A Core Domain Set For Hidradenitis Suppurativa Trial Outcomes: An International Delphi Process L. Thorlacius*1,2, J. R. Ingram*3, B. Villumsen4, S. Esmann1, J. S. Kirby5, A. B. Gottlieb6, J. F. Merola7, R. Dellavalle8, S. M. Nielsen2, R. Christensen2, Amit Garg‡9, G. B. E. Jemec‡1 on behalf of the HIdradenitis SuppuraTiva cORe outcomes set International Collaboration (HISTORIC) 1) Department of Dermatology, Zealand University Hospital, Roskilde; Health Sciences Faculty, University of Copenhagen, Denmark 2) Musculoskeletal Statistics Unit, The Parker Institute, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark 3) Institute of Infection & Immunity, Cardiff University, University Hospital of Wales, Heath Park, Cardiff, UK 4) The Patients' Association HS Denmark, Denmark 5) Department of Dermatology, Penn State Hershey Medical Center, Hershey, USA 6) Department of Dermatology, New York Medical College, Valhalla NY, USA 7) Harvard Medical School, Boston, Massachusetts, USA; Department of Dermatology and Department of Medicine, Division of Rheumatology, Brigham and Women's Hospital, Boston, Massachusetts, USA 8) Dermatology Service, US Department of Veteran Affairs Medical Centre, Denver, USA 9) Department of Dermatology, Hofstra Northwell School of Medicine, New Hyde Park, New York, USA * The first two authors share co-first authorship ‡The last two authors share co-senior authorship British Journal of Dermatology. DOI: 10.111/bjd.16672

DEPARTMENT OF DERMATOLOGY, ZEALAND UNIVERSITY HOSPTIAL, DENMARK HISTORIC An international steering group consisting of researchers, clinicians and a patient research partner under the HISTORIC initiative has been formed to guide the development of the COS. The steering group consists of nine members; a patient research partner who is a board member of The HS Patients' Association in Denmark, two dermatologists with expertise in both HS research and clinical work; four dermatologists with a special interest in outcome measures in dermatology; a biostatistician from OMERACT experienced in COS development and a MD Ph.D. student.

Introduction What’s already known? Outcome measure instruments used for hidradenitis suppurativa are markedly heterogeneous, with 30 instruments recently found in 12 randomised trials. Lack of consensus regarding outcome measure instruments limits evidence synthesis and increases the risk of outcome reporting bias. A core domain set is an agreed minimum set that should be measured and reported in all clinical trials for a specific condition

Objective To achieve global multi-stakeholder consensus on a Core Outcome Set (COS) of domains regarding what to measure in clinical trials for HS.

Methods An international Delphi consensus project Using a multi-stakeholder approach, involving patients and healthcare professionals (HCPs) including dermatologists, surgeons, HS nurses, the pharmaceutical industry and medical regulators. Aiming to have a 1:1 ratio of patients:HCPs Patients were identified from patient associations and via dermatologists with a special interest in HS The meeting locations were planned for both Europe and North America to ensure that patient and HCP opinions from both continents were incorporated

Methods Phase 1: Identification of candidate items Systematic literature review Qualitative data from patient interviews and focus group studies Conducted in both Denmark and North America Interviews were conducted until the point of saturation (meaning, no new constructs or ideas are added) Survey of healthcare professionals Participants were asked to list all areas of importance regarding HS, related to any aspect of the disease or treatment of the disease

Methods Phase 2: Consensus process HS stakeholders participated in a Delphi process which included five anonymous e-Delphi rounds and four face-to-face consensus meetings to reach consensus on the final COS The combined list of potential items identified in Phase 1 were scored (1-3 = not important, 4-6 = important but not critical or 7-9 = critical) Items were discussed, rescored and then linked into over-arching domains and rediscussed Items were then included in COS or excluded, based on consensus opinion

DEPARTMENT OF DERMATOLOGY, ROSKILDE HOSPTIAL, DENMARK Phase 1 Phase 2

Patient global , Physician global Flare frequency and duration, Results Pain Physical Signs Anatomic location, Surface area, Total lesion count, Inflammatory lesion count, Number of abscesses, Number of inflamed nodules, Number of sinus tracts, Number of fistulae HS specific QOL Physical functioning, Psychological functioning, Psychosocial functioning, Emotional well-being, Ability to work or study Global assessment Patient global , Physician global Progression of course Flare frequency and duration, Time to recurrence Inner ring: the core set Domains and items that reached ‘consensus in’ for patients and HCPs Outer ring: Items that did not reach ‘consensus in’ but were marked as a specific research agenda or important in specific trials at consensus meetings Symptoms Biomarkers Time to heal Middle ring: Domains and items that reached ‘consensus in’ for patients or HCPs

Discussion The HISTORIC initiative has begun the process to develop a Core Outcome Set (COS) for HS trials The final core domain set includes five domains: pain physical signs hidradenitis suppurativa-specific quality of life global assessment progression of course A sixth domain, symptoms, was highly supported by patients and not by healthcare professionals; it was recommended for inclusion in the COS by the HISTORIC Steering Committee as an additional domain, given the importance of patient-reported domains

Conclusions What does this study add? Our study provides global multi-stakeholder consensus on core outcome domains for hidradenitis suppurativa The implementation of a COS for HS clinical trials should improve the interpretation and comparison of future studies testing interventions for HS and reduce the risk of outcome reporting bias and heterogeneity across studies After achieving consensus on what to measure in HS clinical trials, the next step for the HISTORIC initiative will be to reach consensus on the outcome measurement instruments best suited to measure each of the core domains in the COS

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