University of Groningen Hand eczema Oosterhaven, Jart

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University of Groningen

Hand eczema

Oosterhaven, Jart

DOI:

10.33612/diss.98242014

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Publication date:

2019

Link to publication in University of Groningen/UMCG research database

Citation for published version (APA):

Oosterhaven, J. (2019). Hand eczema: impact, treatment and outcome measures.

https://doi.org/10.33612/diss.98242014

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Chapter 11

Interpretability of the

Quality Of Life in Hand

Eczema Questionnaire

JAF Oosterhaven, RF Ofenloch, MLA Schuttelaar

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ABSTRACT

The Quality Of Life in Hand Eczema Questionnaire (QOLHEQ) is used to measure impairment

of health-related quality of life (HRQoL) in hand eczema. Here, we prospectively studied the

interpretability of international QOLHEQ scores at three time points: baseline, after 1-3 days

(T

₁

) and after 4-12 weeks (T

₂

). Adult patients with hand eczema completed the QOLHEQ and

anchor questions for overall assessment of HRQoL impairment. Interpretability of single

scores was assessed at baseline by defining severity bands based on agreement with the

anchor questions. Smallest detectable change (SDC) was calculated at T

₁

. Minimally important

change (MIC) of improvement was calculated at T

₂

using three methods: mean cut-off, receiver

operating curve (ROC) and 95% limit. N=294 adult patients were included (N=160 males, mean

age 44.9). The final proposed severity band of overall QOLHEQ single scores (κ-coefficient of

agreement, 0.431) was: not at all, 0-10; slightly, 11-39; moderately, 40-61; strongly, 62-86; very

strongly, ≥87. Separate overall severity bands were proposed for males and females, and the

four subscales of the QOLHEQ. The SDC in N=166 unchanged patients was 18.6 points. The

preferred MIC, obtained with the ROC method was 21.5 points. An overall QOLHEQ score of

≥ 22 is recommended as cut-off for a minimally important, real change.

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11 INTRODUCTION

The Quality Of Life in Hand Eczema Questionnaire (QOLHEQ) is a measurement instrument that

was developed with a group of international experts in cooperation with patients (Ofenloch

et al. 2014). It is used to measure impairment of health-related quality of life (HRQoL) in hand

eczema patients. The QOLHEQ was validated for national use in Germany and Japan (Minamoto

et al. 2018; Ofenloch et al. 2014). Furthermore, a cross-cultural validation was performed

involving six countries (Ofenloch et al. 2017), classifying the QOLHEQ as a third generation

measurement instrument for assessing HRQoL (Nijsten 2012). Now that the measurement

properties of the QOLHEQ are extensively studied, it is useful to obtain an understanding of

what QOLHEQ scores actually mean; especially regarding international scores from the

cross-cultural validation study. Also, it is useful to investigate what changes on the QOLHEQ and its

subscales constitute an important improvement, to aid clinical decision making and sample

size calculation of clinical trials. Interpretability is defined as ‘the degree to which one can assign

qualitative meaning (i.e. clinical or commonly understood connotations) to an instrument’s

quantitative scores or change in scores’ (Mokkink et al. 2010). In this study we aimed to assess

the interpretability of international QOLHEQ scores.

RESULTS

INTERPRETABILITY OF SINGLE SCORES

At baseline, N=294 patients were included in this study; see Table 1 for basic characteristics.

Clinical severity of hand eczema was also determined at baseline according to the ‘Photographic

guide for severity’ (Coenraads et al. 2005): almost clear, N=77 (26.2%); moderate, N=114

(38.8%); severe, N=81 (27.6%); very severe, N=22 (7.5%). The distribution of QOLHEQ overall

scores stratified by Global anchor categories for HRQoL impairment is shown in Figure 1. All

anchor questions correlated > 0.50 with the QOLHEQ overall and subscale scores. In total, 18

bands for HRQoL impairment were tested for the overall QOLHEQ; 8 bands were tested both

for the Symptoms and Emotions subscales; 4 bands for the Functioning subscale; and 18 bands

for the Treatment and Prevention subscale. See Table 2 for the final chosen bands. See Table

S2-15 and Figure S2-5 in the Supplementary Material for details on the testing of single scores.

overviewofqolheqoverallscoresfallingoutsidetheproposedbanding

N=29 patients (9.9%) had a Global anchor score > 1 point outside of that predicted by the final

overall QOLHEQ band. There were 81 (27.6%) patients with an actual Global anchor score 1

point lower than the final QOLHEQ band predicted. In this group there were significantly more

females (P < 0.05). There were 51 patients (17.3%) with an actual Global anchor score 1 point

higher than the final overall QOLHEQ band predicted. In this group there were significantly

more males (P < 0.01). Because of this, we decided to propose separate bandings for males

and females for the overall QOLHEQ (see Table 2). For subscales, there were no sex and age

distribution differences between patients falling within the proposed banding and those

falling outside it. Only for the Treatment and Prevention scale there were significantly more

females in the group with an anchor score 1 point lower than the final band predicted and

significantly more males in the group with an anchor score 1 point higher. For the sake of

clarity and simplicity, we decided not to propose separate bandings for males and females for

only this subscale.

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HRQoL impaired _{Coefficient of} agreement (κ) with anchor question Correlation (r) with anchor question Not at all Slightly Moderately Strongly Very strongly

QOLHEQ overall 0 – 10 11 – 39 40 – 61 62 – 86 ≥ 87 0.431 0.58 QOLHEQ overall (M) 0 – 10 11 – 35 36 – 53 54 – 83 ≥ 84 0.461 0.61 QOLHEQ overall (F) 0 – 13 14 – 40 41 – 61 62 – 86 ≥ 87 0.407 0.54 Symptoms subscale 0 1 – 8 9 – 13 14 – 19 ≥ 20 0.529 0.69 Emotions subscale 0 – 6 7 – 12 13 – 20 21 – 26 ≥ 27 0.531 0.71 Functioning subscale 0 – 2 3 – 9 10 – 15 16 – 24 ≥ 25 0.564 0.73 Treatment and Prevention

subscale 0 – 6 7 – 9 10 – 14 15 – 18 ≥ 19 0.440 0.58 See Table S2-15 in the Supplementary Material for all tested bands. HRQoL, health-related quality of life; M, males; F, females.

Table 1 Basic characteristics of study population.

Males (n = 160) Females (n = 134) Total (n = 294)

Age (years) Mean (SD) 45.0 (14.5) 44.8 (17.5) 44.9 (15.9) Range 18–74 18–83 18–83 QOLHEQ overall Mean (SD) 38.8 (21.1)1 _{48.8 (22.3)}1 _{43.3 (22.2)} Range 2 – 96 0 – 103 0 – 103 Symptoms subscale Mean (SD) 10.9 (5.3)1 _{13.1 (5.4)}1 _{11.9 (5.5)} Range 0 – 23 0 – 25 0 – 25 Emotions subscale Mean (SD) 9.6 (6.6)1 _{12.2 (7.1)}1 _{10.8 (7.0)} Range 0 – 27 0 – 30 0 – 30 Functioning subscale Mean (SD) 9.9 (7.0)1 _{13.2 (7.7)}1 _{11.4 (7.5)} Range 0 – 28 0 – 30 0 – 30 Treatment and Prevention subscale

Mean (SD) 8.4 (4.7)1 _{10.4 (4.8)}1 _{9.3 (4.9)}

Range 0 – 20 0 – 21 0 – 21 HRQoL impaired – Global Not at all, No. (%) 32 (20.0) 30 (22.4) 62 (21.1) Slightly, No. (%) 56 (35.0) 31 (23.1) 87 (29.6) Moderately, No. (%) 42 (26.3) 42 (31.3) 84 (28.6) Strongly, No. (%) 24 (15.0) 25 (18.7) 49 (16.7) Very strongly, No. (%) 6 (3.8) 6 (4.5) 12 (4.1) HRQoL impaired – Symptoms1

Not at all, No. (%) 3 (1.9) 6 (4.5) 9 (3.1) Slightly, No. (%) 55 (34.4) 22 (16.4) 77 (26.2) Moderately, No. (%) 40 (25.0) 39 (29.1) 79 (26.9) Strongly, No. (%) 43 (26.9) 53 (39.6) 96 (32.7) Very strongly, No. (%) 19 (11.9) 14 (10.4) 33 (11.2) HRQoL impaired – Emotions

Not at all, No. (%) 68 (42.5) 45 (33.6) 113 (38.4) Slightly, No. (%) 39 (24.4) 33 (24.6) 72 (24.5) Moderately, No. (%) 29 (18.1) 28 (20.9) 57 (19.4) Strongly, No. (%) 18 (11.3) 23 (17.2) 41 (13.9) Very strongly, No. (%) 6 (3.8) 5 (3.7) 11 (3.7) HRQoL impaired – Functioning

Not at all, No. (%) 38 (23.8) 24 (17.9) 62 (21.1) Slightly, No. (%) 44 (27.5) 31 (23.1) 75 (25.5) Moderately, No. (%) 41 (25.6) 29 (21.6) 70 (23.8) Strongly, No. (%) 24 (15.0) 34 (25.4) 58 (19.7) Very strongly, No. (%) 13 (8.1) 16 (11.9) 29 (9.9) HRQoL impaired – Treatment and Prevention

Not at all, No. (%) 56 (35.0) 42 (31.3) 98 (33.3) Slightly, No. (%) 52 (32.5) 37 (27.6) 89 (30.3) Moderately, No. (%) 33 (20.6) 35 (26.1) 68 (23.1) Strongly, No. (%) 13 (8.1) 17 (12.7) 30 (10.2) Very strongly, No. (%) 6 (3.8) 3 (2.2) 9 (3.1)

1_{Significant difference between males and females (P < 0.01). HRQoL, health-related quality of life; QOLHEQ,}

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11

HRQoL impaired _{Coefficient of} agreement (κ) with

anchor question

Correlation (r) with anchor

question Not at all Slightly Moderately Strongly Very strongly

QOLHEQ overall 0 – 10 11 – 39 40 – 61 62 – 86 ≥ 87 0.431 0.58 QOLHEQ overall (M) 0 – 10 11 – 35 36 – 53 54 – 83 ≥ 84 0.461 0.61 QOLHEQ overall (F) 0 – 13 14 – 40 41 – 61 62 – 86 ≥ 87 0.407 0.54 Symptoms subscale 0 1 – 8 9 – 13 14 – 19 ≥ 20 0.529 0.69 Emotions subscale 0 – 6 7 – 12 13 – 20 21 – 26 ≥ 27 0.531 0.71 Functioning subscale 0 – 2 3 – 9 10 – 15 16 – 24 ≥ 25 0.564 0.73 Treatment and Prevention

subscale 0 – 6 7 – 9 10 – 14 15 – 18 ≥ 19 0.440 0.58 See Table S2-15 in the Supplementary Material for all tested bands. HRQoL, health-related quality of life; M, males; F, females.

Figure 1 Box-and-whisker plots of the distribution of the Quality Of Life in Hand Eczema Questionnaire

(QOLHEQ) overall score by Global anchor for health-related quality of life (HRQoL) impairment. Boxes represent 25-75th_{percentile with the middle line representing the median. The ends of the whiskers represent 10-90}th

percentile. Outliers are plotted as circles beyond the whiskers.

Table 2 Final bands for health-related quality of life impairment expressed as single-scores on the Quality Of

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INTERPRETABILITY OF CHANGE SCORES

smallestdetectablechange

The SDC of the QOLHEQ was calculated based on the analysis of N=166 unchanged patients

on the Global anchor question of change between T

₀

and T

₁

. This gave the following results:

• QOLHEQ overall: SEM

_agreement

= 6.7 points; SDC = 18.6 points.

• Symptoms subscale: SEM

_agreement

= 2.0 points; SDC = 5.5 points.

• Emotions subscale: SEM

_agreement

= 2.3 points; SDC = 6.4 points.

• Functioning subscale: SEM

_agreement

= 2.6 points; SDC = 7.3 points.

• Treatment and Prevention subscale: SEM

_agreement

= 1.8 points; SDC = 4.9 points.

minimallyimportantchange

The correlation between the change in QOLHEQ score and the change in the global anchor

question for change in HRQoL impairment between T

₀

and T

₂

was r = 0.51. The correlations for

the subscales were:

• Symptoms: r = 0.55.

• Emotions: r = 0.44.

• Functioning: r = 0.52.

• Treatment and Prevention: r = 0.28.

Therefore, the anchor questions were considered to be acceptable anchors for

determination of the MIC, except for the anchor question for the Treatment and Prevention

subscale (Cella et al. 2002; Revicki et al. 2008). We did determine the MIC for this scale, but the

lack of good correlation between the change anchor and the change score must be seriously

considered when using the values for the Treatment and Prevention subscale. The correlations

were not influenced by sex or age, except for the correlation between sex and the Emotions

subscale where there was a significant difference between males and females (P < 0.01). For

the sake of clarity and simplicity, we decided not to calculate separate MICs for males and

females for only this subscale. Calculation of the MIC of improvement according to our three

used methods resulted in the values shown in Table 3. The distribution of the overall QOLHEQ

change scores was visualized as anchor-based distribution for improved and unchanged

patients, along with the three MIC values. For this, along with details on calculation of the

MIC for the QOLHEQ and subscales, see Table S16-20 and Figure S6-10 in the Supplementary

Material.

Table 3 Minimally important change (MIC) indicated as points improvement on the Quality Of Life in Hand

Eczema Questionnaire (QOLHEQ); defined using three methods.

MIC method QOLHEQ overall Symptoms Emotions Functioning Treatment and Prevention1

Mean cut-off 12.6 3.0 2.9 4.5 0.5 ROC curve 21.5 3.5 3.5 5.5 2.5 95% limit 22.5 7.6 9.6 9.3 6.5 MIC values are presented for the overall QOLHEQ and its subscales. ROC, receiver operating characteristic.

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11

floorandceilingeffects

For the overall QOLHEQ, the Symptoms subscale and the Treatment and Prevention subscale,

<9% of patients scored the highest score or the lowest score at all three time points. For

the Emotions subscale and Functioning subscale, respectively 17.6% and 19.5% of patients

reached the lowest score at T

₂

. On the anchor question for Emotions at T

₂

, all these patients

indicated that they were ‘not at all’ impaired in their HRQoL. For the Functioning anchor at T

₂

only one patient indicated a ‘slight’ impairment in HRQoL, all other patients reported they were

‘not at all’ impaired. Therefore, we consider these scores as truly low and do not consider these

subscales to have a floor effect. There were no ceiling effects for the Emotions and Functioning

subscale. For details, see Table S21 in the Supplementary Material.

DISCUSSION

In this study we presented values to aid interpretability of single scores and change scores

of international QOLHEQ values. This will contribute to the comparison of QOLHEQ values

obtained in different countries when these values are (re)scored using the scoring structure

from the cross-cultural validation study (Ofenloch et al. 2017). The QOLHEQ can also be

used to assess HRQOL impairments in four specific domains. For these domains (subscales)

interpretability values were reported separately.

Differences were found between the three values obtained for the MIC in this study. The

best method to define the MIC has not yet been determined. However, of the anchor-based

methods, the ROC method was suggested as a good choice because it is aimed at minimizing

misclassification of patients who are importantly improved and patients who are unchanged

(Terwee et al. 2010).

The ROC method gave a MIC value of 21.5 points for the overall QOLHEQ, while the SDC

was 18.6 points. This means that a change in QOLHEQ score of 22 or higher can be considered

an ‘important’ change for patients, as well as a real change beyond measurement error. We

therefore recommend using a score of ≥ 22 as cut-off for a minimally important, real change.

For subscales, the cut-offs are based on the SDC, because the established MIC was smaller

than the SDC. Therefore, the MIC is meaningless and the SDC is the smallest value beyond

measurement error closest to it. Thus, the cut-offs are: Symptoms, 6 points; Emotions, 7 points;

Functioning, 8 points; Treatment and Prevention, 5 points.

Although internationally values can now be compared, still only in three countries

(Germany, Japan and the Netherlands (manuscript in preparation)) validation studies have

been performed to assess measurement properties and precision of QOLHEQ measurements

specifically for that country (Minamoto et al. 2018; Ofenloch et al. 2014). To use the QOLHEQ in

a new language version, a validation study should still be performed (Oosterhaven et al. 2017).

Ultimately, results from national studies should both report national values and international

values.

It is important to realize that the values presented in the current study are particularly

valid for Germany, Japan and the Netherlands, as for Sweden, Finland and Turkey several

subscales were adjusted for differential item functioning (DIF) (Ofenloch et al. 2017). This

means that the interpretability values presented here might be slightly deviating from true

values for these countries. However, until interpretability studies are performed with patients

specifically from these countries we advise to use the values presented in the current study for

international comparison.

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subsequently indicating whether this change was important to them, the MIC is considered

from the perspective of the patient. For patient reported outcomes (PROs), this is highly

recommended (de Vet et al. 2011).

A limitation of this study is that only one anchor question was used for each domain,

while it is now recommended to use multiple anchors (Prinsen et al. 2018). This interpretability

study was part of a larger validation study. The use of only one anchor was chosen to minimize

the burden on patients who had to complete many questionnaires. Another limitation is that

some correlations between the anchor questions and scores were only modest, similar to what

was found for other patient-reported measures in dermatology (Charman et al. 2013; Hongbo

et al. 2005; Vakharia et al. 2018). This most likely means that there are aspects to the anchor

questions that are not fully covered by the items in the QOLHEQ. A different choice of anchor

or a different wording of the anchor question might yield different results. However, for all

but one subscale (the Treatment and Prevention change score), the correlations were within

recommended values to perform a proper interpretability study. Therefore, clinicians can be

fairly confident that the bands accurately reflect the degree of impact experienced by the

patient. A third limitation is that patients with very severe hand eczema are underrepresented

in this study (7.5%). However, this adequately reflects our clinical experience, as we encounter

very severe hand eczema less often than milder severities. A final limitation is that answers to

the anchor questions were only provided by Dutch patients. In the cross-cultural validation

study it was already assessed whether patients with the same level of HRQoL impairment

respond similarly to the items from the QOLHEQ. However, the same might not necessarily be

true for the anchor questions. This needs to be taken into consideration when using the values

presented in the current study, as it may influence generalizability.

In conclusion, we suggest using the QOLHEQ as measurement instrument for PROs

in studies involving hand eczema patients, as it is extensively validated and now tested for

interpretability. In this regard, the QOLHEQ might also be considered for incorporation into a

core-outcome-set for hand eczema, which is currently under development (Rönsch et al. 2019).

PATIENTS AND METHODS

STUDY POPULATION AND DESIGN

This prospective study was performed at the department of Dermatology in the University

Medical Center Groningen (UMCG); a tertiary referral center for hand eczema. The study

was part of a longitudinal validation study of the Dutch version of the QOLHEQ, for which

we previously published a guideline (Oosterhaven et al. 2017). The design is in accordance

with guidelines by the COnsensus-based Standards for the selection of health Measurement

INstruments (COSMIN) (Mokkink et al. 2010; de Vet et al. 2011). In short, we included adult

patients (≥18 years) with hand eczema of all clinical severities, lasting at least one week, as

diagnosed by a dermatologist according to current guidelines (Diepgen et al. 2015; Menné et

al. 2011). Patients completed the QOLHEQ and multiple anchor questions at three time points:

at baseline (T

₀

); after 1-3 days (T

₁

) to identify as many unchanged patients as possible; and

after 4 to 12 weeks (T

₂

) to obtain a sample of deteriorated, unchanged and improved patients.

In the time between T

₀

and T

₂

, patients were allowed to use any form of treatment for their

hand eczema. See Figure S1 in the Supplementary Material for a study flow chart. Recruitment

was done between March 2017 and December 2018. The Medical Ethical Review Board of the

UMCG confirmed that this study did not fall under the scope of the Medical Research Involving

Human Subjects Act (reference: METc 2014/391).

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11 STUDIED INSTRUMENT

The QOLHEQ is an instrument with thirty questions covering four subscales (Ofenloch et al.

2014). It measures overall HRQoL impairment and for each domain (subscale) separately:

Symptoms (7 questions); Emotions (8 questions); Functioning (8 questions); Treatment and

Prevention (7 questions). Response categories are never, rarely, sometimes, often, always. These

are initially scored as 0-1-2-3-4. In the cross-cultural validation study a rescoring of certain items

was defined using methods within the framework of item response theory. Also, question

number 18 from the Treatment and Prevention subscale, concerning ‘visiting physicians’, was

removed from the scoring (Ofenloch et al. 2017). See Table S1 in the Supplementary Material

for the rescoring, which was also used in the current study.

ANCHORS

The following single-score anchor questions were used at T

₀

to assess the degree of HRQoL

impairment perceived by patients (Oosterhaven et al. 2017). In a cognitive interview pilot,

these anchor questions were tested for content validity in hand eczema patients with varying

disease severity. Answer categories were equal for all questions: not at all, slightly, moderately,

strongly, very strongly.

• Global (overall): How did your hand eczema bother you in your overall health state in

the past seven days?

• Symptoms subscale: How did the symptoms of your hand eczema (like pain, itch,

fissuring, redness) bother you in the past seven days?

• Emotions subscale: How strong did your hand eczema affect your emotional

well-being (e.g. making you angry, frustrated, or anxious about the future) in the past

seven days?

• Functioning subscale: How strong did your hand eczema affect your functioning (e.g.

performing your (home)work or doing hobbies) in the past seven days?

• Treatment and Prevention subscale: How did treatment and prevention of your hand

eczema bother you in the past seven days?

At T

₁

and T

₂

anchor questions for change in impairment were asked. Answer categories

were: much improvement, moderate improvement, minor improvement, no change, minor

deterioration, moderate deterioration, much deterioration.

• Global (overall): Overall, has there been any change in how your hand eczema bothers

you since the last time you completed the QOLHEQ?

• Symptoms subscale: Has there been any change in how the symptoms of your

hand eczema (like pain, itch, fissuring, redness) bother you since the last time you

completed the QOLHEQ?

• Emotions subscale: Has there been any change in how strongly your hand eczema

affects your emotional well-being (e.g. making you angry, frustrated or anxious about

the future) since the last time you completed the QOLHEQ?

• Functioning subscale: Has there been any change in how strong your hand eczema

affects your functioning (e.g. performing your (home)work or doing hobbies) since

the last time you completed the QOLHEQ?

• Treatment and Prevention subscale: Has there been any change in how the treatment

and prevention of your hand eczema bother you since the last time you completed

the QOLHEQ?

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For each of the change anchors, a follow-up question was asked to determine the

importance of a change:

• If you indicated a change (improvement or deterioration), was this change important

for you? (Answer categories: no, yes).

INTERPRETABILITY ASSESSMENTS

singlescores

We used an anchor-based method to define severity bands (stratified scores indicating

thresholds of severity categories) for the QOLHEQ with scores obtained at T

₀

, using the

single-score anchor questions. Several numerical cut-offs of the QOLHEQ single-score and subscale single-scores

were tested against the impairment indicated on the anchor questions using a weighted kappa

(κ) coefficient of agreement to determine level of agreement between these. Numerical cut-off

points were considered based on QOLHEQ scores that corresponded to a one-step increase

in mean, median and/or mode on the anchor (see Supplementary Material for additional

information). Sensitivity analysis consisted of tests for differences in sex and age distribution

between patients of whom severity could be predicted based on the final chosen band and

those of whom scores disagreed with the predicted severity according to that band (Charman

et al. 2013; Chopra et al. 2017; Hongbo et al. 2005). In order not to underestimate the burden

for patients when using the banding, we investigated the bands with the highest κ-values

and those within a distance of 0.01. The final band chosen was that for which the amount of

patients reporting a higher impairment according to the anchor question compared to the

band was lowest.

changescores

Smallest detectable change (SDC) is defined as “the smallest change in score that can be

detected by the instrument, beyond measurement error” (de Vet et al. 2011). The SDC for the

QOLHEQ and subscales was determined in unchanged patients at T1, as identified using the

Global change anchor. For this, the standard error of measurement (SEM

_agreement

) was obtained

using the square root of the within-subject total variance of an analysis of variance (ANOVA)

analysis. The SDC was then calculated with: SDC = 1.96 * √2 * SEM

_agreement

(de Vet et al. 2006).

Minimally important change (MIC) is defined as “the smallest change in the construct

to be measured which patients perceive as important” (de Vet et al. 2011). The MIC for the

QOLHEQ score and subscales was determined in changed patients at T

₂

, as identified using

the anchor questions for change. The anchor questions were deemed appropriate to use as

anchor for determination of the MIC if their correlation with the QOLHEQ score was at least

> 0.30, but preferably > 0.50 (Cella et al. 2002; Revicki et al. 2008). Change scores were calculated

for the QOLHEQ and anchor questions by subtracting the score at T

₀

from the score at T

₂

. Thus,

negative scores correspond to deterioration and positive scores to improvement in HRQoL.

Patients were stratified according to their degree of change, taking into account the indication

of their change as important/not important (see above). Three MIC values were determined for

the QOLHEQ overall and subscale scores:

• The MIC based on the mean change in QOLHEQ value that corresponds with a

one-step important change on the anchor questions for change.

• The MIC of the receiver operating characteristic (ROC) cut-off point, indicating the

point closest to the upper-left corner, where the sum of percentages of correctly

classified patients is highest.

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11 importantly changed’) patients, which corresponds to mean

_change

+ 1.645 * SD

_change

of

this group (or strictly to the mean

_difference

and SD

_difference

since this concerns theoretically

unchanged patients).

These values for the MIC of the QOLHEQ change score were graphically presented using

the anchor-based MIC distribution method (de Vet et al. 2007). We only determined the MIC for

improved patients. Too few patients (N < 50) deteriorated compared to baseline to draw sound

conclusions about the MIC for deterioration.

floorandceilingeffects

It was determined what proportion of patients achieved the highest and lowest possible scores

on the QOLHEQ. Floor and ceiling effects were considered to be present if the lowest or highest

QOLHEQ score was achieved by > 15% of patients (McHorney and Tarlov 1995).

DATA ANALYSIS

No sample size calculation was performed. A general recommendation for interpretability

studies is to use a minimum of 50, but preferably at least 100 patients. With a minimum of

N=50 patients in the smallest subgroup to calculate the MIC using the ROC method (de Vet et

al. 2011). This study meets these recommendations. Spearman’s rho (r) was used to calculate

correlation. The χ

2

_{-test and Student’s t-test were used to calculate differences between groups.}

In eight cases, the QOLHEQ was missing one item. For these, the value 0 was imputed (Ofenloch

et al. 2014). At T

₁

, four cases had skipped a whole page, containing ten QOLHEQ items. These

four cases were excluded from analysis. Analyses were performed with IBM SPSS Statistics for

Windows, Version 23.0 (IBM Corp. Armonk, NY), and GraphPad Prism version 7.02 for Windows

(GraphPad Software, La Jolla California USA, www.graphpad.com).

DATA AVAILABILITY

The authors confirm that the data supporting the findings of this study are available within the

article and its supplementary materials.

CONFLICT OF INTEREST

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Charman CR, Venn AJ, Ravenscroft JC, Williams HC. Translating Patient-Oriented Eczema Measure (POEM) scores into clinical practice by suggesting severity strata derived using anchor-based methods. Br. J. Dermatol. 2013;169(6):1326–32.

Chopra R, Vakharia PP, Sacotte R, Patel N, Immaneni S, White T, et al. Severity strata for Eczema Area and Severity Index ( EASI ), modified EASI , Scoring Atopic Dermatitis ( SCORAD ), objective SCORAD , Atopic Dermatitis Severity Index and body surface area in adolescents and adults with atopic dermatitis. Br. J. Dermatol. 2017;177(5):1316– 21.

Coenraads PJ, Van Der Walle H, Thestrup-Pedersen K, Ruzicka T, Dreno B, De La Loge C, et al. Construction and validation of a photographic guide for assessing severity of chronic hand dermatitis. Br. J. Dermatol. 2005;152(2):296–301.

Diepgen TL, Andersen KE, Chosidow O, Coenraads PJ, Elsner P, English J, et al. Guidelines for diagnosis, prevention and treatment of hand eczema. J. der Dtsch. Dermatologischen Gesellschaft. 2015;13(1):e1-22.

Hongbo Y, Thomas CL, Harrison MA, Salek MS, Finlay AY. Translating the science of quality of life into practice: What do dermatology life quality index scores mean? J. Invest. Dermatol. 2005;125(4):659–64.

McHorney CA, Tarlov AR. Individual-patient monitoring in clinical practice: are available health status surveys adequate? Qual. Life Res. 1995;4(4):293–307.

Menné T, Johansen JD, Sommerlund M, Veien NK. Hand eczema guidelines based on the Danish guidelines for the diagnosis and treatment of hand eczema. Contact Dermatitis. 2011;65(1):3–12.

Minamoto K, Diepgen TL, Sato K, Noguchi H, Yamashita N, Yoshimura K, et al. Quality of Life in Hand Eczema Questionnaire: Validation of the Japanese version of a disease-specific measure of quality of life for hand eczema patients. J. Dermatol. 2018;45(11):1301–5.

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. J. Clin. Epidemiol. 2010;63(7):737–45.

Nijsten T. Dermatology Life Quality Index: Time to Move Forward. J. Invest. Dermatol. 2012;132(1):11–3. Ofenloch RF, Oosterhaven JAF, Susitaival P, Svensson Å, Minamoto K, Onder M, et al. Cross-Cultural Validation of the Quality of Life in Hand Eczema Questionnaire (QOLHEQ). J. Invest. Dermatol. 2017;137(7):1454–60. Ofenloch RF, Weisshaar E, Dumke AK, Molin S, Diepgen TL, Apfelbacher C. The Quality of Life in Hand Eczema Questionnaire (QOLHEQ): validation of the German version of a new disease-specific measure of quality of life for patients with hand eczema. Br. J. Dermatol. 2014;171(2):304–12.

Oosterhaven JAF, Schuttelaar MLA, Apfelbacher C, Diepgen TL, Ofenloch RF. Guideline for translation and national validation of the Quality Of Life in Hand Eczema Questionnaire (QOLHEQ). Contact Dermatitis. 2017;77(2):106– 15.

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. Qual. Life Res. 2018;27(5):1147–57.

Revicki D, Hays RD, Cella D, Sloan J. Recommended methods for determining responsiveness and minimally important differences for patient-reported outcomes. J. Clin. Epidemiol. 2008;61(2):102–9.

Rönsch H, Apfelbacher C, Brans R, Matterne U, Molin S, Ofenloch R, et al. Which outcomes have been measured in hand eczema trials? A systematic review. Contact Dermatitis. 2019;80(4):201–7.

Terwee CB, Roorda LD, Dekker J, Bierma-Zeinstra SM, Peat G, Jordan KP, et al. Mind the MIC: large variation among populations and methods. J. Clin. Epidemiol. 2010;63(5):524–34.

Vakharia PP, Chopra R, Sacotte R, Patel N, Immaneni S, White T, et al. Severity strata for five patient-reported outcomes in adults with atopic dermatitis. Br. J. Dermatol. 2018;178(4):925–30.

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determined by a visual method integrating an anchor-based and a distribution-based approach. Qual. Life Res. 2007;16(1):131–42.

de Vet HC, Terwee CB, Knol DL, Bouter LM. When to use agreement versus reliability measures. J. Clin. Epidemiol. 2006;59(10):1033–9.

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SUPPLEMENTARY MATERIAL

Figure S1 Study flow diagram. a_{This case had almost clear hand eczema (assessed by both study personnel and}

patient) but had answered all items of the QOLHEQ with ‘always’. b_{N=4 patients were excluded for T}

1 analyses,

because they had skipped a whole page of the QOLHEQ, thus bringing the total to N=166. QOLHEQ, Quality Of Life in Hand Eczema Questionnaire.

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11

Table S1 Items in the Quality Of Life in Hand Eczema Questionnaire (QOLHEQ) with rescored international

values.1

Item No. Short description of the item (never – rarely – sometimes – often –always)Raw score

Symptoms 1 pain 0 – 1 – 2 – 3 – 4 6a itch _{0 – 1 – 1 – 2 – 3} 9 affecting sleep 0 – 1 – 2 – 3 – 4 11a fissuring _{0 – 1 – 1 – 2 – 3} 20 redness 0 – 1 – 2 – 3 – 4 23 bleeding 0 – 1 – 2 – 3 – 4 28* dryness 0 – 1 – 1 – 2 – 3 Emotions 5 frustrated 0 – 1 – 2 – 3 – 4 8 annoying 0 – 1 – 2 – 3 – 4 10a anxious _{0 – 1 – 1 – 2 – 2} 16 hide hands 0 – 1 – 2 – 3 – 4 19 sad/depressed 0 – 1 – 2 – 3 – 4 21 irritated 0 – 1 – 2 – 3 – 4 27 embarrassed 0 – 1 – 2 – 3 – 4 30 nervous 0 – 1 – 2 – 3 – 4 Functioning 2 job 0 – 1 – 2 – 3 – 4 3 homework 0 – 1 – 2 – 3 – 4 12 hobbies 0 – 1 – 2 – 3 – 4 14 washing 0 – 1 – 2 – 3 – 4 15 dressing 0 – 1 – 2 – 3 – 4 17 social contacts 0 – 1 – 2 – 3 – 4 25 family 0 – 1 – 2 – 3 – 4 29 partner 0 – 1 – 2 – 3 – 4

Treatment & Prevention

4a wearing gloves _{0 – 1 – 1 – 2 – 3} 7 time consuming 0 – 1 – 2 – 3 – 4 13 creams 0 – 1 – 2 – 3 – 4 18b visiting physicians _{0 – 0 – 0 – 0 – 0} 22 avoiding contact 0 – 1 – 2 – 3 – 4 24 side effects 0 – 1 – 2 – 3 – 4 26 costs 0 – 1 – 2 – 3 – 4

a_{Scoring structure adjusted.}b_{Item was removed from the scoring of the scale.}

REFERENCES

1. Ofenloch RF, Oosterhaven JAF, Susitaival P, et al. Cross-Cultural Validation of the Quality of Life in Hand Eczema Questionnaire (QOLHEQ). J Invest Dermatol. 2017;137(7):1454-1460.

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DETAILS ON SINGLE SCORE INTERPRETABILITY FOR THE QUALITY OF LIFE IN HAND

ECZEMA QUESTIONNAIRE (QOLHEQ)

ELABORATION ON THE ANCHOR-BASED APPROACH

To illustrate the anchor-based approach, we here elaborate on the selection of potential

thresholds for quality of life impairment, using Table S2 as an example. A mean, median and

mode anchor score of 1 (slightly) first occurred at a QOLHEQ score of 0, but that did not make

sense to us. Therefore, we looked at the next instance, which was at a score of 2. However,

QOLHEQ scores of 6-10 were associated with mean, median and mode scores of 0 or 0.5. A

QOLHEQ of 11 was the next score to be associated with a mean, median and mode anchor

of 1. Therefore, a QOLHEQ score of 11 was also considered as a potential threshold for slight

quality of life impairment. Another of these instances occurred at a QOLHEQ score of 13.

After this, the majority of mean, median and mode scores turned to ≥1.0, which is why we

started looking for the next instance of a mean, median and mode score of 2, to identify

the threshold for moderate impairment. In Table S3, the identified and tested thresholds

are reported. When incidentally a mean, median and mode increase of 1 was found, but the

scores around this QOLHEQ score all had a lower mean, median and mode, we disregarded

that score as potential threshold, knowing it would provide a low kappa and therefore high

misclassification.

OVERALL QOLHEQ SCORES

overallqolheq

–

mean

,

medianandmodeoftheglobalanchorperscore

Table S2 Number of patients with each total Quality Of Life in Hand Eczema Questionnaire (QOLHEQ) score

encountered in this study and corresponding mean, median and mode of the Global anchor question scores: 0 (‘not at all’) to 4 (‘very strongly’).

QOLHEQ score

(baseline) Number of cases

Global anchor question (baseline) (indicating global HRQoL impairment)

Mean Median Mode Not at all Slightly Moderately Strongly stronglyVery

0 2 1 1 1.00 1 0/2 1 1 1 0.00 0 0 2 1 1 1.00 1 1 4 1 1 2.00 2 2 6 2 2 0.00 0 0 7 4 2 2 0.50 0.5 0/1 8 2 2 0.00 0 0 9 5 3 1 1 0.60 0 0 10 4 4 0.00 0 0 11 1 1 1.00 1 1 12 2 2 0.00 0 0 13 6 1 5 0.83 1 1 14 4 2 2 0.50 0.5 0/1 15 3 1 1 1 1.00 1 0/1/2 16 3 1 1 1 1.00 1 0/1/2 17 3 1 2 1.67 2 2 18 3 2 1 0.33 0 0

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11

19 3 2 1 0.67 0 0 20 7 2 4 1 0.86 1 1 21 3 1 1 1 1.00 1 0/1/2 22 2 1 1 0.50 0.5 0/1 23 4 1 1 2 1.25 1.5 2 24 2 1 1 1.00 1 0/2 25 2 1 1 1.50 1.5 0/3 26 4 2 1 1 0.75 0.5 0 27 3 2 1 1.33 1 1 28 4 3 1 1.25 1 1 29 3 1 2 0.67 1 1 30 6 4 1 1 1.50 1 1 31 4 2 1 1 0.75 0.5 0 32 2 1 1 1.50 1.5 1/2 33 4 1 1 2 1.25 1.5 2 34 3 1 2 0.67 1 1 35 7 2 4 1 0.86 1 1 36 5 2 1 2 1.00 1 0/2 37 1 1 1.00 1 1 38 5 2 2 1 1.80 2 1/2 39 5 1 4 0.80 1 1 40 5 2 2 1 1.80 2 1/2 41 3 2 1 2.33 2 2 42 6 2 4 1.67 2 2 43 5 1 2 1 1 1.40 1 1 44 5 1 2 1 1 1.40 1 1 45 4 2 2 1.00 1 0/2 46 8 1 1 3 3 2.00 2 2/3 47 5 1 2 2 1.20 1 1/2 48 7 1 2 3 1 1.71 2 2 49 7 3 3 1 1.71 2 1/2 50 1 1 0.00 0 0 51 3 1 2 0.67 1 1 52 9 4 3 2 1.78 2 1 53 4 1 2 1 1.00 1 1 54 3 1 1 1 1.67 2 0/2/3 55 5 2 2 1 1.80 2 1/2 56 8 1 1 2 4 2.13 2.5 3 57 8 2 1 3 2 1.63 2 2 58 3 3 2.00 2 2 59 6 1 3 2 2.17 2 2 60 3 1 2 1.67 2 2 61 3 1 1 1 2.33 2 1/2/4 62 3 2 1 3.33 3 3 Table S2 Continued

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63 2 1 1 2.00 2 1/3 64 5 1 2 2 2.60 2 2/4 65 3 2 1 2.33 2 2 66 2 1 1 1.00 1 0/2 67 3 2 1 2.33 2 2 68 2 1 1 1.50 1.5 1/2 69 2 1 1 2.50 2.5 2/3 71 2 1 1 2.50 2.5 2/3 72 1 1 1.00 1 1 74 3 3 3.00 3 3 75 3 1 2 2.67 3 3 76 3 3 3.00 3 3 77 1 1 3.00 3 3 78 1 1 3.00 3 3 79 3 2 1 2.33 2 2 80 1 1 0.00 0 0 82 2 1 1 3.00 3 2/4 83 1 1 3.00 3 3 85 1 1 3.00 3 3 86 1 1 0.00 0 0 87 4 1 3 3.75 4 4 89 1 1 3.00 3 3 91 1 1 3.00 3 3 93 3 1 2 3.67 4 4 95 1 1 3.00 3 3 96 1 1 4.00 4 4 103 1 1 3.00 3 3 Total 294 62 87 84 49 12 HRQoL, health-related quality of life.

Table S2 Continued

2 1 1 1.00 1 1 4 1 1 2.00 2 2 6 2 2 0.00 0 0 7 4 2 2 0.50 0.5 0/1 8 2 2 0.00 0 0 9 4 2 1 1 0.75 0.5 0 10 3 3 0.00 0 0 11 1 1 1.00 1 1 12 1 1 0.00 0 0 13 4 4 1.00 1 1

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11

overallqolheq

–

testedseveritybands

Table S3 Kappa coefficients of agreement for different proposed sets of the Quality Of Life in Hand Eczema

Questionnaire (QOLHEQ) impairment bands.

Band no.

Possible QOLHEQ total score bandings

(indicating global HRQoL impairment) Coefficient of _{agreement (κ) with} Global anchor question Not at all Slightly Moderately Strongly Very strongly

1 0-1 2-37 38-61 62-86 ≥87 0.379 2 0-10 11-37 38-61 62-86 ≥87 0.420 3 0-12 13-37 38-61 62-86 ≥87 0.426 4 0-1 2-39 40-61 62-86 ≥87 0.391 5 0-10 11-39 40-61 62-86 ≥87 0.431 6 0-12 13-39 40-61 62-86 ≥87 0.437 7 0-1 2-37 38-68 69-86 ≥87 0.369 8 0-10 11-37 38-68 69-86 ≥87 0.411 9 0-12 13-37 38-68 69-86 ≥87 0.417 10 0-1 2-39 40-68 69-86 ≥87 0.381 11 0-10 11-39 40-68 69-86 ≥87 0.423 12 0-12 13-39 40-68 69-86 ≥87 0.429 13 0-1 2-37 38-72 73-86 ≥87 0.366 14 0-10 11-37 38-72 73-86 ≥87 0.409 15 0-12 13-37 38-72 73-86 ≥87 0.415 16 0-1 2-39 40-72 73-86 ≥87 0.379 17 0-10 11-39 40-72 73-86 ≥87 0.421 18 0-12 13-39 40-72 73-86 ≥87 0.427 The final chosen band is highlighted in yellow. HRQoL, health-related quality of life.

OVERALL QOLHEQ SCORES – MALES

overallqolheq

(

males

) –

mean

,

Table S4 Number of male patients with each total Quality Of Life in Hand Eczema Questionnaire (QOLHEQ)

score encountered in this study and corresponding mean, median and mode of the Global anchor question scores: 0 (‘not at all’) to 4 (‘very strongly’).

2 1 1 1.00 1 1 4 1 1 2.00 2 2 6 2 2 0.00 0 0 7 4 2 2 0.50 0.5 0/1 8 2 2 0.00 0 0 9 4 2 1 1 0.75 0.5 0 10 3 3 0.00 0 0 11 1 1 1.00 1 1 12 1 1 0.00 0 0 13 4 4 1.00 1 1

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59 2 2 3.00 3 3 60 2 1 1 1.50 1.5 1/2 61 2 1 1 2.50 2.5 1/4 62 2 1 1 3.50 3.5 3/4 63 2 1 1 2.00 2 1/3 64 1 1 2.00 2 2 65 2 1 1 2.50 2.5 2/3 66 1 1 2.00 2 2 67 2 2 2.00 2 2 68 1 1 1.00 1 1 69 1 1 3.00 3 3 71 1 1 2.00 2 2 74 1 1 3.00 3 3 75 2 2 3.00 3 3 76 1 1 3.00 3 3 77 1 1 3.00 3 3 83 1 1 3.00 3 3 87 2 1 1 3.50 3.5 3/4 93 1 1 4.00 4 4 96 1 1 4.00 4 4 Total 160 32 56 42 24 6 HRQoL, health-related quality of life.

overallqolheq

(

males

) –

Table S5 Kappa coefficients of agreement for different proposed sets of the Quality Of Life in Hand Eczema Questionnaire

(QOLHEQ) impairment bands for males.

Band no.

1 0-10 11-35 36-53 54-83 ≥84 0.461 2 0-12 13-35 36-53 54-83 ≥84 0.465 3 0-15 16-35 36-53 54-83 ≥84 0.464 4 0-10 11-40 41-53 54-83 ≥84 0.463 5 0-12 13-40 41-53 54-83 ≥84 0.466 6 0-15 16-40 41-53 54-83 ≥84 0.466 7 0-10 11-35 36-58 59-83 ≥84 0.457 8 0-12 13-35 36-58 59-83 ≥84 0.461 9 0-15 16-35 36-58 59-83 ≥84 0.461 10 0-10 11-40 41-58 59-83 ≥84 0.459 11 0-12 13-40 41-58 59-83 ≥84 0.463 The final chosen band is highlighted in yellow. HRQoL, health-related quality of life.

14 3 2 1 0.33 0 0 15 2 1 1 0.50 0.5 0/1 16 1 1 1.00 1 1 17 3 1 2 1.67 2 2 18 1 1 0.00 0 0 19 2 1 1 1.00 1 0/2 20 6 2 3 1 0.83 1 1 21 2 1 1 1.50 1.5 1/2 22 1 1 0.00 0 0 23 1 1 2.00 2 2 24 2 1 1 1.00 1 0/2 25 1 1 0.00 0 0 26 2 1 1 1.00 1 0/1 27 1 1 2.00 2 2 28 4 3 1 1.25 1 1 29 2 2 1.00 1 1 30 4 3 1 1.25 1 1 31 1 1 1.00 1 1 32 1 1 1.00 1 1 33 3 1 1 1 1.00 1 0/1/2 34 2 2 1.00 1 1 35 6 2 3 1 0.83 1 1 36 3 1 2 1.67 2 2 38 3 1 2 1.67 2 2 39 3 1 2 0.67 1 1 40 4 2 2 1.50 1.5 1/2 41 2 1 1 2.50 2.5 2/3 42 2 1 1 1.50 1.5 1/2 43 2 1 1 0.50 0.5 0/1 44 2 1 1 2.00 2 1/3 45 2 1 1 1.00 1 0/2 46 4 1 3 2.75 3 3 47 2 2 1.00 1 1 48 5 1 1 2 1 1.80 2 2 49 4 2 1 1 1.75 1.5 1 51 1 1 1.00 1 1 52 6 2 3 1 1.83 2 2 53 1 1 0.00 0 0 54 1 1 3.00 3 3 55 1 1 1.00 1 1 56 2 2 3.00 3 3 57 5 1 1 2 1 1.60 2 2 58 2 2 2.00 2 2

HRQoL, health-related quality of life.

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11

59 2 2 3.00 3 3 60 2 1 1 1.50 1.5 1/2 61 2 1 1 2.50 2.5 1/4 62 2 1 1 3.50 3.5 3/4 63 2 1 1 2.00 2 1/3 64 1 1 2.00 2 2 65 2 1 1 2.50 2.5 2/3 66 1 1 2.00 2 2 67 2 2 2.00 2 2 68 1 1 1.00 1 1 69 1 1 3.00 3 3 71 1 1 2.00 2 2 74 1 1 3.00 3 3 75 2 2 3.00 3 3 76 1 1 3.00 3 3 77 1 1 3.00 3 3 83 1 1 3.00 3 3 87 2 1 1 3.50 3.5 3/4 93 1 1 4.00 4 4 96 1 1 4.00 4 4 Total 160 32 56 42 24 6 HRQoL, health-related quality of life.

overallqolheq

(

males

) –

(QOLHEQ) impairment bands for males.

Band no.

1 0-10 11-35 36-53 54-83 ≥84 0.461 2 0-12 13-35 36-53 54-83 ≥84 0.465 3 0-15 16-35 36-53 54-83 ≥84 0.464 4 0-10 11-40 41-53 54-83 ≥84 0.463 5 0-12 13-40 41-53 54-83 ≥84 0.466 6 0-15 16-40 41-53 54-83 ≥84 0.466 7 0-10 11-35 36-58 59-83 ≥84 0.457 8 0-12 13-35 36-58 59-83 ≥84 0.461 9 0-15 16-35 36-58 59-83 ≥84 0.461 10 0-10 11-40 41-58 59-83 ≥84 0.459 11 0-12 13-40 41-58 59-83 ≥84 0.463 The final chosen band is highlighted in yellow. HRQoL, health-related quality of life.

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Band no.

12 0-15 16-40 41-58 59-83 ≥84 0.462 13 0-10 11-35 36-68 69-83 ≥84 0.441 14 0-12 13-35 36-68 69-83 ≥84 0.445 15 0-15 16-35 36-68 69-83 ≥84 0.445 16 0-10 11-40 41-68 69-83 ≥84 0.443 17 0-12 13-40 41-68 69-83 ≥84 0.447 18 0-15 16-40 41-68 69-83 ≥84 0.447 The final chosen band is highlighted in yellow. HRQoL, health-related quality of life.

overviewofqolheqoverallscoresformalesfallingoutsidetheproposedbanding

N=15 patients (9.4%) had a Global anchor score > 1 point outside of that predicted by the final overall

QOLHEQ band. There were 44 (27.5%) patients with an actual Global anchor score 1 point lower than

the final QOLHEQ band predicted. There were 26 patients (16.3%) with an actual Global anchor score 1

point higher than the final overall QOLHEQ band predicted. There were no age distribution differences

between the patients falling within the proposed banding and those falling outside it.

OVERALL QOLHEQ SCORES – FEMALES

overallqolheq

(

females

) –

mean

,

Table S6 Number of female patients with each total Quality Of Life in Hand Eczema Questionnaire (QOLHEQ) score

0 2 1 1 1.00 1 0/2 1 1 1 0.00 0 0 9 1 1 0.00 0 0 10 1 1 0.00 0 0 12 1 1 0.00 0 0 13 2 1 1 0.50 0.5 0/1 14 1 1 1.00 1 1 15 1 1 2.00 2 2 16 2 1 1 1.00 1 0/2 18 2 1 1 0.50 0.5 0/1 19 1 1 0.00 0 0 20 1 1 1.00 1 1 21 1 1 0.00 0 0 22 1 1 1.00 1 1 23 3 1 1 1 1.00 1 0/1/2 25 1 1 3.00 3 3 26 2 1 1 0.50 0.5 0/1 27 2 2 1.00 1 1

HRQoL, health-related quality of life.

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11

29 1 1 0.00 0 0 30 2 1 1 2.00 2 1/3 31 3 2 1 0.67 0 0 32 1 1 2.00 2 2 33 1 1 2.00 2 2 34 1 1 0.00 0 0 35 1 1 1.00 1 1 36 2 2 0.00 0 0 37 1 1 1.00 1 1 38 2 1 1 2.00 2 1/3 39 2 2 1.00 1 1 40 1 1 3.00 3 3 41 1 1 2.00 2 2 42 4 1 3 1.75 2 2 43 3 1 1 1 2.00 2 1/2/3 44 3 1 1 1 1.00 1 0/1/2 45 2 1 1 1.00 1 0/2 46 4 1 1 2 1.25 1.5 2 47 3 1 2 1.33 2 2 48 2 1 1 1.50 1.5 1/2 49 3 1 2 1.67 2 2 50 1 1 0.00 0 0 51 2 1 1 0.50 0.5 0/1 52 3 2 1 1.67 1 1 53 3 2 1 1.33 1 1 54 2 1 1 1.00 1 0/2 55 4 1 2 1 2.00 2 2 56 6 1 1 2 2 1.83 2 2/3 57 3 1 1 1 1.67 2 0/2/3 58 1 1 2.00 2 2 59 4 1 3 1.75 2 2 60 1 1 2.00 2 2 61 1 1 2.00 2 2 62 1 1 3.00 3 3 64 4 1 1 2 2.75 3 4 65 1 1 2.00 2 2 66 1 1 0.00 0 0 67 1 1 3.00 3 3 68 1 1 2.00 2 2 69 1 1 2.00 2 2 71 1 1 3.00 3 3 72 1 1 1.00 1 1 74 2 2 3.00 3 3 75 1 1 2.00 2 2 Band no.

12 0-15 16-40 41-58 59-83 ≥84 0.462 13 0-10 11-35 36-68 69-83 ≥84 0.441 14 0-12 13-35 36-68 69-83 ≥84 0.445 15 0-15 16-35 36-68 69-83 ≥84 0.445 16 0-10 11-40 41-68 69-83 ≥84 0.443 17 0-12 13-40 41-68 69-83 ≥84 0.447 18 0-15 16-40 41-68 69-83 ≥84 0.447 The final chosen band is highlighted in yellow. HRQoL, health-related quality of life.

overviewofqolheqoverallscoresformalesfallingoutsidetheproposedbanding

N=15 patients (9.4%) had a Global anchor score > 1 point outside of that predicted by the final overall

QOLHEQ band. There were 44 (27.5%) patients with an actual Global anchor score 1 point lower than

the final QOLHEQ band predicted. There were 26 patients (16.3%) with an actual Global anchor score 1

point higher than the final overall QOLHEQ band predicted. There were no age distribution differences

between the patients falling within the proposed banding and those falling outside it.

OVERALL QOLHEQ SCORES – FEMALES

overallqolheq

(

females

) –

mean

,

Table S6 Number of female patients with each total Quality Of Life in Hand Eczema Questionnaire (QOLHEQ) score

0 2 1 1 1.00 1 0/2 1 1 1 0.00 0 0 9 1 1 0.00 0 0 10 1 1 0.00 0 0 12 1 1 0.00 0 0 13 2 1 1 0.50 0.5 0/1 14 1 1 1.00 1 1 15 1 1 2.00 2 2 16 2 1 1 1.00 1 0/2 18 2 1 1 0.50 0.5 0/1 19 1 1 0.00 0 0 20 1 1 1.00 1 1 21 1 1 0.00 0 0 22 1 1 1.00 1 1 23 3 1 1 1 1.00 1 0/1/2 25 1 1 3.00 3 3 26 2 1 1 0.50 0.5 0/1 27 2 2 1.00 1 1 Table S6 Continued

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76 2 2 3.00 3 3 78 1 1 3.00 3 3 79 3 2 1 2.33 2 2 80 1 1 0.00 0 0 82 2 1 1 3.00 3 2/4 85 1 1 3.00 3 3 86 1 1 0.00 0 0 87 2 2 4.00 4 4 89 1 1 3.00 3 3 91 1 1 3.00 3 3 93 2 1 1 3.50 3.5 3/4 95 1 1 3.00 3 3 103 1 1 3.00 3 3 Total 134 30 31 42 25 6 HRQoL, health-related quality of life.

overallqolheq

(

females

) –

(QOLHEQ) impairment bands for females.

Band no.

1 0-13 14-29 30-61 62-86 ≥87 0.370 2 0-19 20-29 30-61 62-86 ≥87 0.379 3 0-13 14-40 41-61 62-86 ≥87 0.407 4 0-19 20-40 41-61 62-86 ≥87 0.415 The final chosen band is highlighted in yellow. HRQoL, health-related quality of life.

overviewofqolheqoverallscoresforfemalesfallingoutsidetheproposedbanding

N=19 patients (14.2%) had a Global anchor score > 1 point outside of that predicted by the final overall

QOLHEQ band. There were 39 (29.1%) patients with an actual Global anchor score 1 point lower than the

final QOLHEQ band predicted. There were 16 patients (11.9%) with an actual Global anchor score 1 point

higher than the final overall QOLHEQ band predicted. There were no age distribution differences between

the patients falling within the proposed banding and those falling outside it.

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11 SYMPTOMS SUBSCALE SCORES

symptomssubscale

–

distribution

Figure S2 Box-whisker plots of the distribution of the Quality Of Life in Hand Eczema Questionnaire (QOLHEQ)

Symptoms subscale score by Symptoms anchor for health-related quality of life (HRQoL) impairment. Boxes represent 25-75th _{percentile with the middle line representing the median. The ends of the whiskers represent 10-90}th_percentile.

Outliers are plotted as circles beyond the whiskers.

symptomssubscale

–

mean

,

medianandmodeofthesymptomsanchorperscore

Table S8 Number of patients with each Quality Of Life in Hand Eczema Questionnaire (QOLHEQ) subscore for the

Symptoms subscale encountered in this study and corresponding mean, median and mode of the Symptoms anchor question scores: 0 (‘not at all’) to 4 (‘very strongly’).

QOLHEQ Symptoms score

Symptoms anchor question (baseline) (indicating HRQoL impairment in the Symptoms domain

0 3 2 1 0.33 0 0

1 3 1 2 0.67 1 1

2 4 3 1 1.25 1 1

76 2 2 3.00 3 3 78 1 1 3.00 3 3 79 3 2 1 2.33 2 2 80 1 1 0.00 0 0 82 2 1 1 3.00 3 2/4 85 1 1 3.00 3 3 86 1 1 0.00 0 0 87 2 2 4.00 4 4 89 1 1 3.00 3 3 91 1 1 3.00 3 3 93 2 1 1 3.50 3.5 3/4 95 1 1 3.00 3 3 103 1 1 3.00 3 3 Total 134 30 31 42 25 6 HRQoL, health-related quality of life.

overallqolheq

(

females

) –

(QOLHEQ) impairment bands for females.

Band no.

1 0-13 14-29 30-61 62-86 ≥87 0.370 2 0-19 20-29 30-61 62-86 ≥87 0.379 3 0-13 14-40 41-61 62-86 ≥87 0.407 4 0-19 20-40 41-61 62-86 ≥87 0.415 The final chosen band is highlighted in yellow. HRQoL, health-related quality of life.

overviewofqolheqoverallscoresforfemalesfallingoutsidetheproposedbanding

N=19 patients (14.2%) had a Global anchor score > 1 point outside of that predicted by the final overall

QOLHEQ band. There were 39 (29.1%) patients with an actual Global anchor score 1 point lower than the

final QOLHEQ band predicted. There were 16 patients (11.9%) with an actual Global anchor score 1 point

higher than the final overall QOLHEQ band predicted. There were no age distribution differences between

the patients falling within the proposed banding and those falling outside it.

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3 10 1 7 2 1.10 1 1 4 6 6 1.00 1 1 5 13 1 7 3 2 1.46 1 1 6 12 1 10 1 1.08 1 1 7 15 9 3 3 1.60 1 1 8 21 10 9 2 1.62 2 1 9 20 2 5 6 6 1 1.95 2 2/3 10 12 5 5 2 1.75 2 1/2 11 17 3 9 5 2.12 2 2 12 20 1 3 8 3 5 2.40 2 2 13 23 12 10 1 2.52 2 2 14 15 2 5 6 2 2.53 3 3 15 19 1 4 13 1 2.74 3 3 16 21 2 5 10 4 2.76 3 3 17 19 1 4 13 1 2.74 3 3 18 8 2 5 1 2.88 3 3 19 8 6 2 3.25 3 3 20 5 1 4 3.80 4 4 21 6 1 3 2 3.17 3 3 22 4 2 2 3.50 3.5 3/4 23 6 2 4 3.67 4 4 24 3 1 2 3.67 4 4 25 1 1 4 4 4 Total 294 9 77 79 96 33 HRQoL, health-related quality of life.

symptomssubscale

–

(QOLHEQ) impairment bands for the Symptoms subscale.

Band no.

Possible QOLHEQ Symptoms subscale score bandings

(indicating HRQoL impairment in the Symptoms domain) Coefficient of agreement (κ) with Symptoms anchor question Not at all Slightly Moderately Strongly stronglyVery

1 0_(-3.962) 1-8_{(-3.273 to -0.754)} 9-13_{(-0.566 to 0.126)} 14-19_{(0.299 to 1.299)} ≥20_{(≥ 1.557)} 0.529 2 0-1 2-8 9-13 14-19 ≥20 0.530 3 0 1-10 11-13 14-19 ≥20 0.524 4 0-1 2-10 11-13 14-19 ≥20 0.525 5 0 1-8 9-13 14-22 ≥23 0.509 6 0-1 2-8 9-13 14-22 ≥23 0.510 7 0 1-10 11-13 14-22 ≥23 0.505 8 0-1 2-10 11-13 14-22 ≥23 0.506

The final chosen band is highlighted in yellow. Corresponding Rasch values, valid for Finland, Germany, Japan, The Netherlands and Turkey, are shown between parentheses. HRQoL, health-related quality of life.

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11

overviewofsymptomsscoresfallingoutsidetheproposedbanding

N=25 patients (8.5%) had a Symptoms anchor score > 1 point outside of that predicted by the

final Symptoms band. There were 49 (16.7%) patients with an actual Symptoms anchor score

1 point lower than the final Symptoms band predicted. There were 56 patients (19.0%) with an

actual Symptoms anchor score 1 point higher than the final Symptoms band predicted. There

were no sex or age distribution differences between the patients falling within the proposed

banding and those falling outside it.

EMOTIONS SUBSCALE SCORES

emotionssubscale

–

distribution

Figure S3 Box-whisker plots of the distribution of the Quality Of Life in Hand Eczema Questionnaire (QOLHEQ)

Emotions subscale score by Emotions anchor for health-related quality of life (HRQoL) impairment. Boxes represent 25-75th_{percentile with the middle line representing the median. The ends of the whiskers represent}

10-90th _{percentile. Outliers are plotted as circles beyond the whiskers.}

3 10 1 7 2 1.10 1 1 4 6 6 1.00 1 1 5 13 1 7 3 2 1.46 1 1 6 12 1 10 1 1.08 1 1 7 15 9 3 3 1.60 1 1 8 21 10 9 2 1.62 2 1 9 20 2 5 6 6 1 1.95 2 2/3 10 12 5 5 2 1.75 2 1/2 11 17 3 9 5 2.12 2 2 12 20 1 3 8 3 5 2.40 2 2 13 23 12 10 1 2.52 2 2 14 15 2 5 6 2 2.53 3 3 15 19 1 4 13 1 2.74 3 3 16 21 2 5 10 4 2.76 3 3 17 19 1 4 13 1 2.74 3 3 18 8 2 5 1 2.88 3 3 19 8 6 2 3.25 3 3 20 5 1 4 3.80 4 4 21 6 1 3 2 3.17 3 3 22 4 2 2 3.50 3.5 3/4 23 6 2 4 3.67 4 4 24 3 1 2 3.67 4 4 25 1 1 4 4 4 Total 294 9 77 79 96 33 HRQoL, health-related quality of life.

symptomssubscale

–

(QOLHEQ) impairment bands for the Symptoms subscale.

Band no.

Possible QOLHEQ Symptoms subscale score bandings

(indicating HRQoL impairment in the Symptoms domain) Coefficient of agreement (κ) with Symptoms anchor question Not at all Slightly Moderately Strongly stronglyVery

1 0_(-3.962) 1-8_{(-3.273 to -0.754)} 9-13_{(-0.566 to 0.126)} 14-19_{(0.299 to 1.299)} ≥20_{(≥ 1.557)} 0.529 2 0-1 2-8 9-13 14-19 ≥20 0.530 3 0 1-10 11-13 14-19 ≥20 0.524 4 0-1 2-10 11-13 14-19 ≥20 0.525 5 0 1-8 9-13 14-22 ≥23 0.509 6 0-1 2-8 9-13 14-22 ≥23 0.510 7 0 1-10 11-13 14-22 ≥23 0.505 8 0-1 2-10 11-13 14-22 ≥23 0.506

The final chosen band is highlighted in yellow. Corresponding Rasch values, valid for Finland, Germany, Japan, The Netherlands and Turkey, are shown between parentheses. HRQoL, health-related quality of life.

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emotionssubscale

–

mean

,

medianandmodeoftheemotionsanchorperscore

Table S10 Number of patients with each Quality Of Life in Hand Eczema Questionnaire (QOLHEQ) subscore for the Emotions

subscale encountered in this study and corresponding mean, median and mode of the Emotions anchor question scores: 0 (‘not at all’) to 4 (‘very strongly’).

QOLHEQ Emotions score

Emotions anchor question (baseline) (indicating HRQoL impairment in the Emotions domain)

0 17 17 0.00 0 0 1 10 8 1 1 0.30 0 0 2 12 12 0.00 0 0 3 12 8 4 0.33 0 0 4 13 12 1 0.08 0 0 5 15 9 5 1 0.47 0 0 6 13 7 4 2 0.62 0 0 7 10 4 4 2 0.80 1 0/1 8 17 7 6 3 1 0.88 1 0 9 14 5 5 3 1 1.00 1 0/1 10 24 8 8 6 2 1.08 1 0/1 11 10 3 5 2 0.90 1 1 12 12 5 3 2 2 1.08 1 0 13 12 2 4 2 4 1.67 1.5 1/3 14 18 2 7 6 3 1.56 1.5 1 15 11 2 3 4 1 1 1.64 2 2 16 10 2 5 2 1 2.20 2 2 17 10 1 6 3 2.20 2 2 18 11 1 1 4 3 2 2.36 2 2 19 7 3 2 2 1.86 2 1 20 9 2 3 4 2.22 2 3 21 4 1 3 2.75 3 3 22 6 3 2 1 1.67 1.5 1 23 2 2 3.00 3 3 24 5 3 2 3.40 3 3 25 4 1 2 1 2.50 3 3 26 1 1 3.00 3 3 27 2 2 4.00 4 4 29 1 1 3.00 3 3 30 2 2 4.00 4 4 Total 294 113 72 57 41 11 HRQoL, health-related quality of life.

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11

emotionssubscale

–

(QOLHEQ) impairment bands for the Emotions subscale.

Band no.

Possible QOLHEQ Emotions subscale score bandings

(indicating HRQoL impairment in the Emotions domain) Coefficient of agreement (κ) with Emotions anchor question Not at all Slightly Moderately Strongly stronglyVery

1 0-6 (-4.010 to -1.642) 7-12 (-1.420 to -0.491) 13-20 (-0.322 to -0.878) 21-26 (1.061 to 2.126) ≥27 (≥ 2.419) 0.531 2 0-8 9-12 13-20 21-26 ≥27 0.525 3 0-6 7-14 15-20 21-26 ≥27 0.520 4 0-8 9-14 15-20 21-26 ≥27 0.515 5 0-6 7-12 13-22 23-26 ≥27 0.528 6 0-8 9-12 13-22 23-26 ≥27 0.522 7 0-6 7-14 15-22 23-26 ≥27 0.517 8 0-8 9-14 15-22 23-26 ≥27 0.512

The final chosen band is highlighted in yellow. Corresponding Rasch values, valid for Germany, Japan and The Netherlands, are shown between parentheses. HRQoL, health-related quality of life.

overviewofemotionsscoresfallingoutsidetheproposedbanding