Use of Intermediate Predictive and Surrogate Endpoints in Medical Device Trials

• Activity Number: 54 - Methods and Modeling for Medical Device and Clinical Studies
• Type: Contributed
• Date/Time: Monday, August 3, 2020 : 10:00 AM to 2:00 PM
• Sponsor: Section on Medical Devices and Diagnostics
• Author(s): Manuela Buzoianu*
• Companies: FDA
• Keywords: intermidiate endpoint; surrogate endpoint; adaptive design; predictive models; two-phase design; Bayesian design

Abstract

In this talk I plan to discuss some study design considerations related to the use of intermediate and surrogate endpoints in device trials. More recently, FDA guidance for Breakthrough Devices specifies the need for study designs that are “as efficient and flexible as practicable, when scientifically appropriate”, advocating for efficiency in terms of sample size, follow-up duration, or use of less invasive/costly measurements in clinical trials. These study designs may include intermediate or surrogate endpoints as substitutes for the clinically relevant endpoints when they are likely to predict the device clinical benefit. Prediction models in particular are often used in prospective studies to predict the ultimate long-term endpoint from an intermediate temporal one and, thus, reduce the time and resources for the primary analysis. Other design methods would allow the collection of data in two-phases, including an initial (pre-market) phase based on surrogate endpoint, shifting the burden to assess the hard endpoint in the second (post-market) phase. These methods will be discussed from a reviewer’s perspective.