Platform for the Evaluation of innovations in Radiation oncology through registry-based conduct of multi-centric pragmatic randomized trials: PERa implementation

Abstract

Abstract Purpose Radiotherapy has achieved substantial progress often attributed to accelerated technological innovation over decades. However, randomized controlled trials (RCTs) are costly, difficult to fund and to conduct, such that the generation of quality evidence is outpaced by changes in practice. We sought to evaluate the implementation performance of a platform approach to the conduct of pragmatic RCTs in radiation oncology. Methods We implemented PERa, a platform consisting of a prospective registry of patients receiving standard-of-care radiation therapy, designed to support pragmatic registry-based RCT (rRCT) methods and staged informed consent. Implementation performance metrics included rate of registry enrollment, acceptability of re-contact and/or serving as controls for interventional trials, activation and recruitment of embedded comparative effectiveness rRCTs, compliance to study arms, and completeness of ePRO data acquired at scale. Results Between January 1, 2018 and December 31, 2023, the registry accrued 1415 participants across 5 participating institutions. At time of stage 1 consent, 93% agreed to re-contact for participation in a clinical trial, and 97% consented to serve as control. Seven embedded rRCTs were activated, and one third of participants (n = 477) were randomized. Only two study arm non-compliance events were recorded. Although 97% of subjects consented to ePROs, completion rate was only 53% in those with stage 1 only consent, rising to 62% in those subjects also consented at a second stage to a companion rRCT. Conclusion The PERa platform is met with high acceptance demonstrating efficient conduct of rRCTs embedded in routine radiation oncology practice. Future work to improve ePRO completions and automate harmonization with EMR data lakes have the potential to improve the quality of evidence generation and support learning health systems. Trial registration NCT03378856: Registered on December 12, 2017. NCT04100174: Registered on September 20, 2019. NCT04178174: Registered on November 17, 2019. NCT05457699: Registered on July 04, 2022. NCT04405401: Registered on May 24, 2020. NCT04901234: Registered on May 17, 2021. NCT05317026: Registered on March 08, 2022.