Abstract
Before a high-risk medical device is approved for implantation into patients, there should be evidence not only of its performance and safety with a favourable benefit-risk ratio, but also of its clinical efficacy. Regulatory guidance on study methodologies is lacking, however, so the European Commission funded the CORE-MD project (Coordinating Research and Evidence for Medical Devices) to advise regulators on appropriate designs for clinical trials of high-risk devices. The CORE-MD consortium recommends that evaluation should be planned in four stages. Randomised controlled trials should be performed more often, against active comparators reflecting the best available treatment, or using sham interventions with ethical safeguards. Large trials can be managed efficiently using an electronic database or registry. Non-randomised clinical studies can apply objective performance criteria or other validated patient-relevant outcome measures, with adjustments to minimise bias. Full transparency of results from clinical investigations is essential. Proportionate regulation of breakthrough or orphan devices for independently-defined serious unmet needs may involve approval with less evidence, but on condition of subsequent confirmatory studies. These CORE-MD consensus proposals have been submitted to European Union medical device regulators, to be considered as a basis for more transparent and predictable requirements for clinical evidence. FUNDING: The CORE-MD project was funded as a Coordination and Support action from the European UnionHorizon 2020 research and innovation programme, under grant agreement 965246.