1

The valuation of disease-specific questionnaires for QALY analysis

To rescue data in absence of an utility measure Growth hormone deficiency in adults

To increase sensitivity Benign Prostatic Hyperplasia (BPH)

2

Mapping

Trying ‘to map’ disease characteristics on EQ-5D etc. Nord E. Cost-utility analysis of

Melphalan plus Prednisone with or without Interferon Alfa-2b in newly diagnosed multiple myeloma. Pharmacoeconomics 1997;12:89-103.

Can be done behind the desk Very quick…

Very dirty…

A low face validity…

3

Mapping DALY style

4

QoL-AGHDA

Quality of Life Adult Growth Hormone Deficiency Assessment 25 yes/no items

Internet panel N = 1075

Both AGDHA and EQ-5D

5

From AGDHA to utilities (QALY)

EQ-5D: 5 dimensions AGHDA: 25 dimensions

UtilityAlgorithm Sum

Score

Utilities Total scoreRegression

Regression

6

Regression Dutch AGHDA sum score on EQ-5D

0

0.2

0.4

0.6

0.8

1

0 5 10 15 20 25

AGHDA

EQ

-5D

NL

EQ-5D = 0.980 - 0.0198 x AGHDAR2 = .344

EQ-5D-3L versus EQ-5D-5l

Zet bij iedere groep in de lijst hieronder een kruisje in het hokje achter de zin die het best past bij uw eigen gezondheidstoestand vandaag. Mobiliteit

Ik heb geen problemen met lopen

Ik heb een beetje problemen met lopen

Ik heb matige problemen met lopen

Ik heb ernstige problemen met lopen

Ik ben niet in staat niet om te lopen

Zelfzorg

Ik heb geen problemen met mijzelf wassen of aankleden

Ik heb een beetje problemen met mijzelf wassen of aankleden

Ik heb matige problemen met mijzelf wassen of aankleden

Ik heb ernstige problemen met mijzelf wassen of aankleden

Ik ben niet in staat mijzelf te wassen of aan te kleden

Dagelijkse activiteiten (bijv. werk, studie, huishouden,

gezins- en vrijetijdsactiviteiten)

Ik heb geen problemen met mijn dagelijkse activiteiten

Ik heb een beetje problemen met mijn dagelijkse activiteiten

Ik heb matige problemen met mijn dagelijkse activiteiten

Ik heb ernstige problemen met mijn dagelijkse activiteiten

Ik ben niet in staat mijn dagelijkse activiteiten uit te voeren

Pijn/ongemak

Ik heb geen pijn of ongemak

Ik heb een beetje pijn of ongemak

Ik heb matige pijn of ongemak

Ik heb ernstige pijn of ongemak

Ik heb extreme pijn of ongemak

Angst/somberheid

Ik ben niet angstig of somber

Ik ben een beetje angstig of somber

Ik ben matig angstig of somber

Ik ben erg angstig of somber

Ik ben extreem angstig of somber

Zet bij iedere groep in de lijst hieronder een kruisje in het hokje achter de zin die het best past bij uw eigen gezondheidstoestand vandaag. Mobiliteit

Ik heb geen problemen met lopen

Ik heb enige problemen met lopen

Ik ben bedlegerig

Zelfzorg

Ik heb geen problemen om mijzelf te wassen of aan te kleden

Ik heb enige problemen om mijzelf te wassen of aan te kleden

Ik ben niet in staat mijzelf te wassen of aan te kleden

Dagelijkse activiteiten (bijv. werk, studie, huishouden,

gezins- en vrijetijdsactiviteiten)

Ik heb geen problemen met mijn dagelijkse activiteiten

Ik heb enige problemen met mijn dagelijkse activiteiten

Ik ben niet in staat mijn dagelijkse activiteiten uit te voeren

Pijn/klachten

Ik heb geen pijn of andere klachten

Ik heb matige pijn of andere klachten

Ik heb zeer ernstige pijn of andere klachten

Stemming

Ik ben niet angstig of somber

Ik ben matig angstig of somber

Ik ben erg angstig of somber

Cross walk

8

Validation

9

Calculation

10

11

The AGHDA has generic features… AGHDA

I have to struggle to finish jobs

I feel a strong need to sleep during the day

I often feel lonely even when I am with other people

EQ-5D I have some problems with performing my usual activities

I am moderate anxious or depressed

Correlation makes sense AGHDASUM

AGHDASUM

24.00

22.00

20.00

18.00

16.00

14.00

12.00

10.00

8.00

6.00

4.00

2.00

.00

Pe

rce

nt

30

20

10

0

12

But what if the measure has little generic features?

International Symptom Prostate Score (IPSS) BPH

Enlargement of the prostate Causes voiding problems in elderly men

• Difficulties to pee 7 questions: How often have you

had to push or strain to begin urination? had a sensation of not emptying your bladder completely? had to urinate again less than two hours after you finished urinating?

found you stopped and started again several times when you urinated?

you find it difficult to postpone urination? had a weak urinary stream? How many times did you most typically get up to urinate from the time

you went to bed at night until the time you got up in the morning?

13

Does the EQ-5D make sense in BPH? MOBILITY

I have no problems in walking about I have some……. I am confined to bed

SELF-CARE I have no problems with self-care I have some problems….. I am unable…

USUAL ACTIVITIES I have no problems with performing my usual

activities I have some problems… I am unable….

PAIN/DISCOMFORT I have no pain or discomfort I have moderate ….. I have extreme……..

ANXIETY/DEPRESSION I am not anxious or depressed I am moderately…….. I am extremely…..

Not sensitive fo

r BPH

14

Can we convert the IPSS outcomes into utilities?

Attribute TTO values to the IPSS health states Problem: IPSS has 279.936 health states

7 items, 6 answer levels = 6x6x6x6x6x6x6 = 279.936 health states

Too many to value with TTO

Reduce number of health states Reduce items

• Factor analysis

Reduce answer levels

• Combine answer levels

15

Factor analysis on patients IPSS responses N = 1414

Two main factors Obstructive (alpha= 0.8018) Irritative (alpha= 0.7165)

• Confirmed in literature

Factors divided in 3 levels Number of health states reduced to 33 = 9

Can be valued directly

TTO General public, representative for gender/age (N=170)

Reduce number of health states

16

Exercise

Value the 9 health states of the reduced IPSS Tests feasibility: can it be done?

Compare values with earlier research Test reliability: can we repeat the observation?

• Scientific prove (observation is independent of examination)

• Do different groups of people have different values

17

QALY weights for BPH

almost always

sometimes

seldom/never

almost alwayssometimes

seldom/never

0,5

0,55

0,6

0,65

0,7

0,75

0,8

0,85

0,9

0,95

1

utilities (TTO)

obstructive

irritative

18

0.00.10.20.30.40.50.60.70.80.91.0

11 12 13 21 22 23 13 23 33

Health states IPSS

TT

O

ISPOR 2003 Population

Comparing ISPOR 2003 with population

19

How to come to these values?

Obstructive score Sum (IPSS1 + IPSS2 +IPSS4 + IPSS6)

Irritative score Sum (IPSS3 + IPSS5 +IPSS7)

Answer levels:

Domain score Level

Obstructive ( <= 4) Obstructive 1

( >= 5 & <= 16) Obstructive 2

( >= 17) Obstructive 3

Irritative (<= 3) Irritative 1

( >= 4 & <= 9) Irritative 2

( >= 10) Irritative 3

irritative

1.00 .97 .95 1

.97 .94 .92 2

.92 .90 .87 3

1 2 3

Obstructive

As example: obstructive 1 and irritative 2 = uti 1_2

Quality of life values:

20

Treatment effect

0,9

0,91

0,92

0,93

0,94

0,95

0,96

0,97

0,98

baseline follow up

uti

litie

s

surgery (n= 144) alpha-blockers (n=33)

finasteride (n=35) watchful waiting (n=159)

Disease specific utilities are not on a generic scale

Generic top anchor absence of any impairment

Specific top anchor absence of specific impairment

Co morbidity might still be present

No disease specific problems

All disease specific complains

Death

Healthy

Disease specific utilities are a subscale of a generic scale

Rescaling necessary

No disease specific problems

All disease specific complains

Death

Healthy

23

Raw disease specific trade-off ten to overestimated gains

Value of life years “traded off” in TTO differently Healthy subject: 1 life year is 1.0 QALY

Sick subject: 1 life year is 0.8 QALY

Life years of healthy persons are more worth than those of sick

Disutility is proportional 20% trade off at 1.00: disutility = 0.20

20% trade off at 0.80: disutility = 0.16

20% trade off at 0.60: disutility = 0.12

24

Specific utilities should be corrected for average morbidity Solution: multiplicative model Multiply disease specific value with average value Values have to be multiplied by average value for age

group. For instance in IPSS

• male age 55-64: overall QoL utility: 0.81

• Most severe BPH: 0.87

• Male age 55-64 with most severe BPH: 0.81 x 0.87 = .7047

Maximum gain reduces from Raw score 1.00 - 0.87 = 0.13

Adjust score 0.81 - 0.70 = 0.11

15 % reduction

25

Rue of thumb

Overestimated CE-ration by 15% using specific utilities Proposed by Fryback & Lawrence, MDM 1997

• For not completely the same problem…

• …for own health states, not imaginable health states

26

We validated the IPSS for the use in economic appraisal Now, IPSS has QALY-weights

New and already published research can be converted into QALYs

Advantage use specific QALYs measures High sensitive disease specific measures for QALY-analysis

Rescuing data

Disadvantages Not directly compatible with generic utilities

± 15 % correction needed in disease specific

Conclusion