Impact of NCI-mandated scientific review on protocol development and content.

Abstract

The NCI requirement that clinical trials at NCI-designated cancer centers undergo scientific review in addition to Institutional Review Board review is unique among medical specialties. We evaluated the impact of this process on protocol development and content. We analyzed cancer clinical trials that underwent full board review by the Harold C. Simmons Cancer Center Protocol Review and Monitoring Committee (PRMC) from January 1, 2009, through June 30, 2013. We analyzed associations between trial characteristics, PRMC decisions, and protocol modifications using Chi-square testing, Fishers exact testing, and logistic regression. A total of 226 trials were analyzed. Of these, 77% were industry-sponsored and 23% were investigator-initiated. Initial PRMC decisions were: approval (40%), provisional approval (52%), deferral (7%), and disapproval (1%). These decisions were associated with study sponsor (P<.001) and phase (P<.001). Ultimately, 97% of industry-sponsored and 90% of investigator-initiated trials were approved (P=.05). Changes were requested for 27% of industry-sponsored trials compared with 54% of investigator-initiated trials (P<.001). Total changes requested (mean, 5.6 vs 2.4; P<.001) and implemented (mean, 4.6 vs 2.1; P=.008) per protocol were significantly greater for investigator-initiated trials. Changes related to study design were more commonly requested (35% vs 13% of trials) and implemented (40% vs 5% of trials) for investigator-initiated trials compared with industry-sponsored trials (P=.03). NCI-mandated scientific protocol review seems to have a substantial impact on investigator-initiated trials but less effect on industry-sponsored trials. These findings may provide guidance on development and prioritization of institutional protocol review policies.