Does the Dermatology Life Quality Index (DLQI) underestimate the disease-specific burden of psoriasis patients?

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1 DOI: /jdv JEADV ORIGINAL ARTICLE Does the Dermatology Life Quality Index (DLQI) underestimate the disease-specific burden of psoriasis patients? A. Langenbruch,* M.A. Radtke, M. Gutknecht, M. Augustin Institute for Health Services Research in Dermatology and Nursing (IVDP), University Medical Center Hamburg-Eppendorf (UKE), Hamburg, Germany *Correspondence: A. Langenbruch. Abstract Background The Dermatology Life Quality Index (DLQI) is the most frequently used health-related quality of life (HRQoL) instrument for skin diseases. According to the DLQI instructions, the responses not relevant and my skin problem has not at all affected this aspect of life ( not at all ) have to be scored as 0 = no HRQoL impairments. Objective The aim of this study was to estimate potential bias of DLQI measurements for patients with psoriasis based on items considered to be not relevant. Methods One thousand two hundred forty-three patients with psoriasis were surveyed in a cross-sectional study. Disease severity (Psoriasis Area and Severity Index, PASI) and subjective health state (EuroQoL Visual Analogue Scale, EQ VAS) were compared per DLQI item between patients who answered the respective question not relevant and those who answered not at all. Results Patients who declared a DLQI item to be not relevant showed a higher disease severity and a lower health state. Conclusion Results indicate that patients who declare a DLQI item to be not relevant have a higher disease-related burden than those who do not feel affected by their psoriasis in the same aspect of life. If aspects of life are considered to be not relevant due to high disease burden, this should be reflected by a HRQoL instrument. Received: 5 April 2018; Accepted: 14 August 2018 Conflicts of Interest Anna Langenbruch and Mandy Gutknecht declare no conflicts of interest. Marc Alexander Radtke has received research grants and/or consulting or lecturing fees from AbbVie, Almirall, Amgen, Astellas, Biogen, Biologix, B ohringer, Celgene, Eli Lilly, Galderma, Hexal, Janssen-Cilag, La Roche Posay, Leo, Medac, Merck, MSD, Mundipharma, Novartis, Pfizer, Sandoz, and Sanofi. Matthias Augustin has received research grants and/or consulting or lecturing fees from AbbVie, Almirall, Amgen, Astellas, Biogen, Biologix, B ohringer, Celgene, Eli Lilly, Galderma, Hexal, Janssen-Cilag, La Roche Posay, Leo, Medac, Merck, MSD, Mundipharma, Novartis, Pfizer, Sandoz, and Sanofi. Funding Source Biogen provided financial support for this study. Introduction In past decades, health-related quality of life (HRQoL) has become a major outcomes parameter in dermatology. As recommended by regulatory authorities, measurement of HRQoL is included in almost all clinical trials. 1,2 In clinical care, the use of patient-relevant outcomes has likewise been recommended by guidelines and consensus documents. 3,4 Recommendations for the use of HRQoL instruments have been issued. 5 The Dermatology Life Quality Index (DLQI) has become the most frequently used disease-specific quality of life instrument for skin diseases It has gained high acceptance due to good feasibility and ease of use. Moreover, an anchor-based system of severity classification has been developed, and attempts to establish minimum clinically important differences have been made. 11 However, some drawbacks of the DLQI have been discussed and need to be taken into account Moreover, there are obviously limitations with respect to content validity when indications other than chronic inflammatory skin diseases are investigated. Another potential limitation is its construction as a sum scored HRQoL instrument combined with the fact that missing values and items marked as not relevant are scored as 0 = no

2 124 Langenbruch et al. impairment. Hence, patients who mark an item as not relevant, which is an option in 8 out of 10 items, are considered to be unaffected in that aspect of life. This raises the question whether there are disease-related reasons for considering an item to be not relevant. This could be related to being too impaired by the skin disease to take part in certain areas of life. If so, patients would be ascribed a lower overall DLQI score (=higher HRQoL) in the absence of the corresponding HRQoL. A potential bias in the DLQI score arising from this aspect has not yet been systematically analysed in the literature. Hence, the current study was conducted in a large cohort of psoriasis patients in order to assess the extent of bias that may result from the technical construction of the DLQI, specifically in terms of the treatment of not relevant declarations. The research questions were as follows: 1 What is the proportion of psoriasis patients with missing answers and items declared to be not relevant? 2 Are there any differences with respect to severity indicators between psoriasis patients who state not relevant and those who state my skin problem has not at all affected this aspect of life over the last week ( not at all ) for particular DLQI items? Methods Study design Data were obtained from a large cross-sectional nationwide study conducted with adult patients with psoriasis vulgaris in dermatological care in Germany. 15 Data collection took place between January 2013 and March Patient-related outcomes were gathered by means of questionnaires with both practitioner and patient components. Outcomes Like the other instruments, the DLQI was used in a validated German translation. 16 Based on ten questions about the impact of the skin disease and its treatment on different aspects of the patient 0 s HRQoL over the last week, the DLQI sum score is calculated by summing up the score of each item. Questions are scored on a four-point Likert scale: 0, not at all/not relevant; 1, a little; 2, a lot; and 3, very much. The total DLQI sum score can range from 0 to 30, with lower scores indicating better HRQoL. The patient 0 s subjective health state was measured by means of the German version of the visual analogue scale (EQ VAS) of the EQ-5D 17 in which the patient assesses his/her own current health state on a scale from 0 ( worst imaginable health state ) to 100 ( best imaginable health state ). Severity of psoriasis was measured by means of the German version of Psoriasis Area and Severity Index (PASI). 18 This score combines the severity ratings of three target symptoms (erythema, infiltration and desquamation) and the involvement of the four main body areas (head, trunk, upper and lower extremities). The PASI score ranges from 0 to 72. Higher scores indicate higher severity of the psoriasis. Statistical analysis All data were described with standard statistical parameters (frequencies for categorical data; mean value and standard deviation for continuous data). Means of two groups were compared by unpaired t-tests. Differences with a probability of a type I (a) error of 0.05 were considered as statistically significant in all analyses. Each unpaired t-test was supplemented by effect-size determination (Cohen s d). It is determined by calculating the mean difference between two groups and divided by the pooled standard deviation. According to Cohen, sizes of 0.2, 0.5 and 0.8, respectively, represent weak, medium and strong effects in unpaired t-tests. 19 The analysis was performed using SPSS Statistics 23 for Microsoft Windows (IBM Corp, Armonk, NY, USA). Results Overall, n = 1243 patients with psoriasis from 82 dermatological centres were included. Mean age was 52 years; proportion of female patients was 43.4% (Table 1). 6.0% of the patients had at least one missing value in the DLQI. By contrast, the proportion of items declared not relevant was considerable (Fig. 1). The items most frequently marked as not relevant were item 7 ( work and study, 28.1%), item 6 ( sport, exercise, 26.0%), item 9 ( sexual relationships, 22.1%) and item 8 ( personal relationships, 15.8%). Overall, 48.7% of patients answered all 10 items without not relevant statements or missing answers. By contrast, the proportion of patients with at least one item declared to be not relevant was 48.0% (1 3 items considered not relevant : 36.1%; >3: 11.9%) (Fig. 2). Subjective health (EuroQoL Visual Analogue Scale, EQ VAS) and disease severity (Psoriasis Area and Severity Index, PASI) differed between patients who stated not relevant and those who stated not at all regarding the same DLQI item. Except for Table 1 Characteristics of the 1243 participating patients with psoriasis Age (years, mean SD) % female 43.4 BMI (mean SD) % obese patients (BMI >30) 30.6 % at least one family member affected by psoriasis 38.0 Disease duration (years, mean SD) DLQI (mean SD) % DLQI > PASI (mean SD) EQ VAS (mean SD) BMI, body mass index; DLQI, Dermatology Life Quality Index; EQ VAS, EuroQoL Visual Analogue Scale; PASI, Psoriasis Area and Severity Index; SD, standard deviation.

3 Underestimation of psoriasis burden by DLQI Over the last week, how itchy, sore, painful or stinging has your skin been? 2. Over the last week, how embarrassed or self conscious have you been because of your skin? 3. Over the last week, how much has your skin interfered with you going shopping or looking after your home or garden? 4. Over the last week, how much has your skin influenced the clothes you wear? 5. Over the last week, how much has your skin affected any social or leisure activities? 6. Over the last week, how much has your skin made it difficult for you to do any sport? 7. Over the last week, has your skin prevented you from working or studying? 8. Over the last week, how much has your skin created problems with your partner or any of your close friends or relatives? 9. Over the last week, how much has your skin caused any sexual difficulties? 10. Over the last week, how much of a problem has the treatment for your skin been, for example by making your home messy, or by taking up time? % Missing Not relevant Relevant Figure 1 Frequencies of missing answers and not relevant statements for each Dermatology Life Quality Index (DLQI) item (n = 1243 patients with psoriasis) % items not relevant Figure 2 Distribution of patients by number of Dermatology Life Quality Index (DLQI) items answered not relevant (n = 1243). the PASI difference between patients answering item 4 ( clothing ), patients who declared a DLQI item to be not relevant displayed a higher disease severity and a lower subjective health (Table 2). Discussion The objective of the present study was to identify a potential bias of the Dermatology Life Quality Index in the outcomes measurement of disease-specific HRQoL in psoriasis as a consequence of items declared to be not relevant. This questionnaire is the most frequently used instrument for the assessment of quality of life in skin diseases worldwide. Accordingly, any potential bias associated with its use is of great interest. Unlike formal validity, which has been described in a number of previous studies, 6 no systematic investigations have been conducted analysing the robustness of the instrument with respect to relevant scaling properties, such as the treatment of items declared to be not relevant. Many regulatory bodies and reimbursement agencies require the DLQI as a measure of patient burden. In many countries, a DLQI >10 is the qualifying threshold for the indication of systemic treatment. Moreover, the benefit assessment for systemic drugs largely depends on effectiveness in patients with moderate to severe disease, defined in the field of psoriasis as DLQI and body surface area (BSA) or PASI >10. 3 Hence, any uncertainty in achieving PASI >10 directly impacts reimbursement, treatment indication and access to drugs for patients under real-world conditions. Owing to the use of a sum score built of 10 items that includes 8 items with a not relevant option that is scored as 0 = no impairment, any item missing or declared to be not relevant for reasons other than a lack of disease burden may prejudice fair HRQoL assessments. The present data for psoriasis support the previous findings of good feasibility and acceptability of the DLQI questionnaire. 8,20 By contrast, the high proportion of patients declaring not relevant at least once in the DLQI indicates that this is not a negligible phenomenon. The largest number of not relevant responses was found for the questions on impairment in work and school, sport, sexual relationships, as well as in social activities. Hence, persons with a lack of social contacts, sexual activity and employment, who rate those items as not relevant because they do not experience those areas of life show a lower quality of life burden according to the DLQI. However, this is precisely the

4 126 Langenbruch et al. Table 2 EQ VAS and PASI of patients responding to particular DLQI items not relevant vs. my skin problem has not affected this aspect of my life over the last week ( not at all ) DLQI item no Subject Patients statement PASI EQ VAS n Mean SD P-value d 1 n Mean SD P-value d 1 3 Daily routines not at all not relevant Clothing not at all not relevant Social and leisure not at all not relevant Sport, exercise not at all not relevant Work, study not at all not relevant Personal relationships not at all not relevant Sexual relationships not at all not relevant Treatment not at all not relevant DLQI, Dermatology Life Quality Index; EQ VAS, EuroQoL Visual Analogue Scale; PASI, Psoriasis Area and Severity Index; SD, standard deviation; 1 effect size. population known to be at high risk of psoriasis and related negative impacts on their life. Hence, the presumed underestimation would most likely affect a group that is actually affected by a high disease burden. This interpretation is supported by the finding that the disease-related burden in patients with psoriasis stating not relevant is higher than that of patients stating my skin problem has not at all affected this aspect of life in most of the DLQI items with a not relevant option. This comparison is of particular interest because both statements are treated the same manner, by scoring them 0 (= no impairment ) for each item, according to the DLQI instructions. A possible limitation of this study is that the specific phrasing of the response options in a specific language may influence how patients respond, which in turn may have a (probably small) bearing whether these results from a German study can be generalized to other language versions of the DLQI instrument. This question should be addressed in future studies. Taken together, the data suggest that considering an item to be not relevant because of disease-related disabilities to participate in sports, social events and other activities of everyday life should be treated differently in HRQoL assessment undertaken by means of DLQI. We also recommend the development of further methodology for HRQoL assessment that can be unambiguously applied to all patients with a given skin disease. Acknowledgements The authors wish to thank all participating centres, the German Psoriasis Network (PsoNet) and the Professional Association of German Dermatologists (BVDD) and the German Society of Dermatology (DDG) for their cooperation in this study. We also thank Biogen for providing financial support to this study. References 1 Committee for Medicinal Products for Human Use (CHMP). Reflection paper on the regulatory guidance for the use of Health-Related Quality of Life (HRQL) measures in the evaluation of medicinal products. European Medicines Agency (EMEA). London, URL ropa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_ jsp&amp%3Bmid=WC0b01ac ec4 (last accessed: 2 October 2017). 2 U.S. Department of Health and Human Services FDA Center for Drug Evaluation and Research, U.S. Department of Health and Human Services FDA Center for Biologics Evaluation and Research, U.S. Department of Health and Human Services FDA Center for Devices and Radiological Health. Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims: draft guidance. Health Qual Life Outcomes 2006; 4: Mrowietz U, Kragballe K, Reich K et al. Definition of treatment goals for moderate to severe psoriasis: a European consensus. Arch Dermatol Res 2011; 303: Schmitt J, Spuls P, Boers M et al. Towards global consensus on outcome measures for atopic eczema research: results of the HOME II meeting. Allergy 2012; 67: Prinsen CA, de Korte J, Augustin M et al. Measurement of health-related quality of life in dermatological research and practice: outcome of the EADV Taskforce on Quality of Life. J Eur Acad Dermatol Venereol 2013; 27: Basra MKA, Fenech R, Gatt RM, Salek MS, Finlay AY. The Dermatology Life Quality Index : a comprehensive review of validation data and clinical results. Br J Dermatol 2008; 159: Finlay AY. Current severe psoriasis and the Rule of Tens. Br J Dermatol 2005; 152: Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI): a simple practical measure for routine clinical use. Clin Exp Dermatol 1994; 19:

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