CLINICAL THERAPEUTICSWOL. 23, NO.

I, 200 I

Commentary

The Importance of Health-Related Quality-of-Life Data

in Determining the Value of Drug Therapy

Xavier Badia, PhD, and Michael Herdman, MSc

Health Care Outcomes Research Unit, Clinical Epidemiology and Public Health Service,
Hospital de Santa Creu i San Pau, Barcelona, Spain

ABSTRACT

Background: The rapid evolution of outcomes research during the last decade has led
to increasing emphasis on measures of health-related quality of life (HRQOL). However,
the relatively recent advent of these measures makes it difficult to decide how much
weight to attribute to them in decisions about the value of drug therapy.
Objective: The aim of this article is to discuss the factors that affect the relative im-
portance of HRQOL data in determining the value of drug therapy.
Conclusions: The relative importance of HRQOL data depends on the type of condition
and the type of treatment. In chronic conditions, HRQOL may be considered a primary
measure of efficacy. In acute conditions, HRQOL is not likely to be a primary efficacy
measure, although excluding HRQOL measures may lead to an underestimation of treat-
ment effects. Measures of HRQOL are also likely to be important in the assessment of pal-
liative treatments and, to some extent, preventive treatments (primarily in the measurement
of adverse effects). HRQOL measures will be less important in the assessment of curative
treatments because these types of treatment are most relevant in acute conditions.
Key words: health-related quality of life, drug therapy, value. (Clin Ther. 2001;23:
168-175)

INTRODUCTION

The rapid evolution of outcomes research during the last decade’ has led to the develop-
ment of numerous techniques and instruments for measuring the efficacy of various as-
pects of health care, from comparisons of organizational and financing strategies2 to the
assessment of the cost-effectiveness of treatment options for specific patient groups” to
head-to-head comparisons of different drugs for the same condition.4
Some of the most important tools developed in recent years within the context of out-
comes research are instruments designed to measure health-related quality of life

Accepted for publication October 31, 2000.

Printed in the USA. Reproduction in whole or part is not permitted.

168 0149.2918/01/$19.00
X. BADIA AND M. HERDMAN
(HRQOL)5; the results obtained with such
instruments are increasingly used to com-
plement safety data, survival rates, and tra-
ditional indicators of clinical efftcacy as a
measure of the value of drug treatment.
Regulatory authorities are also increas-
ingly recommending the inclusion of
HRQOL measures as end points in clini-
cal trials.c8 Nevertheless, the relative im-
portance of HRQOL outcomes in deter-
mining the value of a drug therapy may be
difficult to establish because they are new
measures and because their utility depends
on several factors, including the type of
condition and the type of treatment.
The aim of this article is to discuss the
factors that influence the importance of
HRQOL measures in determining the
value of drug treatment.
EFFICACY MEASURES
The effects of treatment can be classified
and measured in several ways. Increases
in survival due to treatment can be mea-
sured using life expectancy data9; the suc-
cess of prophylactic treatment can be as-
sessed by determining the incidence of
disease in treated and untreated groupslo;
and specific clinical measures such as tu-
mor size or blood pressure can be used to
measure the efficacy of treatments for can-
cer and hypertension. However, the pur-
pose of any drug treatment should be to
increase the quantity and/or quality of pa-
tients’ lives, or prevent, as much as possi-
ble, a reduction in either parameter. Thus,
although traditional clinical markers are
important in determining the impact of
treatment at a biologic or chemical level,
and in confirming the underlying meta-
bolic or pharmacologic rationale for a
given drug therapy, the ultimate measure
of a treatment’s success is the extent to
which it improves parameters that are
meaningful to patients, such as the quan-
tity or quality of life. Gains in quality or
quantity of life can be measured using dif-
ferent health indicators, such as life years
gained, reduction in clinical events, or
HRQOL outcomes.
Two major factors influence the impor-
tance of HRQOL data in decisions re-
garding the value of a given drug: the type
of condition and the type of treatment be-
ing assessed.
TYPE OF CONDITION
Acute Conditions
Acute conditions are potentially cur-
able disease states of relatively short du-
ration. In many infectious disease states
or conditions treated primarily with drug
therapy, such as community-acquired
pneumonia’ ’ or Helicobacter pylori erad-
ication in duodenal ulcer,‘* in which a
cure can be expected in a high proportion
of cases, the primary outcome of interest
is not likely to be HRQOL, but more im-
mediate markers of treatment success. In
the case of pneumonia, these markers may
include mortality rates, medical compli-
cations, and symptom resolution’” and in
the case of H pylori infection, eradication
rates, number of days with symptoms, ul-
cer cure rates, and ulcer recurrence rates. I2
Other studies may include indicators such
as disease sequelae, lost productivity, or
treatment costs, depending on the focus
of research.
The focus of treatment in acute condi-
tions is generally curing the condition, as
in the case of bacterial urinary infection
or tuberculosis. HRQOL measures will
likely play a secondary or negligible role
in determining the value of such treat-
169

ments, because they generally cannot be
used to determine whether the condition
has been cured. However, HRQOL mea-
sures may help interpret the significance
of curing the condition, so their use in the
assessment of treatments for acute condi-
tions may sometimes be appropriate. For
example, although the success of treat-
ments for gastroduodenal ulcers is gener-
ally measured by clinical indicators such
as ulcer healing rates, an HRQOL assess-
ment may indicate that patients with gas-
troduodenal lesions induced by non-
steroidal anti-inflammatory drugs report
problems such as lack of energy, sleep
disturbance, emotional distress, and so-
cial isolation in addition to pain and mo-
bility limitations. I4
In such cases, using only the tradi-
tional clinical indicators of treatment
success does not fully capture the range
of benefits from a successful interven-
tion. Thus, in determining the value of
treatments for acute conditions, the em-
phasis should be on traditional clinical
efficacy measures, with HRQOL mea-
sures used as a secondary measure both
for descriptive purposes (to capture the
full range of treatment benefits) and as a
discriminative tool in cases where treat-
ments might be equivalent in terms of
primary efficacy markers, but different
in terms of their impact on HRQOL. For
example, HRQOL measures were used
to distinguish between similar, competing
therapies in a trial of 3 treatment modalities
for mild to moderate Pneumocystis carinii
pneumonia in patients with AIDS.t5 In
this trial, no statistically significant dif-
ferences were found between treatment
groups in the rates of dose-limiting tox-
icity, therapeutic failure, or survival, but
differences were found in serum amino-
transferase levels, hematologic toxicities,
170
CLINICAL THERAPEUTICS@
and scores on a number of HRQOL mea-
sures, including the Duke Activity Status
Index.‘” In this case, decisions regarding
the value of drug treatment would need
to take into account differences in toxic-
ity as well as differences in HRQOL
scores between treatment groups. Never-
theless, HRQOL measures will likely
play only a limited role in determining
the value of drug treatments for most
acute conditions.
Chronic Conditions
Chronic conditions are disease states of
generally long duration; they may be cur-
able, but treatment is often palliative. Be-
cause chronic conditions may cause con-
siderable deterioration in patients’ quality
of life, HRQOL measures are more likely
to be useful in determining the value of
drug therapy for chronic conditions than
for acute conditions. As with acute condi-
tions, HRQOL measures can help capture
the full effects of disease and its treatment
and can help discriminate between other-
wise similar treatments.
Recent guidelines on the assessment of
drugs in development suggest that regula-
tory agencies are recognizing the impor-
tance of HRQOL measurement in chronic
conditions. Eleven of 17 recent guidelines
indicate that HRQOL measures can be of
considerable added value in the assess-
ment of drug therapies for chronic condi-
tions such as cardiac insufficiency, stable
angina, Alzheimer’s and Parkinson’s dis-
ease, osteoarthritis and rheumatoid arthri-
tis, chronic obstructive pulmonary dis-
ease, and cancer.t6 Interestingly, there are
no recommendations within Europe for
the use of HRQOL measures in the as-
sessment of vaccines or antibacterial and
antiretroviral drugs.
X. BADIA AND M. HERDMAN
TYPE OF TREATMENT
The utility of HRQOL measures in as-
sessing the value of a drug treatment is
also influenced by the type of treatment
being evaluated, that is, whether the treat-
ment is preventive, palliative, or curative.
Treatment type is closely linked to
whether the condition is acute or chronic.
Preventive Treatments
Various treatment strategies are used to
manage chronic disease, beginning with
preventive treatments in patients who are
at risk for a disease but have not yet de-
veloped it. The incorporation of HRQOL
instruments as measures of the efficacy of
preventive treatment raises interesting is-
sues, particularly regarding study dura-
tion. For example, in the assessment of
treatments to prevent osteoporosis, the use
of HRQOL instruments may be of partic-
ular relevance because osteoporosis can
have a devastating impact on quality of
life,t7 which effective preventive treat-
ment will presumably improve. There are
3 points to consider concerning preven-
tive treatment. First, preventive treatment
is not likely to lead to gains in quality of
life, but will or should help prevent re-
ductions in quality of life over time. Sec-
ond, showing that a treatment helps pre-
vent reductions in quality of life over time
usually requires studies of relatively long
duration. For example, to demonstrate re-
ductions in fracture risk in osteoporosis
requires studies of ~3 years’ duration.ts
The use of HRQOL measures in studies
of such long duration is not common and
caution is needed in applying such mea-
sures in these circumstances. For exam-
ple, response shift may occur, whereby
patients’ standards for judging what con-
stitutes a good or bad quality of life may
change over time as they adapt to or re-
cover from a given condition.19 Finally, in
shorter studies of preventive treatment,
HRQOL measures may be more likely to
reflect the negative impact of treatment
due to adverse effects; however, such
treatment may also have positive effects
on well-being by alleviating health con-
cerns, although this aspect of preventive
therapy requires further research. The use
of HRQOL instruments to assess the rel-
ative negative impact of competing drug
treatments may be appropriate, but re-
searchers should be clear about their rea-
sons for including HRQOL instruments in
studies of preventive drug therapy.
Palliative Treatments
The measurement of HRQOL may be
most important in the assessment of pal-
liative treatments. Palliative treatments
ameliorate the symptoms of disease and/or
improve patient functioning, but do not
cure the underlying disease. In a recent
example of the use of HRQOL instru-
ments to determine quality-of-life gains
in a palliative setting, patients treated with
temozolomide and those treated with pro-
carbazine for recurrent glioblastoma mul-
tiforme were compared, and differences
between the 2 treatments were observed,
primarily because of the increased toxic-
ity of the procarbazine regimen.*O The au-
thors of this study stressed the importance
of HRQOL measurement in this setting
because of the palliative nature of the
treatment.
Although palliative treatment has come
to be associated with terminal conditions
such as cancer, the term can apply to other
chronic disease states as well. For exam-
ple, in patients with irritable bowel syn-
171

drome, treatment is used to palliate pain or
other symptoms such as diarrhea.*’ In pa-
tients with asthma, treatment often helps
relieve symptoms, which can affect many
areas of functioning over time if not ade-
quately controlled. ** Although symptom-
atic treatment for acute conditions such as
influenza can also be considered palliative,
greater emphasis on the use of HRQOL is
warranted in the assessment of palliative
treatments for chronic conditions.
Curative Treatments
Curative treatments do not currently ex-
ist for many chronic conditions, and for
many acute conditions preventive or pal-
liative drug therapy may not be appropri-
ate. Many of our comments relating to
acute conditions also apply to curative
treatments. The fact that a treatment cures
the condition means that HRQOL mea-
surement will have only a secondary, de-
scriptive role in measuring the impact of
treatment. Clinical and biologic markers
are generally the primary measures of the
efficacy of curative treatments; however,
when the treatment itself may have a par-
ticularly severe impact on HRQOL (eg,
adverse effects), the assessment of com-
peting treatments may include the use of
HRQOL measures to determine whether
treatments differ in this regard.
DISCUSSION
The aim of this article was to discuss the
utility of HRQOL measures in determin-
ing the value of drug therapy. The need
for this type of discussion stems partly
from the relatively recent development
of HRQOL measures and their obvious
appeal for many stakeholders in the
health care system. Moreover, from a reg-
172
CLINICAL THERAPEUTICS@
ulatory point of view, it is not yet clear
how these measures should be incorpo-
rated into decisions regarding the value
of drug therapy.23
In using HRQOL instruments in as-
sessments of drug therapy, 2 points re-
quire special attention. First, the contribu-
tion of HRQOL data in determining the
value of drug treatments is likely to de-
pend heavily on the interpretability of
findings. To date, research on the inter-
pretation of results from HRQOL instru-
ments is insufficient. Only a few authors
have approached the issue of interpreta-
tion of HRQOL measures, for example,
through the investigation of minimal clin-
ically important differences24 or the num-
ber needed to treat.25 Wider use of such
instruments would help both clinicians
and regulatory authorities appreciate what
changes in quality-of-life measures mean;
such instruments are likely to be of par-
ticular importance in equivalence trials.
Second, the issue of how patient pref-
erences should be incorporated into the
decision-making process regarding the
value of drug therapy has not received the
attention it deserves. Because patients are
the end-users of drug therapy, their ap-
preciation of the benefits provided and
the different weights they place on im-
provements in different dimensions (eg,
pain vs mobility, improved symptoms vs
reduction in sexual functioning) require
continuing investigation using suitable in-
struments such as the EuroQol Group’s
EQ-5D,26 the Health Utilities Index,*’ or
the Quality of Well-Being Index2* in com-
bination with preference elicitation tech-
niques such as the standard gamble or the
time trade-off.29 For example, if the
EQ-SD is used with the standard gamble,
some patients may be prepared to take
greater gambles to avoid health states with
X. BADIA AND M. HERDMAN
high levels of pain, whereas others would
risk more to avoid health states with high
levels of restrictions on daily activities.
CONCLUSIONS
The increasing use of HRQOL instruments
should be tempered by considerations of
how best to use them and the amount of
useful information they are likely to pro-
vide in a given therapeutic context. Rather
than a broad application of HRQOL instru-
ments to all treatments and conditions, a
framework is needed to determine whether
HRQOL measurement is necessary and
whether it will provide information that is
useful for patients, clinicians, and regula-
tory authorities in deciding the value of
drug therapy. Such a framework might be
based on the distinction between acute and
chronic conditions and between preventive,
palliative, and curative treatments. The ex-
tent to which such a framework might work
in practice requires continuing input from
empiric studies, but it may provide some
guidance for researchers planning to use
HRQOL measures in assessments of drug
treatments as well as for regulatory author-
ities that want to incorporate HRQOL data
in their decision-making process.
ACKNOWLEDGMENT
The writing of this article was financed by
a grant from Merck & Co, Inc, White-
house Station, New Jersey. The views ex-
pressed are strictly the authors’ own.
Address correspondence to:
Xavier Badia Llach, MD
Unitat de Recerca en Resultats Sanitaris
Servei d’Epidemiologia Clinica i Salut
Pliblica
Hospital de Santa Cteu i San Pau
Casa de Convalescencia 17 1
Barcelona 0804 1
Spain
E-mail: xbadia@cochrane.es
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