Department of BioMechanical Engineering, Delft University of Technology, Delft, The Netherlands.
Leiden University Medical Centre, Leiden, The Netherlands.
Br J Clin Pharmacol. 2023 Jul;89(7):2144-2159. doi: 10.1111/bcp.15685. Epub 2023 Feb 16.
The recent introduction of the European Medical Device Regulation poses stricter legislation for manufacturers developing medical devices in the EU. Many devices have been placed into a higher risk category, thus requiring more data before market approval, and a much larger focus has been placed on safety. For implantable and Class III devices, the highest risk class, clinical evidence is a necessity. However, the requirements of clinical study design and developmental outcomes are only described in general terms due to the diversity of devices.
A structured approach to determining the requirements for the clinical development of high-risk medical devices is introduced, utilizing the question-based development framework, which is already used for pharmaceutical drug development. An example of a novel implantable device for haemodialysis demonstrates how to set up a relevant target product profile defining the device requirements and criteria. The framework can be used in the medical device design phase to define specific questions to be answered during the ensuing clinical development, based upon five general questions, specified by the question-based framework.
The result is a clear and evaluable overview of requirements and methodologies to verify and track these requirements in the clinical development phase. Development organizations will be guided to the optimal route, also to abandon projects destined for failure early on to minimize development risks.
The framework could facilitate communication with funding agencies, regulators and clinicians, while highlighting remaining 'known unknowns' that require answering in the post-market phase after sufficient benefit is established relative to the risks.
欧洲医疗器械法规的最新出台，对在欧盟开发医疗器械的制造商提出了更严格的立法要求。许多设备被归入更高的风险类别，因此在获得市场批准之前需要更多的数据，并且更加关注安全性。对于植入式和 III 类设备（风险最高的类别），临床证据是必要的。然而，由于设备种类繁多，临床研究设计和发展结果的要求仅以一般术语描述。
本文采用基于问题的开发框架，介绍了一种确定高风险医疗器械临床开发要求的结构化方法，该框架已用于药物开发。以一种新型用于血液透析的植入式设备为例，演示了如何建立相关的目标产品概况，定义设备要求和标准。该框架可用于医疗器械设计阶段，根据基于问题的框架中规定的五个一般性问题，确定在随后的临床开发阶段需要回答的具体问题。
结果是对要求和方法的清晰、可评估的概述，可用于验证和跟踪临床开发阶段的这些要求。开发组织将被引导至最佳路径，还可以尽早放弃注定失败的项目，以最大程度地降低开发风险。
该框架可以促进与资助机构、监管机构和临床医生的沟通，同时突出在建立足够的效益相对于风险后，在后市场阶段需要回答的“已知的未知”问题。
