A Critical Comparison of Comparators Used to Demonstrate Credibility of Physics-Based Numerical Spine Models

Abstract

The ability of new medical devices and technology to demonstrate safety and effectiveness, and consequently acquire regulatory approval, has been dependent on benchtop, in vitro, and in vivo evidence and experimentation. Regulatory agencies have recently begun accepting computational models and simulations as credible evidence for virtual clinical trials and medical device development. However, it is crucial that any computational model undergo rigorous verification and validation activities to attain credibility for its context of use before it can be accepted for regulatory submission. Several recently published numerical models of the human spine were considered for their implementation of various comparators as a means of model validation. The comparators used in each published model were examined and classified as either an engineering or natural comparator. Further, a method of scoring the comparators was developed based on guidelines from ASME V&V40 and the draft guidance from the US FDA, and used to evaluate the pertinence of each comparator in model validation. Thus, this review article aimed to score the various comparators used to validate numerical models of the spine in order to examine the comparator's ability to lend credibility towards computational models of the spine for specific contexts of use.

Keywords: Model credibility; Regulatory affairs; Simulation; Uncertainty quantification; Validation; Verification; Virtual patient.