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Patient confidence in trial participation unaffected by knowledge of placebo assignment
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Patients with early breast cancer who participated in a clinical trial did not have negative views on the methods of the trial once they were unblinded and learned they were randomly assigned a placebo rather than an experimental agent, according to study findings.
The use of placebo in cancer clinical trials is controversial due to the difference in ethics of research — or the importance of generating new knowledge — vs. ethics of therapy, in which the emphasis is placed on caring for individuals, according to study background.
Anne H. Partridge
“This analysis evaluated an important consideration when caring for patients on clinical trials in oncology — whether or not patients who are randomized to a placebo rather than experimental therapy feel decisional regret or less confidence in having joined the trial when they find out that they were randomized to the placebo at unblinding,” Anne H. Partridge, MD, MPH, founder and director of the program for young women with breast cancer and director of the adult survivorship program at Dana-Farber Cancer Institute in Boston, told HemOnc Today.
Partridge and colleagues evaluated patient reactions to unblinding during a clinical trial (ECOG5103) for early breast cancer in which patients were assigned to one of three arms evaluating standard adjuvant chemotherapy with placebo or bevacizumab (Avastin, Genentech).
The study was unblinded after the final infusion of placebo or bevacizumab between weeks 18 and 22. Of 550 patients who were still in the trial at the time of unblinding, 492 (89%) responded to an unblinding survey conducted by the investigators.
At the time of the unblinding, 70% of patients believed they had at most a small risk for breast cancer recurrence and 71% believed there was at most a small risk of serious problems as a result of the therapy.
Overall, 87% of patients felt very informed and maintained a high level of confidence in their participation in the trial.
The 102 patients who learned they had been randomly assigned to placebo did not express a perception that they had a greater chance for disease recurrence (P = .48) or fear that they would have disease recurrence (P = .69). These patients also did not report feeling less informed (P = .86) or less confident in their decision to participate in the trial (P = .31) compared with the 390 patients who were randomly assigned to one of the bevacizumab arms.
Further, patients who were randomly assigned bevacizumab believed they had a higher risk for developing a serious treatment-related problem (P = .01).
“The ability to survey patients prospectively shortly after unblinding as well as a high response rate of participants are great strengths of the study and the findings suggest that not only is use of placebo scientifically appropriate in this setting, but there does not appear to be a negative impact on patient participants,” Partridge said.
The researchers cautioned that there could be a higher level of regret once the data from the trial are publicized, and that trial confidence could have been influenced by the FDA’s decision to rescind the use of bevacizumab in patients with metastatic cancer during the study period.
“Our findings … are novel and reassuring,” Partridge and colleagues wrote. “They are particularly compelling given the high-stakes trial studied, including a patient population documented to have generally high levels of anxiety and inaccurate heightened risk perceptions.” – by Anthony SanFilippo
For more information:
Anne H. Partridge, MD, MPH, can be reached at Dana-Farber Cancer Institute, 44 Binney St., Boston, MA 02115; email: ann_partridge@dfci.harvard.edu.
Disclosure: The researchers report consultant/advisory roles with and research funding from Genentech.
Perspective
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Charles L. Shapiro, MD
Some physicians and patients are reluctant to discuss and participate in randomized placebo-controlled trials. Among the reasons is the perception by some that they are unethical (Emanuel EJ, et al. N Engl J Med. 2001;345:915-919) or, from the patient’s point of view, “What if the active drug (relative to placebo) is actually better?” To make matters worse, in a recent survey of 52 randomized-placebo-controlled trials, the justification for the placebo-control was inadequately explained in the informed consent document (Keränen T, et al. BMC Med Ethics. 2015;doi:10.1186/1472-6939-16-2).Partridge and colleagues have made a valuable contribution in that they asked women directly how they felt when they learned they were on placebo in a metastatic breast cancer trial. There were no statistically significant differences in their perceptions of the chance for or fear of recurrence, nor did they feel less informed or have lower confidence in trial participation than those who received the active drug. The findings suggest that unblinding of trial participants, even those who received the placebo, is not harmful. This is reassuring. However, this was a very motivated group of “selected” trial participants, with nearly 90% of them expressing they felt very informed and very confident in their study participation. What would be of interest is to query the women who opted out of the trial to identify the characteristics of this group and the barriers to their participation.
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