Impact of National Cancer Institute (NCI)-Mandated Scientific Review on Cancer Clinical Trial Protocol Development
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BACKGROUND: The National Cancer Institute (NCI) requirement that all clinical trials involving cancer patients at NCI-designated cancer centers undergo a scientific protocol review before Institutional Review Board (IRB) review is unique among all medical specialties. Little is known about the impact of scientific review on protocol development. Given heightened interest in the quality and timeliness of oncology clinical trials, we evaluated the scientific review process at an NCI designated center. METHODS: We collected data on all oncology clinical trials that underwent full board review by the UT Southwestern Harold C. Simmons Cancer Center Protocol Review and Monitoring Committee (PRMC) from January 1, 2009, through June 30, 2013. The following data were collected: trial characteristics, PRMC decisions, protocol clarifications and changes requested by PRMC, and subsequent protocol modifications. We analyzed the association between trial characteristics and PRMC protocol modifications using Chi-square testing, Fisher's exact testing, and logistic regression. RESULT: A total of 226 trials were included in our analysis. Of these studies, 23% were institutional (investigator-initiated) trials. Initial PRMC initial decisions were: approved (40%), approved pending response (52%), defer (7%), and disapprove (1%). Across the 226 trials, the PRMC requested 270 changes; total number of requested changes per protocol ranged from 0 (66% of trials) to 17. The number of requested changes per protocol was significantly associated with trial type (mean 0.7 for industry-sponsored versus 3.0 for investigator-initiated; P<0.001) and study year (mean 0.7 in 2009 versus 2.4 in 2013; P=0.03). Forty-nine percent of requested changes applied directly to trial protocols, with the remainder related to consent form (13%) or other documentation (38%). Protocol-related requested changes were as follows: design (53%), intervention (24%), evidence-background-rationale (14%), and population (11%). Compared to those for industry-sponsored trials, PRMC requested changes for investigator-initiated trials were more likely to be implemented (91% versus 83%; P=0.08). A pronounced difference was noted for requested changes related to trial design: among 154 industry-sponsored trials, 28 changes to study design were requested (average 0.2 per trial), and 8 changes (29% of requests) were implemented; among 52 investigator-initiated trials, 39 changes to study design were requested (average 0.8 per trial), and 35 changes (90% of requests) were implemented. CONCLUSION: To our knowledge, this is the first study to evaluate the impact of NCI-mandated scientific protocol review in cancer clinical trial development. While this process appears to have a substantial impact on investigator-initiated trial protocols, effect on industry-sponsored trials is less clear.