Abstract
Introduction: Netherton syndrome (NS; OMIM#256500) is a rare and severe disorder of epidermal maturation and keratinization caused by pathogenic variants in the serine protease inhibitor Kazal type 5 (SPINK5), leading to severe skin barrier impairment. Although effective treatment is crucial for NS patients, there is a lack of knowledge on what the best treatment options are for these patients. Large heterogeneity in reported outcomes and measurement instruments hinders accurate comparison of treatment results across studies and the development of a treatment guideline. Therefore, we aimed to develop a core outcome set (COS) for NS that can be used in clinical care and research. Methods: This study was performed in accordance with the recommendations of the Core Outcome Measures in Effectiveness Trials (COMET) initiative. After identification of outcomes through a literature search and classification based on the International Classification of Functioning and taxonomies published by the COMET initiative, discussion groups were organized at the 2nd International Netherton Congress 2022 to finalize the provisional outcome list. Through a 2-round e-Delphi, 41 stakeholders (patients and family members, professionals, and representatives of industry) from 14 countries rated the importance of the outcomes using a 9-point Likert scale. An online consensus meeting attended by 14 stakeholders finalized the COS. Results: The COS for NS comprised 21 outcomes in 10 domains. These included four “skin” outcomes, two “sensation” outcomes, two “side-effects of treatment” outcomes, one “vitality” outcome, one “emotional functioning” outcome, two “physical development” outcomes, two “nutrition” outcomes, two “infections” outcomes, two “allergies” outcomes, and three “assessment results” outcomes. Conclusion: In this study, consensus was reached on 21 outcomes to be included in the COS for NS. The selection of outcomes in the COS underlines that NS not only affects the skin but is a disease requiring a broad multidisciplinary approach in clinical care and research. International implementation of this COS will lead to more uniform reporting, thereby enabling comparison of study results, which may facilitate future treatment guideline development. The next step is to further conceptually define the outcomes and reach consensus on how to measure these.
Anouk E.M. Nouwen; Aviël Ragamin; Maria J. Knol; Hagen Ott; Lisa Weibel; Cristina Has; Alain Hovnanian; Amy S. Paller; Christine Bodemer; Virgil A.S.H. Dalm; Suzanne G.M.A. Pasmans; Renske Schappin;
Disease Category: Skin
Disease Name: Netherton Syndrome
Age Range: 0 - 120
Sex: Either
Nature of Intervention: Any
- Clinical experts
- Conference participants
- Consumers (caregivers)
- Consumers (patients)
- Epidemiologists
- Families
- Methodologists
- Patient/ support group representatives
- Pharmaceutical industry representatives
- Researchers
- COS for clinical trials or clinical research
- COS for practice
- Consensus meeting
- Delphi process
- Focus group(s)
- Literature review
- Systematic review
Development of the COS will mainly take place during the 2nd International Netherton conference on November 18-19th. Previous to the conference, existing outcomes are gathered from a systematic review on NS treatment, studies on patient reported outcome measures in NS, ichthyosis treatment guidelines, and information from the previous Netherton conference. At the first conference day, parallel focus groups will be conducted, separately for patients and professionals. At the second conference day, 2 to 3 Delphi rounds will take place. A consensus meeting is planned one week after the conference. The COS development will be performed according to COSMIN guidelines.