Quality Adjusted Life Years and Trade Off Exercises exploring

128 Pages·2006·2.05 MB·English

Quality Adjusted Life Years and Trade Off Exercises
exploring methodology and validity
Marieke Verschuuren
Quality Adjusted Life Years and Trade Off Exercises: exploring methodology and validity
Thesis Utrecht University, Medical Faculty (in English, with a summary in Dutch)
Proefschrift Universiteit Utrecht, faculteit Geneeskunde (in het Engels, met een samenvatting in het Nederlands)

ISBN ISBN-10: 90-393-4240-7
ISBN-13: 978-90-393-4240-4
Author Marieke Verschuuren
Cover Lysbeth Zeinstra
Lay-out Yvonne Jansen .1
Print Drukkerij Jan Evers BV, de Meern
Quality Adjusted Life Years and Trade Off Exercises
exploring methodology and validity
Quality Adjusted Life Years en Trade Off vragen
een exploratie van methodologie en validiteit
(met een samenvatting in het Nederlands)
Promotores

Prof. B.A. van Hout
Julius Center for Health Sciences and Primary Care,
University Medical Center Utrecht
Prof. G.J. Bonsel
Department of Public Health/Epidemiology, Academic
Medical Center Amsterdam

The studies described in this thesis were supported by grants from ZonMw,
the Netherlands Organization for Health Research and Development
(grants no. 945-02-009 HTA and 945-02-014 HTA). The author gratefully
acknowledges financial support for publication of this thesis by the Julius Center for
Health Sciences and Primary Care and ZonMw.
Quality Adjusted Life Years and Trade Off Exercises
exploring methodology and validity
Quality Adjusted Life Years en Trade Off vragen
een exploratie van methodologie en validiteit
(met een samenvatting in het Nederlands)

Proefschrift

Ter verkrijging van de graad van doctor aan de Universiteit Utrecht,
op gezag van de Rector Magnificus, Prof. Dr. W.H. Gispen,
ingevolge het besluit van het College voor Promoties,
in het openbaar te verdedigen op dinsdag 16 mei 2006 des middags te 16.15 uur
door Marieke Verschuuren, Geboren 12 december 1970 te Utrecht

TABLE OF CONTENTS
Introduction 8
Chapter 1. In search for realistic QALYs for short-term pain:
the standard QALY model versus holistic
assessment of profiles
1.1 Capturing the impact of short-term pain:
the holistic valuation of annual health profiles versus
the computation of EQ5D-tariff based QALYs 16
1.2 Time traded off for short episodes of pain: allowing for
extreme negative values in the computation of QALYs? 34
Chapter 2. Time Trade Off: methodology and modeling
2.1 The effect of using life expectancy as time horizon on
time traded off for conditions with a one-year duration 52
2.2 Modeling Time Trade Off values: fitting the boundaries 68
Chapter 3. The cognitive burden associated with trade offs:
reflections upon generalizability and the necessity
of debriefing 88
General Discussion 102
Summary 110

Samenvatting 115

Dankwoord 124

Curriculum Vitae 126

INTRODUCTION
Introduction
General context

The concept of Quality Adjusted Life Years (QALYs) is the point of departure for
the research presented in this thesis. QALYs are a measure of health outcome that
simultaneously capture gains from reduced morbidity (quality gains) and reduced
mortality (quantity gains). This is operationalized through deriving scaling factors for
different health states, which are then used for weighing survival or follow up. In the
remainder we will refer to these scaling factors as values. Because of their compound
character, which enables comparability of cost-effectiveness of treatments for
different conditions, QALYs have become the most widely used outcome measure
in cost-effectiveness analyses (which, in case QALYs are being used as outcome
measure, generally are referred to as cost-utility analyses).
Although an appealing concept, issues with regard to the validity of QALYs have
been the focus of ongoing debate. Broadly speaking these can be divided into
two categories: 1) doubts on assumptions underlying the QALY model and 2)
considerations with regard to the obtainment of values. Assumptions of the QALY
model that have been questioned for example are the independence of the value
of a health state from the duration of that health state, and the assumption of a
zero rate of time preference, implying that the timing of the occurrence of changes
in health does not influence values. Studies that have tested to what extent such
assumptions actually hold have yielded mixed results, casting doubt on their validity
(1-7).
When looking at the obtainment of values, two sources of influence on the values can
be distinguished besides the health state: the respondent and the valuation method
used. While the fact that respondent characteristics determine values can be a threat
to generalizability of results, effects of the valuation method used raise concerns
regarding validity. It has extensively been shown that the valuation method used
influences values (8-11). Moreover, framing of valuation questions is of importance,
implying that substantially different values can arise even when the same valuation
method has been used (12-17). An illustrative example of a framing effect is the use
of disease labels: a health state can be valued very differently depending on whether
the causal condition is left undefined or stated to be cancer (2).
In absence of a golden standard it is unclear which valuation methodology is the right
or most optimal one. Nevertheless, values to a large extent determine cost-utility
ratios, which suggests that different valuation methodologies (including valuation
method, framing of valuation questions, modelling of valuation data for predictive
purposes) may lead to different policy decisions. Obviously, getting insight into the
realization and hence into the validity of values/QALYs is of major importance. The
acquirement of such knowledge will help distinguish wanted or minor influences
from undesirable effects, stimulating the definition of a ‘best practice’ for valuation
methodologies. Such a development will enhance comparability of outcomes of
8 - Quality Adjusted Life Years and Trade Off Exercises
Health Technology Assessments and improve validity of decision-making processes
concerning the allocation of scarce health care resources.
Specific context

Chapter 1 and 2 of this thesis are based on a methodological appendix study to a
trial on the prevention of post-herpetic neuralgia (the PINE trial (18)). In this study
we focused on QALYs for follow up, in which short-term pain occurs. In case of non-
constant health states (from now on: profiles), the Standard QALY Approach (SQA)
applies an Area Under the Curve formula, meaning that for each distinct period of
non-fluctuating health within the profile value and duration are multiplied, after
which these products are added. In this approach, short periods of bad health, like 1
week or 1 month, have little impact on QALYs. While designing the above-mentioned
trial, the question was raised whether SQA would result in an underestimation of
the impact of short-term severe pain (see figure 1). Based on intuition and clinical
experience we hypothesized that indeed it would, which implies that the potential
maximum value of therapies aiming at the relief of short-term intense pain could
be underestimated. We therefore conducted a study in which we obtained QALYs
for profiles including short episodes of severe pain by means of a so-called holistic
method. In contrast to the decomposed standard QALY method, in a holistic
approach profiles are being valued as a whole. If our hypothesis is correct, we should
find considerable trade offs being made by the respondents in the holistic method,
and hence low ‘holistic QALYs’. The results found with regard to this hypothesis are
described in chapter 1.
While preparing and conducting the study, two unanticipated methodological
difficulties due to the applied strategy for the obtainment of the holistic QALYs (a
Time Trade Off (TTO) method (19)) were encountered. Solutions for these problems
were explored and this yielded two articles, which are included in chapter 2.
During a study aimed at obtaining equity-efficiency trade offs for the derivation
of societal weights for QALYs (20), we experienced serious problems due to the
apparently high cognitive burden of the demanded task. Since our findings may
have considerable implications for the generalizablity and validity of trade off values,
an article focusing on these issues is incorporated in this thesis (chapter 3).
Outline of this thesis
Chapter 1: In search for realistic QALYs for short-term pain: the standard QALY model
versus holistic assessment of profiles
In section 1.1 a direct comparison between standard QALYs and holistic QALYs is
described. EuroQol 5 Dimensions (EQ5D) (21) societal tariffs (22) were used as
values in the computation of the standard QALYs, as is commonly done in cost-
effectiveness analyses in the European context.
Section 1.2 is a quantitative description of the time traded off for the pain profiles in
Quality Adjusted Life Years and Trade Off Exercises - 9
the holistic procedure. At this, we were specifically interested in so-called exceeding
trade offs (i.e. trade offs that exceed the duration of the pain episode within the
profile), since such trade offs suggest that (extreme) negative values should be
applied in SQA in order to compute QALYs with comparable magnitudes as holistically
obtained QALYs. Observing frequent and large exceeding trade offs questions the
generally applied lower boundary for values of –1 (worst imaginable health state).
Chapter 2: Time Trade Off: methodology and modeling
In section 2.1 the extent to which time traded off is influenced by the TTO time
horizon applied (i.e. respondents’ individual life expectancies) is quantified. Based
on several expected effects, such as diminishing marginal utility and time preference,
it is hypothesized that respondents with long life expectancies will make larger trade
offs than respondents with short life expectancies.
In section 2.2 different modeling approaches for our TTO data are compared. The
data are truncated (it is not possible to trade off less than nothing) and due to the
threshold effect, which implies that the health states have to exceed a certain level
of severity before respondents start to trade off time, a large cluster of zeros (no time
traded off) was present in the data. This specific distribution of the data requires a
modeling approach other than the usual applied regression techniques.
Chapter 3: The cognitive burden associated with trade offs: reflections upon generalizability
and the necessity of debriefing
Chapter 3 concerns issues associated with the cognitive burden of trade off tasks,
in particular non-participation/dropout and validity of the decision-making process
underlying the values obtained.

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Figure 1. Results of Standard QALY Approach (SQA) applied to a year in which short-term severe
pain occurs (values based on EuroQol5D published tariffs)
10-QualityAdjustedLifeYearsandTradeOffExercises