EPS4.04 Developing a pharmacovigilance framework for an investigator-led, non-commercial platform trial – finding the optimal regimen for Mycobacterium abscessus treatment (FORMaT)

Abstract

Objectives Mycobacterium abscessus pulmonary disease (MABS-PD) is characterised by treatment related toxicity, poor outcomes, and no evidence-based treatment guidelines. We aim to find the optimal treatment for MABS-PD based on microbiological clearance with acceptable treatment tolerance as defined by the Common Terminology Criteria for Adverse Events (CTCAE). Current interventions are standard of care drugs (13 drugs), none of which are registered for a MABS-PD indication. A pharmacovigilance (PV) framework was developed, enabling real time adverse event (AE) reporting and coding across numerous sites and meeting multi-jurisdictional requirements. Methods Safety monitoring and reporting standard operating procedures, data collection tools and a REDCap Safety Database (SD) were developed alongside the Trial Database. Sites report all AEs/serious adverse events (SAEs) in the trial database which are then ported to the SD. AEs are coded and graded according to the CTCAE and a narrative prepared in the SD. Each event is reviewed by two experienced clinicians and senior pharmacist. For drug-related SAEs, reports are emailed from the SD to all Principal Investigators in a Council for International Organisations for Medical Sciences (CIOMS) report, providing real time safety updates. Results So far, 500 AEs, 44 SAEs including 17 CIOMS reports, have been processed by the PV framework. To date, the most common drug related SAEs are liver dysfunction (29%), hearing impairment (17%) and nausea (11%). Conclusion We have developed a PV framework and SD in REDCap for a complex platform trial, that is able to facilitate decisions on removal/exclusion/substitution of treatments with unacceptable toxicities and meet registration standards for potential novel treatments tested in future iterations of the trial. The trial is funded by the Medical Research Future Fund, United States Cystic Fibrosis Foundation, University of Queensland, and the Children’s Health Foundation.