Pharmacovigliance in India: Dreams Vs Reality

8/3/2019 Pharmacovigliance in India: Dreams Vs Reality

1/58

Pharmacovigilance in India: Dreams

Vs RealityNational Seminar on Pharmacovigilance, CADD and Drug

Development

Pushpagiri College of Pharmacy, Tiruvalla16th Sept 2011

Unnikrishnan M KCollege of Pharmaceutical Sciences, Manipal 576 104


2/58

The Healers Doubtful Credentials!

Do you know the meaning of allopathy ? Doctors have been the butt of many jokes!

Vaidayraja namasthubhyam

Yamaraja sahodara

Yamo harathi pranaani

Vaidyo praana dhanaanichaTo undergo treatment you have to be healthy,

because you have to withstand both sicknessand the medicine! - Moliere


3/58

Iatrogenic Deaths in USA

12,000 -----unnecessary surgery 7,000 -----medication errors in hospitals

20,000 -----other errors in hospitals

80,000 -----infections in hospitals 106,000 ----non-error, negative effects of drugs

Total = 250,000 deaths/year are iatrogenic

Third leading cause of death in U S A after heart disease and cancer

Only 60,000 Americans died in Vietnam war!

(Report in JAMA by B Starfield of Johns Hopkins School of Hygiene & Public Health)


4/58

Evolution of Pharmacovigilance

Thalidomide tragedy in 1961 first systematic international efforts toaddress drug safety Led to WHO Pilot Research Project for International Drug Monitoring in 1968

WHO Collaborating Centre for International Drug Monitoring Uppsala Monitoring Centre (UMC)

Creation of International Society of Pharmacoepidemiology (ISPE) in1984 & European Society of Pharmacovigilance (ESOP later ISoPthe International Society) in 1992 PV formally introduced into research & academic world,

PV integrated with clinical practice


5/58


6/58

The Global burden of Unsafe Care

Patient safety global public health problem

WHO estimates

millions of disabling injuries/death every year ~1 in 10 harmed while receiving health care in wellfunded &

technologically advanced hospital settings

Very little evidence for burden of unsafe care in developingcountries where :

16 billion injections administered each year for curative care

40% of this administered by reusing unsterilized syringes & needles


7/58

Global Burden of Unsafe Care

(contd)

Economic burden is compelling Added medical cost in some countries between US$ 6 - 29 billion a year

World Alliance for Patient Safety

Mobilize global efforts in health care safety in WHO MemberStates

Develop a global research agenda & locally adapted research tools Training & research funding

Creating a global research network

Translating research into safer care


8/58

International Pharmacovigilance(PV)

Landscape

ADRs cause of hospitalizations, morbidity & even death

Pharmacovigilance aims at preventing:

ADRs & its impact on patients

both in premarketing & post marketing phases of drug

development


9/58

International Pharmacovigilance(PV)

Landscape

Pharmacovigilance

began with WHOs Program for International Drug

Monitoring (1968)

extends beyond detecting new signals of safetyconcerns

a tool for development & marketing of safer medicines Drug Expertise: a sine qua non for safety

Number of drugs has increased dramatically

36th

Edn of Martindale has > 430 pages of general index!


10/58

Two stories of contrast India Vs

Australia

Zolpidem story

Alendronate story


11/58

Australian ADR Database

Up to 4 January 2008, 1032 reports of suspectedADRs to zolpidem entered TGA's ADR database

394 of 1032 reports mentioned parasomnia events

103 reports (10% ) included sleep driving


12/58

Therapeutic Goods Administration,

Australia Warning Feb 2008

TGA Issues Black Box Warning!

"Zolpidem may be associated with potentially

dangerous complex sleep-related behaviourswhich may include sleep walking, sleep drivingand other bizarre behaviours. Zolpidem is not tobe taken with alcohol. Caution is needed withother CNS depressant drugs. Limit use to fourweeks maximum under close medicalsupervision.


13/58

Bisphosphonatesinduced

osteonecrosis of jaw

Severe pain, numbness, soft tissue infection,loosening of teeth

Excruciating pain, disfigurement leading tosuicides

The strategy is to warn doctors, healthcare team,

dentists etc.


14/58

Picture in UK, a developed country

National Health Services spends ~ 2bn a yeartreating patients with adverse reaction to

prescribed drugsEnough to pay for 10,000 new midwives or cost of

combating MRSA infections

ADRs result in 6.5% of hospital admission = Imillion / year in UK alone

average stay of 8 days in hospital @ 228 a day


15/58

Drug Companies Suppress

Information on ADR

Merck knew that Vioxx, caused heart attacks,

GSK knew that Antidepressant Seroxat, (Paroxetin) increased suicidal thinking in young

There are instances when Glaxo paid up to 3 billionsto escape litigation without admitting guilt

Weve agreed to this settlement to avoid the

delay, expense and uncertainty of litigation,

Mary Anne Rhyne, a company spokeswoman.


16/58

Why dont we have data like

Australia? 1070 million Indians Vs 20 million in Australians

Much more opportunity to gather data

Much more racially diverse,

Many more diseases in abundant numbers!

A visiting team of Australian health care providerswitnessed Typhoid for the first time in India!

Many more systems of medicine

Much more freedom to bend & twist rules

Much greater nefarious opportunity to improvise


17/58

Some Attitude problems; some

Resources problems! We dont have a good system of keeping records Still thrive on an oral tradition

Very little discussion between the Prescriber, the

Dispenser and Patient (Overworked Doctor,busy Pharmacists, high cash transactions)

We lack faith in ourselves

We want our observations to be supported bypublished literature from the West

India has not contributed a single innovation in

therapy


18/58

Major flaw: poor networking!We are working in isolation

We have to learn from our own mistakes

Developed countries learn from others mistakes!


19/58

How things go wrong a Case Study

in Kerala

Nair 47 yrs h/o diabetes goes to hospital withvomiting and respiratory difficulty

Decides for himself that his case must be seenby a gastroenterologist

9 days in the hospital, returns with the foll

diagnosis (Hospital bill > Rs 25000/-) Upper esophageal polyps,

LRT, Pleural effusion, Functional bowel disorder


20/58

Mr Nairs prescription on discharge1 T deriphyllin retard 500 1-0-12 T glimipiride 2 1-0-1

3 T Cefuroxime 500 1-0-1

4 Seroflo 100 (rotahaler) 1-0-1

5 Tegasarod 6mg* 1-0-1

6 Sod picosulphate 10 0-0-2

7 Deflazocort 6 mg 1-0-1

8 Faropenem 200 1-1-19 Flupentixol 0.5 + melitracen 10 1-1-0

10 Clonazepam 1 0-0-1

11 Rappit + (??) 1-0-0


21/58

Nair Discharged!!

At home, Nair is feeling worse

His wife and mother in law very anxious

But they think the treatment is over withdischarge!

Blames fate! Waits for things to worsen!!


22/58

Nair hopelessly ill; off to the next

hospital

Breathless, pedal edema, very sick

Goes to another (bigger, more famous) hospital

The revised diagnosis CCF

Dialated cardiomyopathy

Severe LV dysfunction

Type 2 DM

Coronary angiogram shows Triple vessel disease


23/58

Tegaserod withdrawn from USA

On March 30, 2007, FDA requested Novartis towithdraw Zelnorm from shelves.

FDA found a relationship between tegaserodand increased risks of heart attack or stroke

Was still available as generic in India

Prescribed for constipation, irritable bowel syndrome

Recently banned in India along with Gatifloxacin


24/58

Nairs prescription on discharge T clopidogrel 75 1-0-1

T Amiodarone 100 1-0-0

T Ramipril 5 1-0-0

Glimipiride 2 1-0-1/2 Spironolactone 25 1-0-1

Carvedilol 12.5 1-0-1

Digoxin 0.5 1-0-1 Isosorbide dinitrate 10 1-1-1

Lasix 40 1-0-1-0

Pantoprazole 40 1-0-1


25/58

Nair back on his feet!

Now much better, takes medicines regularly

Short morning walks to the gate and back

Breathless after about 10 min walk

Advised CABG

Now waiting to get fit for CABG


26/58

Male >55 yr

Dx: HTN (uncontrolled)

Rx: Clonidine, Beta blocker & CCB.

After 3 days patient c/o eye pain, dryness & discomfort , Suggests referral to ophthalmology

Pharmacist suspects that it is due toClonidine

Physician decreased the dose of Clonidine & added Prazosin Eye discomfort resolved


27/58

A patient with Zinc phosphide poisoning Physician query: on Clinical presentation &

Treatment

Pharmacists response: an article stating the use ofsteroids and immunosuppressants

Physician:Starts Steroids &

Immunosuppressants


28/58

Female 48 yrs pesticide: contact poisoning

C/o : pigmentation , vesicles, rash & itching, burning on righthand malar area, right side of neck & palmar region of left hand.

H/o application of pesticide powder to buffaloes and whilewashing she came in contact with pesticide on Hands, malar area

and right side of neck

Medication History: Chlophenirmine and dexamethasone. (after8 hr of exposure)

Symptoms didn't subside admission to KMC

Dermatologist's opinion: possible photo toxic reaction byunidentified pesticide


29/58

Pharmacist analysed the pesticide contents & read up on its phototoxic effects

Pesticide found to be " METHYL PARATHION an Organophosphorous compound.

Methyl parathion on exposure to atmosphere reacts with oxygen toform methyl paraoxan, which binds to non vital organs pigmentation, irritation and burning

Pharmacist recommends acetyl cholinesterase level in blood AchE level below normal 4963 ( normal 5300-12500)

No systemic complaints: prescribed betamethasone cream


30/58

Female 54yrs

k/c/o type 2 diabetes mellitus c/o pain abdomen, fever & vomiting for 10 days. On admission CXR showed Rt lower zone(LZ) haziness.

Repeat CXR worsening of left LZ haziness for which

tazobactum was started. She improved significantly 16th day Pt febrile , developed pain abdomen, itching &

rash

WBC drastically decreased (neutropenia). Query to Pharmacist : Pipzo produces neutropenia rarely

Drug stopped WBC Improved to 7300 after 4 days


31/58

A 55 yr old female

k/c/o cellulitis (MRSA) Type 2 DM, Hypertension Rx Inj. H.Actrapid 25-25-15 s/c,

Inj .Tazomac (piperacillin-tazobactam) 4.5 gm, Inj. Linid

(Linezolid) 600mg IV BD,T. wysolone 20mg , T.Calcimax

forte , T.Pantocid 40mg, T.Glytop 5mg, Inj. Tramazac(Tramadol)

Pharmacist: warns interaction b/n linezolid & tramadol

serotonin syndrome (hyperthermia, hyperreflexia,myoclonus,). Can be fatal!

Suggests replacing Linezolid with Inj. CloxacillinPhysician: approves


32/58

Indians Ignore ADRs !

Why?

Reluctance to admit error! (The Indian Ego!)

Ego is part of our Caste-ridden Patriarchy!

Apology is considered as a sign of weakness

Bigger the man, greater the reluctance !

Afraid of legal wrangles!

ADR is NOT medical negligence! Sabrina Brierton Johnson, unsuccessfully sued Johnson &

Johnson, after SJS blinded her

ADR is a part of accepted risk

You cannot sue Maruti when there is a car accident!


33/58

Pharmacovigilance Programme of

India (PvPI)

Constituted Under the..

Central Drugs Standard Control Organization,

Directorate General of Health Services, Min of

Health & Family Welfare Govt of India

in collaboration with

Indian Pharmacopoeia Commission,

Ghaziabad, U.P.


34/58

Goal of PvPI

To ensure that the benefits of use of medicineoutweighs the risks and thus safeguard the

health of the Indian population.


35/58

Objectives

To monitor ADRs in Indian population

To create awareness among health care pros about theimp of ADR reporting in India

To monitor benefit-risk profile of medicines

Generate independent, evidence basedrecommendations on the safety of medicines

Support the CDSCO for formulating safety related

regulatory decisions for medicines Communicate findings with all key stakeholders

Create a national centre of excellence at par with globaldrug safety monitoring standards

P d


36/58

Programme governance and

reporting structures

The PvPI administered and monitored by the

I. Steering Committee

II. Strategic Advisory Committee Technical support will be provided by

I. Signal Review Panel

II. Core Training PanelIII. Quality Review Panel


37/58

ADR MONITORING CENTRES

MCI Approved Medical Colleges & Hospitals

Private Hospitals ( Manipal is among the

proposed centres)

Public Health Programmes

Autonomous Institutes (ICMR etc.)

5 YEAR ROADMAP


38/58

5 YEAR ROADMAP

(Year 20102015 )


39/58

Purpose of collaboration with WHO-Uppsala

Monitoring Centre (UMC)

Training of staff at PvPI national coordinating centre

Usage of UMCs Vigiflow software (for medicines)& Paniflow (for vaccines) at no cost to PvPI

Access to Vigibase, containing worldwide medicinessafety data


40/58

Selection of ADR Monitoring centers

Medical Colleges as centresIn 2012-13 and 2013-14 (100 centres each will be enrolled)

Technical, administrative & financial support by CDSCO

Medical institutes/central institutes/autonomousinstitutes will be included (no CDSCO support)

Public & corporate hospitals inclusion on voluntarybasis (no CDSCO support)


41/58

Operational Aspects

Roles and responsibilities of different personnel in PvPI

Training of program personnel

Centre management (including infrastructure, manpower,status reports)

Processing & reporting of suspected ADRs

Compliance & quality assurance Regulatory decision making

Communication among stakeholders


42/58

Functions of stakeholders in Programme

PvPIADRMonitoring Centre inMedical College

Collection of ADR reports Perform follow up with the complainant Data entry into Vigiflow Reporting to PvPI National

Coordinating Centre Training/ sensitization/ feedback to

physicians through newsletterscirculated by PvPI NCC

PvPIADRMonitoring Centre otherthan medical colleges

[Corporate hospitals, autonomousinstitutes, Pharmaceutical industry,public health programmes]

Collection of ADR reports Perform follow up with the complainant Report the data to CDSCO HQ

PvPI National Coordinating Preparation of SOPs guidance documents &


43/58

PvPI National CoordinatingCentre(PvPI NCC ,IPCGhaziabad)

Preparation of SOPs, guidance documents &training manuals

Data collation, Cross-check completeness,Causality Assessment

Conduct Training workshops of enrolled centers

Publication of Medicines Safety Newsletter Reporting to CDSCO HQ Analysis of the PMS, PSUR, AEFI data received

from CDSCO HQ

ZONAL/Subzonal CDSCO

Offices

Provide procurement, financial and administrative

support to ADR monitoring centers Report to CDSCO HQ

CDSCO, HQ, New Delhi Take appropriate regulatory decision & actions onthe basis of recommendations of PvPI NCC

Propagation of medicine safety related decisions tostakeholders

Collaboration with WHO-Uppsala MonitoringCenter - Sweden

Provide for budgetary provisions & administrativesupport to run National PvPI


44/58

Safety Database

Vigiflow software provided by WHO-UppsalaMonitoring Centre utilized as safety database

All data originating from India will be maintained in asecure and confidential manner


45/58

Risk Management

Ensure availability & management of funds

Conduct frequent training & awareness of

Pharmacovigilance

Detect & respond to under reporting of ADRs

Ensure quality of filled ADR forms

Proper supervision of functioning of centers

Feed back to Health Care Professionals


46/58


47/58

Monitoring & Evaluation

i. Process Indicators No. of ADR monitoring centers, AMC personnel trained

Funds budgeted & spent

ii. Outcome Indicators Software platform established

No. of ADR reports received/processed/submitted to Vigiflow

iii. Impact Indicators No. of signals generated & confirmed

No. of safety related alerts issued by CDSCO


48/58

FDAAA (FDA Amendments Act)

Passed in 2007; Effective since 2008

FDAA Title XI :

demands REMS (Risk Evaluation & Mitigation Strategy)for identified drugs

imposes stricter post marketing safety surveillance frommarketing authorization holders (MAH)

New FDA Initiatives to enhance Drug


49/58


safety during development

Industry guidance document for premarketing safetyassessment for drug induced liver injury

Safe Use Initiative, 2009 - to reduce the likelihood ofpreventable harm from medication use & devisingmechanism to overcome harm

IND regulation revision, Sep 2010 - governs safety reportingrequirements for INDs & BA/BE studies



50/58


safety during development

(contd) New FDA requirements designed to :

Improve usefulness & quality of safety reporting & ability

to review critical information Strengthen ability to review critical safety information

Improve safety monitoring of human drug & biologicals

Harmonize safety reporting with recommendations byICH, CIOMS, EU

Some EU Legislation in


51/58

Some EU Legislation in

Pharmacovigilance development

Risk Management Plan - introduced in 2005

to ensure that benefitsof a particular medicine exceed risks

EU Directive 2010/84 -(published in Dec 2010; to be in effect from July2012) - enforces EU coordination of PV activities via coordinationgroup/PV Risk Assessment Committee

Direct reporting of SAR (suspected adverse reactions)by HCPs &patients

Improved SmPC (Summary of Product Charateristics) of a drug


52/58

Newer EU initiatives in drug safety

ENCePP: European Network of Centres forPharmacoepidemiology & Pharmacovigilance

To enhance post authorization monitoring of medicinalproducts by multicentre safety / lack of efficacy studies

EU Innovative Medicines Initiative : IMI

Stakeholder collaboration to accelerate development ofeffective medicines with fewer adverse effects

by improved predictivity of safety & efficacy; knowledge

management; education & training


53/58

Are we truly committed to

Pharmacovigilance? 1986 Proposal for a formal ADR monitoring in 12

regional centres, each covering 50 million,

1989, Drug controller ,India set up , 6 regional centres

Mumbai, New Delhi, Kolkata, Lucknow, Pondicherry &Chandigarh.

1997, India joined WHO International Drug MonitoringProgram by Uppsala Monitoring Centre, Sweden.

Dept of Pharmacology, AIIMS was identified as thenational centre,

Of the six centres, only Mumbai & Delhi were active,

Yet spontaneous reporting of ADRs was poor.

National Pharmacovigilance


54/58

National Pharmacovigilance

Programme (NPVP) : Abortive

attempt? CDSCO launched NPVP in November 2004. World Bank annual grant of US$ 0.1 million for 5 yrs

Became functional from January 2005

2 zonal centres with 3 regional centres under them

Manipal reported ADRs to regional centre at JIPMER

World bank funds ended in 2009

Manipals ADR reports started piling up

Nobody forwarded our reports to Uppsala

Uppsala suspended its India connection.

PvPI is the third attempt at Pharmacovigilance!!


55/58

Global PV Challenges

Globalization

increased exposure of massive populations to largevolumes of medicines

Web-based sales and information

uncontrolled sale of medicines across nationalborders

Broader safety concerns- array of medicinal productsgrows

Public health versus pharmaceutical industry

economic growth


56/58

Global PV Challenges (contd)

Monitoring of established products

Monitor safety of generics throughout the world

Developing and emerging countries Outside OECD countries, pharma industry not been

committed to pharmacovigilance

Attitudes and perceptions to benefit and harm

Morbidity/mortality from drug-induced diseases recentlybeing recognized as important in public health.

Outcomes and Impact


57/58

Conclusion FROM thalidomide tragedy (1950) TO recent rofecoxib &

rosiglitazone controversy science of PV has come a longway

PVvery reactive nature Evolved from a mere regulatory requirement for marketing

proactive generation of safety signals for marketed drugs

PV most important bridge between patient, HCPs &pharma companies for safer health care

India is waking up!! Professional


58/58

Thank you!

Jai PvPI

Jai Hind!

Date post:	07-Apr-2018
Category:	Documents
Upload:	ameers333
View:	223 times
Download:	0 times

Pharmacovigliance in India: Dreams Vs Reality

Documents