Design and analysis of crossover trials for investigating high-risk medical devices: A review.

During evaluation of new investigational medical devices, the FDA recommends that investigators design a crossover clinical trial, in which the patients are arranged to cross over from one treatment arm to another. The FDA annually receives the premarket applications of investigational medical devices, in which sponsors design and conduct crossover trials as their confirmatory clinical trials for evaluating safety and effectiveness of the devices. This article reviews the use of crossover clinical trial in pivotal clinical trials for high-risk medical devices regulated and approved by the United States Food and Drug Administration (FDA) from 2005 to 2018. As an example, in which a crossover trial was implemented during the regulatory approval process of a new device, the article additionally presents the FDA-approved premarket approval (PMA) submission of the Medtronic MiniMed 530G system, an artificial pancreas device system that mimic a normally functioning pancreas by monitoring glucose levels and administering insulin at a certain threshold maintained by sensing blood glucose levels. The article also reiterates the critical regulatory considerations that the FDA made regarding the design and analysis of crossover trials in its guidance for industry.