Balancing the Perceived Benefits and Risks of Research Participation is No Easy Task for Cancer Patients

Toward A Better Understanding of Patients Perspectives

January 23, 2023

By:

Connie M. Ulrich, PhD, RN

Print:

Every one of the more than 1.8 million people diagnosed with cancer each year must make difficult decisions about their treatment course. This may include deciding whether to participate in a cancer clinical trial or not. But deciphering the potential benefits and risks of these trials can be difficult.

Patients participate in clinical trials in the hopes of receiving a curative treatment and helping future patients, but also worry about receiving a placebo and experiencing unknown adverse effects, among others concerns. For some patients who initially decide to participate in trials, the worries weigh too heavy, leading them to drop out. Such trial attrition doesn’t just affect individual patients—it can stymie scientific and therapeutic progress and contribute to systematic bias and underpowered analyses.

For insight into why some trial participants decide to drop out while others stay, LDI Senior Fellow Connie M. Ulrich, PhD, RN and her research team that included Liming Huang from the School of Nursing, Penn Medicine faculty Victoria Miller and LDI Senior Fellows Mary Naylor, Therese Richmond, and Marilyn Schapira, surveyed more than 300 adult patients participating in a cancer therapeutic clinical trial about how they perceived benefits and burdens of participation. The researchers found that patients were more likely to withdraw from trial participation when they perceived the benefits as less than the burdens: 33.3% of patients who felt this way withdrew compared to 13.4% who perceived the benefits as being equal to or greater than the burdens. Overall, of the 334 patients who completed the survey, 47 (14%) withdrew from the trial, according to the JAMA Network Open study.

The researchers noted that participants’ perceptions of benefits and burdens in a research trial may differ from how researchers, ethicists, and institutional review boards perceive the trial’s acceptability. For instance, the goal of phase one trials, which test the safety of an experimental drug, is not to cure disease while phase three trials are designed to test whether a new drug is better than the standard of care. Proactive, ongoing discussions about expected benefits may help reduce the disconnect between patients’ expectations of the benefits of participation and their actual experience—and support trial retention, according to the researchers.

Patient assessment of risks and benefits is an important bioethics concept. Researchers can provide better protection when they understand the role of benefits in comparison to the risks and burdens that patient-participants are required to bear. Long schooled by ethical guidelines, such as the Belmont Report, researchers are careful not to overstate the benefits of any research study in informed consent documents or in conversations with their patient-participants. In fact, they often indicate that participants will derive no direct benefit from participation. However, potential benefits—even those that were aspirational in nature, such as the desire to help future patients—were clearly important to the patient-participants interviewed in this study.

The way that researchers, ethicists, and institutional review board members think about benefits may indeed differ from how patients perceive benefits. The findings of this study suggest that to reduce attrition from cancer clinical trials, more research is required to determine the various types of benefits, how participants perceive them, and how best to classify them.

The study, “Association of Perceived Benefit or Burden of Research Participation with Participants’ Withdrawal from Cancer Clinical Trials,” was published on November 30, 2022, in JAMA Network Open. Authors include Connie M. Ulrich, Sarah J. Ratcliffe, Qiuping Zhou, Liming Huang, Camille Hochheimer, Thomas Gordon, Kathleen Knafl, Victoria Miller, Mary D. Naylor, Marilyn M. Schapira, Therese S. Richmond, Christine Grady, and Jun J. Mao.