Construct Validity and Responsiveness of EQ-5D-3L in Patients With Rheumatic Disease
Conditions: Rheumatoid Arthritis, Polyarthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Rheumatic Diseases
Sponsor: Karolinska Institutet

Research protocol: Follow-up with patient-
reported outcome measures for improved 
health related quality of life – Construct 
validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
Health Economics and Policy Research Group, Department of Learning, 
Informatics, Management and Ethics, 19 August 2024 
 
 
 

 
 
Table of contents 
Brief summary .......................................................................................................................... 3 
Background ................................................................................................................................ 3 
Methodology............................................................................................................................. 3 
Study design and data collection ............................................................................... 3 
Study population .......................................................................................................... 5 
Outcome measures ............................................................................................................. 5 
EQ-5D-3L and EQ VAS ............................................................................................. 5 
Disease activity ............................................................................................................. 6 
Functional ability ........................................................................................................... 6 
VAS questions ................................................................................................................ 6 
Hypotheses ............................................................................................................................... 6 
Convergent validity EQ-5D-3L ............................................................................ 6 
Known-groups validity EQ-5D-3L ..................................................................... 9 
Responsiveness EQ-5D-3L................................................................................... 12 
Convergent validity EQ VAS ................................................................................. 15 
Known-groups validity EQ VAS .......................................................................... 16 
Responsiveness EQ VAS ......................................................................................... 17 
References ................................................................................................................................ 18 
 

3 (20) 
Karolinska Institutet - Research protocol: Follow-up with patient-reported outcome measures for 
improved health related quality of life – Construct validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
Brief summary 
The aim of this study is to investigate the construct validity (convergent and 
known-groups) and responsiveness of EQ-5D-3L in patients with 
rheumatoid arthritis, polyarthritis, psoriatic arthritis, and ankylosing 
spondylitis. The study is based on retrospective registry data from the 
Swedish Rheumatology Registry (SRQ).  
Background 
Patient-reported outcome measures (PROMs) are used to measure how 
patients themselves experience their health and health related quality of life 
(HRQoL) [1]. One of the most commonly used PROMs is EQ-5D, which is a 
generic instrument used to measure, value and compare health across 
symptoms and diagnoses [2]. When choosing a PROM to follow-up care 
from the patient perspective and to assess HRQoL in patients with 
rheumatic disease, it is important to know that the instrument is valid and 
responsive. An instrument with low validity and responsiveness might not 
capture and describe patients’ health and changes in their health 
accurately. The aim of the study is therefore to investigate the validity and 
responsiveness of EQ-5D-3L. The research questions are: 
1. What is the construct validity of EQ-5D-3L in patients with rheumatic 
disease? 
2. What is the responsiveness of EQ-5D-3L in patients with rheumatic 
disease?  
Methodology 
Study design and data collection 
This study will assess the construct validity and responsiveness of EQ-5D-
3L among patients with rheumatoid arthritis (RA), polyarthritis, psoriatic 
arthritis (PsA), and ankylosing spondylitis (AS) based on retrospective 
registry data. The design of the study will follow the established guidelines 
from COSMIN of how to assess validity and responsiveness of PROMs [3].  
Construct validity refers to the degree to which an instrument measures the 
constructs it intends to measure [4]. Construct validity will be assessed in 
two ways, convergent validity and known-groups validity. Convergent 
validity refers to how well the instrument under study (EQ-5D-3L and EQ 
VAS) correlates with other outcome measures [4]. According to these 

4 (20) 
Karolinska Institutet - Research protocol: Follow-up with patient-reported outcome measures for 
improved health related quality of life – Construct validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
guidelines, convergent validity should be assessed by formulating and 
testing hypotheses regarding the expected direction and magnitude of the 
correlation between the measurement being studied (EQ-5D-3L and EQ 
VAS) and other outcome measures measuring the same or similar 
constructs [3]. The constructs measured by the other outcome measures 
should be clearly described [3].  
Known-groups validity refers to how well the instrument can find differences 
between groups known to differ. Known-groups validity should be assessed 
by formulating and testing hypotheses regarding expected directions and 
magnitude of the differences between subgroups [3]. There should be an 
adequate description of important characteristics of the subgroups, such as 
disease characteristics [3].  
Responsiveness refers to the ability of the instrument to capture change 
over time in the construct that is measured [5]. According to Cosmin, 
responsiveness can be assessed by comparing changes in EQ-5D-3L and 
EQ VAS, with changes in other outcome measures, similar to convergent 
validity explained above [3]. The hypotheses should include the expected 
direction and magnitude of the correlations, and the constructs should be 
clearly described. Responsiveness can also be assessed by analysing 
weather EQ-5D-3L and EQ VAS can discriminate between patients who 
have improved and those that have not, based on changes in another 
outcome, such as changes in disease activity or functional ability [3].  
The analyses will be conducted independently for the different patient 
groups. To support construct validity and responsiveness of EQ-5D-3L and 
EQ VAS in each patient group, 75% of the hypotheses will need to be 
supported [6-9]. Historical registry data from the Swedish Rheumatology 
Register (SRQ) will be used to assess the construct validity and 
responsiveness of EQ-5D-3L and EQ VAS. Data on EQ-5D-3L has been 
collected since 2008 [10] and the study will include data from 2008 until 
the time of data extraction.  
Ethical approval has been granted for the project (2023-04394-01). 
 

5 (20) 
Karolinska Institutet - Research protocol: Follow-up with patient-reported outcome measures for 
improved health related quality of life – Construct validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
Study population 
Inclusion criteria are:  
• 18 years and older at the time of first included measurement  
• A diagnosis of RA, polyarthritis, PsA, or AS 
• Complete registration of responses in the EQ-5D-3L descriptive 
system or EQ VAS on at least one time point in SRQ 
• For patients with RA: At least one measurement with Disease Activity 
Score 28 (DAS28) reported in relation to the same visit as EQ-5D-3L 
• For patients with polyarthritis: At least one measurement with DAS28 
reported in relation to the same visit as EQ-5D-3L 
• For patients with PsA: At least one measurement with DAS28 or 
Disease Activity in Psoriatic Arthritis (DAPSA) reported in relation to 
the same visit as EQ-5D-3L 
• For patients with AS: At least one measurement with the Bath 
Ankylosing Spondylitis Disease Activity Index (BASDAI) reported in 
relation to the same visit as EQ-5D-3L 
For the analyses of construct validity, the latest measurement will be used if 
the individual patients have multiple complete registrations with EQ-5D-3L 
and the other required measure. The hypotheses for responsiveness will be 
tested in patients with newly diagnosed disease (having the diagnosis for 
≤12 months), as changes in disease activity are likely to be present in this 
group. For the analysis of responsiveness, the two first measurements 
during the first year will be used.  
Outcome measures 
EQ-5D-3L and EQ VAS 
The EQ-5D-3L measures HRQoL and consists of two parts. The first part 
contains five questions about mobility, daily activities, self-care, 
pain/discomfort, and anxiety/depression [11, 12]. Each question can be 
answered with no problem (1), some/moderate problem (2) unable to 
perform certain activities/having extreme problems (3). The answers can be 
summarized in an index value based on an existing preference-based value 
set. In this study, the EQ-5D-3L value set by Dolan [13] will be used for the 
main analyses and a Swedish experience-based value set in a sensitivity 
analysis [14]. For the EQ-5D-3L index, 1 represents full health and 0 
represents a value equal to being dead. EQ VAS measures the persons 

6 (20) 
Karolinska Institutet - Research protocol: Follow-up with patient-reported outcome measures for 
improved health related quality of life – Construct validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
health today on a visual analogue scale (VAS) from 0 (worst imaginable 
health) to 100 (best imaginable health) [11, 12].   
Disease activity 
DAS28 was developed for patients with RA and contains questions about 
tender and swollen joints, disease activity and inflammation [15]. DAPSA was 
developed for patients with PsA and contains questions about tender and 
swollen joints, disease activity, pain, and inflammation [16, 17]. BASDAI was 
developed to measure disease activity in patients with AS and contains 
questions about fatigue, pain, swelling and stiffness [18, 19]. ASDAS was 
developed to measure disease activity in patients with AS and contains 
questions about pain, swelling, stiffness, disease activity and inflammation 
[20].  
For all these measures, a higher value indicates higher disease activity.  
Functional ability 
The Health Assessment Questionnaire Disability Index (HAQ-DI) and the 
Bath Ankylosing Spondylitis Functional Index (BASFI) measure functional 
ability through questions about mobility, daily activities, and self-care [19, 
21]. For both scales, a higher value indicates more problems with functional 
ability.  
VAS questions 
The SRQ also contains three questions about pain, fatigue, and general 
health (global score), measured on a VAS. The questions ask who much pain 
the person has had, how fatigue they have been and how their general 
health has been in the last week due to their rheumatic disease. The scale 
ranges from no problem (0) to as bad as it can be (100) [22].  
Hypotheses 
To assess the validity and responsiveness a priori hypotheses for 
convergent validity, known-groups validity, and responsiveness have been 
formulated. The hypotheses for EQ-5D-3L are presented first followed by 
the hypotheses for EQ VAS. 
Convergent validity EQ-5D-3L 
Convergent validity will be assessed by testing hypotheses regarding the 
expected direction and magnitude of correlation between the EQ-5D-3L 

7 (20) 
Karolinska Institutet - Research protocol: Follow-up with patient-reported outcome measures for 
improved health related quality of life – Construct validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
and the other outcome measures. Constructs that are considered to be 
related are expected to have at least a moderate correlation and constructs 
that are considered to be similar are expected to have a strong correlation 
[8]. A moderate correlation is defined as ≥0.3 and a strong correlation is 
defined as ≥0.5 [8]. The hypotheses for all patient groups are presented in 
the text below. 
VAS pain 
• VAS pain and EQ-5D-3L index: a moderate negative correlation is 
expected.  
 
• VAS pain and EQ-5D-3L mobility: a moderate positive correlation is 
expected.  
 
• VAS pain and EQ-5D-3L self-care: a moderate positive correlation is 
expected.  
 
• VAS pain and EQ-5D-3L daily activities: a moderate positive 
correlation is expected.  
 
• VAS pain and EQ-5D-3L pain/discomfort: a strong positive 
correlation is expected.  
 
VAS global score 
• VAS global score and EQ-5D-3L index: a strong negative correlation 
is expected.  
 
VAS fatigue 
• VAS fatigue and EQ-5D-3L index: a moderate negative correlation is 
expected.  
 
• VAS fatigue and EQ-5D-3L mobility: a moderate positive correlation 
is expected.  
 

8 (20) 
Karolinska Institutet - Research protocol: Follow-up with patient-reported outcome measures for 
improved health related quality of life – Construct validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
• VAS fatigue and EQ-5D-3L self-care: a moderate positive correlation 
is expected.  
 
• VAS fatigue and EQ-5D-3L daily activities: a moderate positive 
correlation is expected.  
 
• VAS fatigue and EQ-5D-3L anxiety/depression: a moderate positive 
correlation is expected. 
 
 
DAS28/DAPSA/BASDAI/ASDAS 
• Disease activity measured with DAS28/DAPSA/BASDAI/ASDAS and 
EQ-5D-3L index: a moderate negative correlation is expected.  
 
• Disease activity measured with DAS28/DAPSA/BASDAI/ASDAS and 
EQ-5D-3L mobility: a moderate positive correlation is expected.  
 
• Disease activity measured with DAS28/DAPSA/BASDAI/ASDAS and 
EQ-5D-3L self-care: a moderate positive correlation is expected.  
 
• Disease activity measured with DAS28/DAPSA/BASDAI/ASDAS and 
EQ-5D-3L daily activities: a moderate positive correlation is 
expected. 
 
 
• Disease activity measured with DAS28/DAPSA/BASDAI/ASDAS and 
EQ-5D-3L pain/discomfort: a moderate positive correlation is 
expected.  
 
HAQ-DI/BASFI 
• Functional ability measured with HAQ-DI/BASFI and EQ-5D-3L index: 
a moderate negative correlation is expected.  
 
• Functional ability measured with HAQ-DI/BASFI and EQ-5D-3L 
mobility: a moderate positive correlation is expected.  
 
• Functional ability measured with HAQ-DI/BASFI and EQ-5D-3L self-
care: a moderate positive correlation is expected.  
 

9 (20) 
Karolinska Institutet - Research protocol: Follow-up with patient-reported outcome measures for 
improved health related quality of life – Construct validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
• Functional ability measured with HAQ-DI/BASFI and EQ-5D-3L daily 
activities: a moderate positive correlation is expected.    
 
• Functional ability measured with HAQ-DI/BASFI and EQ-5D-3L 
pain/discomfort: a moderate positive correlation is expected.  
 
Known-groups validity EQ-5D-3L 
In the assessment of known-groups validity, patients will be divided into 
groups for which there is an expected difference in HRQoL. The groups 
represent patients with different levels of disease activity or functional 
ability. Patients with lower disease activity (<3.2 measured with DAS28, ≤14 
measured with DAPSA, <2.1 measured with ASDAS and <4 measured with 
BASFI) are expected to have better health and HRQoL compared to patients 
with higher disease activity (≥3.2 measured with DAS28, >14 measured with 
DAPSA, ≥2.1 measured with ASDAS and ≥4 measured with BASDAI). Likewise, 
patients with better functional ability (<1 measured with HAQ-DI and <4 
measured with BASFI) are expected to have better health and HRQoL 
compared to patients with worse functional ability (≥1 measured with HAQ-
DI and ≥4 measured with BASFI). The cut of values for disease activity 
(DAS28 [23], DAPSA [24], ASDAS [25, 26], BASDAI [25-27]) and functional 
ability (HAQ-DI [28, 29], BASFI [27]) were taken from the literature.  
To assess the magnitude of the differences in the proportions of reported 
problems in the EQ-5D-3L dimensions between groups, the effect size (r) 
will be calculated. The effect size is considered small if it is ≥ 0.1, medium if it 
is ≥0.3 and large if it is ≥0.5 [30-32]. To support the hypotheses for the 
dimensions, at least a small effect size will be required.  
To estimate whether there is a difference in the EQ-5D-3L mean index value 
between groups, cut-off values for minimally important differences (MID) 
will be used. Minimal important differences represent the smallest 
improvement considered worthwhile by a patient [33]. The MID values used 
in this study will be based on the literature. 
The hypotheses for known-groups validity of EQ-5D-3L are presented in 
the text below. 
 

10 (20) 
Karolinska Institutet - Research protocol: Follow-up with patient-reported outcome measures for 
improved health related quality of life – Construct validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
DAS28/DAPSA 
• Lower EQ-5D-3L index values are expected in patients with 
moderate/high disease activity compared to patients in 
remission/with low disease activity. 
 
• More reported problems in EQ-5D-3L mobility are expected for 
patients with moderate/high disease activity compared to patients in 
remission/with low disease activity.  
 
• More reported problems in EQ-5D-3L self-care are expected for 
patients with moderate/high disease activity compared to patients in 
remission/with low disease activity. 
  
• More reported problems in EQ-5D-3L daily activities are expected 
for patients with moderate/high disease activity compared to 
patients in remission/with low disease activity. 
 
• More reported problems in EQ-5D-3L pain/discomfort are expected 
for patients with moderate/high disease activity compared to 
patients in remission/with low disease activity. 
 
ASDAS 
• Lower EQ-5D-3L index values are expected in patients with high/very 
high disease activity compared to patients with inactive disease/low 
disease activity.  
 
• More reported problems in EQ-5D-3L mobility are expected in 
patients with high/very high disease activity compared to patients 
with inactive disease/low disease activity.  
 
• More reported problems in EQ-5D-3L self-care are expected in 
patients with high/very high disease activity compared to patients 
with inactive disease/low disease activity.   
 
• More reported problems in EQ-5D-3L daily activities are expected in 
patients with high/very high disease activity compared to patients 

11 (20) 
Karolinska Institutet - Research protocol: Follow-up with patient-reported outcome measures for 
improved health related quality of life – Construct validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
with inactive disease/low disease activity.   
 
• More reported problems in EQ-5D-3L pain/discomfort are expected 
in patients with high/very high disease activity compared to patients 
with inactive disease/low disease activity.  
 
BASDAI 
• Lower EQ-5D-3L index values are expected in patients with high 
disease activity compared to patients with low disease activity. 
 
• More reported problems in EQ-5D-3L mobility are expected in 
patients with high disease activity compared to patients with low 
disease activity. 
 
• More reported problems in EQ-5D-3L self-care are expected in 
patients with high disease activity compared to patients with low 
disease activity. 
 
• More reported problems in EQ-5D-3L daily activities are expected in 
patients with high disease activity compared to patients with low 
disease activity. 
 
• More reported problems in EQ-5D-3L pain/discomfort are expected 
in patients with high disease activity compared to patients with low 
disease activity. 
 
BASFI/HAQ-DI 
• Lower EQ-5D-3L index values are expected in patients with less 
functional ability compared to patients with more functional ability. 
 
• More reported problems in EQ-5D-3L mobility are expected in 
patients with less functional ability compared to patients with more 
functional ability.  
  
• More reported problems in EQ-5D-3L self-care are expected in 
patients with less functional ability compared to patients with more 

12 (20) 
Karolinska Institutet - Research protocol: Follow-up with patient-reported outcome measures for 
improved health related quality of life – Construct validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
functional ability. 
 
• More reported problems in EQ-5D-3L daily activities are expected in 
patients with less functional ability compared to patients with more 
functional ability. 
 
• More reported problems in EQ-5D-3L pain/discomfort are expected 
in patients with less functional ability compared to patients with more 
functional ability. 
 
Responsiveness EQ-5D-3L 
Responsiveness will be assessed in two ways. One way is by assessing the 
relationship between individual changes in EQ-5D-3L index value and 
dimensions over time with changes in other outcome measures over the 
same time period. The second way is to assess whether EQ-5D-3L can 
discriminate between patients who have improved over time and those that 
have not, based on changes in disease activity or functional ability.  
Correlation between changes in EQ-5D-3L with changes in other 
outcome measurement instruments  
The relationship between changes in the EQ-5D-3L and changes in other 
outcome measures will be assessed by analysing the correlation between 
the changes in the variables between the two first measurements of each 
individual during the first year after diagnosis. The hypotheses for expected 
correlations are presented in the text below. 
VAS pain 
• VAS pain and EQ-5D-3L index: the changes in scores are expected to 
have a moderate negative correlation.  
 
• VAS pain and EQ-5D-3L mobility: the changes in scores are 
expected to have a moderate positive correlation.  
 
• VAS pain and EQ-5D-3L self-care: the changes in scores are 
expected to have a moderate positive correlation.  
 

13 (20) 
Karolinska Institutet - Research protocol: Follow-up with patient-reported outcome measures for 
improved health related quality of life – Construct validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
• VAS pain and EQ-5D-3L daily activities: the changes in scores are 
expected to have a moderate positive correlation. 
 
• VAS pain and EQ-5D-3L pain/discomfort: the changes in scores are 
expected to have a strong positive correlation.  
 
VAS global score 
• VAS global score and EQ-5D-3L index: the changes in scores are 
expected to have a strong negative correlation.  
 
VAS fatigue 
• VAS fatigue and the EQ-5D-3L index: the changes in scores are 
expected to have a moderate negative correlation.  
 
• VAS fatigue and EQ-5D-3L mobility: the changes in scores are 
expected to have a moderate positive correlation.  
 
• VAS fatigue and EQ-5D-3L self-care: the changes in scores are 
expected to have a moderate positive correlation.  
 
• VAS fatigue and EQ-5D-3L daily activities: the changes in scores are 
expected to have a moderate positive correlation.  
 
• VAS fatigue and EQ-5D-3L anxiety/depression: the changes in 
scores are expected to have a moderate positive correlation.  
 
DAS28/DAPSA/BASDAI/ASDAS 
• Disease activity measured with DAS28/DAPSA/BASDAI/ASDAS and 
the EQ-5D-3L index: the changes in scores are expected to have a 
moderate negative correlation.  
 
• Disease activity measured with DAS28/DAPSA/BASDAI/ASDAS and 
EQ-5D-3L mobility: the changes in scores are expected to have a 
moderate positive correlation.  
 

14 (20) 
Karolinska Institutet - Research protocol: Follow-up with patient-reported outcome measures for 
improved health related quality of life – Construct validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
• Disease activity measured with DAS28/DAPSA/BASDAI/ASDAS and 
EQ-5D-3L self-care: the changes in scores are expected to have a 
moderate positive correlation.  
 
• Disease activity measured with DAS28/DAPSA/BASDAI/ASDAS and 
EQ-5D-3L daily activities: the changes in scores are expected to 
have a moderate positive correlation.  
 
• Disease activity measured with DAS28/DAPSA/BASDAI/ASDAS and 
EQ-5D-3L pain/discomfort: the changes in scores are expected to 
have a moderate positive correlation.   
 
HAQ-DI/BASFI 
• Functional ability measured with HAQ-DI/BASFI and EQ-5D-3L index: 
the changes in scores are expected to have a moderate negative 
correlation.  
 
• Functional ability measured with HAQ-DI/BASFI and EQ-5D-3L 
mobility: the changes in scores are expected to have a moderate 
positive correlation.  
 
• Functional ability measured with HAQ-DI/BASFI and EQ-5D-3L self-
care: the changes in scores are expected to have a moderate positive 
correlation.  
 
• Functional ability measured with HAQ-DI/BASFI and EQ-5D-3L daily 
activities: the changes in scores are expected to have a moderate 
positive correlation:  
 
• Functional ability measured with HAQ-DI/BASFI and EQ-5D-3L 
pain/discomfort: the changes in scores are expected to have a 
moderate positive correlation.  
 
 

15 (20) 
Karolinska Institutet - Research protocol: Follow-up with patient-reported outcome measures for 
improved health related quality of life – Construct validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
Analysing EQ-5D-3L in patients who have improved versus patients who 
have not improved based on disease activity and functional ability 
To assess whether EQ-5D-3L can discriminate between patients who have 
improved and those that have not, the area under the receiver operating 
curve ROC curve (AUC) will be calculated. Patients will be considered to 
have improved based on results from the measures of disease activity 
(DAS28, DAPSA, ASDAS or BASDAI) and functional ability (BASFI and HAQ-
DI) using criteria for what is defined as a response from previous studies. To 
determine whether EQ-5D-3L can discriminate between patient groups, the 
AUC is required to be ≥ 0.70 [8]. The hypotheses for these analyses are 
presented in the text below.  
DAS28/DAPSA/ASDAS/BASDAI 
• The EQ-5D-3L index is expected to be able to discriminate between 
patients who have improved disease activity and patients who have 
not improved.  
 
BASFI/HAQ-DI 
• The EQ-5D-3L index is expected to be able to discriminate between 
patients who have improved functional ability and patients who have 
not improved.  
 
Convergent validity EQ VAS 
Convergent validity of EQ VAS will be assessed with the same analyses used 
for EQ-5D-3L (see the section about convergent validity EQ-5D-3L). The 
hypotheses are described in the text below. 
• VAS pain and EQ VAS: a moderate negative correlation is expected.  
 
• VAS global score and EQ VAS: a strong negative correlation is 
expected.  
 
• VAS fatigue and EQ VAS: a moderate negative correlation is 
expected. 
 
 

16 (20) 
Karolinska Institutet - Research protocol: Follow-up with patient-reported outcome measures for 
improved health related quality of life – Construct validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
DAS28/DAPSA/BASDAI/ASDAS 
• Disease activity measured with DAS28/DAPSA/BASDAI/ASDAS and EQ 
VAS: a moderate negative correlation is expected.  
 
HAQ-DI/BASFI 
• Functional ability measured with HAQ-DI/BASFI and EQ VAS: a 
moderate negative correlation is expected.  
 
Known-groups validity EQ VAS 
Known-groups validity of EQ VAS will be assessed for the same groups as 
the EQ-5D-3L index (see section about Known-groups validity EQ-5D-3L). 
To estimate whether there is a difference in EQ VAS, cut-off values for MID 
based on the literature will be used. The hypotheses described in text below 
are regarding the known-groups validity of EQ VAS.  
DAS28/DAPSA 
• Lower EQ VAS values are expected in patients with moderate/high 
disease activity compared to patients in remission/with low disease 
activity.  
 
ASDAS 
• Lower EQ VAS values are expected in patients with high/very high 
disease activity compared to patients with inactive disease/low 
disease activity.   
 
BASDAI 
• Lower EQ VAS values are expected in patients with higher disease 
activity compared to patients with lower disease activity. 
 
BASFI/HAQ-DI 
• Lower EQ VAS values are expected in patients with less functional 
ability compared to patients with more functional ability.   

17 (20) 
Karolinska Institutet - Research protocol: Follow-up with patient-reported outcome measures for 
improved health related quality of life – Construct validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
Responsiveness EQ VAS 
Responsiveness for EQ VAS will be assessed with the same analyses used 
for EQ-5D-3L (see the section about responsiveness EQ-5D-3L). The 
hypotheses are described in the text below. 
Correlation between changes in EQ VAS with changes in other outcome 
measures  
• VAS pain and EQ VAS: the changes in scores are expected to have a 
moderate negative correlation.  
 
• VAS global score and EQ VAS: the changes in scores are expected to 
have a strong negative correlation.  
 
• VAS fatigue and EQ VAS: the changes in scores are expected to have 
a moderate negative correlation.  
 
• Disease activity measured with DAS28/DAPSA/BASDAI/ASDAS and EQ 
VAS: the changes in scores are expected to have a moderate 
negative correlation.  
 
• Functional ability measured with HAQ-DI/BASFI and EQ VAS: the 
changes in scores are expected to have a moderate negative 
correlation.  
 
Analysing EQ VAS in patients who have improved versus patients who 
have not improved based on disease activity and functional ability 
 
DAS28/DAPSA/ASDAS/BASDAI 
• EQ VAS is expected to be able to discriminate between patients who 
have improved disease activity and patients who have not improved.  
 
BASFI/HAQ-DI 
• EQ VAS is expected to be able to discriminate between patients who 
have improved functional ability and patients who have not 
improved.  
 
 

18 (20) 
Karolinska Institutet - Research protocol: Follow-up with patient-reported outcome measures for 
improved health related quality of life – Construct validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
References 
1. 
Sveriges kommuner och regioner. Patientrapporterade mått 2023 [cited 
2024 17 april]. Available from: 
https://skr.se/kvalitetsregister/drivaregister/utbildningomnationellakvalitetsregister/
4itochvisualiseringavdata/patientrapporteradematt.44741.html. 
2. 
Devlin NJ, Brooks R. EQ-5D and the EuroQol Group: Past, Present and Future. 
Appl Health Econ Health Policy. 2017;15(2):127-37. 
3. 
Mokkink L, Prinsen C, Patrick D, Alonso K, Bouter L, de Vet H, et al. COSMIN 
Study Design checklist for Patient-reported outcome measurement instruments 
2019 [cited 2023 14 mars]. Available from: https://www.cosmin.nl/wp-
content/uploads/COSMIN-study-designing-checklist_final.pdf. 
4. 
Fayers PM, Machin D. Quality of life : the assessment, analysis and 
interpretation of patient-reported outcomes. 2. ed. ed. Chichester: J. Wiley; 2007. 
5. 
Mokkink LB, Terwee CB, Patrick DL, Alonso J, Stratford PW, Knol DL, et al. The 
COSMIN study reached international consensus on taxonomy, terminology, and 
definitions of measurement properties for health-related patient-reported 
outcomes. Journal of Clinical Epidemiology. 2010;63(7):737-45. 
6. 
Terwee CB, Bot SD, de Boer MR, van der Windt DA, Knol DL, Dekker J, et al. 
Quality criteria were proposed for measurement properties of health status 
questionnaires. J Clin Epidemiol. 2007;60(1):34-42. 
7. 
Mokkink LB, de Vet HCW, Prinsen CAC, Patrick DL, Alonso J, Bouter LM, et al. 
COSMIN Risk of Bias checklist for systematic reviews of Patient-Reported Outcome 
Measures. Quality of life research : an international journal of quality of life aspects 
of treatment, care and rehabilitation. 2018;27(5):1171-9. 
8. 
Prinsen CAC, Mokkink LB, Bouter LM, Alonso J, Patrick DL, de Vet HCW, et al. 
COSMIN guideline for systematic reviews of patient-reported outcome measures. 
Quality of Life Research. 2018;27(5):1147-57. 
9. 
Terwee CB, Prinsen CAC, Chiarotto A, Westerman MJ, Patrick DL, Alonso J, et 
al. COSMIN methodology for evaluating the content validity of patient-reported 
outcome measures: a Delphi study. Quality of life research : an international journal 
of quality of life aspects of treatment, care and rehabilitation. 2018;27(5):1159-70. 
10. 
Ernstsson O, Janssen MF, Heintz E. Collection and use of EQ-5D for follow-
up, decision-making, and quality improvement in health care - the case of the 
Swedish National Quality Registries. J Patient Rep Outcomes. 2020;4(1):78. 
11. 
EuroQoL. EuroQol--a new facility for the measurement of health-related 
quality of life. Health Policy. 1990;16(3):199-208. 

19 (20) 
Karolinska Institutet - Research protocol: Follow-up with patient-reported outcome measures for 
improved health related quality of life – Construct validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
12. 
Brooks R. EuroQol: the current state of play. Health Policy. 1996;37(1):53-72. 
13. 
Dolan P. Modeling valuations for EuroQol health states. Med Care. 
1997;35(11):1095-108. 
14. 
Burström K, Sun S, Gerdtham UG, Henriksson M, Johannesson M, Levin L, et al. 
Swedish experience-based value sets for EQ-5D health states. Quality of life 
research : an international journal of quality of life aspects of treatment, care and 
rehabilitation. 2014;23(2):431-42. 
15. 
Prevoo ML, van 't Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van 
Riel PL. Modified disease activity scores that include twenty-eight-joint counts. 
Development and validation in a prospective longitudinal study of patients with 
rheumatoid arthritis. Arthritis Rheum. 1995;38(1):44-8. 
16. 
Schoels M, Aletaha D, Funovits J, Kavanaugh A, Baker D, Smolen JS. 
Application of the DAREA/DAPSA score for assessment of disease activity in 
psoriatic arthritis. Ann Rheum Dis. 2010;69(8):1441-7. 
17. 
Nell-Duxneuner VP, Stamm TA, Machold KP, Pflugbeil S, Aletaha D, Smolen JS. 
Evaluation of the appropriateness of composite disease activity measures for 
assessment of psoriatic arthritis. Ann Rheum Dis. 2010;69(3):546-9. 
18. 
Calin A, Nakache J-P, Gueguen A, Zeidler H, Mielants H, Dougados M. Defining 
disease activity in ankylosing spondylitis: is a combination of variables (Bath 
Ankylosing Spondylitis Disease Activity Index) an appropriate instrument? 
Rheumatology. 1999;38(9):878-82. 
19. 
National Ankylosing Spondylitis Society. Ankylosing Spondylitis  (Axial 
Spondyloarthritis) (AS) The Bath Indices 2004 [cited 2024 20 May]. Available from: 
https://nass.co.uk/wp-content/uploads/2018/09/Bath-Indices.pdf. 
20. 
Lukas C, Landewé R, Sieper J, Dougados M, Davis J, Braun J, et al. 
Development of an ASAS-endorsed disease activity score (ASDAS) in patients with 
ankylosing spondylitis. Annals of the Rheumatic Diseases. 2009;68(1):18. 
21. 
Fries JF, Spitz P, Kraines RG, Holman HR. Measurement of patient outcome in 
arthritis. Arthritis Rheum. 1980;23(2):137-45. 
22. 
Svensk Reumatologis Kvalitetsregister (SRQ). PER – Patientens Egen 
Registrering  [cited 2024 20 May]. Available from: https://srq.nu/om-per-patient/. 
23. 
Aletaha D, Smolen JS. The Simplified Disease Activity Index (SDAI) and 
Clinical Disease Activity Index (CDAI) to monitor patients in standard clinical care. 
Best Pract Res Clin Rheumatol. 2007;21(4):663-75. 
24. 
Lindqvist U. Psoriasisartrit Internetmedicin2022 [Available from: 
https://www.internetmedicin.se/reumatologi/psoriasisartrit. 

20 (20) 
Karolinska Institutet - Research protocol: Follow-up with patient-reported outcome measures for 
improved health related quality of life – Construct validity and responsiveness of EQ-5D-3L in 
patients with rheumatic disease 
25. 
Svensk Reumatologisk Förening. Riktlinjer för läkemedelsbehandling vid axial 
spondylartrit och psoriasisartrit 2022 2022 [cited 2024 8 maj]. Available from: 
https://svenskreumatologi.se/wp-content/uploads/2023/01/riktlinjer-axial-
spondylartrit-och-psoriasisartrit-220127.pdf. 
26. 
Lindqvist U. Axial spondylartrit (ankyloserande spondylit, pelvospondylit, 
Bechterews sjukdom) Internetmedicin 2022 [cited 2024 8 maj]. Available from: 
https://www.internetmedicin.se/reumatologi/axial-spondylartrit-ankyloserande-
spondylit-pelvospondylit-bechterews-sjukdom. 
27. 
Boonen A, van der Heijde D, Landewé R, van Tubergen A, Mielants H, 
Dougados M, et al. How do the EQ-5D, SF-6D and the well-being rating scale 
compare in patients with ankylosing spondylitis? Ann Rheum Dis. 2007;66(6):771-7. 
28. 
Bruce B, Fries JF. The Stanford Health Assessment Questionnaire: 
dimensions and practical applications. Health Qual Life Outcomes. 2003;1:20. 
29. 
Thyberg I, Dahlström Ö, Björk M, Arvidsson P, Thyberg M. Potential of the HAQ 
score as clinical indicator suggesting comprehensive multidisciplinary 
assessments: the Swedish TIRA cohort 8 years after diagnosis of RA. Clinical 
Rheumatology. 2012;31(5):775-83. 
30. 
Fritz CO, Morris PE, Richler JJ. Effect size estimates: current use, calculations, 
and interpretation. J Exp Psychol Gen. 2012;141(1):2-18. 
31. 
Coolican H. Research methods and statistics in psychology, 6th ed. New 
York, NY, US: Psychology Press; 2014. xiii, 773-xiii, p. 
32. 
Campbell M, Machin D, Walters S. Medical Statistics. 4 ed: Wiley-Blackwell; 
2007. 
33. 
Copay AG, Subach BR, Glassman SD, Polly DW, Jr., Schuler TC. Understanding 
the minimum clinically important difference: a review of concepts and methods. 
Spine J. 2007;7(5):541-6.