Evaluation of Treatment Effect in Underrepresented Population in Cancer Trials: Discussion with International Regulators

This article provides a summary of discussions from the American Statistical Association (ASA) Biopharmaceutical (BIOP) Section Open Forum on April 8, 2021, and May 13, 2021, organized by the ASA BIOP Statistical Methods in Oncology Scientific Working Group in coordination with the United States Food and Drug Administration (U.S. FDA) Oncology Center of Excellence (OCE) and LUNGevity Foundation. In most cancer trials, disproportionately low numbers of older adults and certain racial minority groups are enrolled, even though a high incidence of cancer is observed in these subpopulations. This results in a lack of sufficient information on efficacy and safety of new treatments in such demographic subpopulations. Discussions with a diverse group of stakeholders including oncologists, patient advocates, experts from international regulatory agencies, academicians, and representatives of the pharmaceutical industry focused on designing future pre- and post-market studies to evaluate treatment effect in demographically underrepresented (UR) cancer populations such as racial and ethnic minority groups and older adults. It is noted that often there is poor or no representation of pediatric cancer patients as well. However, not all adult cancers are observed in pediatric patients and vice-a-versa and these discussions mainly focused on adult cancers. It is recognized that inclusion of broader patient populations can introduce heterogeneity and if the trial includes patients with more comorbidities or poorer prognosis may increase the chances of rejecting an effective therapy. However, there are clinical trial designs and statistical methods to include and evaluate treatment effects in UR cancer patients. Importantly, a commitment and a concerted effort from all stakeholders to change the current practice is necessary to better understand the benefit/risk in these demographically UR patients in cancer clinical trials.