A joint industry-sponsored data monitoring committee model for observational, retrospective drug safety studies in the real-world setting

Abstract

Purpose: To share better practice in establishing data monitoring committees (DMCs) for observational, retrospective safety studies with joint-industry sponsorship. Methods: A DMC model was created to monitor data from an observational, retrospective, post-authorization safety study investigating risk of medullary thyroid cancer in patients treated with long-acting glucagon-like peptide-1 receptor agonists (LA GLP-1RAs) (NCT01511393). Sponsors reviewed regulatory guidelines, best practice and sponsors' standard operation procedures on DMCs. Discussions were held within the four-member consortium, assessing applicability to observational, retrospective, real-world studies. A DMC charter was drafted based on a sponsor-proposed, adapted DMC model. Thereafter, a kick-off meeting between sponsors and DMC members was held to receive DMC input and finalize the charter. Results: Due to this study's observational, retrospective nature, assuring participant safety – central for traditional explanatory clinical trial models – was not applicable to our DMC model. The overall strategy and key indication for our real-world model included preserving study integrity and credibility. Therefore, DMC member independence and their contribution of expert knowledge were essential. To ensure between-sponsor data confidentiality, all study committees/corporations and sponsors, besides the DMC, received blinded data only (adapted to refer to data blinding that revealed the specific marketed LA GLP-1RA/sponsor). Communication and blinding/unblinding of these data were facilitated by the contract research organization, which also provided crucial operational oversight. Conclusions: To our knowledge, we have established the first DMC model for joint industry-sponsored, observational, retrospective safety studies. This model could serve as a precedent for others performing similar post-marketing, joint industry-sponsored pharmacovigilance activities.