Increasing complexity in oncology phase I clinical trials.

Clinical trials in oncology have become increasingly complex because of incorporation of predictive biomarkers and patient selection based on molecular profiling of tumors. We have examined the change in procedures and work intensity in phase 1 oncology trials over the years with several parameters used as surrogates of complexity. Categories that were included as events were clinical evaluations, pharmacokinetic (PK) laboratory tests, non-PK laboratory tests, specific molecular or histological characteristics, questionnaires and subjective assessments, routine clinical and physical examinations, imaging, invasive procedures and others. The information was extracted using a standardized form including study type, tumor type, information on agent, participant characteristics and study mandated events during the first 3 cycles of each protocol. A total of 102 phase I oncology and hematology study protocols that were active at a single institution in 1996, 2006 and 2016 were evaluated. In 2016, there were significantly more (P < 0.05) median number of procedures, outpatient tests, subjective assessments, PK's, molecular profiling, biopsies and medication dispensing times. There were higher median numbers of procedures in studies in hematologic malignancies, testing immunotherapies and those with over 15 inclusion or exclusion criteria. These values also differed significantly (P < .005) when the median values were compared in nonparametric tests. Our results suggest that study related procedures in cancer phase I trials have substantially increased over the last two decades. The successful conduct of early-phase oncology clinical trials in future will require additional research resources.