From the Division of Medical Oncology, Duke University Medical Center, Durham, NC
Author's disclosure of potential conflicts of interest are found at the end of this article.
Address reprint requests to Jeffrey Peppercorn, MD, MPH, Assistant Professor of Medicine, Division of Medical Oncology, Duke University Medical Center, Box 3446, Durham, NC 27710; jeffrey.peppercorn{at}duke.edu
Overview: Investigational cancer therapies being tested in clinical trials may be available outside of trials, or "off-protocol" (OPRx). The availability of and demand for OPRx, coupled with variation in practice and attitudes toward this issue among oncologists, demonstrate a need for wider awareness and discussion of this issue in the oncology community. OPRx raises ethical issues regarding the requirements of informed consent for trial participation; equal access to novel interventions for patients of different socioeconomic backgrounds; professional obligations of academic compared with nonacademic oncologists; and potential conflicts between the interests of patients seeking access to OPRx (autonomy), the interests of patient safety (beneficence), and the interests of society in testing new interventions in clinical trial (justice). Oncologists should understand the arguments for and against wider access to OPRx and, in the absence of clear guidelines, can follow several guiding principles to determine when consideration of OPRx is or is not appropriate. Under most circumstances, treatment with an unproven agent outside of a clinical trial cannot be justified on clinical or ethical grounds.
