Recommendations for Clinical Trials of Off-Label Drugs Used to Treat Advanced-Stage Cancer

Abstract

Purpose To provide recommendations to trialists and sponsors that guide the design and implementation of prospective postapproval clinical trials for oncology drugs used outside US Food and Drug Administration–labeled indications for treatment of late-stage cancers. Methods A meeting was hosted by the Center for Medical Technology Policy in Baltimore, MD, on November 12, 2009. Discussions during the meeting and key informant interviews were conducted before and after this stakeholder meeting. Peer review by multidisciplinary stakeholders was followed by a public comment period. Input was received from patient advocacy groups, medical oncologists, pharmaceutical companies, the US Food and Drug Administration, Centers for Medicare and Medicaid Services, the National Cancer Institute, foreign government agencies involved in health technology assessment, public and private payers, drug compendia, clinical research entities, statisticians, academics, and the American Society of Clinical Oncology. Results To address the needs of patients and their clinical providers, compendia, payers, and policy makers, recommendations are proposed to guide the design of future prospective trials for off-label use of oncology drugs across four areas: trial design and data analysis, patient and site recruitment, comparators, and outcomes. Conclusion The US Food and Drug Administration provides guidance to the pharmaceutical industry and others designing randomized clinical trials for regulatory approval. However, a gap exists for postregulatory decision makers, including patients, prescribers, and payers, because regulatory trials do not answer the questions most relevant to them. Therefore, guidance is needed for trials performed in the postapproval environment for these postapproval decision makers.