Sumithra J. Mandrekar, PhD, Professor of Biostatistics and Oncology, Mayo Clinic
Clinical Trial Designs for Personalized Medicine in Oncology
Clinical trial design strategies have evolved as a means to accelerate the drug development process so that the right therapies can be delivered to the right patients. Basket, umbrella, SMART and adaptive enrichment strategies represent a class of novel designs for testing targeted therapeutics, and individualizing treatment in oncology. Umbrella trials include a central infrastructure for screening and identification of patients, and focus on a single tumor type or histology with multiple sub trials, each testing a targeted therapy within a molecularly defined subset. Basket trial designs offer the possibility to include multiple molecularly defined subpopulations, often across histology or tumor types, but included in one cohesive design to evaluate the targeted therapy in question. Adaptive enrichment designs offer the potential to enrich for patients with a particular molecular feature that is predictive of benefit for the test treatment based on accumulating evidence from the trial. A SMART design strategy is appropriate when comparing adaptive interventions, which are defined by an individual’s sequence of treatment decisions and guided by intermediate outcomes, such as response to therapy. This talk will focus on the fundamentals of these design strategies, the underlying statistical framework, the logistical barriers of implementation, and, ultimately, the interpretation of the trial results, using some case-studies including the National Cancer Institute’s precision medicine initiative trials.
Dr. Mandrekar received her interdisciplinary Ph.D. in Biostatistics, Psychology, Internal Medicine and Biomedical Engineering from the Ohio State University, Columbus OH in December 2002, and joined Mayo Clinic as a research associate in January 2003. She is currently Professor of Biostatistics and Oncology at the Mayo Clinic, Rochester MN, and Section Head for the Cancer Center Statistics within Mayo Clinic Department of Health Sciences Research. She is the Group Statistician for the Alliance for Clinical Trials in Oncology, which is one of the 4 NCI-funded national clinical trials networks for the conduct of phase II and III clinical trials in adult cancer. Dr. Mandrekar also holds an adjunct Professor of Biostatistics appointment at the School of Public Health, University of Minnesota, and at the University of Gainesville, FL.
Dr. Mandrekar’s primary research interests include adaptive dose-finding early phase trial designs, designs for predictive biomarker validation, and general clinical trial methodology related to conduct of clinical trials and identification of alternative Phase II cancer clinical trial endpoints. Dr. Mandrekar has co-authored over 140 original papers; several book chapters and editorials; and has given numerous lectures, invited presentations and workshops on these topics.
Her primary collaborative areas are lung cancer and leukemia. She is the faculty statistician for the national adjuvant lung cancer trial, ALCHEMIST, an approximately 8000 patient trial, which is part of the NCI precision medicine initiative. She was the primary statistician on the Phase III C10603 trial that led to the FDA approval of Midostaurin for AML patients with FLT3 mutations.
Dr. Mandrekar is a voting member of the NCI thoracic malignancies steering committee, past president of the society for clinical trials (2018-2019), voting member on the clinical trials transformation initiative on master protocols, member of the ASCO mCODE executive council, voting member of the international RECIST working group and the biostatistics editor for the Journal of Thoracic Oncology.
She has a national and international presence as an expert in clinical trial design as evidenced by her bibliography and membership on various national and international committees.