Jeffrey M. Peppercorn, MD, PhD

2009-2010 BCRF Project:
ASCO Cancer Foundation Career Development Award for Research on Health Disparities
(made possible by generous support from the David and Barbara B. Hirschhorn Foundation)

BCRF funds are supporting a three-year ASCO-BCRF Career Development Award specifically for research that addresses health disparities; Dr. Peppercorn is the first recipient of this award. His project focuses on access to experimental therapy outside of cancer trials. His goal is to develop a comprehensive analysis of the ethical and policy issues related to access to experimental therapy outside of cancer clinical trials that will lead to development of guidelines for recruitment to clinical trials and oncology practice.

In Dr. Peppercorn's initial work for this project, published recently in the Journal of Clinical Oncology, he found that consideration of off-protocol therapy is common within oncology, but there appears to be little consensus among the oncology community regarding when access to off-protocol therapy should or should not be considered. While a majority of oncologists believe that treatment with an experimental therapy outside of a clinical trial should be discouraged, most want to retain the ability to provide such therapy at their discretion.

As the ethical issues surrounding this problem have been explored, several themes have emerged. This can be considered as two distinct conflicts. First, because wider availability of off-protocol therapy is likely to slow or halt accrual to important clinical trials there is a conflict between the patient's interest in access to the therapy of choice and the interest of society in addressing important scientific questions through clinical research. Second, there is a potential conflict between the patient's interest as described above (called autonomy) and the physician's obligation to protect the medical best interests of the patient (called beneficence), which some would categorize as a conflict between patient choice and patient safety.

This suggests that one of the key questions to address is whether an experimental intervention should truly be considered "treatment", and on a broader level, how we define treatment and acceptable medical practice. In addition, there is the question of whether offering an intervention in a clinical trial indicates that an intervention is viewed as treatment, and if so, why it should not be available outside of trials, and if not, how we can better explain the nature of experimental interventions in trials to both patients and clinicians. Dr. Peppercorn led a team looking at the potential use of experimental therapy outside of recent randomized trials in oncology and found that for nearly two-thirds of trials, the experimental arm is FDA approved and available for off-label use, making the importance of addressing these issues clear. Dr. Peppercorn recently led a panel discussion on this topic at the annual meeting of the American Society of Clinical Oncology and has participated in national conferences sponsored by the National Institutes of Health to address these questions.

His future research on this grant will further explore these questions, and in particular assess how both patients and physicians think about these issues in our future studies. The hope is to identify areas of consensus and controversy that can support development of guidelines for use, or withholding of off-protocol therapy, and identify areas where future research is needed. As a result of this research, Dr. Peppercorn was named ethics co-chair of CALGB, ethics track leader of the ASCO education committee ethics track, and was recently selected to join the ASCO ethics committee.

Mid-Year Progress Report:
In Dr. Peppercorn's initial work for this project, published in 2008 in the Journal of Clinical Oncology, he found that consideration of off-protocol therapy is common within oncology, but there appears to be little consensus among the oncology community regarding when access to off-protocol therapy should or should not be considered. While a majority of oncologists believe that treatment with an experimental therapy outside of a clinical trial should be discouraged, most want to retain the ability to provide such therapy at their discretion.

As the ethical issues surrounding this problem have been explored, several themes have emerged. This can be considered as two distinct conflicts. First, because wider availability of off-protocol therapy is likely to slow or halt accrual to important clinical trials there is a conflict between the patient's interest in access to the therapy of choice and the interest of society in addressing important scientific questions through clinical research. Second, there is a potential conflict between the patient's interest as described above (called autonomy) and the physician's obligation to protect the medical best interests of the patient (called beneficence), which some would categorize as a conflict between patient choice and patient safety.

Key questions that emerge include how we define "therapy", how trial care differs from standard care, and who should make decisions regarding access to experimental therapy. Dr. Peppercorn chaired a session on this subject at the ASCO 2009 annual meeting and published a chapter on ethics of off-protocol therapy for clinicians. He also led a team looking at the potential scope of experimental therapy outside of randomized trials in oncology and found that for nearly two thirds of trials, the experimental arm is FDA approved and available for off-label use which correlated with slower trial accrual. This was presented at ASCO 2009. As a result of this work, Dr. Peppercorn has participated in national conferences sponsored by the National Institute of Health and the Center for Business Intelligence to address these issues. He is now beginning work with the FDA to address similar challenges in assessment of expanded access programs in oncology.

Ongoing research includes focus groups of patients and physicians to identify areas of consensus and disagreement regarding access to experimental therapy. This research will support development of guidelines for use, or withholding of off-protocol therapy, and will identify areas where future research is needed. As a result of this research, Dr. Peppercorn was named ethics co-chair of CALGB, ethics track leader of the ASCO education committee, and was appointed to the ASCO ethics committee. In these roles he is leading efforts to develop guidelines for use of mandatory research biopsies within clinical trials and an ASCO position paper on communication regarding decision making in advanced cancer care.

Bio:
Dr. Jeffrey Peppercorn is a hematologist/oncologist with special interest in breast cancer, medical ethics, and health care policy. His research focuses on the intersection of clinical care and clinical research in breast cancer and is dedicated to improving the care of patients both within and outside of clinical trials. His work has been published in leading medical journals and he speaks nationally on breast cancer management and medical ethics in oncology. His research is currently focused on the ethics of access to experimental therapy outside of clinical trials. Developing a solid ethical foundation for consideration of the use of a promising but unproven intervention outside of a trial has important implications for patient safety, access to care, and our ability to improve care through clinical research. Dr. Peppercorn plans to evaluate differences in access to therapy both within and outside of trials among different racial/ethnic and socioeconomic groups and the perspectives and experience of patients from groups that face health disparities with regard to breast cancer outcomes. He is also conducting studies investigating access to radiation therapy among low income women with breast cancer in North Carolina, and understanding of research in early phase clinical trials.

Dr. Peppercorn attended Harvard Medical School, completed his internal medicine residency at Massachusetts General Hospital, and completed his hematology/oncology fellowship training at the Dana-Farber Cancer Institute as well as the Medical Ethics Fellowship at Harvard Medical School. He is an Assistant Professor of Medicine at Duke University Medical Center in the Division of Medical Oncology specializing in the care of breast cancer patients. He is also an Adjunct Professor in Health Policy and Administration at the UNC School of Public Health and an Adjunct Professor of Social Medicine at the UNC Medical School and an Associate of the Trent Center for Bioethics and Humanties at Duke University. In addition to his research in ethics and health policy, he is lead investigator on several clinical trials of novel therapies for breast cancer, as well as the lead clinical investigator in studies of exercise and quality of life after initial breast cancer therapy. He is currently a BCRF-funded ASCO Career Development Awardee for Research in Health Disparities related to Breast Cancer, and was named a Greenwall Foundation Faculty Scholar in Medical Ethics in 2007. In 2008, he was selected to co-chair the Ethics Committee of the Cancer and Leukemia Group B cooperative group (CALGB) and appointed as the Ethics Track Leader for the ASCO Education Committee.