Date Published: November 27, 2007
Publisher: Public Library of Science
Author(s): Gail E Henderson, Larry R Churchill, Arlene M Davis, Michele M Easter, Christine Grady, Steven Joffe, Nancy Kass, Nancy M. P King, Charles W Lidz, Franklin G Miller, Daniel K Nelson, Jeffrey Peppercorn, Barbra Bluestone Rothschild, Pamela Sankar, Benjamin S Wilfond, Catherine R Zimmer
Abstract: A key component of informed consent to participate in medical research includes understanding that research is not the same as treatment.
Partial Text: For over three decades, bioethics scholarship and research ethics guidelines have identified concerns about the boundaries between research and standard clinical care [1,2]. Ethicists have argued that informed consent to participate in research should include clarification of the differences between these two activities [3–10]. In 1982, Appelbaum and colleagues reported on findings from interviews with patients with psychiatric disorders that documented failure to appreciate the difference between research and treatment, labeling the phenomenon “therapeutic misconception” (TM) .
In Appelbaum and colleagues’ study , the patients interviewed were enrolled in clinical trials that involved randomization, non-treatment control groups and placebos, and double-blind procedures. The researchers found that many trial participants were unaware of study design implications, especially random assignment to a control or comparison group, often believing that they were assigned a medication based on what was best for them, personally. The authors concluded that those patients who are trial participants and who do not adequately appreciate the purpose and methods of research studies are ill-equipped to evaluate risks and benefits of study participation, and may fail “to recognize how personal care may be compromised by research procedures” .
Since the original publication on TM , a number of empirical studies have explored the motivations, understandings, and expectations of patients who participate in research. Researchers have asked such questions as: Why do patients join a study? What is their understanding and recollection of the purpose of the research and particular aspects of study design? Can they differentiate the goals of research from those of clinical care? What are their expectations about the likelihood of direct benefit? These studies have used closed-ended questionnaires analyzed quantitatively , open-ended interviews analyzed qualitatively, or both [11,19]. Some studies included questions relevant to TM as part of a general investigation of ethical dilemmas in clinical trials, whether they set out to study TM  or not [31,35,36].
Discordance in the literature on TM was reflected in our workshop discussions of the purpose of a research study. We considered whether the following question could be part of an instrument designed to measure TM:
Amid the controversies, there is consensus that the defining characteristic of research is to create generalizable knowledge through answering a scientific question. There is disagreement, however, regarding which elements of a trial could plausibly have a therapeutic purpose, whether additional therapeutic benefit ought to be counted as a study purpose, and whether overestimation of direct clinical benefit is part of TM.
Refining the standard measurement of TM will provide a means to assess research understanding in different types of clinical trials and study populations. Such a tool can serve both to improve the protection of trial participants and refine the informed consent process, aiding accrual to clinical trials through a process that is both effective and efficient . Historically, research on TM has been motivated by concern that participants may misunderstand aspects of trial care that lead them to make decisions incompatible with their true preferences and values. Though participants may recognize they are in a trial, failure to understand how care received during a trial can differ from standard care, and confusion over the purpose of these distinct activities, can compromise informed consent to research participation. While debate over other important aspects of informed consent is likely to continue, progress can be made in measuring TM by limiting our attention to those aspects that clearly interfere with trial participants’ decision-making through failure to understand the defining nature and purpose of clinical research.