In Silico Clinical Trials in the Orthopedic Device Industry: From Fantasy to Reality?

The orthopedic device industry relies heavily on clinical evaluation to confirm the safety, performance, and clinical benefits of its implants. Limited sample size often prevents these studies from capturing the full spectrum of patient variability and real-life implant use. The device industry is accustomed to simulating benchtop tests with numerical methods and recent developments now enable virtual "in silico clinical trials" (ISCT). In this article, we describe how the advancement of computer modeling has naturally led to ISCT; outline the potential benefits of ISCT to patients, healthcare systems, manufacturers, and regulators; and identify how hurdles associated with ISCT may be overcome. In particular, we highlight a process for defining the relevant patient risks to address with ISCT, the utility of a versatile software pipeline, the necessity to ensure model credibility, and the goal of limiting regulatory uncertainty. By complementing-not replacing-traditional clinical trials with computational evidence, ISCT provides a viable technical and regulatory strategy for characterizing the full spectrum of patients, clinical conditions, and configurations that are embodied in contemporary orthopedic implant systems.