A core outcome domain set to assess cutaneous neurofibromas related to neurofibromatosis type 1 in clinical trials

Abstract

Background: Cutaneous neurofibromas (cNF) are considered one of the highest burdens of neurofibromatosis type 1 (NF1). To date, no medical treatment can cure cNF or prevent their development. In that context, there is an urgent need to prepare and standardize the methodology of future trials targeting cNF.

Objectives: The objective was to develop a core outcome domain set suitable for all clinical trials targeting NF1-associated cNF.

Methods: The validated approach of this work consisted of a three-phase methodology: (i) generating the domains [systematic literature review (SLR) and qualitative studies]; (ii) agreeing (three-round international e-Delphi consensus process and working groups); and (iii) voting.

Results: (i) The SLR and the qualitative studies (three types of focus groups and a French e-survey with 234 participants) resulted in a preliminary list of 31 candidate items and their corresponding definitions. (ii) A total of 229 individuals from 29 countries participated in the first round of the e-Delphi process: 71 patients, relatives or representatives (31.0%), 130 healthcare professionals (HCPs, 56.8%) and 28 researchers, representatives of a drug regulatory authority, industry or pharmaceutical company representatives or journal editors (12.2%). The overall participation rate was 74%. After round 2, five candidate items were excluded. Between rounds 2 and 3, international workshops were held to better understand the disagreements among stakeholders. This phase led to the identification of 19 items as outcome subdomains. (iii) The items were fused to create four outcome domains ('clinical assessment', 'daily life impact', 'patient satisfaction' and 'perception of health') and prioritized. The seven items that did not reach consensus were marked for the research agenda. The final core outcome domain set reached 100% of the votes of the steering committee members.

Conclusions: Although numerous outcomes can be explored in studies related to cNF in NF1, the present study offers four outcome domains that should be reported in all trial studies, agreed on by international patients, relatives and representatives of patients; HCPs; researchers, representatives of drug regulatory authorities or pharmaceutical companies and journal editors. The next step will include the development of a set of core outcome measurement instruments to further standardize how these outcomes should be assessed.