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

PURPOSE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Recommendations from the iSBTc-SITC/FDA/NCI Workshop on Immunotherapy Biomarkers.

PURPOSE: To facilitate development of innovative immunotherapy approaches, especially for treatment concepts exploiting the potential benefits of personalized therapy, there is a need to develop and validate tools to identify patients who can benefit from immunotherapy. Despite substantial effort, we do not yet know which parameters of antitumor immunity to measure and which assays are optimal for those measurements. EXPERIMENTAL DESIGN: The iSBTc-SITC (International Society for Biological Therapy of Cancer-Society for Immunotherapy of Cancer), FDA (Food and Drug Administration), and NCI (National Cancer Institute) partnered to address these issues for immunotherapy of cancer. Here, we review the major challenges, give examples of approaches and solutions, and present our recommendations. RESULTS AND CONCLUSIONS: Although specific immune parameters and assays are not yet validated, we recommend following standardized (accurate, precise, and reproducible) protocols and use of functional assays for the primary immunologic readouts of a trial; consideration of central laboratories for immune monitoring of large, multi-institutional trials; and standardized testing of several phenotypic and functional potential potency assays specific to any cellular product. When reporting results, the full QA (quality assessment)/QC (quality control) should be conducted and selected examples of truly representative raw data and assay performance characteristics should be included. Finally, to promote broader analysis of multiple aspects of immunity, and gather data on variability, we recommend that in addition to cells and serum, RNA and DNA samples be banked (under standardized conditions) for later testing. We also recommend that sufficient blood be drawn to allow for planned testing of the primary hypothesis being addressed in the trial, and that additional baseline and posttreatment blood is banked for testing novel hypotheses (or generating new hypotheses) that arise in the field.