The Randomized Withdrawal Study Design: A Flexible Study Design for use in Regulated Medical Device Studies

Clinical studies for new medical devices are expensive to conduct and, if not designed efficiently or with sufficient scientific rigor, can add years to the product development life cycle. In the United States, since the implementation of the 1976 Medical Device Regulations, medical device companies have been working with FDA to find innovative and effective methods to bring new devices to the market. The randomized, controlled clinical trial is the gold standard; however this gold standard study design has not always been required to prove safety and effectiveness of medical devices. This paper explores the Randomized Withdrawal Study Design as a novel trial design for regulated medical device studies. A mock-up trial is described and the advantages and disadvantages of the design are analyzed. The randomized withdrawal trial has been successfully implemented in the pharmaceutical industry. In this design, all patients receive the study therapy and are randomized to have the therapy withdrawn at a time point near the end of the treatment phase. In some settings, a randomized withdrawal study may solve some of the problems inherent in either a traditional randomized design or a nonrandomized design. The potential benefits to utilizing such a design include a higher level of scientific evidence from a single arm study, minimization of the amount of time subjects are exposed to a placebo control, and in the case of enrichment designs, the potential for increased power and decreased time to market due to a smaller sample size requirement.