Global Safety, Novo Nordisk A/S, Copenhagen, Denmark.
US Patient Safety Surveillance, AstraZeneca, Wilmington, Delaware, USA.
Pharmacoepidemiol Drug Saf. 2021 Jan;30(1):9-16. doi: 10.1002/pds.5172. Epub 2020 Nov 24.
To share better practice in establishing data monitoring committees (DMCs) for observational, retrospective safety studies with joint-industry sponsorship.
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.
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.
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.
分享与联合行业赞助的观察性、回顾性安全性研究中建立数据监测委员会（DMC）的更好实践。
创建了一个 DMC 模型，以监测一项观察性、回顾性、上市后安全性研究的数据，该研究调查了长期胰高血糖素样肽-1 受体激动剂（LA GLP-1RA）治疗患者发生甲状腺髓样癌的风险（NCT01511393）。赞助商审查了监管指南、DMC 的最佳实践和赞助商标准操作程序。在由四名成员组成的财团内进行了讨论，评估其对观察性、回顾性、真实世界研究的适用性。根据赞助商提出的、改编的 DMC 模型起草了 DMC 章程。此后，赞助商和 DMC 成员举行了启动会议，以征求 DMC 的意见并最终确定章程。
由于这项研究的观察性、回顾性性质，保证参与者的安全性——这是传统解释性临床试验模型的核心——不适用于我们的 DMC 模型。我们的真实世界模型的总体策略和主要指征包括保持研究的完整性和可信度。因此，DMC 成员的独立性及其专业知识的贡献至关重要。为了确保赞助商之间的数据机密性，除了 DMC 之外，所有研究委员会/公司和赞助商都只收到了盲数据（改编后指揭示特定上市的 LA GLP-1RA/赞助商的数据盲法）。合同研究组织促进了这些数据的沟通和盲法/去盲法，该组织还提供了至关重要的运营监督。
据我们所知，我们已经为联合行业赞助的观察性、回顾性安全性研究建立了第一个 DMC 模型。该模型可以为其他进行类似上市后、联合行业赞助的药物警戒活动的人提供先例。
