The valuation of disease-specific
questionnaires for QALY analysis
 To
rescue data in absence of an utility measure
 To
increase sensitivity
 Growth hormone deficiency in adults
 Benign Prostatic Hyperplasia (BPH)
1
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…
2
Mapping
DALY style
3
QoL-AGHDA
 Quality
of Life Adult Growth Hormone
Deficiency Assessment
 25 yes/no items
 Internet
panel
 N = 1075
 Both
AGDHA and EQ-5D
4
From AGDHA to utilities (QALY)
EQ-5D: 5 dimensions
AGHDA: 25 dimensions
Utility
Algorithm
Utilities
Sum
Score
Regression
Total score
5
Regression Dutch AGHDA sum score
on EQ-5D
1
EQ-5D NL
0.8
0.6
EQ-5D = 0.980 - 0.0198 x AGHDA
R2 = .344
0.4
0.2
0
0
5
10
15
20
25
AGHDA
6
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.
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
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





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
Ik heb enige problemen met lopen
Ik ben bedlegerig





Ik heb enige problemen om mijzelf te wassen of aan te kleden
Ik ben niet in staat mijzelf te wassen of aan te kleden
gezins- en vrijetijdsactiviteiten)
Ik heb enige problemen met mijn dagelijkse activiteiten
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



Dagelijkse activiteiten (bijv. werk, studie, huishouden,
Ik heb geen problemen met mijn dagelijkse activiteiten
Dagelijkse activiteiten (bijv. werk, studie, huishouden,



Zelfzorg
Ik heb geen problemen om mijzelf te wassen of aan te kleden
Zelfzorg
Ik heb geen problemen met mijzelf wassen of aankleden
Ik heb geen problemen met lopen





Ik ben niet in staat mijn dagelijkse activiteiten uit te voeren





Stemming



Pijn/klachten
Ik heb geen pijn of andere klachten
Ik heb matige pijn of andere klachten
Ik heb zeer ernstige pijn of andere klachten



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





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
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
makes sense
AGHDASUM
30
20
10
Percent
 Correlation
0
.00
4.00
2.00
AGHDASUM
8.00
6.00
12.00
10.00
16.00
14.00
20.00
18.00
24.00
11
22.00
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?
12
Does the EQ-5D make sense in BPH?



MOBILITY



SELF-CARE




I have no problems with self-care
I have some problems…..
I am unable…
USUAL ACTIVITIES




I have no problems in walking about
I have some…….
I am confined to bed
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…..
13
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
14
Reduce number of health states
 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)
15
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
16
QALY weights for BPH
utilities (TTO)
1
0,95
0,9
0,85
0,8
0,75
0,7
0,65
irritative
0,6
seldom/never
sometimes
almost always
0,55
0,5
ys
es
lwa
a
ver
tim
t
e
e
s
n
/
o
som
om
alm
seld
obstructive
17
TTO
Comparing ISPOR 2003 with
population
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
11
12
13
21
22
23
13
23
33
Health states IPSS
ISPOR 2003
Population
18
How to come to these values?
Obstructive score
Irritative score
Sum (IPSS1 + IPSS2 +IPSS4 + IPSS6)
Sum (IPSS3 + IPSS5 +IPSS7)
 As example: obstructive 1 and irritative 2 = uti 1_2
Answer levels:
Quality of life values:
Domain
score
Obstructive ( <= 4)
Irritative
Level
irritative
Obstructive 1
( >= 5 & <= 16)
Obstructive 2
1.00
.97
.95
1
( >= 17)
Obstructive 3
.97
.94
.92
2
(<= 3)
Irritative 1
.92
.90
.87
3
( >= 4 & <= 9)
Irritative 2
1
2
3
( >= 10)
Irritative 3
Obstructive
19
Treatment effect
0,98
0,97
0,96
utilities
0,95
0,94
0,93
0,92
0,91
surgery (n= 144)
alpha-blockers (n=33)
finasteride (n=35)
watchful waiting (n=159)
0,9
baseline
follow up
20
Disease specific utilities are not on
a generic scale
 Generic
top anchor
 Specific
top anchor
Healthy
No disease specific
problems
Death
All disease specific
complains
 absence of any impairment
 absence of specific impairment
 Co morbidity might still be present
Disease specific utilities are a
subscale of a generic scale
No disease specific
problems
Healthy
 Rescaling
necessary
All disease specific
complains
Death
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
23
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
 Adjust score
 15 % reduction
1.00 - 0.87 = 0.13
0.81 - 0.70 = 0.11
24
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
25
Conclusion
 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
26