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 9

Validation of the Dutch Quality Of

Life in Hand Eczema Questionnaire

JAF Oosterhaven, RF Ofenloch, MLA Schuttelaar

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BULLETED STATEMENTS

WHAT’S ALREADY KNOWN ABOUT THIS TOPIC?

• The Quality Of Life in Hand Eczema Questionnaire (QOLHEQ) measures health-related

quality of life (HRQoL) impairment in hand eczema patients.

• The QOLHEQ was validated in Germany and Japan, but the validity and interpretability

of the Dutch version are unknown.

WHAT DOES THIS STUDY ADD?

• This study shows that the Dutch QOLHEQ is a valid instrument to measure HRQoL

impairment in Dutch hand eczema patients, with good reliability and moderate

responsiveness.

• Methods of item response theory are applied to assess and refine the scoring

structure.

• Severity gradings to interpret single and change scores, specifically in Dutch patients,

are proposed.

WHAT ARE THE CLINICAL IMPLICATIONS OF THIS WORK?

• The Dutch QOLHEQ can now be used to measure HRQoL impairment in Dutch hand

eczema patients.

ABSTRACT

Background: Measurement instruments should be validated for use in the population in

which they are intended to be used.

Objectives: To assess validity, reproducibility, responsiveness and interpretability of the Dutch

version of the Quality Of Life in Hand Eczema Questionnaire (QOLHEQ).

Methods: Prospective validation study in adult patients with hand eczema. At three time

points (T

₀

,

baseline; T

₁

, after 1-3 days; T

₂

, after 4-12 weeks) , data from the QOLHEQ and multiple

reference instruments were collected. Scale structure was assessed using item-response theory

analysis and structural equation modeling (SEM). Single-score validity and responsiveness were

tested with hypotheses on correlations with reference instruments. Concerning reproducibility,

intraclass correlation coefficients (ICC

_agreement

) and standard error of agreement (SEM

_agreement

)

were checked. Regarding interpretability, bands for severity of quality of life impairment were

proposed. Also, smallest detectable change (SDC) and minimally important change (MIC) were

determined.

Results: At T

₀

n=300 subjects participated in the study (54% male, mean age 45 years).

Rescoring of the scale structure resulted in a fit of the Rasch model and the SEM. The ICC

_agreement

was 0.91 (95% confidence interval: 0.85-0.94), the SEM

_agreement

5.2 points. Of the a priori

formulated hypotheses 80% (single score validity) and 64% (change-scores for responsiveness)

was confirmed. SDC was 14.4 points, MIC 11.5 points.

Conclusion: The Dutch version of the QOLHEQ has a good structural validity and reproducibility

and has a high single-score validity and moderate responsiveness. An improvement of ≥15

points should be regarded a real, important change within the Dutch population.

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9 INTRODUCTION

Hand eczema is a disease that is associated with an impaired quality of life.

1,2

_{Until recently this}

was measured using generic (non-specific) health measurement instruments (like the Euroqol

(EQ)-5D questionnaire

3

_{) or skin-specific instruments (like the Dermatology Life Quality Index,}

DLQI

4

_{). Although the use of these instruments might give some insight into global quality of}

life impairment in hand eczema patients, one might wonder whether they indicate the true

extent of the impairment.

5,6

_{In order to assess this properly, the disease-specific Quality Of Life}

in Hand Eczema Questionnaire (QOLHEQ) was designed by an international group. In 2014

the German version of the QOLHEQ was validated in a sample of hand eczema patients. It was

found to be valid, reliable and reproducible in a German population.

7

_{Translations into several}

languages were made and a cross cultural international validation study was performed

to make international comparison possible.

8

_{However, when translating a measurement}

instrument and applying it to a new population, such an instrument still needs to be validated

for use in that new population. In this study we will report on the scale structure, single-score

validity, reproducibility, change-score validity (responsiveness) and interpretability of the

Dutch QOLHEQ.

PATIENTS AND METHODS

This study was performed according to a previously published guideline, which adheres to

the guidelines developed by the Consensus-based Standards for the Selection of Health

Measurement Instruments (COSMIN) group.

9

_{Here, we will describe our methods briefly. The}

QOLHEQ is a thirty-item questionnaire with five response categories (never, rarely, sometimes,

often, all the time) assessing health-related quality of life (HRQoL) impairment, overall and

concerning four subscales: Symptoms; Emotions; Functioning; Treatment and Prevention. It was

translated into Dutch using a six-step method, including forward and backward translations

and pilot testing for content validity.

10

_{See Supplement S1 for the final Dutch version. A}

longitudinal design was used to assess the studied measurement properties. Patients were

asked to complete the QOLHEQ and reference instruments at three time points, while their

hand eczema was also clinically evaluated (see Figure 1).

STUDY POPULATION

Patients were included if they were ≥18 years, and had hand eczema of at least one week

duration, as diagnosed by a dermatologist. Patients with concomitant skin disease on other

parts of the body were also eligible for inclusion. Patients with other dermatological hand

disease and/or who were unable to complete questionnaires by themselves were excluded.

Recruitment was performed between March 2017 and December 2018, and took place at the

dermatology department of the University Medical Center Groningen (UMCG). 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).

REFERENCE INSTRUMENTS

The following reference instruments were used. The questions for the hand eczema specific

assessment and the assessment of change were pilot tested for content validity prior to this

study.

9,10

Hand eczema specific assessment (in Dutch, here freely translated), all with the response

categories ‘not at all’, ‘slightly’, ‘moderately’, ‘strongly’, and ‘very strongly’:

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state in the past seven days?

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

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

• Emotions subscale anchor: 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 anchor: 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 anchor: How did treatment and prevention of

your hand eczema bother you in the past seven days?

Skin specific HRQoL instruments:

• Dermatology life quality index (DLQI): comprising 10 items scored on a 4-point scale,

with six dimensions (symptoms and feelings; daily activities; leisure; work and school;

personal relationships; treatment) .

4

• Skindex-29: comprising 29 (or technically 30) items scored on a 5-point scale, with

three dimensions (symptoms, emotions and functioning).

11

Generic HRQoL instrument:

• Euroqol-5D-5L (EQ-5D-5L): comprising 5 items scored on a 5-point scale, and a visual

analogue scale (VAS) ranging from 0-100.

12

Figure 1 Overview of the longitudinal study design. DLQI, Dermatology Life Quality Index; EQ-5D, quality of life questionnaire of the EuroQOL Group; HECSI, Hand Eczema Severity Index; HRQoL, Health-Related Quality of Life; QOLHEQ, Quality Of Life in Hand Eczema Questionnaire.

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9 Severity (morphological signs and extent):

• The Photographic guide for severity of hand eczema (‘Photoguide’): an instrument

to measure the clinical severity of hand eczema (by study personnel or patient) on a

5-point scale: clear, almost clear, moderate, severe, very severe.

13

• The Hand Eczema Severity Index (HECSI): a continuous scale ranging from 0-360,

assessed by study personnel.

14

Assessment of change:

• A Global Rating of Change (GRC) scale was used to assess which patients were

unchanged compared to baseline at T

₁

and which patients had changed (worsened

or improved) at T

₂

. Patients responded to the question ‘Overall, has there been any

change in how your hand eczema bothers you since the last time you completed

the QOLHEQ?’ using the following seven categories: much improvement, moderate

improvement, minor improvement, no change, minor deterioration, moderate

deterioration, much deterioration.

• Subscale change questions: similar questions were asked to assess changes in the

subscales at T

₂

, but phrased as ‘has there been any change in how [insert subscale]

bothers you since the last time you completed the QOLHEQ?’ (much improvement,

moderate improvement, minor improvement, no change, minor deterioration,

moderate deterioration, much deterioration).

STATISTICAL ANALYSIS

samplesize

We used an item/subject ratio of 1:10. The QOLHEQ has 30 items, which results in a sample size

of 300 subjects.

9

scalestructure

We used techniques of modern test theory to check the scale structure (structural validity) of

the Dutch QOLHEQ. An item response theory (IRT) analysis was performed testing whether

the subscales of the Dutch QOLHEQ fit the assumed unidimensional Rasch model, using

RUMM2030 (RummLab Pty Ltd, Duncraig, WA, Australia). Since we received a significant

likelihood ratio test (p < 0.001) in all four subscales of the QOLHEQ, we applied a model with

an unrestricted parameterization where the thresholds can differ across items: the partial

credit model (a two-parameter logistic model for polytomous response categories. Fit to the

Rasch model was determined using the χ

2

_{-statistic over the item-trait interaction for each}

item and subscale. Also, means and standard deviations (SD) of fit residuals for the

item-person interaction were checked. Individual item fit was also tested with a χ

2

_{-test. To check for}

differential item functioning (DIF) an analysis of variance (ANOVA) was done according to sex

and age group (median split of the study population). DIF was assumed to be clinically relevant

if a mean difference of 0.5 logits was found for an item.

Furthermore, it was tested if the QOLHEQ fitted a predefined structural equation model

(SEM) with confirmatory factor analysis (CFA), using Amos Version 23.0 (Chicago: IBM SPSS). This

predefined model was built to assess a second order construct, health-related quality of life,

measured by four latent factors (subdomains): Symptoms; Emotions; Functioning; Treatment

and Prevention.

7

_{These subdomains are measured using the 30 items of the QOLHEQ. Because}

of a multivariate kurtosis of the data (Mardia’s coefficient = 172.8), various fit indices were

calculated using the unweighted least squares method, which is robust against violations of

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the assumptions of a multivariate normal distribution.

15

Measures of internal consistency of each subscale were reported using Cronbach’s α

and the Person Separation Index (PSI), given by RUMM2030. For both, values between 0.70 –

0 .95 were considered as evidence for good internal consistency.

single

-

scorevalidityandresponsiveness

(

change

-

scorevalidity

)

Tests on the correlation between the Dutch QOLHEQ and the reference instruments were

performed on single scores (at T

₀

) and change scores (at T

₂

) using Pearson’s correlation

coefficient (r). Strong correlation (+++) was defined as r > 0.7, moderate correlation (++) as

0.7> r >0.4, and weak correlation (+) as 0.4> r >0.2. For the change scores, correlation differences

by a minimum of 0.10 were seen as relevant. Furthermore, as recommended by COSMIN, it

was tested whether correlations of changes in QOLHEQ score with changes in instruments

measuring similar constructs were ≥ 0.50, and additionally whether correlations of changes in

QOLHEQ score with changes in instruments measuring related, but dissimilar constructs were

lower, i.e., 0.30–0.50.

16

_{Validity was considered to be high if <25% of hypotheses were rejected,}

moderate if 25–50% were rejected, and poor if >50% were rejected.

reproducibility

Measurement error was reported with the standard error of measurement (SEM

_agreement

) between

subjects at T

₀

and unchanged subjects at T

₁

. Reliability (test-retest) was reported in the same

patients with the intraclass correlation coefficient, using a two-way mixed effects model for

absolute agreement (ICC

_agreement

).

17

_{An ICC}

agreement

value of >0.70 was considered acceptable.

18

interpretability

For single scores, cutoff values for bands indicating how hand eczema affects HRQoL were

calculated using the weighted kappa (κ) coefficient of agreement between QOLHEQ scores

and the global anchor and subscale anchors. In order not to underestimate the burden for

patients when using the banding, we investigated the bands within a distance of 0.01 of

the highest κ-values. The final band chosen was the band for which the amount of patients

reporting a higher impairment according to the anchor question compared with the band

was lowest. For change scores, the smallest detectable change (SDC) was calculated using the

formula SCD = 1.96 * √2 * SEM

_agreement

.

17

_{The minimally important change (MIC) for improvement}

was determined using three different anchor-based methods (see Supplement S2 regarding

change score interpretability). For deterioration no MIC was determined, because too few

patients deteriorated to draw sound conclusions.

missingvalues

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

7

_{At T}

1

,

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

excluded from the analyses for reproducibility. One case was missing one DLQI item. Here, the

value 0 was imputed.

4

_{In four cases, the SKINDEX was missing one item and in one case it was}

missing two items. These cases were divided by 28 and 27 respectively for the calculation of

the total score. Analyses were performed with IBM SPSS Statistics for Windows, Version 23.0

(IBM, Armonk, NY, USA).

RESULTS

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9

Table 1 Baseline (T0) characteristics.

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

Photoguide severity (patient)

Mean (SD) 2.8 (0.9) 2.7 (0.8) 2.7 (0.8)

Range 1–5 1–5 1–5

Photoguide severity (physician)

Mean (SD) 3.2 (0.9) 3.1 (0.9) 3.2 (0.9) Range 2–5 2–5 2–5 DLQI Mean (SD) 7.5 (6.1)a _{9.3 (6.7)}a _{8.4 (6.4)} Range 0–27 0–26 0–27 Skindex-29 Mean (SD) 33.8 (20.7) 38.0 (22.0) 35.7 (21.4) Range 0–91 0–96 0–96 EQ-5D-5L

Mean value score (SD) 0.77 (0.21) 0.74 (0.25) 0.76 (0.23) Range -0.16 to 1.00 -0.24 to 1.00 -0.24 to 1.00 Mean VAS-score (SD) 72.9 (17.1) 73.2 (19.1) 73.1 (18.1) Range 10–100 9–100 9–100 HECSI Mean (SD) 48.6 (41.1) 40.9 (35.5) 45.1 (38.8) Range 3–192 2–144 2–192 QOLHEQ Total mean (SD) 29.0 (15.2)a _{36.3 (16.8)}a _{32.3 (16.3)} Range 3–75 0–82 0–82 Symptoms mean (SD) 8.8 (4.1)a _{10.5 (4.4)}a _{9.6 (4.3)} Range 0–19 0–21 0–21 Emotions mean (SD) 6.8 (4.6)a _{8.5 (5.2)}a _{7.6 (5.0)} Range 0–21 0–24 0–24 Functioning mean (SD) 6.8 (4.6)a _{8.9 (5.4)}a _{7.7 (5.1)} Range 0–20 0–22 0–22

Treatment and Prevention mean (SD) 6.7 (3.7)a _{8.3 (3.8)}a _{7.4 (3.9)}

Range 0–17 0–17 0–17

a_{Differences between males and females are significant (P < 0.05) according to a Student’s t-test. DLQI,}

Dermatology Life Quality Index; EQ-5D, quality of life questionnaire of the EuroQOL Group; HECSI, Hand Eczema Severity Index; QOLHEQ, Quality Of Life in Hand Eczema Questionnaire; SD, standard deviation.

flow chart. Of the n=294 patients included in the T

₀

analyses, 54.4% was male. The mean age

was 44.9 years. While the rating of hand eczema severity did not differ between sexes, females

indicated significantly more impairment in HRQoL than males on the total QOLHEQ and all

subscales, as well as on the DLQI. Detailed characteristics of the study population and mean T

₀

values of the reference instruments are reported in Table 1.

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Figure 2 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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9 SCALE STRUCTURE

When running the Rasch analysis we found disordered thresholds for 10 items, across all subscales.

These items were mostly affected by the categories ‘rarely’ and ‘sometimes’, indicating that the

Dutch population may have problems differentiating between those categories in general.

Therefore we joined those categories for all items, resulting in a scoring structure of 0-1-1-2-3 for

the whole QOLHEQ. This structure fitted the Rasch model for all subscales. However, we still found

relevant disordered thresholds for item 26 ‘Costs’. To fix this, we rescored this item to 0-1-1-1-2. See

Table 2 for detailed item characteristics. Rasch analysis of the subscales then revealed:

• Symptoms: overall χ

2

_{= 28.7; degrees of freedom (d.f.) = 28; P > 0.43. A PSI of 0.85 and a}

Cronbach’s α of 0.86 indicated a good internal consistency.

• Emotions: overall χ

2

_{= 42.7; d.f. = 32; P > 0.09. A PSI of 0.86 and a Cronbach’s α of 0.89}

indicated a good internal consistency.

• Functioning: overall χ

2

_{= 39.8; d.f. = 32; P > 0.16. A PSI of 0.86 and a Cronbach’s α of 0.89}

indicated a good internal consistency.

• Treatment and Prevention: overall χ

2

_{= 33.8; d.f. = 28; P > 0.20. A PSI of 0.78 and a}

Cronbach’s α of 0.78 indicated a good internal consistency.

DIF analysis showed significant uniform DIF for only one item in the Functioning subscale.

Item 3 (‘Home duties’) showed that females have a slightly higher chance (+0.6 logits) to be

impaired for this item. This seems plausible, as females are still more often involved in performing

home duties then males, and corresponds to what was found in the German validation study of

the QOLHEQ.

7

The CFA showed that the Dutch QOLHEQ had a good fit to the proposed SEM (see Table 3).

Total maximum scores that can be obtained with the Dutch QOLHEQ within the Dutch population

are now: total score 89; Symptoms 21; Emotions 24; Functioning 24; Treatment and Prevention 20.

An SPSS syntax can be found in Supplement S3 to recode the QOLHEQ to Dutch scores.

SINGLE-SCORE VALIDITY AND RESPONSIVENESS (CHANGE-SCORE VALIDITY)

Of the a priori formulated hypotheses for single score validity 80% was confirmed, indicating

high validity of the Dutch QOLHEQ (Table 4). In the analysis of responsiveness n=124 cases were

included because these subjects indicated that they had changed at T

₂

according to the GRC

scale, while being unchanged at T

₁

or when compared to baseline if they were non-respondents

at T

_1.

These therefore represented really changed patients. In these patients 64% of the a priori

formulated hypotheses for change scores were confirmed, indicating a moderate responsiveness

of the Dutch QOLHEQ (Table 5).

REPRODUCIBILITY

There were n=166 cases included in the analysis for reproducibility. This concerns the unchanged

patients at T

₁

according to the GRC scale. The SEM

_agreement

of the complete QOLHEQ was 5.2 points.

The ICC

_agreement

was 0.91 (95% confidence interval [CI]: 0.85-0.94), indicating good reproducibility.

For the subscales we found the following values, indicating good reproducibility of all four

subscales:

• Symptoms: SEM

_agreement

= 1.6 points; ICC

_agreement

= 0.88 (95% CI: 0.84-0.91).

• Emotions: SEM

_agreement

= 1.8 points; ICC

_agreement

= 0.88 (95% CI: 0.82-0.92).

• Functioning: SEM

_agreement

= 1.9 points; ICC

_agreement

= 0.88 (95% CI: 0.80-0.92).

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Table 2 Results of Rasch analysis. Item no. in

questionnaire Description Locationa _Rangeb

Fit residual χ2 _P-valuec Scoring structure Symptoms 23 Bleeding 1.40 –1.51 to 3.58 –0.69 2.76 0.60 0–1–1–2–3

9 Causing loss of sleep 1.15 –0.55 to 2.35 1.07 4.79 0.31 0–1–1–2–3

11 Fissuring –0.09 –2.25 to 1.77 0.25 2.98 0.56 0–1–1–2–3 1 Painful –0.30 –3.01 to 1.75 –0.69 7.05 0.13 0–1–1–2–3 20 Redness –0.40 –2.98 to 1.39 1.41 1.46 0.83 0–1–1–2–3 6 Itching –0.58 –3.27 to 1.90 0.73 2.30 0.68 0–1–1–2–3 28 Dryness –1.19 –3.71 to 1.16 –0.32 7.31 0.12 0–1–1–2–3 Emotions 30 Nervous 1.01 –1.07 to 2.47 –2.45 9.25 0.06 0–1–1–2–3 19 Sad/depressed 0.84 –1.51 to 2.53 –2.37 9.34 0.05 0–1–1–2–3 27 Embarrassed 0.81 –1.09 to 2.25 –0.39 1.48 0.83 0–1–1–2–3 10 Anxious about future 0.36 –1.23 to 1.28 1.55 4.25 0.37 0–1–1–2–3

21 Irritated 0.13 –2.66 to 2.18 0.25 1.78 0.78 0–1–1–2–3

16 Hide my hands –0.04 –1.62 to 0.86 3.02 8.51 0.07 0–1–1–2–3

5 Frustrated –1.28 –4.22 to 0.89 –0.68 1.18 0.88 0–1–1–2–3

8 Annoyed –1.84 –4.90 to 0.15 1.30 6.99 0.14 0–1–1–2–3

Functioning

17 Avoiding contact with people 1.33 –0.29 to 2.53 1.06 6.00 0.20 0–1–1–2–3 25 Affecting friendships 1.06 –0.64 to 2.09 0.90 0.48 0.98 0–1–1–2–3 29 Touching partner 0.81 –1.15 to 2.62 0.91 0.73 0.95 0–1–1–2–3 15 Dressing myself 0.48 –1.79 to 2.05 –2.27 11.12 0.03 0–1–1–2–3 12 Leisure time/hobbies –0.51 –3.12 to 1.27 –0.98 9.70 0.05 0–1–1–2–3 14 Washing myself –0.83 –2.82 to 0.70 –0.84 2.24 0.69 0–1–1–2–3 2 Restricting job –0.94 –3.57 to 1.02 –0.26 6.54 0.16 0–1–1–2–3 3 Home duties –1.40 –4.19 to 0.48 –0.41 2.95 0.57 0–1–1–2–3 Treatment and Prevention

26 Costs 0.97 –0.20 to 2.13 1,82 10.48 0.03 0–1–1–1–2d

24 Side-effects 0.60 –0.89 to 1.35 –0,60 7.45 0.11 0–1–1–2–3 18 Visiting physician 0.57 –1.25 to 1.52 –0,28 2.44 0.66 0–1–1–2–3 7 Time consuming 0.05 –2.17 to 1.50 –0,63 4.14 0.39 0–1–1–2–3 4 Wearing gloves –0.33 –1.52 to 0.57 0,33 3.56 0.47 0–1–1–2–3 22 Avoiding certain things –0.67 –2.62 to 0.64 –0,07 1.71 0.79 0–1–1–2–3 13 Using creams –1.19 –3.33 to 0.28 0,35 2.87 0.58 0–1–1–2–3

a_{Location sorted by severity; items assessing most severe impairment are on top of each domain/subscale.}b_{Range of thresholds}

of each item. c_{According to a χ}2_{-test; misfit is considered significant if P < 0.007 or P < 0.008 (dependent on number of items in the}

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9

Table 2 Results of Rasch analysis. Item no. in

questionnaire Description Locationa _Rangeb

Fit residual χ2 _P-valuec Scoring structure Symptoms 23 Bleeding 1.40 –1.51 to 3.58 –0.69 2.76 0.60 0–1–1–2–3

9 Causing loss of sleep 1.15 –0.55 to 2.35 1.07 4.79 0.31 0–1–1–2–3

11 Fissuring –0.09 –2.25 to 1.77 0.25 2.98 0.56 0–1–1–2–3 1 Painful –0.30 –3.01 to 1.75 –0.69 7.05 0.13 0–1–1–2–3 20 Redness –0.40 –2.98 to 1.39 1.41 1.46 0.83 0–1–1–2–3 6 Itching –0.58 –3.27 to 1.90 0.73 2.30 0.68 0–1–1–2–3 28 Dryness –1.19 –3.71 to 1.16 –0.32 7.31 0.12 0–1–1–2–3 Emotions 30 Nervous 1.01 –1.07 to 2.47 –2.45 9.25 0.06 0–1–1–2–3 19 Sad/depressed 0.84 –1.51 to 2.53 –2.37 9.34 0.05 0–1–1–2–3 27 Embarrassed 0.81 –1.09 to 2.25 –0.39 1.48 0.83 0–1–1–2–3 10 Anxious about future 0.36 –1.23 to 1.28 1.55 4.25 0.37 0–1–1–2–3

21 Irritated 0.13 –2.66 to 2.18 0.25 1.78 0.78 0–1–1–2–3

16 Hide my hands –0.04 –1.62 to 0.86 3.02 8.51 0.07 0–1–1–2–3

5 Frustrated –1.28 –4.22 to 0.89 –0.68 1.18 0.88 0–1–1–2–3

8 Annoyed –1.84 –4.90 to 0.15 1.30 6.99 0.14 0–1–1–2–3

Functioning

17 Avoiding contact with people 1.33 –0.29 to 2.53 1.06 6.00 0.20 0–1–1–2–3 25 Affecting friendships 1.06 –0.64 to 2.09 0.90 0.48 0.98 0–1–1–2–3 29 Touching partner 0.81 –1.15 to 2.62 0.91 0.73 0.95 0–1–1–2–3 15 Dressing myself 0.48 –1.79 to 2.05 –2.27 11.12 0.03 0–1–1–2–3 12 Leisure time/hobbies –0.51 –3.12 to 1.27 –0.98 9.70 0.05 0–1–1–2–3 14 Washing myself –0.83 –2.82 to 0.70 –0.84 2.24 0.69 0–1–1–2–3 2 Restricting job –0.94 –3.57 to 1.02 –0.26 6.54 0.16 0–1–1–2–3 3 Home duties –1.40 –4.19 to 0.48 –0.41 2.95 0.57 0–1–1–2–3 Treatment and Prevention

26 Costs 0.97 –0.20 to 2.13 1,82 10.48 0.03 0–1–1–1–2d

24 Side-effects 0.60 –0.89 to 1.35 –0,60 7.45 0.11 0–1–1–2–3 18 Visiting physician 0.57 –1.25 to 1.52 –0,28 2.44 0.66 0–1–1–2–3 7 Time consuming 0.05 –2.17 to 1.50 –0,63 4.14 0.39 0–1–1–2–3 4 Wearing gloves –0.33 –1.52 to 0.57 0,33 3.56 0.47 0–1–1–2–3 22 Avoiding certain things –0.67 –2.62 to 0.64 –0,07 1.71 0.79 0–1–1–2–3 13 Using creams –1.19 –3.33 to 0.28 0,35 2.87 0.58 0–1–1–2–3

a_{Location sorted by severity; items assessing most severe impairment are on top of each domain/subscale.}b_{Range of thresholds}

of each item. c_{According to a χ}2_{-test; misfit is considered significant if P < 0.007 or P < 0.008 (dependent on number of items in the}

subscale). d_{Scoring structure adjusted additionally.}

Table 3 Fit indices for the structural equation model of the QOLHEQ, consisting of four subscales (factors) loading on a higher order factor measuring HRQoL.

Fit index Complete 2

nd

order model Model fit Recommendation for good fita

Recommendation for acceptable fita

SRMR 0.067 Acceptable < 0.05 0.05 < SRMR ≤ 0.10 GFI 0.980 Good > 0.95 0.90 ≤ GFI < 0.95 AGFI 0.976 Good > 0.90 0.85 ≤ AGFI < 0.90 NFI 0.976 Good > 0.95 0.90 ≤ NFI < 0.95 RFI 0.974 Good > 0.95 0.90 ≤ RFI < 0.95

a_{According to guidelines by Schermelleh-Engel et al.}15_{HRQoL, Health-Related Quality of Life; SRMR,}

Standardized Root Mean Residual; GFI, Goodness of Fit Index; AGFI, Adjusted Goodness of Fit Index; NFI, Normed Fit Index; QOLHEQ, Quality Of Life in Hand Eczema Questionnaire; RFI, Relative Fit Index.

Table 4 Single-score validity (at T0), correlations between the QOLHEQ and reference instruments.

Reference measure Correlation hypothesizeda

Correlation found R2 Hypotheses confirmed? DLQI +++ 0.77 0.59 Yes Skindex-29 +++ 0.80 0.64 Yes

Global anchor ++ 0.59 0.35 Yes

EQ-5D-5L (VAS)b ₊₊ _–0.33 _0.11 _No

EQ-5D-5L (Value)b ₊₊ _–0.57 _0.32 _Yes

Photoguide (patient) ++ 0.47 0.22 Yes

Photoguide (physician) + 0.43 0.18 No

HECSI + 0.37 0.14 Yes

Subscalesc

Symptoms anchor +++ 0.70 0.49 Yes

Emotions anchor +++ 0.71 0.50 Yes

Functioning anchor +++ 0.72 0.52 Yes

Treatment and Prevention anchor +++ 0.58 0.34 No

Skindex-29 Symptoms subscale +++ 0.77 0.59 Yes

Skindex-29 Emotions subscale +++ 0.85 0.73 Yes

Skindex-29 Functioning subscale +++ 0.70 0.49 Yes

Specific comparisons

QOLHEQ Symptoms subscale – Photoguide (physician) ++ 0.52 0.27 Yes QOLHEQ Symptoms subscale - HECSI ++ 0.46 0.21 Yes

a_{A priori defined: Strong correlation (+++) r > 0.7; moderate correlation (++) 0.7 > r > 0.4; weak correlation (+)}

0.4 > r > 0.2. b_{Negative value, because the EQ-5D-5L is scored inversely to the QOLHEQ.}c_{Correlation between}

QOLHEQ subscale score and reference instrument. DLQI, Dermatology Life Quality Index; EQ-5D, quality of life questionnaire of the EuroQOL Group; HECSI, Hand Eczema Severity Index; QOLHEQ, Quality Of Life in Hand Eczema Questionnaire; VAS, Visual Analogue Scale.

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INTERPRETABILITY

For single scores, several bands for severity of HRQoL impairment were tested for the overall

QOLHEQ score and subscales. For the overall QOLHEQ, we propose separate bands for males

and females. The final band chosen for the overall QOLHEQ had a κ-value of 0.430: not at all,

0-13; slightly, 14-28; moderately, 29-44; strongly, 45-64; very strongly, ≥65. See Supplement S4

for all proposed bands and for details on the calculation of single score interpretability.

The SCD in N=166 unchanged patients at T

₁

was 14.4 points for the overall QOLHEQ.

The preferred MIC, obtained with the Receiver Operating Characteristic method, was 11.5. See

Supplement S2 for SDC and MIC of the subscales and further details on calculations.

Table 5 Responsiveness (change-score validity) in changed patients between T0 and T2.

Hypothesis on correlations Correlations found Hypotheses confirmed? Change QOLHEQ – GRC > Change DLQI – GRC 0.46 vs 0.38 No

Change QOLHEQ – GRC > Change Skindex-29 – GRC 0.46 vs 0.33 Yes Change QOLHEQ – GRC > Change EQ-5D Value – GRC 0.46 vs –0.27a _Yes

Change QOLHEQ – GRC > Change EQ-5D VAS – GRC 0.46 vs –0.25a _Yes

Change QOLHEQ – change Photoguide (physician) > Change DLQI – change Photoguide

(physician) 0.46 vs 0.45 No

Change QOLHEQ – change Photoguide (physician) > Change Skindex-29 – change

Photoguide (physician) 0.46 vs 0.46 No

Change QOLHEQ – change Photoguide (physician) > Change EQ-5D Value – change

Photoguide (physician) 0.46 vs –0.36a Yes

Change QOLHEQ – change Photoguide (physician) > Change EQ-5D VAS – change

Change QOLHEQ – change HECSI > Change DLQI – change HECSI 0.40 vs 0.35 No Change QOLHEQ – change HECSI > Change Skindex-29 – change HECSI 0.40 vs 0.33 No Change QOLHEQ – change HECSI > Change EQ-5D Value – change HECSI 0.40 vs –0.27a _Yes

Change QOLHEQ – change HECSI > Change EQ-5D VAS – change HECSI 0.40 vs –0.15a _Yes

Hypothesis on subscale correlations

Change QOLHEQ Symptoms – Symptoms change question > Change Skindex-29

Symptoms – Symptoms change question 0.49 vs 0.44 No

Change QOLHEQ Emotions – Emotions change question > Change Skindex-29 Emotions –

Emotions change question 0.47 vs 0.30 Yes

Change QOLHEQ Functioning – Functioning change question > Change Skindex-29

Functioning – Functioning change question 0.54 vs 0.37 Yes

Hypothesis according to COSMIN Instruments measuring similar constructs

Change QOLHEQ – GRC 0.46 No

Change QOLHEQ – Change DLQI 0.56 Yes

Change QOLHEQ – Change Skindex-29 0.63 Yes

Instruments measuring related, but dissimilar constructs

Change QOLHEQ – Change Photoguide (physician) 0.46 Yes

Change QOLHEQ – Change HECSI 0.40 Yes

Change QOLHEQ – Change EQ-5D Value –0.48 a _Yes

Change QOLHEQ – Change EQ-5D VAS –0.26 a _No

a_{Negative value, because the EQ-5D-5L is scored inversely to the QOLHEQ. COSMIN, COnsensus-based Standards for the}

selection of health Measurement INstruments; DLQI, Dermatology Life Quality Index; EQ-5D, quality of life questionnaire of the EuroQOL Group; GRC, Global Rating of Change scale; HECSI, Hand Eczema Severity Index; QOLHEQ, Quality Of Life in Hand Eczema Questionnaire; VAS, Visual Analogue Scale.

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9 DISCUSSION

In this study, we tested various measurement properties of the Dutch QOLHEQ. We proposed

a scoring structure fitting a Rasch model, and demonstrated good validity and reproducibility,

and moderate responsiveness. An improvement of ≥15 points within the Dutch population

should be regarded as a real, important improvement.

Compared to the German version, the Dutch QOLHEQ had to be substantially rescored.

A possible explanation for this is that the Dutch translation for the item ‘sometimes’ (Dutch:

‘nu en dan ‘) was not optimal; possibly in Dutch it was too similar to the category ‘rarely’

(Dutch: ‘zelden’). A future validation study could assess if another translation (for example

changing ‘nu en dan’ to ‘soms’) may yield a better discrimination on the lower end of the

Dutch QOLHEQ-scale. Still the Dutch translation of the QOLHEQ as presented here, fulfills the

rigorous requirements of modern test theory including IRT and SEM. Therefore, it is ready to be

used in any study assessing HRQoL impairments in a Dutch population of patients with hand

eczema. However, when reporting QOLHEQ results of Dutch patients in future studies, both

the national and international values, which were obtained for six languages in a cross-cultural

validation study

8

_{, should be reported for the sake of international comparison.}

The item ‘Costs’ provided the largest issues in the analysis. Subjects could not be

distinguished, based on this item. The health insurance companies in the Netherlands

reimburse the treatment of hand eczema, including several emollients and protective gloves

made of textile. As a result, the out-of-pocket costs for hand eczema are often low. This may

offer a good explanation as to why a large group of patients (n=161) chose ‘never’ for this

item. We chose to keep the item in the instrument, as it may still be important for a small

subgroup of patients. However, if in the future efforts would be made to reduce the amount of

items in the QOLHEQ, for example to increase its ease of use, this item should be the first to be

considered for removal.

Most of our a priori stated hypotheses were confirmed in the analyses for single-score

validity. For the single scores, the Photoguide, as scored by physician, correlated moderately

with the QOLHEQ (0.43), where we had expected it to be only weakly correlated (<0.4).

However, the Photoguide, as scored by the patient, still correlated stronger with the QOLHEQ

than the physician score, which was as we had hypothesized. Therefore, we do not consider this

an issue. For the change scores, the QOLHEQ showed a higher or comparable responsiveness

when compared to the reference instruments, indicating that the QOLHEQ was sensitive to

detect change in HRQoL in hand eczema patients.

This validation study was performed using a paper QOLHEQ version. Over the last

decades, digital questionnaires are increasingly used for capturing Patient Reported Outcomes

(PROs), mainly because they provide direct integration into medical health records and

research databases. If a paper questionnaire is adapted to an electronic version, this may alter

the measurement properties of the questionnaire.

19

_{However, this is not always the case.}

20,21

For the QOLHEQ, consideration should be given to this in future studies.

A limitation of this study was that the identification of unchanged patients at T

₁

and

changed patients at T

₂

was based on the memory of patients. Especially for T

₂

, which was

assessed 4 to 12 weeks following T

₀

, a certain amount of recall bias cannot be ruled out.

Another limitation was that already between T

₀

and T

₁

many patients (N=73) indicated a

change in the impairment they perceived because of their hand eczema, limiting the sample

size for reproducibility and responsiveness,

although the numbers are still acceptable.

22

_This

clearly reflects the variable course that is often associated with the disease. A final limitation

could have been the short time between T

₀

and T

₁

, in which subjects might have been able to

Table 5 Responsiveness (change-score validity) in changed patients between T0 and T2.

Hypothesis on correlations Correlations found Hypotheses confirmed? Change QOLHEQ – GRC > Change DLQI – GRC 0.46 vs 0.38 No

Change QOLHEQ – GRC > Change Skindex-29 – GRC 0.46 vs 0.33 Yes Change QOLHEQ – GRC > Change EQ-5D Value – GRC 0.46 vs –0.27a _Yes

Change QOLHEQ – GRC > Change EQ-5D VAS – GRC 0.46 vs –0.25a _Yes

Change QOLHEQ – change Photoguide (physician) > Change DLQI – change Photoguide

(physician) 0.46 vs 0.45 No

Change QOLHEQ – change Photoguide (physician) > Change Skindex-29 – change

Photoguide (physician) 0.46 vs 0.46 No

Change QOLHEQ – change Photoguide (physician) > Change EQ-5D Value – change

Change QOLHEQ – change Photoguide (physician) > Change EQ-5D VAS – change

Change QOLHEQ – change HECSI > Change DLQI – change HECSI 0.40 vs 0.35 No Change QOLHEQ – change HECSI > Change Skindex-29 – change HECSI 0.40 vs 0.33 No Change QOLHEQ – change HECSI > Change EQ-5D Value – change HECSI 0.40 vs –0.27a _Yes

Change QOLHEQ – change HECSI > Change EQ-5D VAS – change HECSI 0.40 vs –0.15a _Yes

Hypothesis on subscale correlations

Change QOLHEQ Symptoms – Symptoms change question > Change Skindex-29

Symptoms – Symptoms change question 0.49 vs 0.44 No

Change QOLHEQ Emotions – Emotions change question > Change Skindex-29 Emotions –

Emotions change question 0.47 vs 0.30 Yes

Change QOLHEQ Functioning – Functioning change question > Change Skindex-29

Functioning – Functioning change question 0.54 vs 0.37 Yes

Hypothesis according to COSMIN Instruments measuring similar constructs

Change QOLHEQ – GRC 0.46 No

Change QOLHEQ – Change DLQI 0.56 Yes

Change QOLHEQ – Change Skindex-29 0.63 Yes

Instruments measuring related, but dissimilar constructs

Change QOLHEQ – Change Photoguide (physician) 0.46 Yes

Change QOLHEQ – Change HECSI 0.40 Yes

Change QOLHEQ – Change EQ-5D Value –0.48 a _Yes

Change QOLHEQ – Change EQ-5D VAS –0.26 a _No

a_{Negative value, because the EQ-5D-5L is scored inversely to the QOLHEQ. COSMIN, COnsensus-based Standards for the}

selection of health Measurement INstruments; DLQI, Dermatology Life Quality Index; EQ-5D, quality of life questionnaire of the EuroQOL Group; GRC, Global Rating of Change scale; HECSI, Hand Eczema Severity Index; QOLHEQ, Quality Of Life in Hand Eczema Questionnaire; VAS, Visual Analogue Scale.

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recall their answers from T

₀

. However, as was apparent from the number of quickly changed

patients at T

₁

, this short period was needed to ensure a sufficient number of eligible subjects

at T

₁

. Also, we believe that answers given on the 30-item long QOLHEQ will be hard to recall,

even after 1-3 days.

In conclusion, the Dutch version of the QOLHEQ has shown to be a valid, reproducible

and responsive instrument in the Dutch hand eczema population. We recommend its use to

measure impairment of HRQoL in Dutch hand eczema patients.

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9 REFERENCES

1. Moberg C, Alderling M, Meding B. Hand eczema and quality of life: a population-based study. Br J Dermatol. 2009;161(2):397-403.

2. Agner T, Andersen KE, Brandao FM, et al. Hand eczema severity and quality of life: a cross-sectional, multicentre study of hand eczema patients. Contact Dermatitis. 2008;59(1):43-47.

3. Brooks R. EuroQol: the current state of play. Health Policy. 1996;37(1):53-72.

4. Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)--a simple practical measure for routine clinical use.

Clin Exp Dermatol. 1994;19(3):210-216.

5. Coenraads PJ, Bouma J, Diepgen TL. Quality of life of patients with occupationally-induced hand eczema.

Hautarzt. 2004;55(1):28-30.

6. Ahmed A, Shah R, Papadopoulos L, Bewley A. An ethnographic study into the psychological impact and adaptive mechanisms of living with hand eczema. Clin Exp Dermatol. 2015;40(5):495-501.

7. 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):304-312.

8. 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.

9. 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):106-115.

10. Wild D, Grove A, Martin M, et al. Principles of Good Practice for the Translation and Cultural Adaptation Process for Patient-Reported Outcomes (PRO) Measures: report of the ISPOR Task Force for Translation and Cultural Adaptation. Value Health. 2005;8(2):94-104.

11. Chren MM, Lasek RJ, Flocke SA, Zyzanski SJ. Improved discriminative and evaluative capability of a refined version of Skindex, a quality-of-life instrument for patients with skin diseases. Arch Dermatol. 1997;133(11):1433-1440.

12. Herdman M, Gudex C, Lloyd A, et al. Development and preliminary testing of the new five-level version of EQ-5D (EQ-5D-5L). Qual Life Res. 2011;20(10):1727-1736.

13. Coenraads PJ, Van Der Walle H, Thestrup-Pedersen K, et al. Construction and validation of a photographic guide for assessing severity of chronic hand dermatitis. Br J Dermatol. 2005;152(2):296-301.

14. Held E, Skoet R, Johansen JD, Agner T. The hand eczema severity index (HECSI): a scoring system for clinical assessment of hand eczema. A study of inter- and intraobserver reliability. Br J Dermatol. 2005;152(2):302-307. 15. Schermelleh-Engel K, Moosbrugger H, Müller H. Evaluating the fit of structural equation models: Tests of significance and descriptive goodness-of-fit measures. Methods Psychol Res online. 2003;8(2):23-74.

16. Prinsen CAC, Mokkink LB, Bouter LM, et al. COSMIN guideline for systematic reviews of patient-reported outcome measures. Qual Life Res. 2018;27(5):1147-1157.

17. de Vet HC, Terwee CB, Knol DL, Bouter LM. When to use agreement versus reliability measures. J Clin Epidemiol. 2006;59(10):1033-1039.

18. Terwee CB, Bot SD, de Boer MR, et al. Quality criteria were proposed for measurement properties of health status questionnaires. J Clin Epidemiol. 2007;60(1):34-42.

19. Juniper EF, Langlands JM, Juniper BA. Patients may respond differently to paper and electronic versions of the same questionnaires. Respir Med. 2009;103(6):932-934.

20. Bjorner JB, Rose M, Gandek B, Stone AA, Junghaenel DU, Ware JE. Method of administration of PROMIS scales did not significantly impact score level, reliability, or validity. J Clin Epidemiol. 2014;67(1):108-113.

21. Robles N, Rajmil L, Rodriguez-Arjona D, et al. Development of the web-based Spanish and Catalan versions of the Euroqol 5D-Y (EQ-5D-Y) and comparison of results with the paper version. Health Qual Life Outcomes. 2015;13(1):72.

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9 SUPPLEMENT S2 – INTERPRETABILITY OF CHANGE SCORES ON THE DUTCH QUALITY

OF LIFE IN HAND ECZEMA QUESTIONNAIRE (QOLHEQ)

SMALLEST DETECTABLE CHANGE (SDC)

The SDC of the Dutch 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

= 5.2 points; SDC = 14.4 points.

• Symptoms subscale: SEM

_agreement

= 1.6 points; SDC = 4.5 points.

• Emotions subscale: SEM

_agreement

= 1.8 points; SDC = 4.9 points.

• Functioning subscale: SEM

_agreement

= 1.9 points; SDC = 5.2 points.

• Treatment and Prevention subscale: SEM

_agreement

= 1.5 points; SDC = 4.2 points.

MINIMALLY IMPORTANT CHANGE (MIC)

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

question for change in HRQoL impairment was r = 0.51. The correlations for the subscales were:

• Symptoms: r = 0.51.

• Emotions: r = 0.40.

• Functioning: r = 0.53.

• Treatment and Prevention: r = 0.29.

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.

1,2

_{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 emotion 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.

Change scores were calculated for the QOLHEQ and anchor questions by subtracting

the score at T0 from the score at T2. 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 (see

below for detailed results):

• 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) cutoff point, indicating the

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

classified patients is highest.

• The MIC based on the 95% upper limit cutoff point of the unchanged (or ‘not

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).

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Calculation of the MIC of improvement according to our three used methods resulted

in the values shown in Table S2.1. To obtain one final value for the MIC, the MIC obtained

with the ROC method was chosen as the preferred MIC, because it is aimed at minimizing

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

3

This resulted in a value of 11.5 points for the overall QOLHEQ.

Table S2.1 Minimally important change (MIC) indicated as points improvement on the Dutch Quality Of Life in Hand Eczema Questionnaire (QOLHEQ); defined using three methods.

MIC method QOLHEQ overall Symptoms Emotions Functioning Treatment and Preventiona

Mean cutoff 9.0 2.5 2.1 3.0 0.6

ROC curve 11.5 3.5 4.5 2.5 2.5

95% limit 15.7 6.4 6.6 6.2 5.0

MIC values are presented for the overall QOLHEQ and its subscales. ROC, receiver operating characteristic.

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9

overalldutchqolheq

Table S2.2 The mean change scores on the overall Dutch Quality Of Life in Hand Eczema Questionnaire (QOLHEQ), according to changes measured with the Global anchor question for change.

Global anchor of change QOLHEQ overall score in importantly changed patients

Perceived change Change indicated as important N/N_total (%) Mean change SD_change

Much improvement 53/54 (98) +16.1 14.2

Moderate improvement 24/26 (92) +9.8 10.7 Minor improvement (MIC) 14/19 (72) +9.0 13.1

No changea _{42 (n/a)} _+1.9 _8.7

Minor deterioration 6/8 (75) +4.3 5.8

Moderate deterioration 10/13 (77) -5.0 8.0

Much deterioration 4/4 (100) -1.5 7.0

MIC, minimally important change; n/a, not applicable; SD, standard deviation. a_{This group}

includes N=35 patients that indicated ‘No change’, with additionally the patients from the ‘Minor improvement’ and ‘Minor deterioration’ group who indicated that they had not importantly changed.

Figure S2.1 Receiver Operating Characteristic (ROC) curve for various cut-off points for change on the overall Dutch Quality Of Life in Hand Eczema Questionnaire (QOLHEQ) score.

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symptomssubscale

-

dutch

Table S2.3 The mean change scores on the Symptoms subscale of the Dutch Quality Of Life in Hand Eczema Questionnaire (QOLHEQ), according to changes measured with the Symptoms anchor question for change.

Symptoms anchor of change Symptoms score in importantly changed patients

Perceived change Change indicated as important N/Ntotal (%) Mean change SDchange

No changea _{47 (n/a)} _+0.8 _3.4

Minor deterioration 5/7 (71) +0.2 1.3

Much deterioration 7/7 (100) +1.4 3.7

includes N=39 patients that indicated ‘No change’, with additionally the patients from the ‘Minor improvement’ and ‘Minor deterioration’ group who indicated that they had not importantly changed.

Figure S2.2 Receiver Operating Characteristic (ROC) curve for various cut-off points for change on the Symptoms subscale of the Dutch Quality Of Life in Hand Eczema Questionnaire (QOLHEQ).

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9

emotionssubscale

-

dutch

Table S2.4 The mean change scores on the Emotions subscale of the Dutch Quality Of Life in Hand Eczema Questionnaire (QOLHEQ), according to changes measured with the Emotions anchor question for change.

Emotions anchor of change Emotions score in importantly changed patients

No changea _{96 (n/a)} _+1.3 _3.2

Minor deterioration 8/9 (89) -1.3 3.2

Moderate deterioration 9/10 (90) +0.3 2.9

includes N=94 patients that indicated ‘No change’, with additionally the patients from the ‘Minor improvement’ and ‘Minor deterioration’ group who indicated that they had not importantly changed.

Figure S2.3 Receiver Operating Characteristic (ROC) curve for various cut-off points for change on the Emotions subscale of the Dutch Quality Of Life in Hand Eczema Questionnaire (QOLHEQ).

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functioningsubscale

-

dutch

Table S2.5 The mean change scores on the Functioning subscale of the Dutch Quality Of Life in Hand Eczema Questionnaire (QOLHEQ), according to changes measured with the Functioning anchor question for change.

Functioning anchor of change Functioning score in importantly changed patients

No changea _{101 (n/a)} _+1.1 _3.1

Minor deterioration 4/6 (67) 0.0 2.2

includes N=98 patients that indicated ‘No change’, with additionally the patients from the ‘Minor improvement’ and ‘Minor deterioration’ group who indicated that they had not importantly changed.

Figure S2.4 Receiver Operating Characteristic (ROC) curve for various cut-off points for change on the Functioning subscale of the Dutch Quality Of Life in Hand Eczema Questionnaire (QOLHEQ).

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9

treatmentandpreventionsubscale

-

dutch

Table S2.6 The mean change scores on the Treatment and Prevention subscale of the Dutch Quality Of Life in Hand Eczema Questionnaire (QOLHEQ), according to changes measured with the Treatment and Prevention anchor question for change.

Treatment and Prevention anchor of change Treatment and Prevention score in importantly changed patients

No changea _{88 (n/a)} _+0.7 _2.6

Minor deterioration 8/8 (100) -1.8 3.7

MIC, minimally important change; n/a, not applicable; SD, standard deviation. a_{This group includes}

N=85 patients that indicated ‘No change’, with additionally the patients from the ‘Minor improvement’ and ‘Minor deterioration’ group who indicated that they had not importantly changed.

Figure S2.5 Receiver Operating Characteristic (ROC) curve for various cut-off points for change on the Treatment and Prevention subscale of the Dutch Quality Of Life in Hand Eczema Questionnaire (QOLHEQ).

REFERENCES

1. Cella D, Hahn EA, Dineen K. Meaningful change in cancer-specific quality of life scores: differences between improvement and worsening. Qual Life Res. 2002;11(3):207-221.

2. 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):102-109.

3. Terwee CB, Roorda LD, Dekker J, et al. Mind the MIC: large variation among populations and methods. J Clin

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SUPPLEMENT S3 – SPSS SYNTAX TO RECODE THE DUTCH QUALITY OF LIFE IN HAND

ECZEMA QUESTIONNAIRE (QOLHEQ)

The QOLHEQ may be used in daily clinical care for monitoring purpose without seeking permission. The use in academic studies which are not externally

funded is also free. For any other use please send a request to Robert.Ofenloch@med.uni-heidelberg.de

***************************** SPSS SYNTAX TO CODE ************************** ************* Dutch Quality of Life in Hand Eczema Questionnaire *********** ********************************Dutch QOLHEQ ******************************* *

* The variables have to be named according to their order in the questionnaire as “qol1”, “qol2” to “qol30”.

*

* The coding for all variables has to be *”0” for “nooit”.

*”1” for “zelden”. *”2” for “nu en dan”. *”3” for “vaak” and *”4” for “altijd” *

* After running this script you receive four variables for the raw domain scores named “symptoms”. “emotions”. “functions” and “treatment”

* and one variable for the overall score named “qolheq”

********************************* START************************************* ** SYMPTOMS **************************************************************** comp symp_counter=0. comp n_qol1=qol1. if sysmis(qol1) symp_counter=symp_counter+1. if sysmis(qol1) n_qol1=0. recode n_qol1 (2=1) (3=2) (4=3). fre n_qol1. comp n_qol6=qol6. if sysmis(qol6) symp_counter=symp_counter+1. if sysmis(qol6) n_qol6=0. recode n_qol6 (2=1) (3=2) (4=3). fre n_qol6. comp n_qol9=qol9. if sysmis(qol9) symp_counter=symp_counter+1. if sysmis(qol9) n_qol9=0. recode n_qol9 (2=1) (3=2) (4=3). fre n_qol9. comp n_qol11=qol11. if sysmis(qol11) symp_counter=symp_counter+1. if sysmis(qol11) n_qol11=0. recode n_qol11 (2=1) (3=2) (4=3). fre n_qol11. comp n_qol20=qol20.

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if sysmis(qol20) symp_counter=symp_counter+1. if sysmis(qol20) n_qol20=0. recode n_qol20 (2=1) (3=2) (4=3). fre n_qol20. comp n_qol23=qol23. if sysmis(qol23) symp_counter=symp_counter+1. if sysmis(qol23) n_qol23=0. recode n_qol23 (2=1) (3=2) (4=3). fre n_qol23. comp n_qol28=qol28. if sysmis(qol28) symp_counter=symp_counter+1. if sysmis(qol28) n_qol28=0. recode n_qol28 (2=1) (3=2) (4=3). fre n_qol28.

comp symptoms=n_qol1 + n_qol6 + n_qol9 + n_qol11 + n_qol20 + n_qol23 + n_ qol28.

if symp_counter>1 symptoms=99. missing values symptoms(99).

variable labels symptoms ‘symptoms’. fre symptoms. ** EMOTIONS **************************************************************** comp emo_counter=0. comp n_qol5=qol5. if sysmis(qol5) emo_counter=emo_counter+1. if sysmis(qol5) n_qol5=0. recode n_qol5 (2=1) (3=2) (4=3). fre n_qol5. comp n_qol8=qol8. if sysmis(qol8) emo_counter=emo_counter+1. if sysmis(qol8) n_qol8=0. recode n_qol8 (2=1) (3=2) (4=3). fre n_qol8. comp n_qol10=qol10. if sysmis(qol10) emo_counter=emo_counter+1. if sysmis(qol10) n_qol10=0. recode n_qol10 (2=1) (3=2) (4=3). fre n_qol10. comp n_qol16=qol16. if sysmis(qol16) emo_counter=emo_counter+1. if sysmis(qol16) n_qol16=0. recode n_qol16 (2=1) (3=2) (4=3). fre n_qol16. comp n_qol19=qol19. if sysmis(qol19) emo_counter=emo_counter+1. if sysmis(qol19) n_qol19=0.

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recode n_qol19 (2=1) (3=2) (4=3). fre n_qol19. comp n_qol21=qol21. if sysmis(qol21) emo_counter=emo_counter+1. if sysmis(qol21) n_qol21=0. recode n_qol21 (2=1) (3=2) (4=3). fre n_qol21. comp n_qol27=qol27. if sysmis(qol27) emo_counter=emo_counter+1. if sysmis(qol27) n_qol27=0. recode n_qol27 (2=1) (3=2) (4=3). fre n_qol27. comp n_qol30=qol30. if sysmis(qol30) emo_counter=emo_counter+1. if sysmis(qol30) n_qol30=0. recode n_qol30 (2=1) (3=2) (4=3). fre n_qol30.

comp emotions=n_qol5 + n_qol8 + n_qol10 + n_qol16 + n_qol19 + n_qol21 + n_ qol27 + n_qol30.

if emo_counter>1 emotions=99. missing values emotions(99).

variable labels emotions ‘emotions’. fre emotions. ** FUNCTIONING ************************************************************ comp func_counter=0. comp n_qol2=qol2. if sysmis(qol2) func_counter=func_counter+1. if sysmis(qol2) n_qol2=0. recode n_qol2 (2=1) (3=2) (4=3). fre n_qol2. comp n_qol3=qol3. if sysmis(qol3) func_counter=func_counter+1. if sysmis(qol3) n_qol3=0. recode n_qol3 (2=1) (3=2) (4=3). fre n_qol3. comp n_qol12=qol12. if sysmis(qol12) func_counter=func_counter+1. if sysmis(qol12) n_qol12=0. recode n_qol12 (2=1) (3=2) (4=3). fre n_qol12. comp n_qol14=qol14. if sysmis(qol14) func_counter=func_counter+1. if sysmis(qol14) n_qol14=0. recode n_qol14 (2=1) (3=2) (4=3). fre n_qol14.

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comp n_qol15=qol15. if sysmis(qol15) func_counter=func_counter+1. if sysmis(qol15) n_qol15=0. recode n_qol15 (2=1) (3=2) (4=3). fre n_qol15. comp n_qol17=qol17. if sysmis(qol17) func_counter=func_counter+1. if sysmis(qol17) n_qol17=0. recode n_qol17 (2=1) (3=2) (4=3). fre n_qol17. comp n_qol25=qol25. if sysmis(qol25) func_counter=func_counter+1. if sysmis(qol25) n_qol25=0. recode n_qol25 (2=1) (3=2) (4=3). fre n_qol25. comp n_qol29=qol29. if sysmis(qol29) func_counter=func_counter+1. if sysmis(qol29) n_qol29=0. recode n_qol29 (2=1) (3=2) (4=3). fre n_qol29.

comp functions=n_qol2 + n_qol3 + n_qol12 + n_qol14 + n_qol15 + n_qol17 + n_qol25 + n_qol29.

if func_counter>1 functions=99. missing values functions(99).

variable labels functions ‘functions’. fre functions.

**TREATMENT and PREVENTION*************************************************** comp treat_counter=0. comp n_qol4=qol4. if sysmis(qol4) treat_counter=treat_counter+1. if sysmis(qol4) n_qol4=0. recode n_qol4 (2=1) (3=2) (4=3). fre n_qol4. comp n_qol7=qol7. if sysmis(qol7) treat_counter=treat_counter+1. if sysmis(qol7) n_qol7=0. recode n_qol17 (2=1) (3=2) (4=3). fre n_qol7. comp n_qol13=qol13. if sysmis(qol13) treat_counter=treat_counter+1. if sysmis(qol13) n_qol13=0. recode n_qol13 (2=1) (3=2) (4=3). fre n_qol13. comp n_qol18=qol18.

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if sysmis(qol18) treat_counter=treat_counter+1. if sysmis(qol18) n_qol18=0. recode n_qol18 (2=1) (3=2) (4=3). fre n_qol18. comp n_qol22=qol22. if sysmis(qol22) treat_counter=treat_counter+1. if sysmis(qol22) n_qol22=0. recode n_qol22 (2=1) (3=2) (4=3). fre n_qol22. comp n_qol24=qol24. if sysmis(qol24) treat_counter=treat_counter+1. if sysmis(qol24) n_qol24=0. recode n_qol24 (2=1) (3=2) (4=3). fre n_qol24. comp n_qol26=qol26. if sysmis(qol26) treat_counter=treat_counter+1. if sysmis(qol26) n_qol26=0. recode n_qol6 (2=1) (3=1) (4=2). fre n_qol26.

comp treatment=n_qol4 + n_qol7 + n_qol13 + n_qol18 + n_qol22 + n_qol24 + n_ qol26.

if treat_counter>1 treatment=99. missing values treatment(99).

variable labels treatment ‘treatment and prevention’. fre treatment.

**QOLHEQ OVERALL************************************************************* comp counter=symp_counter + emo_counter + func_counter + treat_counter. fre counter.

comp QOLHEQ=n_qol1 + n_qol6 + n_qol9 + n_qol11 + n_qol20 + n_qol23 + n_qol28 + n_qol5 + n_qol8 + n_qol10 + n_qol16 + n_qol19 + n_qol21 + n_qol27 + n_ qol30 + n_qol2 + n_qol3 + n_qol12 + n_qol14 + n_qol15 + n_qol17 + n_qol25 + n_qol29 + n_qol4 + n_qol7 + n_qol13 + n_qol18 + n_qol22 + n_qol24 + n_qol26. if counter>3 QOLHEQ=99.

missing values QOLHEQ(99).

variable labels qolheq ‘QOLHEQ overall score’. fre QOLHEQ.

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9 SUPPLEMENT S4 – INTERPRETABILITY OF SINGLE SCORES OF THE DUTCH QUALITY OF

LIFE IN HAND ECZEMA QUESTIONNAIRE

Table S4.1 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) 29.0 (15.2)a _{36.3 (16.8)}a _{32.3 (16.3)} Range 3 – 75 0 – 82 0 – 82 Symptoms subscale Mean (SD) 8.8 (4.1)a _{10.5 (4.4)}a _{9.6 (4.3)} Range 0 – 19 0 – 21 0 – 21 Emotions subscale Mean (SD) 6.8 (4.6)a _{8.5 (5.2)}a _{7.6 (5.0)} Range 0 – 21 0 – 24 0 – 24 Functioning subscale Mean (SD) 6.8 (4.6)a _{8.9 (5.4)}a _{7.7 (5.1)} Range 0 – 20 0 – 22 0 – 22

Treatment and Prevention subscale

Mean (SD) 6.7 (3.7)a _{8.3 (3.8)}a _{7.4 (3.9)}

Range 0 – 17 0 – 17 0 – 17

HRQoL impaired – Global

Not at all, N (%) 32 (20.0) 30 (22.4) 62 (21.1) Slightly, N (%) 56 (35.0) 31 (23.1) 87 (29.6) Moderately, N (%) 42 (26.3) 42 (31.3) 84 (28.6) Strongly, N (%) 24 (15.0) 25 (18.7) 49 (16.7) Very strongly, N (%) 6 (3.8) 6 (4.5) 12 (4.1) HRQoL impaired – Symptomsa

Not at all, N (%) 3 (1.9) 6 (4.5) 9 (3.1)

Slightly, N (%) 55 (34.4) 22 (16.4) 77 (26.2) Moderately, N (%) 40 (25.0) 39 (29.1) 79 (26.9) Strongly, N (%) 43 (26.9) 53 (39.6) 96 (32.7) Very strongly, N (%) 19 (11.9) 14 (10.4) 33 (11.2) HRQoL impaired – Emotions

Not at all, N (%) 68 (42.5) 45 (33.6) 113 (38.4) Slightly, N (%) 39 (24.4) 33 (24.6) 72 (24.5) Moderately, N (%) 29 (18.1) 28 (20.9) 57 (19.4) Strongly, N (%) 18 (11.3) 23 (17.2) 41 (13.9) Very strongly, N (%) 6 (3.8) 5 (3.7) 11 (3.7) HRQoL impaired – Functioning

Not at all, N (%) 38 (23.8) 24 (17.9) 62 (21.1) Slightly, N (%) 44 (27.5) 31 (23.1) 75 (25.5) Moderately, N (%) 41 (25.6) 29 (21.6) 70 (23.8) Strongly, N (%) 24 (15.0) 34 (25.4) 58 (19.7) Very strongly, N (%) 13 (8.1) 16 (11.9) 29 (9.9)

a_{Significant difference between males and females (P < 0.01). QOLHEQ, Quality Of Life in Hand Eczema}