Online Program

Statistical Approaches to Clinical Trials COVID-19 Operational Impacts (302434)

*Mark Steven Levenson, FDA/CDER 
*Xin Li, Roche 
*Xiaoxi Zhang, Pfizer Inc. 

Keywords: COVID-19, Trial Operation, Missing Data, Patient Recruitment, Decentralized Trial

The COVID-19 pandemic has had effects on multiple operational aspects of clinical trials. Three notable areas of impact are an increase in pandemic-related missing data, disruption to patient recruitment, and acceleration of decentralized trials with alternative methods to conduct patient follow up.

In the area of missing data, operational metrics that are leading indicators of potential issues with the primary efficacy endpoints have been helpful. Work will be presented on sophisticated metrics that have been developed that can flag problems even for complex endpoints such as progression-free survival (PFS). These measures can be used as QTLs and/or in centralized study monitoring at a study level; and can be summarized to quantify risk at a portfolio level.

In the area of patient recruitment, stochastic models are often used in complex trials. The COVID-19 pandemic brought an additional layer of complexity to recruitment modelling: as countries went into shutdown, sponsors faced the dilemma of re-planning study delivery, re-balancing their portfolios “on the fly”. That translated into the need to adapt the recruitment model to account for the effect of COVID-19. Work will be presented on an approach that blends Poisson-Gamma models, real-time recruitment data updates and epidemiological modelling of COVID-19 spread.

In the area of decentralized trials, the use of alternative mechanisms to conduct patient follow-up (eg, telemedicine and remote assessments) in addition to core clinic visits has been accelerated by the COVID-19 pandemic. Clinical trial sponsors had to react quickly to incorporate different methods for managing the conduct of ongoing clinical trials assuring the robust collection of safety and efficacy data. We will share lessons learned on how the impact of changes in study conduct were managed and consequences to the planned analyses.

The panel will share their thoughts and experience and discuss what this means for future drug development.