Work by Project Data Sphere’s (PDS) External Control Arm (ECA) program was the focus of a paper in The Lancet Oncology, published in October, and a panel discussion at the Society for Neuro-Oncology (SNO) Annual Meeting in November in Boston.
Authors of “Leveraging external data in the design and analysis of clinical trials in neuro-oncology” (https://doi.org/10.1016/s1470-2045(21)00488-5) include PDS President Bill Louv and PDS Executive Director Jon McDunn as well as leaders of the ECA Task Force established by PDS.
Two co-authors joined McDunn for the SNO panel discussion:
- Rifaquat Rahman, MD, a faculty member in the Department of Radiation Oncology in Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC) and Harvard Medical School. Dr. Rahman’s research interests include innovative clinical trial designs, clinical outcomes and survival data analysis, and quantitative imaging biomarkers.
- Lorenzo Trippa, PhD, associate professor from the Department of Data Sciences, Dana-Farber Cancer Institute and Harvard T H Chan School of Public Health. Dr. Trippa’s research interests include adaptive clinical trials, evidence generation, and Bayesian analytics.
The Lancet Oncology article was based on a series of presentations given at the 2020 Clinical Trials Think Tank hosted by SNO. It provides an overview on the use of external data in the design and analysis of clinical trials and reviews study designs, statistical methods, risks, and potential distortions in leveraging external data from a variety of data sources.
The authors evaluated these designs and methods using patient-level data from completed trials and real-world data, showcasing ongoing work in glioblastoma. The roles of data-sharing platforms and policy were highlighted as a critical feature for driving the adoption of external information in clinical evidence generation for new medicines and subsequent regulatory decisions.
“Integration of external control data, with patient-level information, in clinical trials has the potential to accelerate the development of new treatments in neuro-oncology by contextualising single-arm studies and improving decision making (eg, early stopping decisions),” the authors wrote in the abstract. “High-quality patient-level records, rigorous methods, and validation analyses are necessary to effectively leverage external data.”
PDS’ ECA program is working to help deliver innovative trial designs that incorporate external data to make it faster and easier to recruit and retain patients in clinical trials. The rise of precision oncology has further reduced the pool of potential trial participants, as genomic biomarkers have reduced the number of eligible patients for many trials. This factor, combined with the increase in open-label trials (where patients are not blinded from their treatment), has resulted in a significant challenge in trial enrollment and poor participant retention, jeopardizing the investment in some clinical trials and delaying new medicine approvals.
In close collaboration with the FDA and a team of academic and industry experts, the ECA program leaders are developing a framework for incorporating external data to streamline trials. In addition to glioblastoma, the PDS ECA program has experience with small cell lung cancer and pancreas cancer. PDS will host peer-reviewed external control arm data sets and algorithms on its open-access platform so that more researchers can evaluate use cases for these algorithms across the clinical trial spectrum.