Mission (almost) impossible: setting up a complex investigator led international adaptive platform trial – Finding the Optimal Regimen for Mycobacterium abscessus Treatment (FORMaT)

Abstract

Objectives To describe the challenges experienced and successes achieved in the multi-jurisdictional set up process of the FORMaT Trial (NCT04310930). Methods Treatment of Mycobacterium abscessus pulmonary disease (MABS-PD) is an evidence-free zone. To address the knowledge gap, we obtained funding from several sources to assemble project management, database and biostatistics teams. Independent trial oversight committees were formed, and the protocol evolved to ensure a pragmatic trial. Infrastructure including a custom electronic data capture (EDC) system, pharmacovigilance framework and trial documentation were developed, accommodating the international nature of the study. The trial was listed on three registries and regulatory approvals obtained in 12 sites across three countries. Current trial interventions include 13 standard of care drugs used for MABS-PD treatment, none of which are registered for a MABS indication. Recruitment opened in Australia in March 2020, but promptly shut down due to COVID. Site set up resumed in early 2022 and we are currently expanding globally and sourcing further funding to support the trial’s post set up phase. Results FORMaT successfully opened in Australia, Denmark and Singapore despite major challenges including: ongoing funding (where opportunities are often disease/country specific and do not accommodate adaptive platform trials), diverse regulatory requirements, complex contractual negotiations, obtaining statistical expertise for complex simulations, navigating data privacy legislation in each jurisdiction (including changes in the UK), managing translation of trial documents, and incorporating drug coding and multiple languages in the EDC system, while delivering milestones on a streamlined budget. Conclusion We have gained experience in the setup of an international adaptive platform trial using available non-commercial systems, and a greater understanding of the human and infrastructure resources needed.