1286 Commentaries medications for autoimmune bullous disorders. Dermatol Clin 2011; 4:591–8. 9 Keith PJ, Wetter DA, Wilson JW, Lehman JS. Evidence-based guidelines for laboratory screening for infectious diseases before initiation of systemic immunosuppressive agents in patients with autoimmune bullous dermatoses. Br J Dermatol 2014; 171:1307– 1317. 10 Sorvillo F, Mori K, Sewake W, Fishman L. Sexual transmission of Strongyloides stercoralis among homosexual men. Br J Vener Dis 1983; 59:342.
Which HOME for atopic dermatitis? DOI: 10.1111/bjd.13448 ORIGINAL ARTICLE, p 1318 The report of the Third International Consensus Meeting to Harmonise Core Outcome Measures for Atopic Eczema/Dermatitis Clinical Trials (HOME III) in this issue of the BJD1 is based on the premise that the rheumatologist’s OMERACT filter needs to be met for atopic dermatitis (AD) outcome measures.2 OMERACT (Outcome Measures in Rheumatology, see http://www. omeract.org/) is an independent initiative of international health professionals interested in outcome measures in rheumatology, which uses a multi-stakeholder process, including patients, to obtain a consensus by vote. With all due respect for our rheumatology colleagues, do we need the same filter or ‘quality check list’ when we examine the core outcome measures in AD? Rheumatology methodologists apply the dogma that subjective and objective measures should be kept distinct in outcome measures instruments. Is this indeed applicable to AD, where pruritus is the hallmark or ‘cardinal’ symptom? The European Task Force on Atopic Dermatitis (ETFAD) was created in 1990 in Bordeaux by J.F. Stalder and me. It produced, with 25 paediatric and adult AD experts, the two initial SCORAD (SCOring Atopic Dermatitis) papers of 1993 and 1997, which together are cited more than 1000 times in the Web of Science database and have been used in academic and industry-sponsored randomized controlled trials (RCTs).3,4 SCORAD design and rationale are frequently misunderstood or misquoted, especially in the HOME papers. Pruritus and sleep loss integration in the final SCORAD composite score derive from a mathematical method (principal component analysis) applied to an initial set of multicentre data and was not an a priori choice of experts as are the Psoriasis Area and Severity Index (PASI) or its AD version Eczema Area and Severity Index (EASI). In addition, the intensity 9 distribution model (as in PASI) was indeed not chosen vs. the additive model (which was in a second step designated as SCORAD) because its distribution was more skewed.3 The point concerning the distinction of objective vs. subjective items was also addressed in the 1997 paper and ‘objective SCORAD’ was defined, and since then used
British Journal of Dermatology (2014) 171, pp1285–1299
and validated in many studies. Today, a good marker of pruritus, scratching, can be measured objectively in human studies,5 which may render this point worthless. In addition, assessing dryness (for all patients) and oozing (for paediatric AD) in the list of objective items of SCORAD has been largely debated and accepted by consensus. A point unfortunately missed in the OMERACT filter is the quality of elaboration of the instrument. For SCORAD, five workshops were needed for the 1993 paper. Three workshops with assessed volunteer children and adult patients were organized in Rotterdam, Hamburg and Bordeaux for the 2007 validation paper. The PO-SCORAD now adds the patient’s dimension to this research. It is fully validated against SCORAD and can be used by patients and professionals with a specific application on smartphones and iPads.6 The HOME initiative took a long time to reach a decision in favour of the EASI scoring system, by a vote that included a large minority of nonexperts and excluded many experts. Web-based voting systems and face-to-face discussion at major dermatology meetings is probably a better method for reaching unambiguous consensus. I urge the HOME initiative, at the time of the development of biologics for AD, to concentrate on how to design RCTs in AD with existing validated outcome measures rather than spending too much time on questionable meta-analyses based on rheumatology checklists. Funding sources No external funding. Conflicts of interest None declared. Service de Dermatologie et Dermatologie Pediatrique, CHU de Bordeaux, Bordeaux, France E-mail: [email protected]
A . T A €IE B
References 1 Chalmers JR, Schmitt J, Apfelbacher C et al. Report from the third international consensus meeting to harmonise core outcome measures for atopic eczema/dermatitis clinical trials (HOME). Br J Dermatol 2014; 171:1318–25. 2 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; 67:1111–17. 3 Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology 1993; 186:23–31. 4 Kunz B, Oranje AP, Labreze L et al. Clinical validation and guidelines for the SCORAD index: consensus report of the European Task Force on Atopic Dermatitis. Dermatology 1997; 195:10–19. 5 Noro Y, Omoto Y, Umeda K et al. Novel acoustic evaluation system for scratching behavior in itching dermatitis: rapid and accurate
© 2014 British Association of Dermatologists
Commentaries analysis for nocturnal scratching of atopic dermatitis patients. J Dermatol 2014; 41:233–8. 6 Stalder JF, Barbarot S, Wollenberg A et al. PO-SCORAD Investigators Group. Patient-Oriented SCORAD (PO-SCORAD): a new selfassessment scale in atopic dermatitis validated in Europe. Allergy 2011; 66:1114–21.
Third time coming HOME: not just EASI DOI: 10.1111/bjd.13449 ORIGINAL ARTICLE, p 1318 There is a multitude of outcome measures for atopic eczema (syn. ‘atopic dermatitis’) in the public domain, including severity scores.1 Only if uniform valid and reliable outcome measures are used across clinical trials can we directly compare study results, for instance as part of meta-analyses. Following the example of the OMERACT (Outcome Measures in Rheumatology) initiative in joint diseases,2,3 the ‘Harmonising Core Outcome Measures for Atopic Eczema/Dermatitis Clinical Trials’ (HOME) initiative previously identified atopic eczema symptoms, physician-assessed clinical signs, a measure of long-term control of flares as well as health-related quality of life, as core outcome measures for atopic eczema trials through an international Delphi exercise.4 The report by Chalmers et al.5 in this issue of the BJD summarizes the third HOME consensus meeting held in San Diego, CA, U.S.A. As on the two previous occasions, a large number of stakeholders participated, including clinicians, nurses, patient representatives, methodologists and the pharmaceutical industry. The focus of the meeting was to decide on core physician-assessed clinical signs. Through a combination of formal presentations of systematic review findings and group discussions, the HOME meeting participants decided through an anonymized vote that the Eczema Area and Severity Index (EASI) should be included as the main physician-assessed outcome in all atopic eczema trials, because it includes the key signs of excoriations, erythema and oedema/papulation, as well as lichenification. The decision in favour of the EASI score might come as a surprise to many European dermatologists, who are more familiar with the SCORing of Atopic Dermatitis (SCORAD) index. The SCORAD is the most commonly used severity score in atopic eczema trials and also covers, among others, the key signs included in the EASI.6 It can also look eye-to-eye with the EASI in terms of its validity and reliability. However, in contrast to the EASI, the SCORAD requires the physician to choose a representative disease site, which can be difficult. The SCORAD also assumes a linear relationship between the extent of the atopic eczema and disease severity, which does not apply in all patients.7 Furthermore, and more importantly, the SCORAD includes two patientassessed modalities, sleep disturbance and itch intensity. Blinding of patients is an important element to avoid bias in clinical trials, © 2014 British Association of Dermatologists
1287
making the SCORAD less suitable from that point of view. Even when the objective SCORAD was considered by the HOME III attendants, excluding the two patient-reported outcomes of sleep disturbance and itch intensity, the EASI remained the favourable outcome for 90% of HOME III attendants. As emphasized in the report, this is not to say that other physician-assessed outcome measures cannot be included in clinical trials. The EASI score does not have to be a primary outcome either. Where do we go from here? Like other European dermatologists, even if I try hard, it will take me some time to get used to a score that I have never used in either clinical practice or a research setting. If HOME truly wants the international dermatology community outside the U.S.A. to warm up to the EASI score, it will be vital to develop electronic assessment tools and provide online training in its use, which already exists for the SCORAD index. HOME is not just about physician-assessed outcomes though, and work has already commenced on measures of long-term disease control, quality of life, and patient-reported symptoms. This will all require us working together, ultimately for the benefit of our patients. More to look forward to from HOME in the future, but it won’t be easy! Funding sources C.F. holds a senior fellowship from the National Institute for Health Research (NIHR). The views expressed in this publication are those of the author and not necessarily those of the National Health Service, the NIHR or the U.K. Department of Health. Conflicts of interest C.F. attended the first two HOME meetings and took part in the initial HOME Delphi exercise in Amsterdam in June 2011. C.F. is also a member of the HOME Scientific Advisory Board. St John’s Institute of Dermatology, Guy’s and St Thomas’ Hospital NHS Foundation Trust, St Thomas’ Hospital, Lambeth Palace Road, SE1 7EH, London,U.K. E-mail: [email protected]
C. FLOHR
References 1 Flohr C. Atopic dermatitis diagnostic criteria and outcome measures for clinical trials: still a mess. J Invest Dermatol 2011; 131:557–9. 2 Tugwell P, Boers M, Brooks P et al. OMERACT: an international initiative to improve outcome measurement in rheumatology. Trials 2007; 8:38. 3 Boers M, Brooks P, Strand CV, Tugwell P. The OMERACT filter for Outcome Measures in Rheumatology. J Rheumatol 1998; 25:198–9. 4 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; 67:1111–17. 5 Chalmers JR, Schmitt J, Apfelbacher C et al. Report from the third international consensus meeting to harmonise core outcome mea-
British Journal of Dermatology (2014) 171, pp1285–1299
This document is a scanned copy of a printed document. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material.
Which HOME for atopic dermatitis? DOI: 10.1111/bjd.13448 ORIGINAL ARTICLE, p 1318 The report of the Third International Consensus Meeting to Harmonise Core Outcome Measures for Atopic Eczema/Dermatitis Clinical Trials (HOME III) in this issue of the BJD1 is based on the premise that the rheumatologist’s OMERACT filter needs to be met for atopic dermatitis (AD) outcome measures.2 OMERACT (Outcome Measures in Rheumatology, see http://www. omeract.org/) is an independent initiative of international health professionals interested in outcome measures in rheumatology, which uses a multi-stakeholder process, including patients, to obtain a consensus by vote. With all due respect for our rheumatology colleagues, do we need the same filter or ‘quality check list’ when we examine the core outcome measures in AD? Rheumatology methodologists apply the dogma that subjective and objective measures should be kept distinct in outcome measures instruments. Is this indeed applicable to AD, where pruritus is the hallmark or ‘cardinal’ symptom? The European Task Force on Atopic Dermatitis (ETFAD) was created in 1990 in Bordeaux by J.F. Stalder and me. It produced, with 25 paediatric and adult AD experts, the two initial SCORAD (SCOring Atopic Dermatitis) papers of 1993 and 1997, which together are cited more than 1000 times in the Web of Science database and have been used in academic and industry-sponsored randomized controlled trials (RCTs).3,4 SCORAD design and rationale are frequently misunderstood or misquoted, especially in the HOME papers. Pruritus and sleep loss integration in the final SCORAD composite score derive from a mathematical method (principal component analysis) applied to an initial set of multicentre data and was not an a priori choice of experts as are the Psoriasis Area and Severity Index (PASI) or its AD version Eczema Area and Severity Index (EASI). In addition, the intensity 9 distribution model (as in PASI) was indeed not chosen vs. the additive model (which was in a second step designated as SCORAD) because its distribution was more skewed.3 The point concerning the distinction of objective vs. subjective items was also addressed in the 1997 paper and ‘objective SCORAD’ was defined, and since then used
British Journal of Dermatology (2014) 171, pp1285–1299
and validated in many studies. Today, a good marker of pruritus, scratching, can be measured objectively in human studies,5 which may render this point worthless. In addition, assessing dryness (for all patients) and oozing (for paediatric AD) in the list of objective items of SCORAD has been largely debated and accepted by consensus. A point unfortunately missed in the OMERACT filter is the quality of elaboration of the instrument. For SCORAD, five workshops were needed for the 1993 paper. Three workshops with assessed volunteer children and adult patients were organized in Rotterdam, Hamburg and Bordeaux for the 2007 validation paper. The PO-SCORAD now adds the patient’s dimension to this research. It is fully validated against SCORAD and can be used by patients and professionals with a specific application on smartphones and iPads.6 The HOME initiative took a long time to reach a decision in favour of the EASI scoring system, by a vote that included a large minority of nonexperts and excluded many experts. Web-based voting systems and face-to-face discussion at major dermatology meetings is probably a better method for reaching unambiguous consensus. I urge the HOME initiative, at the time of the development of biologics for AD, to concentrate on how to design RCTs in AD with existing validated outcome measures rather than spending too much time on questionable meta-analyses based on rheumatology checklists. Funding sources No external funding. Conflicts of interest None declared. Service de Dermatologie et Dermatologie Pediatrique, CHU de Bordeaux, Bordeaux, France E-mail: [email protected]
A . T A €IE B
References 1 Chalmers JR, Schmitt J, Apfelbacher C et al. Report from the third international consensus meeting to harmonise core outcome measures for atopic eczema/dermatitis clinical trials (HOME). Br J Dermatol 2014; 171:1318–25. 2 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; 67:1111–17. 3 Severity scoring of atopic dermatitis: the SCORAD index. Consensus Report of the European Task Force on Atopic Dermatitis. Dermatology 1993; 186:23–31. 4 Kunz B, Oranje AP, Labreze L et al. Clinical validation and guidelines for the SCORAD index: consensus report of the European Task Force on Atopic Dermatitis. Dermatology 1997; 195:10–19. 5 Noro Y, Omoto Y, Umeda K et al. Novel acoustic evaluation system for scratching behavior in itching dermatitis: rapid and accurate
© 2014 British Association of Dermatologists
Commentaries analysis for nocturnal scratching of atopic dermatitis patients. J Dermatol 2014; 41:233–8. 6 Stalder JF, Barbarot S, Wollenberg A et al. PO-SCORAD Investigators Group. Patient-Oriented SCORAD (PO-SCORAD): a new selfassessment scale in atopic dermatitis validated in Europe. Allergy 2011; 66:1114–21.
Third time coming HOME: not just EASI DOI: 10.1111/bjd.13449 ORIGINAL ARTICLE, p 1318 There is a multitude of outcome measures for atopic eczema (syn. ‘atopic dermatitis’) in the public domain, including severity scores.1 Only if uniform valid and reliable outcome measures are used across clinical trials can we directly compare study results, for instance as part of meta-analyses. Following the example of the OMERACT (Outcome Measures in Rheumatology) initiative in joint diseases,2,3 the ‘Harmonising Core Outcome Measures for Atopic Eczema/Dermatitis Clinical Trials’ (HOME) initiative previously identified atopic eczema symptoms, physician-assessed clinical signs, a measure of long-term control of flares as well as health-related quality of life, as core outcome measures for atopic eczema trials through an international Delphi exercise.4 The report by Chalmers et al.5 in this issue of the BJD summarizes the third HOME consensus meeting held in San Diego, CA, U.S.A. As on the two previous occasions, a large number of stakeholders participated, including clinicians, nurses, patient representatives, methodologists and the pharmaceutical industry. The focus of the meeting was to decide on core physician-assessed clinical signs. Through a combination of formal presentations of systematic review findings and group discussions, the HOME meeting participants decided through an anonymized vote that the Eczema Area and Severity Index (EASI) should be included as the main physician-assessed outcome in all atopic eczema trials, because it includes the key signs of excoriations, erythema and oedema/papulation, as well as lichenification. The decision in favour of the EASI score might come as a surprise to many European dermatologists, who are more familiar with the SCORing of Atopic Dermatitis (SCORAD) index. The SCORAD is the most commonly used severity score in atopic eczema trials and also covers, among others, the key signs included in the EASI.6 It can also look eye-to-eye with the EASI in terms of its validity and reliability. However, in contrast to the EASI, the SCORAD requires the physician to choose a representative disease site, which can be difficult. The SCORAD also assumes a linear relationship between the extent of the atopic eczema and disease severity, which does not apply in all patients.7 Furthermore, and more importantly, the SCORAD includes two patientassessed modalities, sleep disturbance and itch intensity. Blinding of patients is an important element to avoid bias in clinical trials, © 2014 British Association of Dermatologists
1287
making the SCORAD less suitable from that point of view. Even when the objective SCORAD was considered by the HOME III attendants, excluding the two patient-reported outcomes of sleep disturbance and itch intensity, the EASI remained the favourable outcome for 90% of HOME III attendants. As emphasized in the report, this is not to say that other physician-assessed outcome measures cannot be included in clinical trials. The EASI score does not have to be a primary outcome either. Where do we go from here? Like other European dermatologists, even if I try hard, it will take me some time to get used to a score that I have never used in either clinical practice or a research setting. If HOME truly wants the international dermatology community outside the U.S.A. to warm up to the EASI score, it will be vital to develop electronic assessment tools and provide online training in its use, which already exists for the SCORAD index. HOME is not just about physician-assessed outcomes though, and work has already commenced on measures of long-term disease control, quality of life, and patient-reported symptoms. This will all require us working together, ultimately for the benefit of our patients. More to look forward to from HOME in the future, but it won’t be easy! Funding sources C.F. holds a senior fellowship from the National Institute for Health Research (NIHR). The views expressed in this publication are those of the author and not necessarily those of the National Health Service, the NIHR or the U.K. Department of Health. Conflicts of interest C.F. attended the first two HOME meetings and took part in the initial HOME Delphi exercise in Amsterdam in June 2011. C.F. is also a member of the HOME Scientific Advisory Board. St John’s Institute of Dermatology, Guy’s and St Thomas’ Hospital NHS Foundation Trust, St Thomas’ Hospital, Lambeth Palace Road, SE1 7EH, London,U.K. E-mail: [email protected]
C. FLOHR
References 1 Flohr C. Atopic dermatitis diagnostic criteria and outcome measures for clinical trials: still a mess. J Invest Dermatol 2011; 131:557–9. 2 Tugwell P, Boers M, Brooks P et al. OMERACT: an international initiative to improve outcome measurement in rheumatology. Trials 2007; 8:38. 3 Boers M, Brooks P, Strand CV, Tugwell P. The OMERACT filter for Outcome Measures in Rheumatology. J Rheumatol 1998; 25:198–9. 4 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; 67:1111–17. 5 Chalmers JR, Schmitt J, Apfelbacher C et al. Report from the third international consensus meeting to harmonise core outcome mea-
British Journal of Dermatology (2014) 171, pp1285–1299
This document is a scanned copy of a printed document. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material.
