Obtaining Informed Consent in Early Phase Oncology Trials is Complex
“Bioethicists, clinicians, and policy makers are concerned about the high estimates some patients give for their expectations of benefit in early-phase clinical trials,” noted Kevin P. Weinfurt, PhD, of Duke Clinical Research Institute, Durham, NC, and colleagues.
“Our findings in this study demonstrate that a portion of these high estimates can be explained by the different conceptions of probability conveyed by the questions investigators ask these patients. This concern is greater in traditional phase I trials, given that the historical chance of direct benefit is low.”
The investigators randomly assigned 171 participants in phase 1 or 2 United States oncology trials who had provided informed consent to participate in a trial but had not yet received treatment to one of three groups that corresponded to three queries about expectations: frequency type, belief type, or both.
“A patient's belief-type statement refers to how confident the patient feels about an individual outcome; the frequency-type statement describes knowledge (or a prediction) about a verifiable state of the world,” Dr. Weinfurt noted.
The study asked questions about patient demographics and clinical characteristics and previous experience with clinical research; other measures included the Subjective Numeracy Scale, Quality of Informed Consent, Life Orientation Test-Revised, Daily Spiritual Experiences Scale, and Organizational Religiousness-Short Form. The primary outcomes were “differences in expectations by question type and the extent to which expectations were associated with demographic characteristics, numeracy, dispositional optimism, religiousness/spirituality, understanding of research, and other measures,” they noted.
“In the ‘confidence' group, participants were asked a belief type question: ‘How confident are you that the experimental therapy will control your cancer?' (response options, 0% to 100%). In the ‘frequency' group, participants were asked a frequency-type question: ‘If 100 people were to participate in this study, how many could be expected to have their cancer controlled as a result of the experimental therapy?' Finally, in the combination group, participants first answered the belief-type question, discussed the answer with the interviewer, and then answered the frequency-type question. The response of interest in the combination group was the response to the frequency-type question. Thus, an expectation of benefit was solicited from each of the three groups by using a different version of the question,” the article states.
Patients in the belief-type group had a higher mean expectation of benefit (64.4 of 100) than the combination group (51.6; P=0.01) and the frequency-type group (43.1; P<0.001). In the combination and frequency groups, mean expectations were not significantly different (P=0.06). Belief-type expectations were associated with a preference for nonquantitative information, knowledge about research, dispositional optimism, and spirituality. Frequency-type expectations were associated with knowledge about clinical research.
The investigators recommended that investigations be continued “of how best to advance the science of medicine while maintaining respect for patients who participate in these trials.”