The Evolution of Burden of Novel Cell Therapy Trials on Research Operations

Introduction Scientific challenges of cell therapies are frequently published and discussed, but the operational burden on research operations is not well documented. We reviewed study operational burdens that are essential to conducting clinical research in the largest commercial cellular therapy specific dataset to date. Methods We reviewed all oncology cellular therapy trials which Swedish was site selected and received a complete regulatory package. We defined operational burden as # of protocol amendments, # of ICF amendments, change to ICF length, and CRS/neurotoxicity guidance. Data from studies terminated and in startup were censored from the metrics when unavailable. Results Of 29 studies, 15 opened, 9 are in startup, and 5 never opened. The average length of study startup was 278 Days (range:147-429); defined as time from protocol release to contracts/budgets to site activation. The average length of an ICF was 29.6 pages (n: 29, Range: 18-58). The average # of pages added to the ICF was 4 (n:6, range: 0-11). The average # of protocol amendments while open at our site was 5 (n: 15); however, an average of 7 amendments were globally released for the same trials. The average # of ICFs per study was 2. When reviewing CRS and neuro-toxicity guidelines, 16 of 29 provided protocol specific guidance with 13 deferring to institutional guidelines. Of the 29 trials, 20 required a separate LTFU protocol. Conclusion The length of ICFs was greater than previously reported (29 vs 21 pages)1. The average # of protocol amendments was greater than reported (7 vs 4)2. Time to trial activation increased (2015-2018 Days to startup: 249 n: 8; 2019-current Days to startup: 312 n: 7). This was directly related to the increasing # of amendments per study year (2015-2018 x̄:1 n:8; 2019-current x̄:2 n:7) with an average of 1 amendment released during startup. It is important to note that cellular therapy trials require concurrent IBC review in addition to IRB review increasing activation work. With the development of ICANS and CARTOX guidelines in 2019, protocols shifted towards standardized methods, prior to 2019 all protocols required an MMSE, post 2019 7 of 8 protocols used ICANS criteria and only 1 required MMSE. In conclusion there has been a shift towards more protocol amendments and lengthier ICF forms since 2015 which directly correlates increased operation burden of processing more pages and amendments; however, portions of the protocols are becoming more standardized with ICANS and CARTOX.