4

2.2

0.9

1.8

2.1

0.5

5.3

0.3

5.6

25.0

MTT

5.7

11.4

0.5

2.8

2.3

3.3

3.6

12.0

0.8

12.7

30.4

MDR-TB

detection

Indirect

LJ5.7

11.4

5.4

4.5

6.2

4.8

0.5

16.1

1.4

17.5

40.1

FastPlaq

ueRe

spon

se5.7

11.4

0.0

3.2

1.6

6.2

8.4

19.4

4.8

24.2

41.3

Inno

Lipa

5.7

11.4

0.0

2.5

1.5

5.5

84.5

94.0

0.7

94.6

111.8

DirectLJ

5.7

11.4

4.3

2.2

2.8

3.0

0.5

8.4

0.5

9.0

30.5

MTT

5.7

11.4

0.5

3.4

2.7

4.7

5.8

16.7

1.1

17.8

35.5


Table3–Av

erag

ecost

percase

detected

(excluding

effectsof

tran

smission

)

Totalfor

1000

patien

ts(unitcost

only)

TotalC

ostfor1000

patien

ts*

Averag

ecost

percase

detected

Prevalen

ceof

Rifa

mpicinresistan

ceor

MDR-TBin

patien

tpo

pulation

50%

20%

5%2%

50%

20%

5%2%

Rifampcin

resistan

cede

tection

IDLJ

3703

460

241

8176

692

528

9468

112

341

718

8948

33FastPlaq

ue41

276

6002

610

5000

1274

8813

1985

129

564

2737

7084

INNOL

1117

8894

059

1166

8612

8000

1302

6220

563

527

8670

88DLJ

2498

027

609

4342

251

329

5291

159

233

1103

2843

MTT

3044

634

404

4581

151

514

5265

585

281

1266

3235

MDR-TB

detection

IDLJ

4006

763

274

8479

995

561

9771

412

943

319

5048

86FastPlaq

ue41

276

8334

914

1985

1713

0317

7166

181

770

3714

9603

INNOL

1117

8811

1384

1445

5016

1134

1644

5024

278

434

9489

14DLJ

3046

240

447

6067

570

789

7281

187

326

1522

3913

MTT

3552

160

452

8431

796

250

9863

615

152

523

9961

46

*Co

stinclud

esun

itcosts,

saving

sfrom

first

linetrea

tmen

t,cost

ofun

necessarily

trea

ting

falsepo

sitives


Table4–Av

erag

ecost

percase

detected

(includ

ingeffectsof

tran

smission

)

Prevalen

ceof

Rif-resistan

ceor

MDR-TBin

patien

tpo

pulation

Totalc

ostinclud

ingsaving

sof

tran

smission

(100

0pa

tien

ts)*

Averag

ecost

percase

detected

50%

20%

5%2%

50%

20%

5%2%

Rifampicinresistan

cede

tection

IDLJ

-327

321

-732

5953

772

7917

8-668

-374

1098

4041

FASTPlaqu

eRe

spon

se-369

360

-667

5484

549

1148

10-793

-358

1815

6162

INNOL

-334

473

-547

2785

146

1131

21-728

-298

1853

6155

DLJ

-382

584

-120

655

1031

036

503

-822

-648

222

1962

MTT

-365

343

-114

088

1154

036

665

-898

-701

284

2253

MDR-TB

detection

IDLJ

-324

287

-702

2656

805

8221

1-662

-358

1159

4111

FastPlaq

ueRe

spon

se-345

420

-295

2312

8426

1599

91-749

-160

2785

8672

INNOL

-317

385

-269

5711

8257

1473

09-688

-146

2564

7985

DLJ

-369

745

-103

402

2976

956

404

-795

-556

640

3031

MTT

-337

908

-750

2756

414

8264

6-842

-468

1406

5150

*Co

stinclud

esun

itcosts,

cost

saving

sfrom

redu

cedfirst

linetrea

tmen

t,cost

oftrea

ting

falsepo

sitives


Table5–Co

stspe

rda

lyga

ined

Prevalen

ceof

Rif-resistan

ceor

MDR-TBin

patien

tpo

pulation

Averag

ecost

perDALY

(excluding

saving

sfrom

redu

cedtran

smission

)�Av

erag

ecost

perDALY

(includ

ingsaving

sfrom

redu

cedtran

smission

)�

50%

20%

5%2%

50%

20%

5%2%

Rifampcin

resistan

cede

tection

IDLJ

6(3-8)

18(13-27

)85

(60-12

4)21

9(154

-317

)Saving*

Saving*

22(0-62)

156(88-25

1)FastPlaq

ueRe

spon

se4(1-8)

16(5-32)

80(23-15

2)20

6(62-39

4)Saving*

Saving*

36(0-106

)16

3(20-34

4)INNOL

5(3-10)

17(6-32)

76(23-14

5)19

2(56-37

1)Saving*

Saving*

33(0-98)

150(14-32

1)DLJ

2(0-6)

7(0-23)

33(0-107

)85

(0-277

)Saving*

Saving*

Saving*

32(0-221

)MTT

3(0-7)

10(0-24)

45(0-115

)11

5(0-297

)Saving*

Saving*

Saving*

67(0-247

)

MDR-TB

detection

IDLJ

6(4-9)

20(14-28

)89

(62-12

8)22

7(160

-328

)Saving*

Saving*

25(0-66)

163(93-26

1)FastPlaq

ueRe

spon

se5(2-9)

22(9-39)

105(45-18

8)27

2(117

-486

)Saving*

Saving*

63(2-139

)23

0(77-43

6)INNOL

6(3-11)

21(9-37)

93(36-16

6)23

7(91-42

7)Saving*

Saving*

50(0-119

)19

4(50-37

8)DLJ

2(0-6)

8(0-23)

36(0-110

)94

(0-284

)Saving*

Saving*

Saving*

41(0-231

)MTT

4(0-8)

12(0-28)

57(0-130

)14

4(0-335

)Saving*

Saving*

8(0-81)

95(0-282

)

*Co

stsaving

,ie

costsfrom

redu

cedtrea

tmen

tin

thefuture

outweigh

costsof

DSTno

w�Num

bers

inbrackets

show

theconfiden

ceintervalsge

neratedby

Mon

tecarloan

alysis


significant. Although DLJ still performs well, the difference in cost per DALY

between alternative DST methods is reduced.

Our study assumes an accuracy of IDLJ of 98%, as is commonly found in pro-

ficiency testing. Using this assumption, our calculations show that IDLJ may

not always be the most cost-effective option for any patient group. In addition,

real-life performance of indirect methods may be much slower than observed

in a clinical trial setting. DLJ is cheaper than and as effective as IDLJ, it yields

results 4 weeks earlier and can be implemented in most laboratories. Our study

shows than MTT is also low cost and faster than IDLJ, although in practice it

may lead to emergence of resistance due to its low sensitivity .

The selection of DST method is not solely dependant on cost-effectiveness, but

also on feasibility. A high TB burden and lack of infrastructure represent signif-

icant obstacles to implementing DST methods in developing countries38.

Therefore, their implementation must be accompanied with a national com-

mitment to improve culture-performing laboratories. Introducing InnoLipa

remains a challenge, because of cost and complexity of performing this assay

based on standard PCR from processed DNA-extracted sputum. However,

DLJ, MTT and FastPlaque Response can be adopted in most laboratories cur-

rently performing conventional culture in LJ media. More research is therefore

required to further examine the feasibility, costs and effectiveness of these

methods in other settings.

It should also be noted that, although Inno Lipa and FastPlaque-Response

appear to be the least cost-effective of the methods studied, their high kit costs

have a significant impact on our results. If NTPs were to have access to conces-

sional prices or less expensive versions, this would considerably increase their

affordability and cost-effectiveness. Furthermore where a test is the most cost

effective but not the most effective method, it should not necessarily be priori-

tized. The question for policy makers is whether extra cost (around $90 000

for Fast Plaque-Response and Innolipa) is justified by the approximate 600

DALYs generated (around 20 deaths averted) compared with other use of their

funds.

We present results for different prevalence groups to assist the generalization of

our findings to other settings. Our results are applicable to countries where

HIV prevalence is low and ambulatory treatment is available. Effectiveness in

terms of DALYs may be higher in countries with high HIV prevalence due to a

higher number of deaths averted, where rapid tests might have a substantial

impact in treatment outcomes.39-40 In addition rapid tests may prevent the

emergence of XDR-TB in settings where quality assured treatment (DOTs) is

not provided.


In conclusion, multi-drug resistant tuberculosis has emerged as a major public

health threat worldwide. The establishment of DOTS-Plus and the Green Light

Committee have greatly improved the availability of treatment, but delays in

the diagnosis of MDR-TB remain a major obstacle to its control.41-45 Our

results indicate that several DST methods are cost-effective and further trials

should now be considered by NTP’s. However, the feasibility of implementing

rapid DST methods and the health benefits that might accrue from their use

require further study. Additional data is needed from other populations and

settings particularly those where HIV is prevalent. If interest and effort con-

tinue in this area of research, this will positively influence MDR-TB policy,

patient care and ultimately TB control.

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Chapter 5

The patient costs of accessingcollaborative TB/HIVinterventions in Ethiopia

A Vassall

A Seme

P Compernolle

F Meheus

Accepted for publicationInternational Journal of Tuberculosis and Lung Disease. July 2009.

SUMMARY

Objective: To measure the patient costs of TB/HIV services from three hospital-based

pilot sites for collaborative TB/HIV interventions in Ethiopia.

Methods: Costs were measured at the point of treatment to estimate both pre-treatment

and treatment costs for a range of TB/HIV services being provided as part of the colla-

borative TB/HIV programme in Ethiopia. Both direct and indirect costs were measured.

Results: Patient costs were found to be substantial compared to income levels. Pre-

treatment costs were 35 % of annual household income for TB patients (with no HIV),

33% for those with TB and HIV, and 40% for those with HIV (with no TB). Direct costs

were particularly significant during this period. Patient costs during treatment for TB

range between 49%- 71% of annual household income. Patient costs the first year of

ART were 21% of annual household income. Costs fall as treatment progresses.

Conclusion: Our results highlight the need to mitigate the economic impact on patients

of both TB and HIV/AIDS treatment in low income countries such as Ethiopia.

Collaborative TB/HIV services may provide an opportunity to reduce pre-treatment costs

by providing an additional channel for the early diagnosis of HIV. Costs and economic

impact may be further reduced by providing both ensuring that diagnostics and thera-

pies are provided free of charge, providing social support particularly at the beginning

of treatment, and bringing services closer to the patient.

INTRODUCTION

The diseases of tuberculosis (TB) and HIV are inextricably linked. Tuberculosis

is the leading cause of death amongst people with an HIV infection, and HIV

can fuel the TB epidemic.1 Countries with a high HIV prevalence urgently

need to develop packages of collaborative TB/HIV prevention and treatment

that adequately address the dual nature of both epidemics. Ethiopia has one of

the highest burdens of TB in the world. The incidence of TB is estimated to be

159 cases of smear positive TB per 100,000 population. Over 1.7 million peo-

ple are living with HIV/AIDS (4.4% of the adult population) and around 30%

of those with TB are HIV positive.2-3

Several countries in sub-Saharan Africa have piloted a district-based strategy

for the collaborative provision of TB/HIV prevention and treatment services.4-5

The approach entails the promotion of HIV counselling and testing as an entry

point into a package of TB/HIV related interventions. An important motiva-

tion is the assumption that by offering a range of services to those with HIV,

the public will increase their use of HIV testing services and eventually change

their risk behaviour, thus reducing the incidence of HIV.

Evidence on the patient costs of collaborative TB/HIV packages is essential to

the development of services that are affordable in low-income settings. There

are several studies that examine the health service cost of providing interven-

tions to address TB and HIV to health service.6-15 However, most of these do

not include an assessment of patient costs. Other studies examine patient costs

and economic impact at the household level and focus either on TB and TB

treatment, or Acquired Immune Deficiency Syndrome (AIDS),16-23 but not the

costs of a combined package. The aim of this study is to estimate the patient

cost for a comprehensive range of services included in the TB/HIV package in

a low income setting.

METHODS

SettingIn 2005, the Federal Ministry of Health in Ethiopia began to respond to the

dual nature of the TB/HIV epidemic. Shortly thereafter TB/HIV collaborative

services were launched in nine pilot sites.24-26 The interventions included are

presented in detail in Table 1. All interventions follow WHO TB/HIV clinical

guidelines. Purposive sampling was used to select study sites from the pilot

sites. We selected hospitals according to type of geographical location (rural,

urban, peri-urban), size and type of facility (district, tertiary, bed size). Three

of the nine pilot sites were selected for this study: Black Lion, Hosanna and

Jimma. Hosanna hospital has 120 beds and is a zonal hospital located in

Hosanna town in the southern part of Ethiopia. Hosanna district is rural, with

The patient costs of accessing collaborative TB/HIV interventions in Ethiopia 75

the population depending on subsistence farming for living. Jimma Specialized

Hospital has 350 beds and is located in the southwest of the country. Jimma

district is rural, in a region where cash crops are grown. The Black Lion

Specialized Teaching Hospital has 850 beds and is located in the capital of

Ethiopia, Addis Ababa, in the centre of the country.

SamplingA stratified sampling technique was used to ensure a mix of patients using the

different TB/HIV services at different points in their treatment. Stratification

was done on the basis of study site, age, gender and disease to be representative

of the pattern in the total eligible population. Convenience sampling was

used; patients within each quota were interviewed at the facility after receiving

treatment. The total sample size was 250 patients, out of an eligible population

of 2928 patients starting TB or HIV treatment in the year of the study. This

sample size was established after a review of similar studies as little is known

about the characteristics of the overall population of TB patients. The study

population was confined to patients using TB/HIV pilot services diagnosed

and receiving treatment for either TB, HIV related illnesses, or both. TB

patients were identified through diagnosis for TB by smear sputum microscopy

and for HIV using a standard rapid test (see Table 1).

Table 1 – TB and HIV services and treatment protocols provided at the study sites

TB smear + treatment outpatient

4 sputumsmears,plus generallaboratoryinvestigations

2 chest X-rays Daily outpatientvisits for 8weeks

Monthlyoutpatient visitsfor six months

DrugsStandard WHOregimens2ERHZ/6EH* forcat 1 patients

TB smear + treatment inpatient

4 sputumsmears, plusgeneral labora-toryinvestigations

2 chest X-rays Inpatient for twomonths

Monthlyoutpatient visitsfor six months

2ERHZ/6EH* forcat 1 patients

Izoniazid Preventative Therapy (IPT)

1 sputum smear 2 chest X-rays Monthlyoutpatient visitsfor six months

Isoniazid (INH)300mg daily forsix months


Cotrimoxazole Preventative Therapy (CPT)

One visit to clini-cian for clinicalassessment,plus generallaboratoryinvestigations

As part of TBvisit weeklyadherence ses-sion for onemonth, two-weekly sessionsfor the secondmonth and onevisit a monththereafter up toeight months

Thereaftermonthly visitsfor adherencecounselling atgeneral out-patients, everythree months toa clinician

Cotromoxizole(CO) 960 mgdaily

Anti-Retroviral Therapy (ART)

1 rapid test(Determine),plus generallaboratory tests

2 CD4 counttests2 chest X-rays

Weekly visits forone month Two-weekly visits forone month

Thereaftermonthly visitsfor adherencecounselling andevery threemonths to aclinician

First line treat-ment only:Stavudine (d4T)+ Lamivudine(3TC) +Nevirapine (NVP)

TB patient attending VCT

1 rapid test(Determine)1 confirmationtest (Capilous)for 10% ofpatients1 discrepancytest (Unigold) for5% of patients

Post-testcounselling

Pre- and post-test counsellingconducted inone visit

Treatment for Opportunistic Infections (OI) outpatient

Diagnostic testaccording totype oftreatment

1-4 visitsaccording totype oftreatment

Drugs accordingto type oftreatment

* Ethambutol (E), Isoniazid (H), Rifampicin (R), Pyrazinamide (Z)

Measuring Patient CostsThe conceptual framework for the measurement of patient costs draws on

guidelines for cost analysis in general27 in addition to specific TB costing

guidelines.28 In addition, the experience of conducting Living Standards

Measurement Surveys (LSMS) in Ethiopia was used to inform both the broad

approach and instrument design. Four types of costs were measured: direct

(non-transport), direct (transport), indirect and carer costs. Direct costs

include the out-of-pocket (monetary) expenditures such as payments for

drugs, transport and food. Indirect costs are defined as loss of household

income from production and employment. Carer costs consist of the costs


made by caregivers and families looking after the patient during treatment.

Costs were estimated for two periods: pre-treatment and during treatment.

Pre-treatment was defined as the period between the onset of symptoms to the

first visit to TB/HIV services. The treatment period was defined from start to

completion of treatment. In the case of antiretroviral treatment (ART) and

cotrimoxazole preventive treatment (CPT) the treatment period was the first

year of treatment.

All patients aged 15 years and above who consented were eligible for the study.

Patients who had completed treatment or who were critically ill were excluded

from the study (for practical reasons and to minimize recall bias). A structured

questionnaire was used. This was pre-tested on similar patients in the same set-

ting. Interviews were conducted by medical professionals not directly involved

in treating the patient. Medically trained interviewers were selected as they

were best able to define the date of onset of illness. Further information about

each patient was gathered from medical records (registries and patient charts).

Indirect costs were estimated using questions based on the ‘Living Standards

Measurement Survey’. This leads interviewees through a series of questions

concerning household income earned from different sources, including agricul-

tural production.

Data AnalysisData were double entered into Statistical Package for Social Science (SPSS soft-

ware version 11.5 for Windows) and the two files were compared using EPI

Info version 6.4. Data analysis was performed using the same software.

Frequencies and percentages were used to describe the socio demographic,

socioeconomic variables, disease and treatment categories of the study popula-

tion. Mean and median direct (non-transport/ transport), indirect and total

costs were determined. All costs are presented in US$2005 and an exchange

rate from Ethiopian birr to dollars used was 8.7 birr to the dollar

(International Monetary Fund, February 2005). Ethical approval for this study

was obtained through the University of Addis Ababa.

RESULTS

A total of 184 patients were successfully interviewed in the three facilities. Fifty

interviews could not take place due to security conditions in Gondar. Sixteen

interviews were conducted but removed from the sample because of poor data

quality. Table 2 summarises the characteristics of the study population.


Table 2 – Description of the study population

Descriptive variables Study population

N %

SexMale 97 52.7Female 87 47.3

Age15-24 yrs 28 15.225-34 yrs 79 42.935-44 yrs 46 25.045-54 yrs 20 10.9>=55 yrs 11 6.0

Marital StatusSingle 47 25.5Married 91 49.5Widowed 23 12.5Divorced 17 9.2Separated 6 3.3

Educational StatusIlliterate 32 17.4Read and write only 5 2.7Grade 1-6 (PE) 33 17.9Grade 7-8 (JSE) 27 14.7Grade 9-12 (SSE) 64 34.8College, university 23 12.5

Primary OccupationEconomically Inactive 68 37.0Daily unskilled Labourers 16 8.7Employed by Government 36 19.6Private and NGO Employee 24 13.0Self employed business with/without employee 19 10.3Self employed merchant, Farmers, Fishers etc 21 11.4

Patient StatusInpatient 47 25.5Outpatient 137 74.5

Disease CategoryTB patients, HIV status unknown 52 28.3TB/HIV co-infection 41 22.3HIV only with no TB 91 49.4

Treatment Category (at point of interview)Tuberculosis treatment 77 41.9ARV Treatment 47 25.5HIV + Prevention of TB with Isoniazid 33 17.9HIV + Treatment or prevention of OI 27 14.7

The distribution of length of delay was highly skewed with a few ‘long-delayers’

significantly influencing the mean. Mean and median delays are therefore pre-

sented here. Median delay from onset of symptoms to arriving at public TB/

HIV services was three and a half months for TB and 1 year for HIV. Table 3

shows treatment delay before accessing TB/HIV services. As with patient delay,


patient costs were found to be highly skewed, with a few patients incurring sig-

nificant costs. Direct costs were found to be most significant (83% of total

mean costs). Table 4 shows mean and median pre-treatment costs.

Table 3 – Mean and median time between first complaints and first visit to TB/HIVservices (days)

Disease category Number of patients Pre-hospital length of complaint (days)

Mean Median

TB only 52 178 105TB/HIV 41 396 230HIV only 91 610 365Total 184 440 180

The study found that on average 48% of annual household income will be lost

due to TB treatment. ART caused an average loss of 21% of annual household

income in the first year of treatment. The annual direct cost for ART treatment

was found to be $65 with some patients paying for drugs although the national

policy states that drugs should be free. Patients receiving IPT, CPT, or using

VCT incurred relatively low costs compared to income levels. Table 5 presents

patient costs for the main treatment interventions, compared to income levels.

Males have higher indirect costs (measured as the loss of paid income) than

females, while the females incur higher direct costs than males. The cost of

caregivers for females is also high. The cost for lower-income groups (< 57.5

US$ per month) is less than higher incomes. Both direct and indirect costs rise

as income increases. Figure 1 shows the mean cost per outpatient visit for TB

patients by gender and by income.

Figure 1 – Mean costs for an outpatient visit for TB patients by income level and gender

(US$ 2005)

0

1

2

3

4

5

6

7

8

9

<23 USD/month 23-57USD/month

>=57.5USD/month

Male Female

Caregiver cost

Transport cost

Indirect cost

Direct cost

Finally, costs for TB treatment during the initial (intensive) phase (first 2

months) and the continuation phase (respectively last 6 months) are illustrated


in Figure 2. Patient costs per visit were high during intensive phase of treat-

ment, but decline drastically over time. In particular, indirect costs are high

during the intensive phase. Thereafter, in the continuation phase, when symp-

toms are less severe, indirect costs decrease.

Figure 2 – Mean cost per month for TB Smear + treatment and Anti-Retroviral Treatment (ART)

(US$2005)

0

20

40

60

80

100

120

Month 0-2 Months 3-8 Month 1 Month 2 Month 3-12 TB Smear + ART

US$

200

5 Caregiver CostTransport CostIndirect CostDirect Cost

DISCUSSION

This study finds that TB patients and HIV positive patients suffer substantial

financial losses before and during treatment relative to income levels. This

study finds a long delay in seeking treatment for those patients with TB (3

months). Delays in seeking treatment are longer for HIV positive patients

without TB than for those with TB. This indicates that the first contact of

some HIV positive patients with health services is for the treatment of TB.

Treatment seeking delay is also longer for TB/HIV patients compared to

patients with TB only. This is likely to be because the proportion of smear

negative TB (likely to be less symptomatic), compared to smear positive TB is

higher in those patients also suffering from HIV. All these delays result in sub-

stantial costs to the patient, especially prior to treatment caused by seeking and

paying for ineffective treatment to relieve their symptoms prior to accurate

diagnosis.

Patient costs as a percentage of annual income during treatment are compar-

able to other studies which estimate the economic impact of TB and AIDS.13-19

Although both TB treatment and ART are provided for free in Ethiopia, we

found that many patients still spend considerable sums on diagnostic tests and

some patients paying informally for drugs. Direct costs therefore remain high.

However, the main cost throughout treatment is the loss of income i.e. the


Table4–Mea

nan

dmed

ianpre-trea

tmen

tcosts(US$20

05)

Disea

secatego

ryNum

ber

ofPa

tien

tsPre-Trea

tmen

tCo

sts

(US$20

05)

Directcosts

(non

tran

sport)

DirectTran

sport

Costs

Indirect

Costs

TotalC

osts

(Mea

n)Mon

thly

Hou

seho

ldIncome

Totalc

ostas

a%

ofAn

nual

Income

Mea

nMed

ian

Mea

nMed

ian

Mea

nMed

ian

TBon

ly52

104

1416

110

012

931

35TB

/HIV

4113

348

146

229

170

4333

HIV

Only

9124

335

233

205

287

5345

Total

184

179

2919

318

321

645

40

Table5–Mea

ntrea

tmen

tcost

(US$20

05)

Trea

tmen

tCa

tego

ryDirectCo

st(non

-tran

sport)

Direct

Cost

(Trans

port)

Indirect

Cost

Care

-giver

Cost

TotalC

ost

Mon

thly

Hou

seho

ldIncome

TotalC

ostas

%of

Mon

thly

Hou

seho

ldIncome

TBTrea

tmen

tSmea

r+Outpa

tien

t69

6478

1422

538

49TB

Trea

tmen

tSmea

r+Inpa

tien

t22

512

7020

327

3871

INHProp

hylaxisOutpa

tien

t15

817

242

3410

COProp

hylaxis

Outpa

tient

Firstyear

oftrea

tmen

t4

34

112

602

VoluntaryCo

unselling

andTesting

01

20

340

1An

ti-RetroviralT

herapy

Firstyear

oftrea

tmen

t65

867

114

155

21Trea

tmen

tforOIreq

uiring

1ou

tpatient

visit*

42

11

855

1Trea

tmen

tforOIreq

uiring

2ou

tpatient

visit*

83

32

1555

2Trea

tmen

tforOIreq

uiring

3ou

tpatient

visit*

125

43

2355

3Trea

tmen

tforOIreq

uiring

4ou

tpatient

visit*

166

54

3155

5

*Th

etrea

tmen

tof

mosttheOIs

trea

tedin

Ethiop

iarequ

ires

betwee

n1an

d4ou

tpatient

visits


income loss due to lost productivity. Income loss is highest at the start of treat-

ment. This is likely to be due to the severity of the disease at this point and the

time necessary to access treatment. As treatment progresses, costs falls, because

patients need to make fewer visits to hospital. In addition, as symptoms

improve income levels begin to rise again. Costs for preventative interventions

are considerably lower than treatment. For example, the cost of IPT and CPT

are considerably less than the cost of TB treatment and treatment of opportu-

nistic infections. The provision of these services is therefore likely to provide

an overall economic benefit to the patients as well as health services.

This study has a number of limitations. Firstly, although we used standard

methods, reflecting that facility based interviews are considered a valid (and

practical) method when estimating patient costs in low income countries, the

accuracy of income levels and indirect costs is difficult to verify (compared to

household surveys). Our results however are broadly comparable to household

based studies. Secondly, patient delay and costs prior to treatment were

assessed retrospectively by defining the date of onset of symptoms.

Considerable effort was made to identify the point of onset of symptoms using

trained medical interviewers. However, for HIV/AIDS patients it is extremely

difficult to identify the point of onset of symptoms, as symptoms are varied

and may not be associated with being HIV+. Even with TB patients (particu-

larly smear negative patients) reported delay is difficult to verify. It is difficult

to estimate the impact of this uncertainty on our results. Thirdly, the sample

primarily consists of those living nearby to the hospital in an urban setting.

This group is likely to have higher than average household income in Ethiopia

and our results may not be representative of lower income groups. Finally,

although our methods are standard for facility based patient cost studies, they

do not rely on statistical methods for sampling.

These findings have several policy implications. Firstly, patients face substantial

income loss and increased health expenditure at the start of treatment.

Exemptions for fees for TB/HIV often only apply to drugs, and not the cost of

associated diagnostics. Policy makers wishing to ensure that services are truly

free should also consider reducing the price of these associated procedures. In

addition, economic impact at the household level when starting treatment can

be severe. Typically economic support/incentives have been provided by TB ser-

vices to encourage patients to adhere to treatment. However, consideration

should also be given to provide social support at this early stage in order to

mitigate the economic impact at the household level of both TB and HIV, par-

ticularly for those with low incomes, where these expenditures may be

catastrophic.

Secondly, substantial costs are incurred due to the time and transport required

to access treatment. The majority of patients interviewed for our study are

locals; 70% living within one hour walking distance from the hospital.


Nevertheless these costs remain high. Figure 1 shows that for poor TB patients,

transport costs are the most significant proportion of costs. This finding high-

lights the importance of considering both patient and provider costs when

planning how closely to provide services to the patient (through communities/

primary health/ through hospitals) in situations where the transport system is

poor. Following our study, in 2005, the government in Ethiopia began to build

the capacities of Primary Health Care Units (PHCU) to provide TB/HIV

services.

Finally, our study finds that patients incur high costs prior to treatment. The

relatively high level of direct costs indicates that, although patients recognise

their symptoms need treatment, they are not going to the TB/HIV services as

their first port of call. This study did not specifically address reasons for patient

delay, from either the patient and health systems perspective. However, it does

suggest that efforts to reduce treatment seeking delay, not only benefits the

health status of the patient, but can also in principle substantially reduce the

economic burden on those who are ill. Efforts to intensify case finding for

both TB and HIV through a collaborative TB/HIV programme may reduce the

economic burden for those with TB and HIV. In particular, early case finding

of HIV+ cases through TB clinics may reduce the time that HIV+ patients

spend on seeking relief for their HIV related symptoms. Further research is

needed to see if these potential economic gains can be realised and whether

collaborative TB/HIV efforts reduce patient and provider costs over time.

CONCLUSION

This study reports on the costs of TB/HIV services for patients in pilot TB/

HIV sites in Ethiopia. It broadly finds that despite free TB and HIV treatment

costs are substantial, both before and during treatment, although they may

reduce over time in less intensive stages of treatment. These results can be used

to help support TB/HIV services to determine the models of care that mini-

mize the economic burden of these illnesses on patients and their families, par-

ticularly for those with low incomes.

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Geneva 2004.

6. Hausler HP, Sinanovic E, Kumaranayake L, Naidoo P, Schoeman H, Karpakis B and Godfrey

Fausett P. Costs of measures to control tuberculosis/HIV in public primary care facilities in

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9. Aisu T, Raviglione M, van Praag E, Eriki P, Narain JP, Barugahare L . Preventative chemother-

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seling and testing centre. AIDS 1995; 9:267-73.

10. Foster S, Godfrey–Fausett P, Porter J. Modelling the economic benefits of tuberculosis preven-

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14. Hansen K, Chapman G, Chitske I. The costs of HIV/AIDS care at government hospitals in

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Wnagmanee S, Jittimanee S, Payanandana V. Economic impact of tuberculosis at the house-

hold level. International Journal of Tuberculosis and Lung Disease. 1999. 3(7):596-602.

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the economic impact and burden on patients prior to diagnosis. International Journal of

Tuberculosis and Lung Disease. 1998: 2(10):811-817.

18. Rajeswari R, Balasubramanian R, Muniyandi M, Geetharamani S, Thresa X, Venkatesan P.

Socio-economic impact of tuberculosis on patients and family in India. International Journal

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Chapter 6

Estimating the resource needsof scaling-up HIV/AIDS andtuberculosis interventions insub-Saharan Africa: asystematic review for nationalpolicy makers and planners

A Vassall

P Compernolle

Health Policy. 2006 Nov;79(1):1-15.

SUMMARY

Considerable effort has been made to estimate the global resource requirements of

scaling-up HIV/AIDS and tuberculosis (TB) interventions. There are currently several

medium and long-term global estimates available. Comprehensive country-specific esti-

mates are now urgently needed to ensure the successful scaling-up of these services.

This paper reviews evidence on the global resource requirements of scaling-up HIV/

AIDS and TB interventions. The purpose of this review is to summarise and critically

appraise the methods used in the global estimates and to identify remaining knowledge

gaps, particularly those relevant to country level estimation.

This review found that the estimates of global resource requirements provide sound

methodological guidance for countries on the basic steps to follow. However, there are

still many areas that require further development or evidence. These include the follow-

ing. Firstly, the methods used to assess the capacity to scale up HIV/AIDS and TB ser-

vices need to be further refined. In particular countries need simple methods to assess

human resource capacity. Secondly, investments need to be made to improve country

level data on the costs and effectiveness of HIV/AIDS and TB services. In particular

efforts should be focused on producing standardised unit costs for each intervention by

country, which reflect the reality of domestic resource use. Thirdly, simple costing mod-

els which appropriately integrate systems costs need to be developed for use at the

country level. Finally, resources needs estimation needs to be embedded by countries

in multi-sectoral expenditure planning processes.

Countries and global agencies will continue to need estimates for different purposes at

different times. Therefore attention should move away from specific estimates, to the

longer-term aim of building capacity at the country level, supported by global agencies.

This will be of mutual benefit. Those making national resource estimates can learn from

the experience of global estimation. Concurrently, global resource estimates can build

on the evidence emerging from improved national resource estimates.

INTRODUCTION

The burden of ill health from HIV/AIDS and tuberculosis (TB) in sub-SaharanAfrica is considerable. HIV/AIDS accounts for about 20% of all deaths in sub-Saharan Africa, making it the single biggest killer. The diseases of HIV/AIDSand TB are inextricably linked. TB is the leading cause of death amongst peoplewith HIV infection, and HIV, through the reduction of immunity, fuels the TBepidemic. Up to a third of all the new TB cases in sub-Saharan Africa aredually infected with HIV. Yet the countries facing this dual disease burden aresome of the poorest on the planet. Scaling-up effective HIV/AIDS and TB stra-tegies, including collaborative TB/HIV interventions, is therefore one of themost important public health challenges facing sub-Saharan African countriestoday.1 Ensuring that these programmes are sustainably financed will be a keyfactor in their success, and reduce the risk that resources are diverted from otheressential health services.

In order to plan the rapid scaling up of HIV/AIDS and TB interventions, many

countries are currently estimating the resource requirements of these services.

At the same time, several estimates of the global resource requirements of HIV/

AIDS and TB interventions have been produced, primarily to advocate for

increased funding. However, the line between such global and country esti-

mates is now being blurred. Increasingly, countries are applying for interna-

tional funding and planning for long-term global goals such as the Millennium

Development Goals (MDGs). At the same time those making global estimates

are being asked to reflect the realities of domestic health sectors.

To support this process, this review provides a summary and critical examina-

tion of the global estimates for HIV/AIDS and TB. In particular, it aims to

identify the remaining knowledge gaps in terms of both methods and data in

order to inform the process of producing high quality country-specific

estimates.

METHODS

The electronic databases MEDLINE and ECONLIT were searched for articles

published between 1995 to mid-2005, using the following key words: “cost”,

“tuberculosis”, “HIV”, “AIDS”, “resources”, “scale”. The search was limited to

English-language abstracts. The websites of the main global agencies and tech-

nical institutes involved in TB and HIV/AIDS, and the International AIDS

Economics Network (IAEN) electronic database were searched to identify non-

published literature. Related articles and references of key papers were identi-

fied and experts consulted to ensure that no important papers were missed.

Abstracts of all retrieved papers were assessed to identify those containing

resource needs estimates in low and middle-income countries. The methods of

Estimating the resource needs of scaling-up hiv/aids and tuberculosis interventions 89

those relevant to the review were summarised and critically appraised. The

summary and critical appraisal focused on methods, data and identifying

knowledge gaps.

The starting point of the review was to identify whether the estimates followed

the four main stages involved in costing. These are outlined in guidelines on

costing HIV/AIDS, TB and other health interventions. The appraisal of meth-

ods used consisted of summarising self-reported limitations. This took into

account costing guidelines and key methodological papers. Likewise, the critical

appraisal of data was assessed by summarising self-reported data constraints.

This also took into account past reviews of the evidence base on both cost and

epidemiological data related to HIV/AIDS and TB.

This paper aims to identify knowledge gaps for making global estimations that

are most relevant to those making country level resource estimations. It there-

fore takes into account two important differences between global and national

estimates of resource requirements. Firstly, that the purpose differs. Global esti-

mates are often solely aimed at resource mobilisation to meet internationally

defined targets. They may be constrained by their appeal to potential finan-

ciers. In contrast, domestic estimates are likely to be used as the basis for med-

ium-term expenditure planning and funding applications. Therefore, these

estimates are more likely to be constrained by both the financial and institu-

tional capacities to scale-up. In addition, they generally require a higher level

of accuracy than the headline figures best suited for resource mobilisation.

Secondly, there is a much greater depth of data available at the national level,

as the possibility exists to conduct primary data collection. Global estimates

are usually restricted to data from secondary sources and information made

available through global programmes and their networks. The methods they

use will reflect this constraint.

RESULTS

This review found 19 articles/ papers estimating the global resource require-

ments of scaling up TB or HIV/AIDS interventions. No studies specifically on

the costs of collaborative TB/HIV interventions. A list of the papers is pre-

sented in table 1. Estimates of resource requirements have been standardised to

2000 $ prices using a deflator of 5%.

HIV/AIDSFor HIV/AIDS, the estimates found can be seen as a progression, as later esti-

mates explicitly build upon the methods used in earlier ones. The first esti-

mate, made in 1996, focused on the resource requirements of HIV prevention

globally. This work was followed by an estimate for sub-Saharan Africa made

by the World Bank that included care and anti-retroviral (ARV) treatment. A


third set of estimates was made for the United Nations General Assembly

Special Session on HIV/AIDS (UNGASS) in June 2001. Building on this work,

global estimates were again made by UNAIDS in 2002. In 2003, Partnerships

for Health Reform also published a tool for estimating the costs of AIDS care

and treatment.

Between 2002 and 2004 UNAIDS led an effort to further develop methods

with other UN and donor agencies. As part of this, the Inter-American

Development Bank developed a tool to estimate resource needs for prevention,

mitigation and care. By 2004, a new global estimate for treatment and care was

made by the World Health Organisation (WHO) and UNAIDS for the “3 by

5” AIDS treatment initiative. Following this, in 2004, UNAIDS published its

preliminary estimates for global resource estimation for a comprehensive

response, based on revised methods, inter-agency collaboration and extensive

in-country data gathering. This methods and results of this work were also

summarised in paper published in 2004. A final version of the estimates was

published by UNAIDS in 2005.

Global estimates of the annual resource requirements of HIV/AIDS prevention

range from 1.25 to 8.9 billion (2000$). The estimates for treatment and care

range from 1.95 – 13.1 billion (2000$). Although this range appears wide, there

is some consistency between estimates. The lower figures are for resource

requirements in the near future (2001) and reflect current capacity constraints.

The higher estimates are to reach international targets in the medium/long

term (2015). The larger estimates for treatment and care are for much higher

levels of coverage of ARV treatment than the lower ones. On the other hand,

later estimates take into account falling drugs prices for ARV therapy. The

most recent global estimate by UNAIDS (2005) for a comprehensive response

in the year 2008 is approximately US$ 22.1 billion (2005$).

In comparison to the wealth of international estimates, published country spe-

cific estimates for comprehensive HIV/AIDS programmes are rare. There are,

however, several papers that measure the costs of implementing key HIV/AIDS

interventions at a national level. For example, both researchers and the govern-

ment in South Africa have published resource needs estimations for ARV treat-

ment and care. However, no estimation of the resources for the comprehensive

HIV/AIDS response is available. The country reports for the UN Millennium

Project do cover both HIV/AIDS and TB, yet they only report on the whole

MDG package per sector or per country, and not per disease.

TuberculosisFor TB control, two papers were identified that describe estimates for the

Global Plan to Stop Tuberculosis, and two papers for the Global DOTS

Expansion Plan. The estimate for the cost of TB control is 1.91 billion (2000$),

with Directly Observed Treatment Strategy (DOTS) costing 1.2 billion (2000$)


annually. Further estimates were published in the Progress Report on the

Global Plan to Stop TB in 2004. In addition, country specific estimates of

required funding are reported annually in the WHO Global Tuberculosis

Control Report. Finally, the Commission in Macroeconomics and Health

(CMH) produced a series of papers, which include estimates for both HIV/

AIDS and TB interventions for specific regions (e.g. sub-Saharan Africa and

Latin America).

It should be noted that despite the apparent consistency of the estimates, their

closeness should not be read as a validation. As shown below, most of the con-

sistency is the result of similarities in the modelling methods. The estimates

can only be validated when HIV/AIDS and TB interventions are scaled-up and

their real resource needs become evident.

DISCUSSION

This discussion aims to summarise and critically appraise the methods and

data used by the global estimates. The focus is on identifying remaining knowl-

edge gaps, particularly those most relevant for planners and economists mak-

ing country based estimates.

The definition of interventionsThe first step in estimating resource needs is to determine the scope of the pro-

gramme. The selection of interventions has commonly been based on the poli-

cies of global agencies. This has changed over time, reflecting new knowledge

about the effectiveness of interventions. For example, UNAIDS estimates have

only included care and treatment interventions since 2002. In a few cases, the

package of interventions has also been limited by other factors. The estimates

made for the CMH report in 2002 excluded HIV/AIDS interventions for coun-

tries where HIV prevalence is very low (below 1%). Estimates for the Global

Plan to Stop TB also did not include collaborative TB/HIV services and the

provision of multi-drug resistant TB (MDR-TB) treatment for all countries.

However, aside from these exceptions, the packages costed have generally been

defined as widely as possible. In contrast, countries may prefer to restrict the

package of interventions using priority setting techniques. They will need to

decide whether it is better to scale up the whole range of interventions at a

slower pace or scale-up selected interventions at a faster one.

Despite the comprehensive definition of interventions, most of the global esti-

mates have narrowly defined the range of inputs required to implement inter-

ventions. This is particularly noticeable in the area of human resources. Most

global estimates have focused on the number of medical staff in standard cate-

gories (doctors and nurses) required for each intervention. For example, the

latest UNAIDS estimate covered some of the human resources required to


Table1–Sum

maryof

theMainGloba

lResou

rceReq

uiremen

tEstimates

Year

Mod

elPa

ckag

eof

interven

tion

sCo

untries

Time-

fram

eTotal/

Addition

alResou

rces

Billion

peryear

($in

publi-

cation

)

Billion

peryear

($20

00)

HIV

Preven

tion

1996

Broom

berg

J,Sod

erlund

N,Mills

A15

IECInterven

tion

s(m

assan

dtar-

geted)

Blood

safety

Trea

tmen

tof

STIs

Cond

omsocial

marketing

All,ba

rafewsm

all

island

nation

s19

96Total

1.4–2.2

($19

90)

2.3–3.6

2001

ACTafrica1

6As

Broom

berg,plus

Stren

gthe

ning

public

sector

con-

dom

distribu

tion

Voluntarycoun

selin

gan

dtesting

(VCT

)Preven

tionof

mothe

r-to-child

tran

smission

(PMTC

T)

37coun

tries

Sub

-sah

aran

Africa

2005

Additio

nal

1.5-2.2

($20

00)

1.5–2.2

2002

Schwartlan

derB,

StoverJ,WalkerN,

Bollin

gerLet

al17

AsBroom

berg,plus

Voluntarycoun

selin

gan

dtesting

(VCT

)Preven

tionof

mothe

r-to-child

tran

smission

(PMTC

T)

135coun

tries

2005

Total

4.8

($20

00)

4.8

2002

UNAIDS18

AsBroom

berg,plus

Public

sector

cond

omdistribu

-tion

andmarketing

Voluntarycoun

selin

gan

dtesting

(VCT

)

135coun

tries

2001

2005

2007

Total

1.25

4.1

5.85

($20

00)

1.25

4.1

5.85


Year

Mod

elPa

ckag

eof

interven

tion

sCo

untries

Time-

fram

eTotal/

Addition

alResou

rces

Billion

peryear

($in

publi-

cation

)

Billion

peryear

($20

00)

Preven

tionof

mothe

r-to-child

tran

smission

(PMTC

T)Po

st-exp

osureprop

hylaxis

Safeinjections

,un

iversalp

recau-

tion

sPo

licy,

advocacy,ad

ministration

andresearch

2002

Commission

onMacro-econo

mics

andHea

lth(CMH)

34,35

AsBroom

berg,plus

Voluntarycoun

selin

gan

dtesting

(VCT

)Preven

tionof

mothe

r-to-child

tran

smission

(PMTC

T)

83coun

tries

Gross

Nationa

lProdu

ct(GNP)

percapita

<$12

00

2007

2015

Total

3.6-6.5

8.3

($20

02)

3.3-5.9

7.53

2005

UNAIDS24

AsUNAIDS20

0213

5coun

tries

2008

Total

11.4

($20

05)

8.9

HIV

Trea

tmen

tan

dCa

re

2001

ACTAfrica

16

AsSchwartlan

der,plus

Psycho

-socials

uppo

rtan

dcoun

-selin

gHom

eba

sedcare

forAIDS

patien

tsCa

reforchild

ren

37coun

tries

Sub

-sah

aran

Africa

2005

Additio

nal

1.5-2.4($20

00)

1.5-2.4

2002

Schwartlan

derB,

StoverJ,WalkerN,

Bollin

gerLet

al17

Diagn

osticHIV

testing

Palliativecare

Clinical

Man

agem

entof

oppo

rtu-

nistic

infections

(OI)

135coun

tries

2005

Total

4.4($20

00)

4.4


Year

Mod

elPa

ckag

eof

interven

tion

sCo

untries

Time-

fram

eTotal/

Addition

alResou

rces

Billion

peryear

($in

publi-

cation

)

Billion

peryear

($20

00)

Prop

hylaxisforpreven

tion

ofOI

Sup

portfororph

ans

HAA

RT

2002

UNAIDS18

AsSchwartlan

der

135coun

tries

2001

2005

2007

Total

1.95

6.4

9.15

($20

00)

1.95

6.4

9.15

2002

Commission

onMacro-

econ

omicsan

dHea

lth

(CMH)34,35

AsSchwartlan

derplus

Hom

e-ba

sedcare

83coun

tries

GNPcapita

<$12

0020

0720

15Total

2.6-7.8

14.4

($20

02)

2.36

-7.1

13.1

2004

3*5initiative

21

ARVtherap

y34

coun

triesintend

ing

toim

plem

entAR

T20

05Total

2.55

-2.95

($20

00)

2.55

-2.95

2004

BertozziS

,Gutierrez

J,Opu

niM,Walker

N,Schwartlan

derB

23

AsSchwartlan

der,minus

Sup

portfororph

ans

Allc

ountries

witha

Gross

Nationa

lIncom

epe

rcapita

<$92

65

2005

2007

Total

4.4

7.5

($20

00)

4.4

7.5

2005

UNAIDS24

AsSchwartlan

der,includ

ingsu

p-po

rtfororph

ans

135coun

tries

2008

Total

8 ($20

05)

6.3


Year

Mod

elPa

ckag

eof

interven

tion

sCo

untries

Time-

fram

eTotal/

Addition

alResou

rces

Billion

peryear

($in

publi-

cation

)

Billion

peryear

($20

00)

Tube

rculos

is

2001

Globa

lPlanto

Stop

TB28,29

DOTS

Expa

nsion

TB/H

IVMDR-TB

New

diag

nostics/

drug

san

dvac-

cine

sStopTB

Partne

rshipactiv

ities

114coun

tries

2005

Total

1.82

($19

99)

1.91

Asab

ove

Asab

ove

Asab

ove

Additio

nal

0.75

5($19

99)

0.75

520

01Globa

lDirectly

Obs

ervedTrea

tmen

tStrateg

y(DOTS

)Expa

nsionPlan

30,31

DOTS

Expa

nsion

Alllow

andmiddle

incomecoun

tries

2005

Total

1.2

($20

00)

1.2

Asab

ove

Asab

ove

Asab

ove

Additio

nal

0.25

($20

00)

0.25

2002

Commission

onMacro-econo

mics

andHea

lth(CMH)

34,35

Asab

ove

83coun

tries(GNPpe

rcapita

less

than

US$

1200

($19

99)

2007

2015

Total

0.4-0.5

0.9

($20

02)

0.36

-0.45

0.82


expand services, and included the training of nurses and doctors. However, it

did not include the subsequent cost of expanding institutions to carry out

training. Human resource requirements can also include other types of health

professionals, such as adherence workers and non-professional health workers.

Moreover, given the scarcity of human resources for health, the resource impli-

cations of human resource management strategies such as task shifting,

improved re-numeration, and policies to increase retention should have also

been included. Guidance on a comprehensive list of human resource inputs of

TB/HIV/AIDS interventions is therefore still required by national resource

planners, especially as more countries scale-up to the limits of their existing

human resource capacity.

TB/HIV/AIDS interventions are spread across different programmes and sec-

tors, and the definition of interventions should reflect this. For example, most

of the global estimates for HIV/AIDS have included interventions that are

delivered in the education sector (school education programmes) and by the

private sector (social marketing). Reflecting this, the process for estimating glo-

bal resource requirements has become increasingly multi-sectoral and multi-

agency based over time. Nevertheless, the process of creating coherent and con-

sistent estimates include all sectors remains a challenge. In practice, different

agencies, sectors and disease programmes are likely to be in direct competition

for funds. This issue will need to be carefully addressed at the country level

where disparate processes will stretch already limited capacity. Ideally, the esti-

mation of requirements will be linked to broader national processes and insti-

tutions, such as medium term expenditure frameworks and multi-sectoral

HIV/AIDS committees.

Estimating the population in needOnce the scope of the programme has been determined, the next step is to

identify the population in need for each intervention. Table 2 provides exam-

ples of the methods used to define the population in need for four key inter-

ventions. Generally, estimates of the population in need for HIV/AIDS and TB

interventions have been based on the levels of HIV infection, AIDS and TB

incidence and information on risk factors. All the estimates for TB treatment

have defined the population in need as new cases of TB. This is derived from

estimates of incidence made by National Tuberculosis Programmes (NTP’s)

and the WHO.


Table 2 – Defining Population in Need for VCT, HIV treatment, TB treatment

Study VCT HIV treatment TB treatment PreventativeTherapy for TB

ACT Africa16 Current sexu-ally activepopulation

People who are HIVinfected and symp-tomatic and haveaccess to healthservices

People who areHIV infectedand haveaccess tohealth services

People who areHIV infectedand sympto-matic and haveaccess tohealth services

Schwartlanderet al17

2/5 * Adult HIVprevalence

New symptomaticsSurvival of 5 years.

NA Unclear

UNAIDS18 Adult HIVPrevalenceRate * tests peryear.

New symptomatics NA Unclear

AIDSTREAT-COST 19

HIV prevalenceUser can enterscreeningprotocol

New symptomatics. NA NA

3*5 Intiative21 NA Those expecting todie within two yearsin the absence oftreatment

NA NA

Boulle A et al25 Unclear New symptomaticsor WHO stage 3and 4Survival 4.5-5 yearsCountry specificdynamic demo-graphic andepidemiologicalmodel that allowsfor the effect of anti-retroviral therapyand voluntary coun-selling and testing

NA NA

Global Plan toStop TB29

NA NA TB Incidence(constantacross the2001-2005 per-iod) * popula-tion each year

Stock of TB /HIV infectionsat the end2000 and newinfection s over2001 – 2005.

Global DirectlyObservedTreatmentStrategy (DOTS)ExpansionPlan30,31

NA NA TB incidencefollows trend in2000 * popula-tion each year

NA


A key issue in the estimation of the population in need is how to estimate

changes in incidence in the medium or long-term. Many of HIV/AIDS and TB

interventions are preventative. They therefore will have an impact on future

incidence which may result in cost savings. However, most global estimates of

resource requirements for HIV/AIDS and TB have not used endogenous epide-

miological models (i.e. those that react to the level of service delivery being

covered). Generally, global estimates have assumed a fixed progression of inci-

dence over time adjusted for population growth. This is a pragmatic response

to the lack of data, especially on the effectiveness of interventions. There are

however a couple of exceptions. For example, the AIDSTREATCOST model

allows users to make assumptions decreasing the AIDS mortality rate and the

rate at which mothers transmit HIV to their newborn infants.

The CMH report states that at present the direction and extent of the overall

bias attributable to fixed incidence remains unclear. However, in the longer

term the assumption of no demographic or epidemiological impact is likely to

weaken. For example, the likelihood that scaling-up ARV treatment will have a

substantial impact on incidence of the opportunistic infections associated with

HIV/AIDS will increase. More evidence is therefore required particularly on

the impact of ARV and TB treatment in HIV prevalent settings to inform these

models. In addition, methodological guidance on the design of endogenous

models will also become necessary in the near future for those making country

specific estimates.

For the population in need of ARV treatment, most the estimates have

assumed that the number of people who are symptomatic and require treat-

ment is equal to the expected death cohort from AIDS one or two years

hence2. The length of survival for those who receive treatment has commonly

included assumptions about adherence failure and discontinuation. Survival is

also thought to depend on monitoring, consistency of drugs supply and psy-

chosocial support. The Resource Needs Model uses a maximum survival from

the point of treatment of seven years, depending on the infrastructure of the

health services providing the care. Schwartlander uses a more conservative esti-

mate of 5 years. These assumptions have a significant impact on overall

resource requirements and remain uncertain. Unfortunately, however, it may

be some while before these assumptions can be validated.

For preventative measures additional information on risk behaviours is

required, though most estimates do not provide details of the assumptions

used. The authors of the CMH report state that they were able to find informa-

tion on current morbidity and risk patterns for most countries. For VCT, the

ACT Africa report has estimated the population in need based on the size of

the currently sexually active population. Other estimates have linked the need

for VCT more directly to HIV prevalence itself. The estimate by Schwartlander

multiplied HIV prevalence by two and then assumed that this population will


visit a VCT centre every five years. Again, these assumptions will need to be

validated as programmes are scaled up.

Establishing baseline levels and target coverage of servicesOnce the population in need has been determined, a target level of population

coverage has to be set for each intervention. Resource estimates are based on

moving from current coverage levels to these targets. This requires assumptions

about the existing and future capacity to scale-up interventions. Table 3 shows

a selection of the targets used in the global estimates, demonstrating that there

is little consistency of approach. The most recent UNAIDS report acknowl-

edges this. It also states that it’s ‘targets’ should not be seen as agreed targets,

but as the outcomes that could be expected if the resources are spent as

described.

Some of the estimates have used multiple targets depending on the timeframe.

Estimates for the near future are constrained by current service capacity. For

example, the CMH report has estimated resource requirements for three differ-

ent scenarios: first, for services levels achievable by expanding lower levels of

the district health system by 2007; second, for service levels assuming substan-

tial investments in existing health systems at all levels of service delivery by

2007; and third, for achieving international targets by 2015. Schwartlander has

also constrained targets using a composite indicator of existing health service

capacity. This measures access to four facility-based services, such as TB treat-

ment and access to antenatal care. The Resource Needs model sets targets for

reducing unmet need (rather than increasing coverage) in a similar way, allow-

ing users to enter data for the current coverage for services such as TB treat-

ment and antenatal care, and the income level of the country. The latter

adjustment has significant consequences. For lower income countries the target

coverage is based on meeting an additional 10% of the unmet need each year,

whereas in richer countries the rate of scaling-up is 25%.

However, these approaches focus on supply rather than demand-side con-

straints at the household and community level (i.e. the determinants of utilisa-

tion of services, such as perceived quality of care and accessibility of care). This

implies that when interventions are provided, people will use them. The only

exception is the AIDSTREATCOST model which allows users to enter assump-

tions on the level of acceptance of treatment. Even where supply side con-

straints have been assessed, this has been done primarily in terms of physical

resources, rather than the ‘software’ constraints such as the health services

management capacity, knowledge, skills and motivation of staff. Assessing these

‘software’ constraints to scaling-up is important not only to determine the

capacity to absorb services, but also the capacity to adopt new approaches.

Therefore, guidance for resource planners on what these constraints may be

and further evidence on how these constraints affect the pace of scaling-up is

urgently required.


Table3–Targetsby

Interven

tion

forSelectedInterven

tion

s

Estimate

Broom

berg

etal

15AC

TAfrica

16Sc

hwart-

land

er17

UNAIDS18

3*5

Initiative

21

Commission

onMacro-

econ

omics

andHea

lth

(CMH)29

Commission

onMacro-

econ

omics

andHea

lth

(CMH)29

Globa

lPlan

toStopTB

29

Globa

lDirectly

Obs

erved

Trea

tmen

tStrategy

(DOTS

)ex

pans

ion

plan

31

Year

bywhich

target

need

sto

reache

d

(Ann

ual)

(200

5)(200

5)(200

7)(200

5)(200

7)(201

5)(200

5)(200

5)

HIV

Preven

tion

Prom

otionof

safersexu

albe

haviou

rsthroug

hmass

med

iaprog

rammes

0.5-

10million

coun

trypo

pula-

tion

1pro-

gram

me

10-50million

pop.

2prog

rammes

>50

million

pop.

1ad

ditio

nal

prog

rammepe

r50

millionpo

p.

6campa

igns

peryear

2-6campa

igns

percoun

trype

ryear

30-100

%NA

40-70%

80%

NA

NA

Provisionof

combine

dsex/

HIV

education

Alls

econ

dary

scho

olpu

pils

40-60%

ofpri-

maryteache

rs;

60-80%

sec-

onda

ryscho

ol

10-33%

ofpri-

maryteache

rs:

2-12

%of

sec-

onda

rytea-

49%

NA

40-70%

80%

NA

NA


insecond

ary

scho

ols

teache

rs;10-

50%

outof

scho

olyouth

chers;

10-50%

ofou

tof

scho

olyouth

Provisionof

Sexua

llyTran

smitted

Infection(STI)

trea

tmen

tservices

Lowincome

25%-50%

ofincide

ncecov-

ered

Middleincome

30-50%

ofthosewith

symptom

atic

STIstrea

ted

60-100

%of

symptom

atic

STI

caseswith

access

tohe

alth

care

facilities

74%

NA

20-40%

70%

NA

NA

Provisionof

cond

oms

throug

hsocial

marketing

pro-

gram

mes

and

public

distribu

tion

Betwee

n15

-30

%of

males

aged

15-49

supp

liedwith

52cond

oms

peryear

Onlyurba

nmen

includ

edin

lowinci-

dencecoun

tries

Urban

and50

%males

inmed

-ium

incide

nce

coun

tries

Allm

enin

high

incide

nce

coun

tries

10-40%

ofsex

acts

inwhich

public

sector

cond

omsus

ed;

30-50%

inwhich

cond

oms

from

social

marketing

used

;10

%cond

omsare

female

cond

oms

20-60%

ofcasu

alsex

acts;10

-30%

ofcoup

leswith

casu

alpa

rtne

rsus

econd

omsin

marital

sex

10-20%

ofcon-

domsdistribu

-tedthroug

hsocial

market-

ing;

10%

ofcond

omsare

female

cond

oms

60%

forcon-

dom

usein

riskysex

NA

40-70%

80%

NA

NA

Voluntary

Coun

selin

gan

dTesting(VCT

)

NA

5%coverage

ofVC

Tforag

egrou

p5-49

Twicethenu

m-

berof

HIV

infected

peo-

100%

NA

20-40%

70%

Varies

bycoun

tryup

to3-10

%of

NA


ple,

with

access

tohe

alth

care

facilities,

tested

every5years

popu

lation

accessing

TB/H

IVservices

Preven

tionof

Mothe

rto

Child

Tran

smission

(PMTC

T)

NA

5-10

%of

preg

-na

ntwom

entested

;90

%of

wom

enoffered

regimen

requ

estan

dcomplete;

50%

used

form

ula

feed

ing

10-50%

ofwom

enattend

-ingclinic

tested

:of

HIV+

wom

en,90

%accept

trea

t-men

tan

d50

%us

ereplace-

men

tfeed

ing

70%

ofthose

with

access

NA

10-45%

70%

NA

NA

HIV

Care

andTrea

tmen

t

Trea

tmen

tof

Opp

ortunistic

Infections

(OI’s)

NA

20%

ofthose

with

access

tohe

alth

services

receivecare

10%

-20

%of

unmet

need

74%

NA

25-40%

70%

NA

NA

Anti-retroviral

(ARV

)therap

yNA

10-25%

10%

-20

%of

unmet

need

53%

3million

peop

le10

-45%

70%

NA

NA

Tube

rculos

is

Directly

Obs

erved

Trea

tmen

tStrateg

y(DOTS

)Expa

nsion

NA

AsOItreatmen

tab

ove

AsOItreatmen

tab

ove

AsOItreat-

men

tab

ove

NA

50-60%

case

detec-

tion

rate

70%

case

detection

rate

100%

DOTS

expa

nsion

70%

detec-

tion

rate

85%

cure

rate

11

70%

ofesti-

mated

total

ofsm

ear

positive

patien

ts


In addition, global estimates have not taken into account the fact that other

programmes may be scaling-up at the same time. If the estimation is based on

one intervention in isolation, it will most probably severely underestimate the

extra resources required, as it implicitly assumes that all current spare capacity

will be used for this intervention alone. Given that achieving the MDG’s

involves a package of interventions, resource requirement models will need to

be developed that include costs of scaling-up the health system to provide a

package of essential services. These models will need to simultaneously set sys-

tems targets (such as the expansion of access to a health facility) with disease

targets (such as services delivered).

One of the main reasons that the models in this area have been limited is lack

of data. Very few of the global estimates have managed to assess capacity using

data from systematic country analyses of the current level of services.

Beginning to address this gap, the most recent UNAIDS estimates have

included a process of data collection with substantial country involvement,

through regional workshops with national experts and a global survey of cur-

rent coverage levels. It will be important to continue this effort and to further

support countries in their production of evidence assessing health system capa-

city and coverage.

In addition, most of the global estimates have adjusted targets for HIV preva-

lence. For example, UNAIDS estimates have used a target of 100% access of

school children to HIV/AIDS education in high prevalence areas. In low preva-

lence counties a lower target was considered sufficient. In other cases, estimates

have assumed that the higher the HIV burden, the slower the pace of scaling

up. High prevalent countries are affected by both the extent of the epidemic

and the burden of HIV/AIDS on health services. The latest UNAIDS estimates

model the growth in coverage based on most recent evidence of scale-up rates,

for example from the Progress Report on the 3x5 Initiative.

CostingThe next step in resource needs estimation is to multiply the level of interven-

tion provided (or people served) by the costs of each intervention. Incremental

costs are assessed rather than total costs. In other words, the resource require-

ments for expanding services over and above what is available rather than the

resources required for the total programme. Table 4 summarises the methods

used to do this for each of the global estimates.

Global estimates of resource requirements have either used cost data for inter-

ventions from existing studies or identify and value the inputs required to pro-

vide an intervention (ingredients approach). Most of the global estimates have

relied on cost data from published sources or from programme documents.

This data has been subsequently extrapolated to fit different contexts.

UNAIDS, for example, initially sourced its costs from over 70 published,


Table4–Co

stingMetho

dsUsed

Estimate/

Mod

elSo

urce

ofcost

data

Metho

dfor

gene

ralis

ing

Drugs

prices

Adjustmen

tsfor

scale

Uncertainty

Cost

Saving

sSy

stem

scosts

Broom

berg

etal

15

Costingstud

ies

Unclear

Cons

tant

Non

eNon

eNon

eNon

e

ACTAfrica

16

Ingred

ients

Unclear,averag

ecost

catego

rised

byincomelevel

Threedifferen

tAR

Vdrug

scost

used

Non

eRa

ngeof

resu

lts

presen

ted

Non

eNon

e

Schwartlan

der17

Costingstud

ies

Usedlowen

dcostsfrom

the

rang

eof

region

alcost

data

stud

ies

Cons

tant

Non

eRa

ngeof

resu

lts

presen

ted

Non

eTotalp

revention

costsincrea

sed

by10

%to

accoun

tforsys-

temscosts

UNAIDS

18

Cost

stud

ies

Nationa

lStrateg

icPlan

s

Costsdivide

dtrad

ed/no

n-trad

edan

dthen

non-trad

edad

justed

Cons

tant

Non

eLowen

dof

rang

eselected

.Non

eAllw

ithin

existing

human

andph

ysi-

calinfrastructure

3*5Initiative

21

Ingred

ients

Using

WHO-

Choice

metho

d40

Cons

tant

Using

WHO-

Choice

Metho

d40

Unclear

Non

eUsing

WHO-

Choice

Metho

d40

Globa

lPlanto

StopTB

29

Costingstud

ies

Nationa

lTB

Prog

rammes

Unitcosts

Nineregion

alclus

ters.

Costsdivedinto

locala

ndinterna-

tion

al.

Localc

osts

adjusted

bypu

r-chasingpo

wer

Cons

tant,aside

from

second

line

drug

swhe

rea

20%

redu

ctionin

prices

was

antic

ipated

Sep

arates

out

initial

costsan

drecurringcosts

andfix

edan

dvariab

lecosts

Unclear

Non

eProg

rammecosts

includ

esomesys-

temscostssu

chas

mon

itoringan

devalua

tion

and

man

agem

entan

dsu

pervision


Estimate/

Mod

elSo

urce

ofcost

data

Metho

dfor

gene

ralis

ing

Drugs

prices

Adjustmen

tsfor

scale

Uncertainty

Cost

Saving

sSy

stem

scosts

parity

(PPP

).Fixedcosts

adjusted

totake

into

accoun

tpo

pulation

size

Globa

lDirectly

Obs

erved

Trea

tmen

tStrateg

y(DOTS

)Expa

nsion

Plan

30,31

Bud

getestimates

Nationa

lPlans

Costingstud

ies

Using

quality

assessed

budg

ets

supp

lemen

tedby

cost

data

adjusted

byPP

P

Cons

tant

Non

eSen

sitivity

Analysis.Ra

nge

ofresu

lts

presen

ted

Non

eNon

e,bu

tas

abovemostsys-

temscosts

includ

edin

coun

-tryplan

san

dpro-

gram

mecosts

Commission

onMacro-econo

mics

andHea

lth(CMH)

34,35

Costingstud

ies

Coun

triesstrati-

fiedby

income

levela

ndregion

.Non

-trada

ble

compo

nentsof

costsad

justed

byPP

P

Cons

tant

Non

eLow-highrang

ecosts

Non

eIm

plem

entation

costs*2

Bou

lleet

al25

Ingred

ients

NA

Insomestud

ies

pricefalls

antic

ipated

Unclear

Differen

tscen

ar-

ioscosted

taking

into

accoun

tvary-

ing:

drug

sprices,su

r-vivalb

enefit,cov-

erag

elevels

Yes

Unclear

Resource

Nee

dsMod

el20

Ingred

ients

NA

Non

eNon

eNon

eNon

eNon

e

AIDSTR

EATCOST

19

Ingred

ients

NA

Non

eNon

ePresen

tsarang

eof

scen

arios

Non

eBuildings

includ

ed


unpublished reports and national strategic plans. However, cost data from pub-

lished studies is scarce and when available most studies are context-specific.

Costing studies vary in their perspective, scope and methods and data and may

not be presented in sufficient detail to be generalised to other situations. Cost

data from published studies will also reflect context-specific technical ineffi-

ciencies, which may lead to over- or under-estimation of true costs in other

settings.

The alternative method, specifying the inputs required using service protocols

and valuing them, is a common approach when data is scarce. The

AIDSTREATCOST model uses this approach and estimates disease and con-

struction costs separately. However, implicitly assuming an optimal/efficient

resource use runs the risk of severely under-estimating the real costs of imple-

mentation. This inevitably will involve some degree (often a high degree) of

inefficiency. Some models adjust for this, for example the WHO-CHOICE

model which includes an assumption of 80% efficiency.

For global estimates it is sufficient to use global cost averages. However, esti-

mates at the country level are likely also to be used as a basis for expenditure

planning. Ideally these should be based on realistic costs, reflecting achievable

efficiency improvements over time. In order to do this, countries will need to

include data collection and unit costing studies as part of the process of esti-

mating resource requirements. These unit costing studies will need to be com-

prehensive in that they should reflect a mixture of geographical settings and

services utilisation, both key determinants of costs. This requires investment in

capacity building, as well as time and resources. However, even a basic under-

standing of the country-specific cost structure of basic services, (e.g. costs of

inpatient bed-days or outpatient visit), will be extremely helpful as an indica-

tion of country specific resource requirements.

It is also important to consider how costs vary depending on the scale of a ser-

vice or the facility providing a service.3 Moreover, as programmes become inte-

grated or collaborate, there may be gains from economics of scope when costs

can be shared. However, at present the cost data available for HIV/AIDS and

TB interventions is not comprehensive enough to determine the extent of the

effect of scale or scope on cost. Reflecting this data constraint, most global stu-

dies have assumed no economies of scale or scope. An exception is the estimate

made for the Global Plan to Stop TB. Here average cost was broken down into

fixed, variable and start-up costs. The need for fixed and variable inputs was

assessed separately. Another possible method would be to estimate resources

for different pre-defined stages in the scaling-up. However, data to inform such

estimates will only become available as scaling-up proceeds.

To be useful for global estimations the methods used for country level costing

need to standardised. There are some areas that require specific attention. For


example, costs are commonly divided into different categories, intervention

costs, system costs, programme costs etc. However, because these are defined

differently, the comparison between global estimates is problematic.

Commonly, intervention costs (i.e. directly associated with a particular inter-

vention), have included both service delivery costs (e.g. supplies and drugs)

and programme costs (management, quality assurance). In some estimates sys-

tems costs are also included. The definition of systems costs has varied between

estimates, and can include items such as overheads, the cost of expanding plan-

ning and management capacity, training the additional staff, information and

financial systems, drugs management costs and capital management/ mainte-

nance costs (repair workshops etc). Guidance needs to be provided to ensure

consistency in this area.

Most the estimates do not measure systems costs directly, but assume a percen-

tage mark-up of intervention costs. The CMH report assumes that systems

costs (in this case defined as investment, management and administration

costs) are equivalent to intervention costs. Schwartlander increases prevention

costs by ten percent to account for policy, advocacy, administration, research,

surveillance and monitoring tasks. However, work by Johns demonstrates that

programme costs vary considerably for different interventions. For example,

the programme costs for prevention from mother to child transmission

(PMTCT) range between 4-18% of total costs, whereas the programme costs

for HIV/AIDS prevention are as high as 97%. This variability suggests that

standard assumptions about programme costs are not sufficient. More studies

into how the systems costs vary by intervention are therefore urgently needed

and where possible need to be incorporated into estimates.

Alternatively, as many interventions are being scaled-up to meet the MDG’s,

estimating the costs of scaling-up the health care system first and adding costs

for each intervention might be a better approach. Such an approach is used by

the Marginal Budgeting for Bottlenecks framework (MBB). The MBB method

sets broad targets for a health system and its resource needs, and then adds the

disease specific costs to reach those targets. This may be a more expedient

where estimates need to be made for a wide range of health interventions.

More attention needs to be given to explore whether simple models can be

developed for use by countries based on this approach.

Dealing with uncertaintyThe standard way of dealing with uncertainty in resource requirement esti-

mates is to conduct a sensitivity analysis. This is a process whereby estimates

are tested to see how sensitive they are to changes in key variables, such as

costs or assumptions of population in need. Most of the global estimates

reported an analysis of the sensitivity of their results to changes in assump-

tions. The country specific estimate for ARV treatment and care from South

Africa goes into more detail. It takes into account uncertainty in several other


key variables, such as drugs prices, survival benefits and levels of service cover-

age. These variables were demonstrated to have a significant impact on the

overall estimates.

For country level estimations, closely linked to planning processes, comprehen-sive sensitivity analyses will also be useful. Aside from improving estimates,this should further the understanding of the key variables that influence resourcerequirements. This will have the added benefit of highlighting which of themany knowledge gaps are most urgent to fill. Moreover, communication withpolicy makers about the extent of uncertainty involved is important for achiev-ing buy-in and acceptance of the estimates. As more data becomes available asprogrammes are implemented and scaled-up, estimates can continuously berefined to with the newest evidence. Resource needs estimation will then ideallybecome a continuous process of data collection, monitoring and evaluation, sup-porting country and global level planning to combat TB and HIV/AIDS.

CONCLUSION

This review does not aim to establish the validity of any of the estimates made

at the international level. The combined effect of the different areas requiring

further work is hard to determine. For example, on the one hand, current esti-

mates do not take into account the impact of interventions on the demand for

services, while it is clear that over time scaling-up to MDG target levels could

have a significant impact. On the other hand, current estimates may underesti-

mate the inputs required, demand side constraints and the ‘software’ and sys-

tems costs of scaling-up. Validation of the estimates will only happen in the

coming years as countries begin to scale-up HIV/AIDS and TB interventions

and much of the data required to make good estimates becomes available.

However, this review does aim to identify the current knowledge gaps in order

to inform those at the global and country level who are currently planning

rapid expansion of these services. It finds that although the global estimates

provide sound methodological guidance, there are still many challenges in

terms of methods, data and processes. Sound resource based planning at coun-

try-level will continue to be key to the success of scaling-up of HIV/AIDS and

TB services. It can enable the sustainability of these services in the long-run. It

is therefore essential that investments are made to generate the data required

and national level capacity to use it. In some areas additional tools need to be

developed. In other areas guidance needs given to country planners on how to

best use the models and costing tools currently available. Countries need to

examine how best to institutionalise resource needs estimation within existing

planning processes. If this is done, over time those making global estimates

will increasingly be able to build on the outcomes of country-led efforts, and


both countries and donors will have the information required to efficiently

fund the scale-up of these important health and development interventions.

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Chapter 7

General discussion andconclusion

A Vassall

DISCUSSION

This thesis has reported on four studies and one review. This chapter discusses

its implications for policy makers and researchers in the future. It takes into

account additional research published during the time of researching and writ-

ing this thesis.

DOTSThe studies presented in this thesis concerning DOTS in Egypt, Syria and

Ukraine demonstrate that DOTS is cost-effective in middle income countries.

In addition, a further study, published during the time of writing this thesis,

found DOTS to be cost-effective in Brazil (1). Furthermore, the World Health

Organisation recently conducted a global analysis of the cost-effectiveness of

DOTS. This used extrapolated costs for each country combined with an epide-

miological model to estimate effectiveness, including the effects of transmission

(2). This analysis found that average cost per DALY gained by DOTS ranged

from $6 to $15 international dollars in Africa and Asia. The study concluded

that DOTS for new smear-positive cases is a highly cost-effective global public

health intervention. Finally, in South Africa (3), researchers examined the

impact of MDR-TB on the cost-effectiveness of DOTS. This study found that

the inclusion of MDR-TB in the transmission models used to estimate DALYs

further improved the estimated effectiveness of DOTS, thus strengthening pre-

vious results.

Whilst it is clear that DOTS is cost-effective, the studies presented here from

Ukraine, Egypt and Syria show that the mode of delivery of TB control

(whether through communities, primary, clinics or hospitals) has a significant

impact on provider and patients costs. Developing a better understanding of

the effect that different health systems models have on the cost-effectiveness of

DOTS is essential for planning the expansion of DOTS. In situations where

current public health systems do not reach significant proportions of the popu-

lation, DOTS coverage will be limited, and therefore TB control will fail to

achieve it targets. Faced with this situation, some argue that the focus should

be on expanding the scale of the public health system, whilst others look to

partnerships with communities or with the private sector to expand DOTS.

Several additional studies have been published in the past few years that

address this issue. These focus on two areas. Firstly, there are several studies

examining whether DOTS can be made more cost-effective when delivered in a

community based way in Africa (4-10). These find that, within pilots, effective-

ness can be maintained whilst costs are substantially reduced. It would be

interesting to see if whether models involving the community remain cost-

effective when done at scale. Secondly, there are several studies examining the

cost-effectiveness of DOTS implemented through the private sector (11-15).

These find that the private sector (including facility and workplace models)


can deliver DOTS in a cost-effective way. In one study from India, the public

subsidy required for DOTS through private clinics was found to be signifi-

cantly lower than the costs of public provision (11). A further study in India,

comparing the costs of DOTS and non-DOTS to the private sector, also found

substantial cost savings for private providers when adopting DOTS compared

to previous practices (12). Combined this studies suggest that private provision

of DOTS is at least as feasible and potentially cost-effective as increased public

provision.

However, changing the health systems/institutional framework for implement-

ing TB control can be complex. The study presented from Ukraine, shows that

economic studies can assist this effort by providing policy makers and health

systems specialists with an indication of the economic winners and losers in

any institutional change. More studies that examine both the cost-effectiveness

and economic benefits of different health systems approaches (at scale) to sup-

port TB control objectives are needed, especially from countries where DOTS

has already been successfully expanded throughout the existing health system,

and a broader range of interests and stakeholders are involved.

In recent years several studies have been published on enhancing the effective-

ness of DOTS with new technologies. Most of these have focused on improved

diagnostics. The first of these (16) examines the cost-effectiveness of polymer-

ase chain reaction (PCR) in Kenya. This study found that, where there are large

numbers of patients, this relatively expensive technology can be cost-effective.

A further study in Zambia examined the cost-effectiveness of culture testing

(17). Its findings are similar to the ones presented on MDR-TB diagnostics in

this thesis for IDLJ culture (i.e. costs of around $35 dollars per test). In addi-

tion, it found that liquid and solid media compare are both cost-effective.

However, like the PCR study above costs vary considerably depending on the

throughput of the machines used for liquid culture (MGIT). The study pre-

sented in this thesis also shows that prevalence is a key determinant of cost-

effectiveness. The question now facing future researchers is therefore not

whether it is potentially cost-effective to employ these new diagnostic technolo-

gies, but when/ where to employ them.

One approach to answering this question is modeling. In 2008, a study waspublished modeling the incremental cost-effectiveness of a hypothetical newpoint-or-care TB diagnostic test in South Africa, Brazil and Kenya (18). Thisstudy assumed set prevalence rates and concluded that price and specificitywere key determinants of cost-effectiveness of diagnostic technologies for TB.The cost of false positives was found to be a significant element in overallcosts, due to cost of avoidable treatment. As increasing funds are being investedin new technologies to enhance DOTS, these decision analysis models will bean important area for development in the future. Those funding new TB control

General discussion and conclusion 115

technologies will need to assess when and where a technology is likely to becost-effective and produce estimates of demand for these technologies.

MDR-TBThe study presented in this thesis examining the cost-effectiveness of MDR-TB

diagnostics, is one of several recent studies looking at the cost-effectiveness of

controlling MDR-TB. Following the first study of MDR-TB treatment in Peru

(19) two more studies examining the cost-effectiveness of MDR-TB have been

published (20-21). A further study from Peru compares different ways of diag-

nosing and treating MDR-TB (20). It uses a dynamic state-transmission model

to examine the transmission benefits of MDR-TB treatment, estimating out-

comes for a population of 100,000 people. It finds that using a combination of

drug susceptibility testing followed by either locally standardised second-line

drugs or individualised treatment for previously treated cases is significantly

more cost-effective than; a) DOTS (including retreatment); b) providing locally

standardised drugs for previously treated cases (without testing); or c) indivi-

dualised treatment after drug susceptibility testing for all cases. The study

authors conclude that the treatment of MDR-TB using second-line drugs is

highly cost-effective in Peru, and is likely to be so in a wide range of other set-

tings. Finally, a study from and MDR-TB pilot in the Philippines (21) reports

that MDR-TB diagnosis and treatment were found to be cost-effective, even

where the drugs costs were significantly higher than those used in Peru and

patient costs were included.

The combined findings of these studies suggest that the diagnosis and treat-

ment of MDR-TB is likely to be cost-effective, and this may be further

enhanced by the development of new technologies. Whilst broadly this conclu-

sion has not been challenged, these studies have attracted a number of letters

in scientific journals (22). These responses highlight a number of issues. Firstly,

it has been suggested that these studies are not independent, as they are con-

ducted, supported or funded by a small group of technocrats at the global

level. Secondly, there is concern that these findings cannot be generalized to

other settings as these pilots are not sufficiently robust enough to justify scaling

up MDR-TB diagnosis or treatment. In particular, attention has been drawn to

their small-scale, external funding and the use of the best clinicians and scien-

tists. Finally, there has been a concern that a focus on MDR-TB will distract

limited resources away from the main public health priority treating drug sus-

ceptible smear-positive TB (i.e. DOTS).

This last issue highlights a common problem in applying economic evalua-

tions. Economic evaluations simply demonstrate the potential cost-effectiveness

of MDR-TB treatment. In the real world, rather than attracting additional

funding for TB control, additional interventions may pull resources away from

the existing strategy i.e. (first line treatment) DOTS. This consequence needs

to be better addressed in the discussion of research results in the future. In


particular, the resource requirement implications of cost-effectiveness studies

need to be made more explicit. As resources (particularly human resources) are

fixed in the short-run, it should be clear that investments need made over a

sufficient time scale. Finally, now the pilots have established potential cost-

effectiveness, further research should be focused on establishing the feasibility

and cost-effectiveness of MDR-TB in routine and real-life settings to provide

the basis for more accurate estimates of true resource requirements.

TB/HIVThe study on TB/HIV patient costs from Ethiopia presented in this thesis

argues that the early detection of the TB and HIV has both public health and

economic benefits to households. This is complemented by a recent study, con-

ducted in South Africa, which concludes that the ProTEST package of TB/HIV

services (which includes the expansion of VCT and linking of TB/ HIV ser-

vices) is cost saving from a health service perspective (23). Despite these posi-

tive indications, the same study shows whilst TB services can substantially

improve the case detection of HIV, using VCT to detect TB cases seems to be

less successful. Further studies from different settings are still required to con-

firm these findings.

More broadly as DOTS coverage increases it is likely that more attention will

be paid to trying to identify low cost methods of active forms of TB case detec-

tion in high prevalence HIV settings. This issue is explored in a recent study

modeling the population wide benefits of different interventions to control TB

in high prevalence HIV settings (24). This study finds that improving the TB

case detection rate is potentially the most cost-effective approach to TB control

in high prevalence HIV settings. This finding is based on the assumption that

the unit costs of case detection will increase 2-4 times when activities to

improve case detection rates to 70% are implemented. TB treatment, a combi-

nation of case detection and treatment, and the treatment of latent TB infec-

tion (with IPT) also were found to be cost-effective, confirming previous

studies. ART was significantly less cost-effective. Further studies are required

to confirm these findings. Whilst there is no doubt that case finding is essential

to TB control, a key issue now will be to verify the preliminary cost estimates

of enhanced case detection.

Estimating the resource needs of scaling up TB/HIV interventionsThe studies presented or referred to in this thesis demonstrate that there are a

variety of cost-effective interventions available to control TB. Furthermore, sev-

eral new interventions or enhancements to current interventions to control TB

are likely to become available the coming years. In order to support the scale-

up of these interventions, economists working in TB control are now becoming

increasing concerned with how to finance them. Whilst this thesis does not

focus on health care financing, the review contained in the final chapter exam-

ines the resource implications of scaling up cost-effective TB/HIV interven-


tions. This review highlights several of the methodological issues involved and

areas that require further research. However, in reality, financial planning

capacity within Ministries of Health, let alone TB services, in many countries

remains weak. Supporting the development of simple tools that TB services

can use to estimate their resource needs are required. The WHO has been

assisting in this effort in its production of its annual TB control report and

other activities over the past few years, however efforts remain focused on TB-

specific costs.

The review presented in this thesis draws attention to the estimation of the sys-

tems costs required to scale up TB control interventions. The review found

that most estimates of systems costs were made by simple ‘rule of thumb’ cal-

culations. Estimates of long term costs of the investments in human and phy-

sical health systems capacity, based on different health systems modalities of

scaling up TB control, are now required. As the Ukraine and Ethiopian study

both illustrate, obtaining a better understanding on who bears the costs of

expanding TB control interventions can be used to support the necessary sys-

tems reform. In addition, investments in the long term systems development

costs for TB control may help address skepticism about the feasibility of adopt-

ing new technologies in weak health systems. In summary, the economic

research focus in the future TB control needs to move beyond filling the gaps

in knowledge regarding the cost-effectiveness of different interventions, to a

thorough examination of the (costed) system implications of expanding these

interventions.

CONCLUSION

Directly Observed Treatment Strategy remains the cornerstone for TB control.

The studies presented in this thesis demonstrate that DOTS expansion in mid-

dle income countries may face institutional rigidities, but is feasible and cost-

effective. The study into the MDR-TB highlights the potential cost-effective-

ness of new cost technologies to tackle this disease; particularly if they are

proved successful in preventing future transmission and spread of this danger-

ous disease. All the cost-effectiveness studies in this thesis highlight the impor-

tance of the cost to the patient in accessing and adhering to TB treatment. In

the case of Ethiopia this cost is significant compared to annual household

income. Attention needs to be give to mitigating these costs when planning ser-

vices, particularly for the very poor. Finally the last part of this thesis examines

the use of the cost information in the financial planning of TB services. Whilst

the cost-effectiveness of many TB control interventions is well established,

there is still significant work to be done to plan and estimate the resource

requirements required to implement and scale-up both TB and HIV interven-

tions. A particular area of concern is the estimation of systems costs of TB con-

trol expansion.


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Chapter 8

Summary/Samenvatting

SUMMARY OF MAIN FINDINGS

Chapter One presents a literature review of studies into the cost and cost-effec-

tiveness of Tuberculosis (TB) control prior to researching this thesis. Although

the broad strategy for TB control, Directly Observed Treatment Strategy

(DOTS), is well established, it identifies areas for further research. These

include the assessment of the cost-effectiveness of: re-structuring health ser-

vices in middle income countries to provide DOTS; new strategies for case

detection; new strategies/ tools to combat the growing threat of MDR-TB; and,

the integration of TB/HIV services.

Chapter Two presents the findings of a study into the cost-effectiveness of TB

control in Egypt and Syria. In Syria, the study compared DOTS delivered

through the Primary Health Care (PHC) system to traditional TB diagnosis

and treatment at specialized TB clinics. The study finds that DOTS delivered

through the primary health care system is the most cost-effective TB control

strategy. With DOTS implementation, health service costs fall, patient costs

remain unchanged and effectiveness increases. In Egypt, the study compared

DOTS delivered through various institutions, (primary health care, specialized

chest clinics and hospitals) to the traditional TB control strategy delivered

through specialized clinics and hospitals. As with Syria, DOTS delivered

through the primary health care system is also the most cost-effective TB con-

trol strategy. However, the difference between the cost-effectiveness of alterna-

tives is much less striking. In both countries, in part due to the results of these

studies, DOTS was expanded nationwide, and the role of the specialist clinics

in TB control was re-examined.

Chapter Three presents the findings of a study into the cost-effectiveness of

DOTS in Ukraine. The study presents the results of two pilot projects in Kyiv

City and Mariupol. Although, the research was initially designed as a study of

cost-effectiveness, as the pilots progressed it became apparent that other factors

needed to be assessed in order to satisfy the concerns of policy makers in

Ukraine. The scope of the study was therefore expanded to include an assess-

ment of feasibility and economic incentives. The study finds that providing

DOTS integrated in general health services is likely to be feasible, effective and

cost-effective.

The study identifies several economic dis-incentives to the expansion of DOTS

to both patients and providers. Most patients incur substantial costs from hos-

pitalization, and therefore ambulatory DOTS has the potential to reduce

patient costs. However a small number of patients (the homeless and very

poor) benefit economically from being in hospital. In this case, social support

may need to be provided. In addition, TB hospitals/ providers are funded

based on the number of occupied beds. There is therefore a strong incentive to

ensure high levels of occupancy. By challenging this approach and integrating


DOTS in the general health system, the economic well-being of TB profes-

sionals is directly threatened. This situation is exasperated by the reductions in

state pensions that offer little incentive for retirement for TB professionals. The

study also finds low levels of informal payments to doctors treating TB.

Compared to anecdotal evidence of the high payments associated with other

areas of general medicine, there also appears to be little economic incentive for

general practitioners to treat TB. Health planners will need to address these

dis-incentives if DOTS scale-up is to be successful in Ukraine.

Chapter Four examines the cost-effectiveness of new diagnostic technologies

for Multi-Drug Resistant Tuberculosis (MDR-TB). Five different methods are

examined, including the gold standard Indirect Lowenstein Jensen method.

The study estimates the cost-effectiveness for population groups with different

levels of MDR-TB prevalence. It finds that average cost per case detected ranges

from $59 for a low cost test in a high prevalence group, to $8914 dollars with a

high cost test in a low prevalence group. However, when the costs associated

with reduced transmission are taken into account, all tests conducted on

groups with more than a 20% MDR-TB prevalence are cost saving. Even for

high costs tests, the costs per Disability Adjusted Life Year (DALY) remain low.

This study suggests that these technologies need to be further explored and

piloted more widely in other low and middle income settings.

Chapter Five examines patient costs prior to and during treatment at TB/HIV

services in Ethiopia. Prior to treatment, patients incur substantial direct costs

seeking alternative therapies for their symptoms. Attention is therefore drawn

to the importance of early diagnosis both for health, but also economic rea-

sons. Thereafter TB treatment results in average economic loss of 71% of

annual household income. At the start of both TB and ART treatment costs

rise, as patients spend time accessing treatment and symptoms worsen.

However, after a short period of treatment, costs begin to fall as the visits

become less frequent and symptoms improve. During treatment, direct pay-

ments to health services remain substantial, even where treatment is provided

free of charge, due to the payments for diagnostics. For the very poor, trans-

port costs are the most significant cost associated with accessing treatment.

Chapter Six reviews the global estimates of the costs of TB control and inter-

ventions to address HIV to inform the process of estimating national resource

requirements. The review identifies the steps taken to define the interventions

to be costed, estimate the population in need of TB or HIV services, set base-

line and target levels of coverage and apply cost data. It highlights several areas

where methods and practices need to improve in order to obtain reliable

resource estimates. Firstly, most the estimates do not adequately assess current

capacity and therefore incorrectly measure incremental costs. Secondly, insuffi-

cient care is taken when applying costs from one setting to another, (between

Summary/Samenvatting 123

and within countries). Lastly, methods for estimating the systems costs of inter-

ventions remain very weak.

Chapter Seven summarises the main findings, conclusions of the studies pre-

sented in this thesis and discusses the implications for further research. It con-

cludes that the research presented in this thesis demonstrate that DOTS

expansion in middle income countries is feasible and cost-effective, but may

face substantial institutional rigidities. Further research is required into the

most cost-effective systems/ institutional structures best suited to deliver DOTS

in these environments. The study into the MDR-TB highlights the potential

cost-effectiveness of new cost technologies to tackle this disease; but further

studies are required to further confirm these early findings and then examine

the cost implications of scaling-up new technologies. Several of the studies in

these highlight the importance of patient cost. Attention needs to be give to

mitigating these costs when planning services, particularly for the very poor.

More research is required to identify the best ways of doing this. Finally the

last part of this thesis examines the use of the cost information in the financial

planning of TB services. Whilst the cost-effectiveness of many TB control inter-

ventions is well established, there is remains thereafter significant work to be

done to plan and estimate the resource requirements required to implement

and scale-up these TB and HIV interventions. A particular area of concern is

the estimation of systems costs of TB control expansion.

SAMENVATTING

Hoofdstuk een presenteert een literatuuroverzicht van studies naar de kosten

en kosteffectiviteit van tuberculose (tbc) bestrijding, beschikbaar tot aan dit

thesisonderzoek. Hoewel dit overzicht een duidelijk beeld schetst van DOTS,

de brede strategie om TB te bestrijden, wordt een aantal gebieden

geıdentificeerd voor verder onderzoek. Deze gebieden omvatten de beoordeling

van de kosteffectiviteit van: herstructurering van de gezondheidsvoorzieningen

voor het leveren van DOTS in middle income countries; nieuwe strategieen om

ziektegevallen op te sporen, nieuwe strategieen / instrumenten om de groeiende

bedreiging van MDR-TB te bestrijden en van geıntegreerde TB/HIV zorg.

In hoofdstuk twee worden de resultaten van een studie naar de kosten-effecti-

viteit van TB bestrijding in Egypte en Syrie gepresenteerd. In Syrie werd DOTS

zoals uitgevoerd door de eerste lijnsgezondheidszorg vergeleken met de tradi-

tionele TB diagnose en behandeling in gespecialiseerde TB klinieken. Het

onderzoek toonde aan dat DOTS uitgevoerd door de eerstelijnsgezondheids-

zorg de meest kosteffectieve TB bestrijdingsstrategie was. Het toepassen van

DOTS resulteerde in lagere gezondheidszorgkosten, gelijkblijvende patientkos-

ten en een verbeterde kosten-effectiviteit. In Egypte werd DOTS zoals uitge-

voerd door verschillende instituten (eerstelijnsgezondheidzorg, gespecialiseerde


longklinieken en ziekenhuizen) vergeleken met de traditionele tbc-behandeling

door gespecialiseerde klinieken en ziekenhuizen. Net als in Syrie, was DOTS

uitgevoerd door de eerstelijnsgezondheidszorg de meest kosten-effectieve TB

bestrijdingsstrategie. Echter, verschillen in kosten-effectiviteit tussen de

verschillende alternatieven waren veel minder opvallend dan in Syrie. Mede

gebaseerd op de uitkomsten van deze onderzoeken, werd het toepassen van

DOTS in beide landen uitgebreid. De rol van de in TB behandeling gespeciali-

seerde klinieken werd heroverwogen.

Hoofdstuk drie beschrijft de resultaten van een onderzoek naar de kosten-

effectiviteit van DOTS in de Oekraıne in twee pilots in Kiev en Mariupol. Het

onderzoek was aanvankelijk ontworpen als een kosten-effectiviteitsstudie.

Echter, gedurende de voortgang van de pilots werd duidelijk dat andere facto-

ren meegenomen moesten worden om beleidsmakers in de Oekraıne tevreden

te stellen. Een aantal aandachtsgebieden werden aan de studie toegevoegd o.a.

het beoordelen van de haalbaarheid van DOTS en financiele stimuli voor het

opschalen van DOTS. Uit het onderzoek kwam naar voren dat het uitvoeren

van DOTS, geıntegreerd in de algemene gezondheidszorg, haalbaar, effectief en

kosten-effectief was.

Echter, de studie identificeerde ook verscheidene economische factoren die de

uitbreiding van DOTS voor zowel patienten als zorgverleners tegengaan. Het

kostte de meeste patienten veel geld om in een ziekenhuis opgenomen te wor-

den, en in het geval van ambulante DOTS waren de kosten lager. Echter voor

een klein aantal patienten (daklozen en zwaar verarmden) was het economisch

voordelig om opgenomen te worden. Voor deze patienten was sociale onder-

steuning een voorwaarde om DOTS succesvol te maken. Daarnaast kregen TB

ziekenhuizen/zorgleveranciers betaald voor het aantal bezette bedden dat ze

hadden. Er was hierdoor een sterke prikkel om een hoge bezettingsgraad te

hebben. Door dit systeem op de helling te zetten en DOTS te integreren in de

algemene gezondheidszorg, zou het economische welbevinden van TB profes-

sionals direct worden bedreigd. Deze negatieve prikkel zou worden versterkt

door de verlaging van de staatspensioenen van TB professionals waardoor het

voor hen belangrijk blijft het oude systeem met een hoge bedbezettingsgraad te

handhaven. De studie toonde verder aan dat informele betalingen aan behan-

delende TB artsen beperkt voorkwamen. Vergeleken met de hoge betalingen op

andere gebieden van de gezondheidszorg, gebaseerd op anekdotisch bewijs, zou

het behandelen van TB huisartsen weinig economisch gewin bieden.

Gezondheidsplanners zullen met deze negatieve effecten rekening moeten hou-

den om het opschalen van DOTS in de Oekraıne succesvol te maken.

Hoofdstuk vier onderzoekt de kosten-effectiviteit van nieuwe diagnostische

technieken voor MDR-TB. Vijf verschillende methoden werden onderzocht,

inclusief the gouden standaard ‘Indirect Lowenstein-Jensen’ methode. De studie

schat de kosten-effectiviteit voor populaties met verschillende niveaus van


MDR-TB prevalentie. Een uitkomst is dat de gemiddelde opsporingskosten va-

rieren van $59 met goedkope testen in populaties met een hoge prevalentie tot

$8914 met dure testen in een populatie met een lage prevalentie. Echter wan-

neer de kosten verbonden aan verlaagde overdracht van de ziekte ook mee-

genomen worden, blijkt dat alle testen verricht op populaties met meer dan

20% MDR-TB prevalentie een kostenbesparing opleveren. Zelfs voor de dure

testen blijven de kosten per Disability Adjusted Life Year laag. Dit onderzoek

suggereert dat de gebruikte technieken verder onderzocht en getest moeten

worden in pilots in low en middle income countries.

Hoofdstuk vijf presenteert kosten die patienten maken voor en gedurende de

behandeling in TB/HIV centra in Ethiopie. Op zoek naar alternatieve thera-

pieen voor hun symptomen maken patienten voorafgaand aan hun behandel-

ing substantiele kosten. Vanuit het oogpunt van gezondheid, maar ook

vanwege economische redenen, is het belangrijk voldoende aandacht op een

vroege diagnose te richten. Als de tbc-behandeling eenmaal begonnen is, leidde

een ziekenhuisopname tot een economisch verlies van 71% van het jaarlijkse

inkomen. Bij het begin van een gecombineerde tbc en hiv-behandeling waren

de kosten hoger, Echter na een korte periode van behandeling namen de kosten

af omdat de frequentie van de behandelingsbezoeken afnam hetgeen mogelijk

was doordat de symptomen verminderden. Hoewel de behandeling gratis was,

bleven directe kosten voor diagnostiek gedurende de behandeling aanzienlijk.

Voor de allerarmsten waren transportkosten, gemaakt om toegang te krijgen

tot behandeling, de belangrijkste kostenpost.

Hoofdstuk zes bespreekt globale schattingen van de kosten van TB en hiv

bestrijding, die gebruikt worden ten behoeve van het schatten van benodigde

nationale middelen. Er worden stappen geıdentificeerd die genomen moeten

worden om de kosten van de interventies te definieren, schattingen gemaakt

van de populatie die TB of HIV zorg behoeft, baseline en gewenste niveaus

voor de dekkingsgraad vastgesteld en kosten informatie toegepast. Het over-

zicht identificeert verscheidene gebieden waarvoor betere nodig zijn om te

komen tot betrouwbare schattingen van de benodigde middelen. Ten eerste

geven de meeste schattingen geen adequate beoordeling van de actuele capaci-

teit en meten daarom verkeerde periodiek toenemende kosten. Ten tweede

wordt onvoldoende zorgvuldig omgegaan met het overzetten van kosten van

een situatie naar een andere (tussen en binnen landen). Tot slot, methoden om

de systeemkosten van interventies te schatten blijven zwak.

Hoofstuk zeven vat de belangrijkste bevindingen in dit proefschrift samen en

bespreekt de implicaties voor vervolgonderzoek. Het onderzoek in dit proef-

schrift toont aan dat de uitbreiding van DOTS in middle income countries

haalbaar en kosten-effectief is, maar kan stuiten op aanzienlijke institutionele

belemmeringen. Er is behoefte aan vervolgonderzoek naar de de meest kosten-

effectieve systemen en institutionele structuren die geschikt zijn om de DOTS


strategie in deze omgeving uit te voeren. De studie naar MDR-TB geeft de

potentiele kosten-effectiviteit aan van nieuwe technologieen voor de diagnose

van deze ziekte, maar er is meer onderzoek nodig om deze bevindingen te be-

vestigen en vervolgens de kost- implicaties van het opschalen van nieuwe tech-

nologieen te onderzoeken. Verschillende studies in dit proefschrift tonen het

belang aan van patientenkosten. Wanneer gezondheidszorg gepland wordt

moet er aandacht besteed worden aan het verlichten van deze kosten, speciaal

voor de allerarmsten. Er is meer onderzoek nodig naar hoe dit het beste gedaan

kan worden. Het laatste gedeelte van dit proefschrift onderzoekt tot slot het

gebruik van kostinformatie in de financiele planning van TB zorg. Terwijl de

kosten-effectiviteit van veel TB bestrijdingsmaatregelen goed bekend zijn, moet

er nog veel werk gedaan worden om de benodigde middelen voor de toepassing

en opschaling van TB en HIV interventies in te schatten. Een specifiek veld dat

aandacht behoeft is het schatten van systeemkosten ten behoeve van het uit-

breiden van TB bestrijdingsmaatregelen.



The Costs and Cost-effectiveness of Tuberculosis Control

Anna Vassall

Tuberculosis is a leading cause of ill-health and death in low and middle income coun-tries. Tuberculosis control is essential for achieving the Millennium Development Goalsrelating to health by 2015. However, despite efforts made to expand tuberculosis controlover the past decades, tuberculosis remains a serious global health problem. This bookaims to assist the expansion of tuberculosis control by adding to the evidence on thecost-effectiveness of different tuberculosis control strategies. It presents research fromfive countries: Egypt, Ethiopia, Syria, Peru and Ukraine. It examines the implementation of the World Health Organization recommended strategy, Directly Observed TreatmentStrategy (dots). New technologies currently being developed to tackle drug resistanceare also assessed. Emphasis throughout is placed on the importance of health systemsand the costs for patients accessing treatment. This book is essential reading for anyoneinterested in economic aspects of tuberculosis control.

Anna Vassall is a leading advisor to several international organizations and govern-ments in the area of health economics. Her specific focus is on strengthening healthsector planning and investments in low and middle income countries, by supportingthe generation and use of economic evidence.

UvA Dissertation

Faculty of Economics and Business

9 789056 295950

Anna Vassall The Costs and Cost-effectiveness of Tuberculosis Control

AUP-Vassall:AUP/Buijn 10-09-2009 15:30 Pagina 1

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