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The Harmonising Outcome Measures for Eczema (HOME) initiative established a core outcome set (COS) for atopic eczema (AE) clinical trials in 2019. This set encompasses four core outcome domains and corresponding measurement instruments: clinical signs (EASI), patient-reported symptoms (POEM and NRS 11 point for worst itch over the last 24 h), quality of life (DLQI/CDLQI/IDQoLI), and long-term control (Recap or ADCT). Following its roadmap, the HOME initiative is now focused on supporting implementation of the COS. To identify barriers and facilitators to implementation of the COS, and to guide the effort to promote COS uptake, a virtual consensus meeting was held over 2 days (September 25–26, 2021) attended by 55 participants (26 healthcare professionals, 16 methodologists, 5 patients, 4 industry representatives, and 4 students). Implementation themes were identified by a pre-meeting survey distributed to HOME members, presentations, and whole-group discussion. Participants were divided into five multi-professional small groups which ranked their top 3 most important themes, followed by whole-group discussion and anonymous consensus voting (consensus criteria: < 30% disagreement). Three most important implementation themes were identified and agreed upon: (1) awareness and stakeholder engagement, (2) universal applicability of the COS, and (3) ensuring minimum administrative burden. Working groups to address these issues are now a priority for the HOME initiative. The results from this meeting will inform the development of a HOME Implementation Roadmap in an effort to support other COS groups planning for effective implementation of their core sets. [ABSTRACT FROM AUTHOR]

Core outcome sets are critically important outcomes that should be measured in clinical trials. Their absence in atopic dermatitis is a form of research waste and impedes combining evidence to inform patient care. Here, we articulate the rationale for core outcome sets in atopic dermatitis and review the work of the international Harmonising Outcome Measures for Eczema group from its inception in Munich, 2010. We describe core domain determination (what should be measured), to instrument selection (how domains should be measured), culminating in the complete core outcome measurement set in Tokyo, 2019. Using a "road map," Harmonising Outcome Measures for Eczema includes diverse research methods including Delphi and nominal group techniques informed by systematic reviews of properties of candidate instruments. The 4 domains and recommended instruments for including in all clinical trials of atopic dermatitis are patient symptoms, measured by Patient-Oriented Eczema Measure and peak Numerical Rating Scale 11 for itch intensity over 24 hours, clinical signs measured using the Eczema Area and Severity Index, quality of life measured by the Dermatology Life Quality Index series for adults, children, and infants, and long-term control measured by either Recap of atopic eczema or Atopic Dermatitis Control Tool. [ABSTRACT FROM AUTHOR]

Background: Standardized outcome reporting is crucial for trial evidence synthesis and translation of findings into clinical decision‐making. The OMERACT 2.0 Filter and COMET outcome domain taxonomy propose frameworks for consistent reporting of outcomes. There is an absence of a uniform dermatology‐specific reporting strategy that uses precise and consistent outcome definitions. Objectives: Our aim was to map efficacy/effectiveness outcomes assessed in dermatological trials to the OMERACT 2.0 Filter as a starting point for developing an outcome taxonomy in dermatology. Methods: We critically appraised 10 Cochrane Skin Reviews randomly selected from all 69 Cochrane Skin Reviews published until 01/2015 and the 220 trials included covering a broad spectrum of dermatological conditions and interventions. Efficacy/effectiveness outcomes were mapped to core areas and domains according to the OMERACT 2.0 Filter. The extracted trial outcomes were used for critical appraisal of outcome reporting in dermatology trials and for the preliminary development of a dermatology‐specific outcome taxonomy. Results: The allocation of 1086 extracted efficacy/effectiveness outcomes to the OMERACT 2.0 Filter resulted in a hierarchically structured dermatology‐specific outcome classification. In 506 outcomes (47%), the outcome concept to be measured was insufficiently described, hindering meaningful evidence synthesis. Although the core areas assessed in different dermatology trials of the same condition overlap considerably, quantitative evidence synthesis usually failed due to imprecise outcome definitions, non‐comparable outcome measurement instruments, metrics and reporting. Conclusions: We present an efficacy/effectiveness outcome classification as a starting point for a dermatology‐specific taxonomy to provide trialists and reviewers with the opportunity to better synthesize and compare evidence. Linked Commentary: A. Ragamin et al. J Eur Acad Dermatol Venereol 2021; 35: 276‐277. https://doi.org/10.1111/jdv.17103. [ABSTRACT FROM AUTHOR]

The development of core outcome sets (COSs; ie, a minimum set of core outcomes that should be measured and reported in all trials or in clinical practice for a specific condition) in dermatology is increasing in pace. A total of 44 dermatology-related COS projects have been registered in the online Core Outcome Measures in Effectiveness Trials database (http://www.comet-initiative.org/studies/search) and include studies on 26 different skin diseases. With the increasing number of COSs in dermatology, care is needed to ensure the delivery of high-quality COSs that meet quality standards when using state-of-the-art methods. In 2015, the Cochrane Skin-Core Outcome Set Initiative (CS-COUSIN) was established. CS-COUSIN is an international, multidisciplinary working group aiming to improve the development and implementation of COSs in dermatology. CS-COUSIN has developed guidance on how to develop high-quality COSs for skin diseases and supports dermatology-specific COS initiatives. Currently, 17 COS development groups are affiliated with CS-COUSIN and following standardized COS development processes. To ensure successful uptake of COSs in dermatology, researchers, clinicians, systematic reviewers, guideline developers, and other stakeholders should use existing COSs in their work. [ABSTRACT FROM AUTHOR]

Summary: This is the report from the fifth meeting of the Harmonising Outcome Measures for Eczema initiative (HOME V). The meeting was held on 12–14 June 2017 in Nantes, France, with 81 participants. The main aims of the meeting were (i) to achieve consensus over the definition of the core domain of long‐term control and how to measure it and (ii) to prioritize future areas of research for the measurement of the core domain of quality of life (QoL) in children. Moderated whole‐group and small‐group consensus discussions were informed by presentations of qualitative studies, systematic reviews and validation studies. Small‐group allocations were performed a priori to ensure that each group included different stakeholders from a variety of geographical regions. Anonymous whole‐group voting was carried out using handheld electronic voting pads according to predefined consensus rules. It was agreed by consensus that the long‐term control domain should include signs, symptoms, quality of life and a patient global instrument. The group agreed that itch intensity should be measured when assessing long‐term control of eczema in addition to the frequency of itch captured by the symptoms domain. There was no recommendation of an instrument for the core outcome domain of quality of life in children, but existing instruments were assessed for face validity and feasibility, and future work that will facilitate the recommendation of an instrument was agreed upon. [ABSTRACT FROM AUTHOR]

Summary: Results of clinical trials are the most important information source for generating external clinical evidence. The use of different outcomes across trials, which investigate similar interventions for similar patient groups, significantly limits the interpretation, comparability and clinical application of trial results. Core outcome sets (COSs) aim to overcome this limitation. A COS is an agreed standardized collection of outcomes that should be measured and reported in all clinical trials for a specific clinical condition. The Core Outcome Set Initiative within the Cochrane Skin Group (CSG‐COUSIN) supports the development of core outcomes in dermatology. In the second CSG‐COUSIN meeting held in 2017, 11 COS development groups working on skin diseases presented their current work. The presentations and discussions identified the following overarching methodological challenges for COS development in dermatology: it is not always easy to define the disease focus of a COS; the optimal method for outcome domain identification and level of detail needed to specify such domains is challenging to many; decision rules within Delphi surveys need to be improved; appropriate ways of patient involvement are not always clear. In addition, there appear to be outcome domains that may be relevant as potential core outcome domains for the majority of skin diseases. The close collaboration between methodologists in the Core Outcome Set Initiative and the international Cochrane Skin Group has major advantages for trialists, systematic reviewers and COS developers. [ABSTRACT FROM AUTHOR]

Background Symptoms have been identified as a core outcome domain for atopic eczema (AE) trials. Various instruments exist to measure symptoms in AE, but they vary in quality and there is a lack of standardization between clinical trials. Our objective was to systematically evaluate the quality of the evidence on the measurement properties of AE symptom instruments, thereby informing consensus discussions within the Harmonising Outcome Measures for Eczema (HOME) initiative regarding the most appropriate instruments for the core outcome domain symptoms. Methods Using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist and predefined criteria for good measurement properties on identified development and validation studies of AE symptom instruments, a best evidence synthesis was performed to draw an overall conclusion on quality of the instruments and to provide recommendations. Results Eighteen instruments were identified and evaluated. When the quality and results of the studies were considered, only five of these instruments had sufficient validation data to consider them for the core outcome set for the core outcome domain symptoms. These were the paediatric Itch Severity Scale (ISS), Patient-Oriented Eczema Measure (POEM), Patient-Oriented SCOring Atopic Dermatitis (PO-SCORAD), Self-Administered Eczema Area and Severity Index (SA-EASI) and adapted SA-EASI. Conclusions ISS (paediatric version), POEM, PO-SCORAD, SA-EASI and adapted SA-EASI are currently the most appropriate instruments and therefore have the potential to be recommended as core symptom instrument in future clinical trials. These findings will be utilized for the development of a core outcome set for AE. [ABSTRACT FROM AUTHOR]

This report provides a summary of the third meeting of the Harmonising Outcome Measures for Eczema (HOME) initiative held in San Diego, CA, U.S.A., 6-7 April 2013 (HOME III). The meeting addressed the four domains that had previously been agreed should be measured in every eczema clinical trial: clinical signs, patient-reported symptoms, long-term control and quality of life. Formal presentations and nominal group techniques were used at this working meeting, attended by 56 voting participants (31 of whom were dermatologists). Significant progress was made on the domain of clinical signs. Without reference to any named scales, it was agreed that the intensity and extent of erythema, excoriation, oedema/papulation and lichenification should be included in the core outcome measure for the scale to have content validity. The group then discussed a systematic review of all scales measuring the clinical signs of eczema and their measurement properties, followed by a consensus vote on which scale to recommend for inclusion in the core outcome set. Research into the remaining three domains was presented, followed by discussions. The symptoms group and quality of life groups need to systematically identify all available tools and rate the quality of the tools. A definition of long-term control is needed before progress can be made towards recommending a core outcome measure. [ABSTRACT FROM AUTHOR]

The lack of core outcome sets for atopic eczema (AE) is a major obstacle for advancing evidence-based treatment. The global Harmonising Outcome Measures for Eczema (HOME) initiative has already defined clinical signs, symptoms, quality of life, and long-term control of flares as core outcome domains for AE trials. This article deals with the standardization of measurement instruments to assess clinical signs of AE. To resolve the current lack of standardization of the assessment of clinical signs of AE, we followed a structured process of systematic reviews and international consensus sessions to identify 1 core outcome measurement instrument for assessment of clinical signs in all future AE trials. Systematic reviews indicated that from 16 different instruments identified to assess clinical signs of AE, only the Eczema Area and Severity Index (EASI) and the objective Scoring Atopic Dermatitis (SCORAD) index were identified as extensively validated. The EASI has adequate validity, responsiveness, internal consistency, and intraobserver reliability. The objective SCORAD index has adequate validity, responsiveness, and interobserver reliability but unclear intraobserver reliability to measure clinical signs of AE. In an international consensus study, patients, physicians, nurses, methodologists, and pharmaceutical industry representatives agreed that the EASI is the preferred core instrument to measure clinical signs in all future AE trials. All stakeholders involved in designing, reporting, and using clinical trials on AE are asked to comply with this consensus to enable better evidence-based decision making, clearer scientific communication, and improved patient care. [ABSTRACT FROM AUTHOR]

Background: Patients with severe atopic eczema frequently require systemic treatment to control their disease. Methotrexate and azathioprine are proposed as off-label treatment options, but direct comparisons are lacking. Objectives: We sought to compare the efficacy and safety of methotrexate versus azathioprine in adults with severe atopic eczema. Methods: Patients with severe atopic eczema were randomly assigned in a 1:1 ratio to receive either methotrexate (dosage, 10-22.5 mg/wk) or azathioprine (dosage, 1.5-2.5 mg/kg/d) for 12 weeks, followed by a 12-week follow-up period. Primary outcome was the mean change in the severity scoring of atopic dermatitis index after 12 weeks. Efficacy assessors blinded for allocation of treatment were used to perform clinical outcome assessment. Analyses were done on an intention-to-treat basis. Results: Of the 45 patients screened, 42 were included. At week 12, patients in the methotrexate group had a mean relative reduction in the severity scoring of atopic dermatitis index of 42% (SD, 18%) compared with 39% (SD, 25%) in the azathioprine group (P = .52). Proportions of patients achieving at least mild disease and reductions on impact of quality of life, symptoms, and levels of thymus and activation-regulated chemokine were similar in both groups at weeks 12 and 24. No statistically significant differences were found in the number and severity of adverse events. Abnormalities in blood count were more common in the azathioprine group. No serious adverse events occurred. Conclusion: Both treatments achieved clinically relevant improvement and were safe in the short term. Methotrexate and azathioprine are appropriate options for the treatment of severe atopic eczema. [ABSTRACT FROM AUTHOR]

The Eczema Area and Severity Index is an investigator‐assessed instrument reporting clinical signs of atopic dermatitis. The instrument is extensively validated in both adult and paediatric populations and recommended as a core outcome measure to assess clinical signs by the Harmonising Outcome Measures for Eczema initiative in clinical trials and was recently recommended as an option to measure signs in clinical practice. Here, we review the validation of the instrument using standard assessment criteria, explore controversies and challenges to its universal applicability and highlight future electronic adaptations. We find that the instrument demonstrates adequate performance in the measurement properties recommended by the COnsensus‐based Standards for the selection of health Measurement INstruments initiative for instruments reporting clinical signs, is clinically interpretable, and is suitable for all atopic dermatitis severities. Some validation gaps remain. Information reporting on its performance in diverse populations, with emphasis on deeply pigmented skin, is promising though limited. Technological adaptations are demonstrating promising initial validation results and may facilitate remote and/or automated assessments assisting clinical care and decentralized clinical trials in the future. We find no strong evidence limiting its use in trials or clinical practice although questions pertaining to the effect of investigator training remain. We recommend that the Eczema Area and Severity Index be used in all interventional atopic dermatitis trials and be considered alongside other recommended clinical practice severity instruments. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB), caused by Mycobacterium tuberculosis, is a significant global health problem. In immunocompetent individuals, the microorganism can remain in a latent, non‐contagious form, however, it may become active under conditions of immunosuppression. Tumour necrosis factor (TNF) inhibitors, which are frequently used for the management of immune‐mediated disorders like psoriasis, have been associated with a significantly increased risk of reactivating latent TB. Consequently, international guidelines recommend TB screening and preventive treatment before starting anti‐TNF therapy. These recommendations have extended to IL‐12/23, IL‐17, IL‐23 and TYK2 inhibitors under a caution principle, despite their different mechanisms of action. However, current evidence suggests that some of these agents are arguably not associated with an increased risk of TB reactivation or development of TB disease after infection, which calls for a critical reassessment of these guidelines. We have conducted a literature search evaluating the risk of TB reactivation associated with these innovative therapies, integrating findings from both randomized clinical trials and real‐world evidence. The identified evidence is limited but the low number of identified cases of reactivation with IL‐17 and IL‐23 inhibitors prompts reconsidering the need for preventive treatment for latent TB in all cases, regardless of biologic class or individual patient's risk of TB reactivation or drug toxicity. This review, along with the clinical insight of a panel of experts on behalf of the SPIN‐FRT, led to the development of these consensus recommendations for managing psoriasis treatment in patients with latent TB infection or at risk of TB infection, who are receiving or are intended to receive biologic and non‐biologic targeted therapies. These recommendations highlight the need for updates to the existing guidelines, aiming to provide a more differentiated approach that reflects the evolving landscape of psoriasis treatment and its implications for TB management. [ABSTRACT FROM AUTHOR]

Summary: One of the important complications of the skin disease, psoriasis, is the appearance of changes in the nails. These range from the formation of small pits across the surface of the nail to painful separation of the nail plate from the underlying nail bed and disfiguring enlargement and thickening of the nail itself. Given this wide range of changes in appearance it is important that, in assessing the results of treatment, researchers can use simple, but accurate, criteria for measuring changes in psoriatic nails under treatment; these are known as core outcome sets. This study, organised by investigators from the departments of dermatology in the Universities of Amsterdam and Nijmegen in the Netherlands, surveyed 65 clinical trials focussing on nail psoriasis, all of which used assessment measures for nail changes in psoriasis, the commonest of which is called the nail psoriasis severity index. However, they found that several different methods were used in the various studies. A detailed analysis of these studies has identified a number of variations in the methods used which make the results of different treatments difficult to compare. This is particularly because there was no standard way of expressing the final scores of the severity of nail disease found in these studies and also that the different aspects of severity were rated differently. Some of these assessment scoring systems have not been validated (substantiated) either. The authors call for a rethink of the use of nail assessments in psoriasis and highlight the need to develop new methods which are sufficiently robust to stand up to close scrutiny. These should allow investigators to assess the different changes seen in the diseased nails in a standardised way, so that results of different studies can be compared. They suggest that a consensus group should be established to carry out this work. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article about multiple randomized controlled trials, which appeared in the previous issue.