Chapter 1

An Introduction to EQ-5D Instruments

and Their Applications

The aims of this chapter are

• to introduce the EQ-5D ‘family’ of questionnaires: what they are for, how they
are used and what they measure;
• to explain the nature of the data that the EQ-5D questionnaires generate and how
that affects the way that EQ-5D data should be analysed;
• to examine how the purposes for which EQ-5D data are collected affect the ways
that they should be analysed and reported; and
• to describe good practice in data handling and preparing for statistical analysis of
EQ-5D data.
Our focus, throughout this book, is on the analysis of EQ-5D data. The book is
designed to meet the needs of those who have, or are planning to collect, EQ-5D
data. Our hope is that this book will encourage all analysts, both those new to the
EQ-5D and those experienced in using EQ-5D questionnaires, to make full use of
the data provided by respondents, and to maximise the insights possible from those
data.
It is also important to say what this book does not address. We do not provide
guidance on methods of Patient Reported Outcome (PRO) data collection or PRO
study design. For such guidance, you may wish to consult resources such as the
SPIRIT-PRO1 guidelines on inclusion of PROs in clinical trials (Calvert et al. 2018),
the United States Food and Drug Administration (FDA) guidance to industry on the
use of PRO measures in evidence to support labelling claims (FDA 2009); the Euro-
pean Medicines Agency (EMA) guidance regarding use of health-related quality of
life (HRQoL) in labelling studies (EMA 2006); and the various good practice guide-
lines published by the International Society for Pharmacoeconomics & Outcomes
Research (ISPOR), for example on electronic PROs (Zbrozek et al. 2013), and on
collection of PROs in paediatric studies (Matza et al. 2013). Also, we do not offer

1 SPIRIT: Standard Protocol Items: Recommendations for Interventional Trials.

© The Author(s) 2020 1

N. Devlin et al., Methods for Analysing and Reporting EQ-5D Data,
https://doi.org/10.1007/978-3-030-47622-9_1
2 1 An Introduction to EQ-5D Instruments and Their Applications

guidance on which EQ-5D questionnaire to use in what circumstances—for example,

in what populations to use the youth version of the EQ-5D (the EQ-5D-Y); whether
to use the three- or five-level version; and how and when to use the paper, telephone,
proxy or digital versions. Information on these Issues is provided in the User Guides
available online at: www.euroqol.org.
A glossary of the EQ-5D terms used in this and subsequent chapters is in an
appendix.

1.1 Measuring Health Using the EQ-5D

The EQ-5D is a concise, generic measure of self-reported health which is accom-

panied by weights reflecting the relative importance to people of different types
of health problems. The concept of health being measured by EQ-5D is variously
described as health status or HRQoL,2 the latter of which might be defined as:
The value assigned to duration of life as modified by the impairments, functional status,
perceptions and social opportunities that are influenced by disease, injury, treatment or
policy. (Patrick and Erickson 1993)

The EQ-5D is ‘generic’ because it measures health in a way that can be compared
across different sorts of patients, disease areas, and treatments. The researchers who
developed it—the EuroQol Group—aimed to develop a questionnaire which was
brief, minimised the burden of data collection, and could be used in a wide variety of
health care sector applications (Devlin and Brooks 2017). The ‘5D’ in its name refers
to its use of 5 dimensions for describing health states: Mobility, Usual Activities,
Self-care, Pain & Discomfort and Anxiety & Depression. In the original EQ-5D
questionnaire (Fig. 1.1), now known as the EQ-5D-3L, three levels of problems are
described in each dimension, representing no, moderate, or extreme problems in the
Pain & Discomfort and Anxiety & Depression dimensions and no, some, and inability
to in the Mobility, Usual Activities and Self-care dimensions.3 In the more recent
EQ-5D-5L (Fig. 1.2), the number of levels has been expanded from three to five and
these are explicitly expressed as no, mild, moderate, severe and extreme or unable
to (Herdman et al. 2011). A version of the instrument, the EQ-5D-Y (Fig. 1.3), has
been developed for young people and children, retaining the same five dimensions
(Wille et al. 2010).
In each case, the questionnaires are designed mainly for self-completion, either
by people who are receiving treatment (for example patients in a clinical trial) or
people in other settings (for example a sample of the general public in a population
health survey). (As well as the self-report questionnaire, there are also ‘interview’

2 For a discussion of definitional and conceptual issues relating to HRQOL, see Morris et al. (2012),

Sect. 11.3.
3 Forthe Mobility dimension the worst level is ‘confined to bed’.
1.1 Measuring Health Using the EQ-5D 3

Fig. 1.1 EQ-5D-3L descriptive system. Source EuroQol Research Foundation. EQ-5D-3L User
Guide, 2018. Latest version available from: https://euroqol.org/publications/user-guides

and ‘proxy’ versions, designed for special cases where people whose EQ-5D data
are being collected cannot complete a self-report questionnaire themselves.) For
this reason, the EQ-5D belongs to a category of questionnaires often referred to
as PROs and sometimes as Patient Reported Outcome Measures (PROMs). PROs
aim to measure people’s subjective assessment of their own health in a manner that
is systematic, valid and reliable. There is growing recognition that such data from
4 1 An Introduction to EQ-5D Instruments and Their Applications

Fig. 1.2 EQ-5D-5L descriptive system. Source EuroQol Research Foundation. EQ-5D-5L User
Guide, 2019. Latest version available from: https://euroqol.org/publications/user-guides
1.1 Measuring Health Using the EQ-5D 5

Fig. 1.3 EQ-5D-Y. Source EuroQol Research Foundation. EQ-5D-Y User Guide, 2014. Latest
version available from: https://euroqol.org/publications/user-guides
6 1 An Introduction to EQ-5D Instruments and Their Applications

patients provides important information that complements the clinical endpoints

traditionally used in medical care, and can pick up problems and issues missed by
them (Appleby et al. 2015). For example, Robert Temple from the FDA stated that
“The use of Patient Reported Outcome instruments is part of a general movement
toward the idea that the patient, properly queried, is the best source of information
about how he or she feels” (Bren 2006). The EQ-5D is one of the most widely
used PRO measures internationally, and by 2016 the EQ-5D-3L was available in
176 language versions the EQ-5D-5L 123 and the EQ-5D-Y 40 (Devlin and Brooks
2017).
The EQ-5D questionnaire comprises two parts. The first is the EQ-5D descriptive
system, as shown in Figs. 1.1, 1.2, and 1.3. Respondents are asked to tick boxes to
indicate the level of problem they experience on each of the five dimensions. The
combination of these ticks under each dimension describes that person’s EQ-5D self-
reported health state, often called an ‘EQ-5D profile’, which is described in more
detail below.
The second part of the questionnaire is the EQ VAS, so called because it incorpo-
rates a Visual Analogue Scale. This captures the respondent’s overall assessment of
their health on a scale from 0 (worst health imaginable) to 100 (best health imagin-
able). The current versions of the EQ-5D-3L and 5L use the same EQ VAS, shown
in Fig. 1.4, but the original version of the 3L had a slightly different format, as does
the EQ-5D-Y.
The EQ-5D profile data can also be supplemented by using a ‘scoring’ or
‘weighting’ system to convert profile data to a single number—EQ-5D values. These
scoring systems are usually based on preferences—that is, the problems on each
dimension are weighted to reflect how good or bad people think they are. So, for
example, many studies have shown that problems with pain and discomfort often
carry more weight than problems with self-care as reported by the EQ-5D (see Szende
et al. 2007), and this is reflected in the way questionnaire respondents’ profile data
is summed. These EQ-5D values—which are sometimes referred to in the literature
as the EQ-5D Index, or quality of life weights or utilities—are constructed to lie on
a scale anchored by the value 1, full health, and 0, dead. EQ-5D values cannot take
a value higher than 1, but values less than 0 are possible for health states considered
to be worse than dead.
A full set of values for each possible EQ-5D profile is often called a ‘value set’.
These values are obtained from stated preference studies, where members of the
general public4 are asked to imagine living in health states described by the EQ-5D
descriptive system, and to engage in a series of tasks designed to gauge how good
or bad they consider those health states to be. A variety of methods can be used to
elicit these preferences and to model them to create weights for the components of

4 By convention, and for normative reasons, the general public’s stated preferences are usually
argued to be those relevant to constructing these value sets (see, for example, Neumann et al. 2017).
Value sets and their use are discussed in more details in Chap. 4.
1.1 Measuring Health Using the EQ-5D 7

Fig. 1.4 EQ VAS (current EQ-5D-5L and EQ-5D-3L version). Source EuroQol Research Founda-
tion. EQ-5D-5L User Guide, 2019. Latest version available from: https://euroqol.org/publications/
user-guides
8 1 An Introduction to EQ-5D Instruments and Their Applications

the EQ-5D profiles. The resulting ‘value sets’—the complete lists of values for each
of the 243 profiles described by the EQ-5D-3L and EQ-5D-Y, and for the 3125 states
described by the EQ-5D-5L—differ depending on what methods were used to elicit
and model the preferences. They may also differ by country, reflecting differences in
preferences across cultures and regions. Being aware of the properties of these value
sets, and the difference they might make to your analysis of EQ-5D profile data, is
important, and we discuss this further below and in Chap. 4.

1.2 What does the EQ-5D Measure?

The two parts of the EQ-5D questionnaire, combined with the value sets, means that
the instrument generates three distinct types of data: the EQ-5D profile; the EQ VAS;
and the EQ-5D values.
Each of these elements measures a somewhat different underlying construct of
health. It is important to understand the nature of what is being measured in each
case, since this affects hypotheses both about the expected relationship between these
elements and between them and other data collected on respondents’ health and other
characteristics.

1.2.1 The EQ-5D Profile

A respondent’s EQ-5D profile is a summary of the responses that they give to the
descriptive system component of the EQ-5D self-report questionnaire. It can be
described as five sentences, or summarised as a series of numbers representing the
levels of problems in the order that the dimensions appear. Boxes 1.1, 1.2, and 1.3
give a fuller description.
1.2 What does the EQ-5D Measure? 9

Box 1.1. What are EQ-5D profiles?

A set of responses to the statements given in the descriptive system element
of the EQ-5D questionnaire describes a health state or ‘profile’ as a combina-
tion of dimensions and levels within dimensions. For example, a completed
questionnaire may be like this:

This profile can be described as a series of five sentences. For example, this
respondent has:
• No problems in walking about
• No problems with self-care
• Some problems with performing their usual activities
• Extreme pain or discomfort
• Moderate anxiety or depression
10 1 An Introduction to EQ-5D Instruments and Their Applications

In Box 1.2 we describe how these profiles may be more concisely summarised.

Box 1.2. Summarising EQ-5D profiles

A simpler way than using five sentences to summarise a profile is to assign each
level a number and describe the profile as a five-number string, representing the
level of each dimension in the order in which they appear in the questionnaire.
The numbers used are: no problems = 1; some problems = 2; and extreme
problems or unable to = 3. So, for example, no problems in any dimension is
11111, some problems in every dimension is 22222, and extreme problems in
every dimension is 33333. The profile shown in Box 1.1 is 11232.
EQ-5D-5L profile data can be summarised in the same way. 11111 again
means no problem on any of the five dimensions of health and the worst health
state is 55555. The profile labels are not directly equivalent between the 3L and
the 5L, except for 11111, which means no problems on any dimension. The
worst health profiles, 33333 and 55555, describe different underlying health
states because the worst level for mobility in the 3L is ‘confined to bed’ whereas
in the 5L it is ‘unable to walk about’. Similarly, the ‘middle’ states, 22222 and
33333, mean different things, as 3L level 2 refers to ‘some’ problems, but 5L
level 3 refers to ‘moderate’ problems.
The numbers given to levels within dimensions are ordinal—for example, 3
is worse than 2 and 2 is worse than 1. However, the profile labels are categories,
not numbers, and do not even have ordinal properties. They do have a limited
logical ordering—see Devlin et al. (2010) and Parkin et al. (2010) for further
details—and in some cases can be used to compare profiles. For example,
profile 11111 is better than profile 11112 (it logically dominates it) and 11112
is better than 11122. But we cannot say anything about how much better 11111
is compared to 11112. Moreover, we cannot say whether 11112 is better or
worse than a profile such as 11121. That depends on the relative importance
attached to some problems with anxiety & depression compared with some
problems with pain & discomfort.
Chapter 2 demonstrates how health profiles can be compared to make judge-
ments about whether health has improved, using only the ordinal properties
of the levels within profiles. But to compare health profiles such as 11112 and
11121 and to measure the magnitude of the difference between any profiles
requires a scoring system that assigns weights to each profile. EQ-5D value sets
achieve that, using data from stated preferences studies to convert the profile
data into a single, cardinal number. We examine the use of value sets in detail
in Chap. 4.
1.2 What does the EQ-5D Measure? 11

Box 1.3. How many EQ-5D profiles?

For the EQ-5D-3L, there are 35 = 243 possible profiles. There are three groups
of profiles that include only two levels (1 and 2, 2 and 3 or 1 and 3), with 25 =
32 profiles (13% of all profiles) in each group. Therefore, for each level there
are 35 –25 = 211 profiles that include at least one of that level. So:
• 32 (13%) do not include a level 3 in any dimension
• 32 (13%) include only level 2 and 3
• 211 (87%) include at least one level 1
• 211 (87%) include at least one level 3
The number of unique profiles described by the EQ-5D-5L is 55 = 3125.
There are five groups of profiles that include only four levels, with 45 = 1024
profiles (33% of all profiles) in each group. Therefore, for each level there are
55 –45 = 2101 profiles that include at least one of that level, 55 –35 = 2882
that contain at least one of each of two different levels and 55 –25 = 3100 that
contain at least one of each of three different levels. So:
• 1024 (33%) do not include a level 1 in any dimension
• 1024 (33%) do not include a level 5 in any dimension
• 2101 (67%) include at least one level 5
• 2882 (92%) include at least one level 4 or a level 5
• 32 (1%) include only levels 1 and 2
• 32 (1%) include only levels 4 and 5
• 3093 (99%) include levels 1, 3 and 5
• 243 (8%) include only levels 1, 3 and 5.

In practice, not all profiles have an equal probability of being observed. For
example, data obtained from the general population often contain a large propor-
tion of profile 11111. In patient data sets, observations are often clustered on a
sub-set of profiles relevant to those patients’ condition; and some profiles are almost
never observed because they contain unusual combinations of levels—for example
the EQ-5D-3L profile 33133, in which there are extreme problems with everything
except usual activities, where there are no problems.
The profile element of the EQ-5D questionnaire can be categorised as an example
of a Health Status Measurement questionnaire, broadly defined (Bowling 2001,
2004). As noted earlier, the EQ-5D is often also described in the literature as
measuring HRQoL. However, the concept of quality of life, and which aspects of
it are seen as health-related, is often not precisely defined. Because the EQ-5D is a
generic instrument, the EQ-5D profile will not capture everything that matters to all
people with respect to their health status or HRQoL, and does not claim to do so.
That means that, for some diseases and patients, there may be aspects of health that
are important which the EQ-5D does not fully reflect, and this may be important to
consider in your analysis of the data.
12 1 An Introduction to EQ-5D Instruments and Their Applications

1.2.2 EQ VAS

The EQ VAS can be thought of as showing how patients feel about their own health
overall. Their overall score will reflect both the relative importance that they place
on the different aspects of their health that are included in the EQ-5D descriptive
system and other dimensions of health that are not. The EQ VAS therefore provides
information that is complementary to the EQ-5D profile. For example, it is often
observed that some people who report no problems in any EQ-5D dimension rate
their health as less than 100 on the EQ VAS (for example, see Devlin et al. 2004).
Chapter 3 discusses other evidence for this, for example that the average EQ VAS
scores decline with age even for those whose profile is 11111. Further, although
profiles are systematically related to the EQ VAS scores in regression analyses, they
only partially explain them (Feng et al. 2014).

1.2.3 EQ-5D Values

As noted above, EQ-5D values data are produced by applying value sets to summarise
the EQ-5D profile data. The nature of these value sets, and their characteristics,
are influenced by their principal application, which is in the estimation of quality-
adjusted life years (QALYs). It is their use in this context that determines the anchors
for the scale of 1 for full health and 0 for dead.5
It is important to note that using these value sets to generate EQ-5D values data
introduces a source of exogenous variance into the analysis of profile data which
can bias statistical inference (Parkin et al. 2010). Each value set places a different
weight on the various levels and dimensions of the profile data, reflecting underlying
differences in preferences, the methods used to elicit them, or both. This means that
whether there are statistically significant differences in the EQ-5D values between,
for example, two arms of a clinical trial, or between two regions in a national health
survey, may depend on which value set is used, and the relative importance it puts
on the different types of health problems and improvements in them.
More generally, there is no neutral way to summarise the data from the EQ-5D
profile into a single number. This is not an issue that is only relevant to the EQ-5D
instruments: these same points are relevant to the scoring and weighting systems
used in all generic or condition specific PROs. Any method of combining responses
to multiple questions must entail some weight being placed on each question. Even if
preference-based weights were not used, and the dimensions of a PRO were equally
weighted, that would imply a strong value judgement about the relative importance
of various kinds of health problems that may or may not reflect the views of the
people who self-reported their health on that PRO. Analysts should be aware of this,
and check for the sensitivity of results to the choice of value set.

convention of anchoring at dead = 0 is very widely accepted, but could be debated—see

5 The

Sampson et al. (2019).

1.2 What does the EQ-5D Measure? 13

1.2.4 Which Aspect of the Information Provided

by the EQ-5D Should be the Primary Focus of My
Analysis?

When considering which element of the EQ-5D data should be the primary focus of
analysis, and what methods of analysis should be used, users should be guided by
the purpose of collecting EQ-5D data and how the results will be used. Table 1.1
provides an overview of the main contexts in which EQ-5D data are collected, and
implications regarding the analysis of the resulting data.
There are advantages in being able to summarise and represent a health profile by a
single number like the EQ-5D values—for example, it simplifies statistical analysis.
However, as we have already emphasised, there is no neutral set of weights that
can be used for that purpose: they all embody judgements about what is meant by
importance and the appropriate source of information for judging importance. It is
therefore not possible to offer generalised guidance about which set of weights should
be used if the sole purpose is to summarise profile data for descriptive or inferential
statistical analysis. Users should consider the wider purpose for which the summary
will be used. If the purpose is simply to provide descriptive information, then it may
be better not to use EQ-5D values, but to focus analysis on the profile data themselves
(see Chap. 2). This may also be preferable because the EQ-5D value provides less
detailed information than the EQ-5D profile it is summarising. Focussing on the
EQ-5D values may obscure the underlying information on the type and severity of
problems affecting patients that the profile data provide (for example, see Gutacker
et al. 2013).
Further, in some cases where a single number is required to represent health, for
example, in the generation of population norms (Kind et al. 1999), it may be more
appropriate to focus on the EQ VAS data provided by patients or populations, rather
than applying the EQ-5D value sets to their profile data.
Economic Evaluation
Where the economic evaluation of treatment is the main goal of analysis, this has
implications for the analysis of EQ-5D data. A key requirement for a health measure
to use in cost effectiveness analysis is that it should provide an unambiguous measure
of effectiveness. That is, higher EQ values should represent a better state of health and
the same differences between EQ values should have the same level of importance.
For example, the difference between 0.87 and 0.91 should represent the same degree
of change as between 0.22 and 0.26. However, there is arguably a further requirement
if the measure of effectiveness is to be based on economics principles, such as those
embodied in cost utility analysis—essentially, that the weights need to represent
‘values.’ Just as costs represent the total value of resources used, that is the volume
of each type of resource weighted by their individual value, effectiveness in the
context of economic evaluation should represent the value of health output, that is
the amount of health generated weighted by its value.
14 1 An Introduction to EQ-5D Instruments and Their Applications

Table 1.1 Example of types of studies and some considerations for analysis
Types of studies or health care What questions are being What are the implications for
contexts in which EQ-5D data asked? data analysis?
are collected
Clinical trials Is this technology effective and EQ-5D values are required for
cost-effective relative to the estimation of QALY gains.
comparator in the sample of The EQ-5D profile and EQ
patients included in this trial? VAS can provide additional
evidence on relative
effectiveness. Cluster analysis
can be used to identify
responder/non-responder
groups
Observational studies of The focus of these studies Descriptive analysis of
patient populations varies but could include: how EQ-5D profile and EQ VAS at
does self-reported health each observation and analysis
change through time in a given of changes between repeated
patient group? How do observations. EQ-5D values
patients’ health compare to the will be required if estimation
general public? What evidence of QALYs is a goal. Cluster
is there of response to analysis can be used to
treatment? identify
responder/non-responder
groups
Population health surveys How does the health of a Comparisons of EQ-5D
population compare with that profile and EQ VAS between
of others? What is the burden sub-populations. EQ-5D
of ill health? values can provide a means of
summarising profile data as a
single number (although there
are caveats about the use of
values in this context, as we
note in the following
paragraphs)
Routine data collection in the How much variation is there Comparisons of profile and
health care system (‘PROMs between providers in EQ VAS. EQ-5D values can
programmes’) improving patient health? be used as a way of
How do patients’ health and summarising profile data as a
health improvements compare single number, although
between different conditions caution is required (see p. 12)
and treatments? EQ-5D values are relevant
How does the cost where QALY estimation is
effectiveness of different required
procedures compare?
Shared decision making What problems is this patient The individual patient’s
between a patient and their reporting? How difficult do profile and EQ VAS are the
doctor they find these problems focus. These may be
overall? How should this effect benchmarked against
choice of treatment? evidence from other patients
1.2 What does the EQ-5D Measure? 15

There is ongoing debate over the extent to which the commonly-used stated pref-
erences methods used adequately reflect underlying notions of ‘value’, and about
the adequacy of QALYs as a measure of societal benefit from treating ill health.
However, there appears to be general acceptance (for example, among Health Tech-
nology Appraisal bodies, like the National Health Care Institute (Zorginstituut) in
The Netherlands, and the United Kingdom’s National Institute for Health and Care
Excellence) that value sets available for EQ-5D instruments, based on the prefer-
ences of adult members of the general public, are usually appropriate for use in cost
effectiveness analysis (NICE 2013; Zorginstituut Nederland 2016; Neumann et al.
2017).
Further detail on EQ-5D values, including which value set to use, and the analysis
of EQ-5D values data, is provided in Chap. 4.

1.3 EQ-5D Data Collection and Data Handling

Where EQ-5D data are captured electronically, manual data entry is not required.
However, in many cases, EQ-5D questionnaires are still completed in paper format.
Where this is the case, data will need to be coded and entered manually. As this
process is subject to human error, best practice for EQ-5D questionnaires is the same
as any other self-completed paper questionnaire and entails double entry—that is,
data being entered twice, and files compared for anomalies, which are then checked
against the hardcopy.
Coding and data entry for the descriptive system are relatively straightforward.
It is recommended that levels are coded as 1, 2 and 3 (for the EQ-5D-3L) and 1,
2, 3, 4 and 5 (for the EQ-5D-5L) in each dimension, to enable easy generation of
the conventional 5-number profile label. Missing data need to be flagged as do any
unusual responses, for example if more than one level is ticked on a dimension,
although the latter are relatively rare.
EQ VAS data collected electronically are also very straightforward. However, the
paper format of the original and current versions of the EQ VAS used in the EQ-5D-
3L and EQ-5D-5L (see Figs. 1.4 and 1.5) and the current version of the EQ-5D-Y
(see Fig. 1.6) require respondents to draw a line or mark a cross on the VAS to record
their response. The resulting data can require a considerable degree of interpretation
in coding responses. For example, Feng et al. (2014) noted, from qualitative analysis
of a sub-sample of English National Health Service (NHS) PROMs data, a number
of common response types with respect to the EQ VAS data (see Table 1.2).
Whereas a type 1 response in Table 1.2 is the only response which strictly complies
with the EQ VAS instructions, Feng et al. (2014) argue that types 2 and 3 also provide
unambiguous responses that can be captured accurately and reflect the same meaning
to the score intended by respondents. Together, types 1–3 covered 88% respondents
in the data presented in Table 1.2. Other types, including missing and ambiguous
responses (types 5 and 6) require separate codes to flag these issues in analysis.
Similar issues may exist with EQ VAS data from the EQ-5D-Y.
16 1 An Introduction to EQ-5D Instruments and Their Applications

Fig. 1.5 EQ VAS (Original EQ-5D-3L version). Source EuroQol Research Foundation. EQ-5D-3L
User Guide, 2015. Latest version available from: https://euroqol.org/publications/user-guides
1.3 EQ-5D Data Collection and Data Handling 17

Fig. 1.6 EQ VAS (EQ-5D-Y version). Source EuroQol Research Foundation. EQ-5D-Y User Guide,
2014. Latest version available from: https://euroqol.org/publications/user-guides
18 1 An Introduction to EQ-5D Instruments and Their Applications

Table 1.2 Types of responses to the original EQ-5D-3L EQ VAS

EQ VAS response type, from most to least frequent % responses
1 Drew a line from the box towards the EQ VAS, sometimes touching or 45
crossing it. This is the way that the EuroQol Group intends the EQ VAS to be
completed
2 Indicated precisely a horizontal level on the VAS, but did not draw a line to it. 32
For example, ticks, crosses, lines, arrows, asterisks on or beside the VAS, or a
tightly drawn circle around a specific number or tick mark
3 Drew a vertical line extending from 0 up to a point parallel with a point on the 11
VAS
4 Missing 8
5 Drew a vertical line parallel to the VAS, but not extending from 0, or circled 4
an area of the VAS. This indicated a range rather than a single point
6 Gave an unclear response. For example, multiple markings on the VAS or 1
vertical lines drawn from 100 downwards
Source Feng et al. (2014). Response types have been combined across both pre-and post-surgery
responses and re-ordered by frequency

The current format of the EQ VAS in the EQ-5D-5L and EQ-5D-3L (see Fig. 1.4)
entails respondents both noting a number in the box and marking a cross on the
scale. In electronic data capture, the two are identical. In paper completion, there is
potential for the two responses to differ, and best practice would suggest capturing
both and reporting any such discrepancies.

1.4 Before Starting Your Analysis

1.4.1 Treatment of Missing Data—What to Do, What Not

to Do

There are broadly two types of missing EQ-5D data. Data can be missing altogether—
for example, where an elective surgery patient in the English NHS fails to complete
and return their post-surgery PROMs questionnaire. Or data can be missing in part—
for example, where the patient completes an EQ-5D questionnaire, but provides
incomplete profile data, or does not complete the EQ VAS.
General guidelines (i.e. relating to PRO data, rather than specifically the EQ-5D)
often indicate that a substantial amount of missing data can compromise the validity
of analysis—but what constitutes ‘substantial’ is a matter of opinion. For example,
based on the German Institute for Quality and Efficiency in Health Care (Institut
für Qualität und Wirtschaftlichkeit im Gesundheitswesen) standard approach, data
from at least 70% of patients at both baseline and one follow up visit are needed to
consider analysis of that data valid for its purposes. However, ‘percent missing’ is not
1.4 Before Starting Your Analysis 19

defined consistently across the literature and different definitions on how to estimate
the amount of missing data may lead to different practices and results (Coens et al.
2020). Further, even where there are high rates of missing data, analysis of available
data may still yield insights into the sub-group who did respond, even if results cannot
be generalised to non-responders. In short, there are no hard and fast rules. However,
it is important for analysts to report missing data, and to be mindful of potential
limitations arising from loss of generalisability.
In general, you should provide data descriptions, state the assumptions underlying
the handling of the missing EQ-5D data, and conduct sensitivity analyses to the
selected assumption. Included in the data description should be the amount of missing
data, missing data patterns, and the association between missing data and observed
data, for example respondents’ age, gender and any previously observed EQ-5D data
for that respondent (Faria et al. 2014).
Analytical methods used for missing data in general are applicable to the EQ-5D;
users are advised to consult a statistical text for details. Essentially, it is neces-
sary to consider the assumed form that missingness takes for the data—Missing
Completely At Random (MCAR), Missing At Random (MAR) or Missing Not At
Random (MNAR) (Little and Rubin 1987)—and to select a method for dealing with
this appropriate to that form.
If MCAR, where a respondent’s missing data are not related to that person’s
socio-demographic or other characteristics, analysis can assume that the missing
data follow the same patterns as the non-missing data.
If MAR, where a respondent’s missing data is related to their observed charac-
teristics, but not any unobserved characteristics, analysis can assume that we have a
random sample of respondents with those characteristics and make inferences from
that sample about the data that are missing. Multiple Imputation (MI) has been
increasingly used in recent years for EQ-5D data with MAR (Ratcliffe et al. 2005;
Kaambwa et al. 2012; Simons et al. 2015).
If MNAR, where a respondent’s data are missing because of their characteristics,
we do not have random samples of people with different characteristics and require
more complex analytical methods to deal with resulting selection bias. The Heckman
selection model has been applied to EQ-5D values data that are assumed to be MNAR
(Kaambwa et al. 2012).
Recent guidance suggests that data analysts should evaluate the sensitivity of
the analysis to the MAR assumption using methods such as the weighting or pattern
mixture approaches (Faria et al. 2014; Simons et al. 2015). In particular the evaluation
should examine how the results might change when a MNAR assumption is made to
the missing EQ-5D data.
There are two missing data issues specific to EQ-5D data. First, there is the
issue of what should be done where the user wishes to analyse profiles and some
but not all of the profile items are missing. Bad practice includes substituting for a
respondent’s missing profile items an average derived from their non-missing items
and substituting an average derived from the non-missing items in the sample as
a whole. It might be possible to use MI in this context, but there are currently no
20 1 An Introduction to EQ-5D Instruments and Their Applications

examples on which to base guidance. Conservative guidance is therefore to treat as

missing any profiles based on missing profile items.
The second is where some or all of the profile items are missing, and the user
wishes to analyse EQ-5D values. For this, MI may be an appropriate method if the
data are assumed MAR, but an issue is whether this should be applied to profile
items, from which an EQ-5D value is calculated, or to EQ-5D values directly (Faria
et al. 2014). In practice, the decision depends on the observed missing data pattern
and the sample size available for analysis (Simons et al. 2015).

1.4.2 Planning Your Analysis

A systematic review of the use of PROs in oncology conducted by the Setting Inter-
national Standards in Analyzing Patient-Reported Outcomes and Quality of Life
Endpoints Data (SISAQOL) Consortium (Pe et al. 2018) showed a widespread lack
of clearly-specified a priori research hypotheses and a link with the design and statis-
tical methods to be employed. New guidelines for protocol development (for example
SPIRIT-PRO) and reporting of PROs (for example CONSORT-PRO6 —see Calvert
et al. 2013) also recognise this to be a common issue in PRO studies generally.
Before beginning analysis of EQ-5D data, you should therefore consider what
questions you want to answer with your data. What are your hypotheses about, for
example, how a treatment arm is expected to behave relative to a reference arm in
a clinical trial? What assumptions underpin these hypotheses, for example what is
your rationale and what evidence has informed that? This, in turn, should inform the
statistical analysis plan (SAP) developed prior to analysis. Note that the content of
SAPs will vary depending on the study type and study aims.

1.5 Guide to the Rest of this Book

In the remainder of this book, we explain in detail how each element of the data gener-
ated from using EQ-5D instruments—the profile data, EQ VAS and EQ values —
can be analysed. We provide both a basic introduction to analysis in each case,
assuming no prior knowledge of analysis of EQ-5D data, as well as introducing
more advanced topics relating to analysis of EQ-5D data.

6 CONSORT: Consolidated Standards Of Reporting Trials.

References 21

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