The influence of blinded independent central review on subject eligibility in oncology studies.

Abstract

e13603 Background: Oncology clinical trials that use imaging based surrogate endpoints such as Progression Free Survival (PFS) and Overall Response Rate (ORR) generally have eligibility criteria based on imaging. Examples include but are not limited to the presence of a RECIST measurable lesion at baseline for studies where ORR is the primary endpoint, the absence of disease at baseline in recurrence studies, the absence of exclusionary brain metastases, and the presence or absence of a particular stage of disease at baseline, such as the absence of T4b, M1, and >N2 disease in studies of muscle invasive bladder cancer. Our experience suggested the percentage of subjects who did not meet those criteria during Blinded Independent Central Review (BICR) may be higher than expected and could have a significant effect on the statistical power of studies. We reviewed a large cohort of subjects (n = 8746) to determine the fraction of subjects who were considered for enrollment or enrolled in oncology clinical trials by investigators and were deemed ineligible during BICR. Methods: We analyzed 66 trials with a total of 8,746 total subjects. Trials were selected based on initiation between June 2020 and June 2021 and involvement of one (1) or more imaging eligibility criteria. Trials in this cohort fit into 2 categories: those that had prospective real time eligibility review where subjects could not be enrolled until the eligibility review was completed in real time (“eligibility review trials”) and those trials that did not have a prospective eligibility review however the data was available for retrospective analysis (“efficacy only trials”). Our analysis determined the fraction of subjects that were prospectively and retrospectively ineligible under each respective category. Results: In these categories, 56% of the subjects (n = 4934) were involved in efficacy only trials. Following BICR review, 12% (n = 614) of the subjects were found to be ineligible retrospectively. Conversely, 44% of the subjects (n = 3812) were enrolled in trials where Clario performed a prospective eligibility review. We found that only 89 of those subjects were deemed ineligible at the time of the prospective eligibility review (2%). This translates to 2% of the subjects were deemed eligible by the investigators, but ineligible by the Clario review. The 10% difference suggests that the eligibility review prevents inclusion of a significant number of subjects that are subsequently determined to have not met the initial imaging eligibility requirements. Conclusions: Eligibility review appears to improve standardization of subject eligibility. These data suggest that the omission of an eligibility review can cascade into censoring more than 10% of subjects. This could have significant impacts on the statistical power of a study and should be considered during study designs.