Least Burdensome Approach: FDA Says Do Less to Succeed More
[Posted on: Thursday, December 21, 2017]
FDA would like developers of new medical devices do fewer clinical trials, use clinical trial data from outside the US, rely on data from uncontrolled open-label studies, and use unconventional data to support PMA and 510k applications. Manufacturers should try to “use the minimum amount of information necessary to adequately address a regulatory question or issue” according to a new FDA guidance document released last week. If you are surprised, don’t be; the least burdensome policy is not new (it was originally published in November 2000) but the details in which FDA describes alternative approaches is. In the guidance, several examples are presented to clarify the kind of information that may be useful to support market approval discussions with the reviewers. The guiding principles of the policy is to allow manufacturers to customize the information submitted to the least needed to answer specific questions, have multiple discussions with the reviewers to evaluate answers to regulatory issues in a timely fashion, and present a holistic case in support of their products based on the its development history, evidence generation needs in support of the intended use, and measures to assure timely patient access with reasonable assurance of safety and efficacy. The goal of the program should be to reduce the burden of conducting traditional clinical trials by using other sources of clinical data such as non-US clinical trials, data from compassionate use trials, use non-clinical data, and use real world data (RWD) where available. Although valid scientific evidence from well-controlled trials is still the preferred data, FDA is willing to consider other sources of credible data such as that from open-label uncontrolled clinical trials, clinical trials with historical controls, well-documented case histories, and reports of significant human experience with a marketed device, from which it can fairly and responsibly be concluded by qualified experts that there is reasonable assurance of the safety and effectiveness of a device under its conditions of use. There is significant variability in the evidence FDA is willing to accept. The characteristics of the device, its conditions of use, the existence and adequacy of warnings and other restrictions, and the extent of experience with its use, all could define what additional information FDA may be willing to accept, hence the need for extensive discussions with the reviewers. However, anecdotal evidence will not be acceptable, so isolated case reports, random experiences, reports lacking sufficient details to permit scientific evaluation, and unsubstantiated opinions are not acceptable. Although the guidance is written for medical devices, similar principles can be applied to drug and biologics. This guidance formalizes about two decades of conventional wisdom used by strategists to design clinical development plans for new products and should be a welcome document for all developers looking for written strategic general advice from FDA.