Breakthroughs in cancer biology have defined new research programs emphasizing the development of therapies that target specific pathways in tumor cells or promote anti-cancer immunity. Innovations in clinical trials have followed with statistical designs devised to consolidate traditional phases of oncologic drug development as well as facilitate inclusive eligibility and evaluations of multiple indications. These so-called “seamless” trial designs have many potential benefits but have not yet been objectively considered.
The National Cancer Institute (NCI) has recognized the need for more careful consideration of seamless trial design. A special working group was formed as a sub-committee of NCI’s Clinical Trials Design Task Force with the goal of providing national, consensus recommendations for first-in-human cancer drug trials. NCI selected Brian Hobbs, PhD, of the Lerner Research Institute’s Department of Quantitative Health Sciences, to lead the group. Dr. Hobbs is an expert in statistical methods for clinical trial design.
Dr. Hobbs and his group identified 1,786 first-in-human, early-phase trials conducted from 2010-2017. They selected high-impact studies playing an important role in oncologic drug development. They examined several factors in each study, including infrastructure, statistical design and inference, oversight, reporting, selection of dose and schedule, and late-stage toxicities, as well as considered the design’s potential impact on regulatory policy and drug developers upon widespread adoption for “multiple indication” drug development strategies. Dr. Hobbs and his colleagues published their findings and recommendations in the Journal of the National Cancer Institute. They compare seamless versus conventional discrete-phase trials as well as provide recommendations for future study planning.
“With targeted and immune-oncology agents demonstrating both successes and treatment benefit heterogeneity in early-phase trials, trialists require design methodology that is more appropriate for precision medicine contexts and better suited to overcoming assumptions that were established for the development of cytotoxic agents,” Dr. Hobbs said. “Accelerating the pace of human experimental inquiry, however, elevates the need for oversight and sufficient scientific rigor to ensure that established standards are being followed.”
The Task Force hopes that the published recommendations will help guide drug developers to plan ethical, scientifically sound trials that are better suited to elucidate heterogeneities in treatment benefit for targeted and immunotherapies across multiple treatment indications.
Dr. Hobbs joined Cleveland Clinic as Associate Staff and Section Head of Cancer Biostatistics in the Lerner Research Institute. He holds a joint appointment in Cleveland Clinic’s Taussig Cancer Institute. He also serves as Co-Director of the Biostatistics and Bioinformatics Core for the Case Comprehensive Cancer Center. His methodological expertise comprises Bayesian inference, subtyping, prediction, and trial design as well as cancer radiomics. Before joining Cleveland Clinic, Dr. Hobbs was a tenured Associate Professor in the Department of Biostatistics at The University of Texas MD Anderson Cancer Center in Houston, Texas.