RESUMO
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.
Assuntos
Comitês de Monitoramento de Dados de Ensaios Clínicos , Preparações Farmacêuticas , Confidencialidade , Humanos , Estudos RetrospectivosAssuntos
Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/terapia , Carcinoma/diagnóstico , Carcinoma/terapia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/química , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/terapia , Animais , Carcinoma/epidemiologia , Carcinoma Neuroendócrino/epidemiologia , Aprovação de Drogas , Humanos , Incidência , Vigilância de Produtos Comercializados , Sistema de Registros , Neoplasias da Glândula Tireoide/epidemiologia , Estados UnidosRESUMO
Detection of off-target cardiovascular (CV) effects remains a significant challenge to drug development. Documentation of CV events in non-CV trials is often inadequate to interpret imbalances between treatment arms, which may lead to concerns about potential CV safety "signals." The Cardiac Safety Research Consortium (CSRC) public-private partnership has developed CV case report forms (CRFs) for adverse CV events, including death. These CRFs are intended to encourage collection, as near to the occurrence of an event as possible, of the minimum information necessary to assess, or possibly adjudicate, the event. A broad range of stakeholders (representing industry, academia, and regulatory authorities) developed these forms with the goal of balancing the collection of key information with the resources likely to be available. Use of these forms is optional, and sponsors may modify them. These forms have not undergone any type of "validation" process. The CSRC will continue to sponsor a working group to invite public comment and feedback on these forms.