Towards Global Consensus on Core Outcomes for Hidradenitis Suppurativa Research: An Update from the HISTORIC Consensus Meetings I and II

BACKGROUND: A core outcomes set (COS) is an agreed minimum set of outcomes that should be measured and reported in all clinical trials for a specific condition. Hidradenitis suppurativa (HS) has no agreed-upon COS. A central aspect in the COS development process is to identify a set of candidate outcome domains from a long list of items. Our long list had been developed from patient interviews, a systematic review of the literature and a healthcare professional survey, and initial votes had been cast in two e-Delphi surveys. In this manuscript, we describe two in-person consensus meetings of Delphi participants designed to ensure an inclusive approach to generation of domains from related items. OBJECTIVES: To consider which items from a long list of candidate items to exclude and which to cluster into outcome domains. METHODS: The study used an international and multistakeholder approach, involving patients, dermatologists, surgeons, the pharmaceutical industry and medical regulators. The study format was a combination of formal presentations, small group work based on nominal group theory and a subsequent online confirmation survey. RESULTS: Forty-one individuals from 13 countries and four continents participated. Nine items were excluded and there was consensus to propose seven domains: disease course, physical signs, HS-specific quality of life, satisfaction, symptoms, pain and global assessments. CONCLUSIONS: The HISTORIC consensus meetings I and II will be followed by further e-Delphi rounds to finalize the core domain set, building on the work of the in-person consensus meetings

Development and initial validation of the HS‐IGA: a novel hidradenitis suppurativa‐specific investigator global assessment for use in interventional trials

Abstract: Background: Few validated instruments exist for use in hidradenitis suppurativa (HS) trials. Objectives: To develop a novel HS Investigator Global Assessment (HS‐IGA) and to validate its psychometric properties. Methods: Development of HS‐IGA involved discussion among stakeholders, including patients, within HISTORIC. Data from replicate phase III randomized controlled trials evaluating HS treatment were utilized. Multivariate models identified lesion type and body region as variables of importance. Classification and regression trees for ordinal responses were built. Validation included assessment of test–retest reliability, predictive validity, responsiveness and clinical meaningfulness. Results: There were 3024 unique measurements available in PIONEER I. Mean and median lesion counts by region were largely <10 and were highest in axillary and inguinal regions. The mean and median number of regions involved were ≤ 3 for individual lesions and combinations. Regardless of lesion type, axillary and inguinal regions most influenced the HS‐IGA score. Accordingly, regions were combined into a six‐point IGA based on the maximum lesion number in either upper or lower body regions with a score of 0 (0–1 lesions), 1 (2–5), 2 (6–10), 3 (11–15), 4 (16–20) and 5 (≥ 20 lesions). The intraclass correlation coefficient for test–retest reliability was 0·91 (95% confidence interval 0·87–0·94). Spearman’s rank order correlations (SROCs) with HS‐PGA and Hidradenitis Suppurativa Clinical Response (HiSCR) were 0·73 and 0·51, respectively (P < 0·001 for both comparisons). SROCs with Dermatology Life Quality Index (DLQI), pain numerical rating scale and HS‐QoL were 0·42, 0·34 and –0·25, respectively (P < 0·001 for all comparisons). HS‐IGA was responsive at weeks 12 and 36. Predictive convergent validity was very good with HS‐PGA (area under the curve = 0·89) and with HiSCR (area under the curve = 0·82). Predictive divergent validity was low with DLQI and HS‐QoL. Conclusions: HS‐IGA has moderate‐to‐strong psychometric properties and is simple to calculate

Global consensus process to establish a core dataset for hidradenitis suppurativa registries

Background: Several registries for hidradenitis suppurativa (HS) already exist in Europe and the USA. There is currently no global consensus on a core dataset (CDS) for these registries. Creating a global HS registry is challenging, owing to logistical and regulatory constraints, which could limit opportunities for global collaboration as a result of differences in the dataset collected. The solution is to encourage all HS registries to collect the same CDS of information, allowing registries to collaborate. Objectives: To establish a core set of items to be collected by all HS registries globally. The core set will cover demographic details, comorbidities, clinical examination findings, patient-reported outcome measures and treatments. Methods: Beginning in September 2022, 20 participants - including both clinicians with expertise in HS and patient advocates - from eight countries across three continents participated in a Delphi process consisting of four rounds of voting, with all participants completing each round. A list of potential items for inclusion in the core set was generated from the relevant published literature, including systematic reviews of comorbidities in HS, clinical and examination findings, and epidemiology. For disease severity and progression items, the Hidradenitis SuppuraTiva Core outcome set International Collaboration (HiSTORIC) core set and other relevant instruments were considered for inclusion. This resulted in 47 initial items. Participants were invited to suggest additional items to include during the first round. Anonymous feedback was provided to inform each subsequent round of voting to encourage consensus. Results: The eDelphi process established a CDS of 48 items recommended for inclusion in all HS registries globally. Conclusions: The routine adoption of this CDS in current and future HS registries should allow registries in different parts of the world to collaborate, enabling research requiring large numbers of participants.</p

The Global Hidradenitis Suppurativa Atlas (GHiSA) methodology: Combining global proportions in a pooled analysis

Introduction: Data concerning the global burden of Hidradenitis Suppurativa (HS) are limited. Reported prevalence estimates vary between 0.0003% and 4.1%, and data from various geographical regions are still to be collected. Previously reported prevalence rates have been limited by the methodological approach and source of data. This has resulted in great heterogeneity as prevalence data from physician-diagnosed cases poorly match those of self-reported apparent HS disease. Methods: The Global Hidradenitis Suppurativa Atlas (GHiSA) introduces an innovative approach to determine the global prevalence of HS. This approach involves using a previously validated questionnaire to screen apparently healthy adults accompanying a patient to a non-dermatological outpatient clinic visit in a hospital. The screening questionnaire (i.e., the index test) is combined with a subsequent physician-based in-person validation (i.e., the reference standard) of the participants who screen positive. Ten percent of the screen-negative participants are also clinically assessed to verify the diagnostic precision of the test. The local prevalence (pi) will be estimated from each country that submits the number of patients who are HS positive according to the index test and clinical examination (n), and the corresponding total number of observations (N). Conclusion: The GHiSA Global Prevalence studies are currently running simultaneously in 58 countries across six continents (Africa, Europe, Australia, North America, South America, and Asia). The goal of the combined global proportion is the generation of a single summary (i.e., proportional meta-analysis), which will be done after a logit transformation, and synthesized using a random-effects model. The novel standardization of the Global Prevalence studies conducted through GHiSA enables direct international comparisons, which were previously not possible due to substantial heterogeneity in past HS prevalence studies

Protocol for the development of a core domain set for hidradenitis suppurativa trial outcomes

Introduction: Randomised controlled trials (RCTs) should have well-defined primary and secondary outcomes to answer questions generated by the main hypotheses. However, for the chronic, inflammatory skin disease hidradenitis suppurativa (HS), the reported outcome measures are numerous and diverse. A recent systematic review found a total of 30 outcome measure instruments in 12 RCTs. This use of a broad range of outcome measures can increase difficulties in interpretation and comparison of results and may potentially obstruct appropriate evidence synthesis by causing reporting bias. One strategy for dealing with these problems is to develop a core outcome set (COS). A COS is a list of outcomes that are meant as mandatory and should be measured and reported in all clinical trials. The aim of this study is to develop a COS for the management of HS. Method and analysis An international steering group of researchers, clinicians and a patient research partner will guide the COS development. 6 stakeholder groups are involved: patients, dermatologists, surgeons, nurses, industry representatives and drug regulatory authorities. A 1:1 ratio of patients:healthcare professionals is aimed for. The initial list of candidate items will be obtained by combining three data sets: (1) a systematic review of the literature, (2) US and Danish qualitative interview studies involving patients with HS and (3) an online healthcare professional (HCP) item generation survey. To reach consensus on the COS, 4 anonymous online Delphi rounds are then planned together with 2 face-to-face consensus meetings (1 in Europe and 1 in the USA) to ensure global representation. Ethics and dissemination The study will be performed according to the Helsinki declaration. All results from the study, including inconclusive or negative results, will be published in peer-reviewed indexed journals. The study will involve different stakeholder groups to ensure that the developed COS will be suitable and well accepted