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Originally published as JCO Early Release 10.1200/JCO.2007.15.2850 on January 28 2008 © 2008 American Society of Clinical Oncology.
Social Psychological Factors in Placebo-Controlled Clinical TrialsCancer Research Center of Hawaii, University of Hawaii, Honolulu, HI In this issue of the Journal of Clinical Oncology, Daugherty et al1 have provided elegant and thoughtful reasoning to identify the circumstances under which placebos may be acceptable, or even advisable, in cancer clinical trials. Although the scientific concerns they so skillfully elucidate provide a guide for clinical trial design, additional considerations are likely to affect the successful completion of clinical trials that include placebos. The social psychology of the clinical trials process is important to consider when it comes to the acceptability and use of such trials. Social psychological factors include individual and social influences on behavior, some of which will be discussed further: public perceptions, patient and oncologist preferences, and patient communication. PUBLIC PERCEPTIONS The word "placebo," often coupled with "guinea pig," conjures up nearly visceral reactions in the population. Considerable literature confirms that the fear of receiving a placebo is one of the most frequently cited barriers to participation in clinical trials. A recent meta-analysis of 33 studies that examined this issue found that "dislike possibility of placebo" was the second most commonly reported barrier to trial participation, reported by an average of over half of respondents.2 In response to such concerns, educational materials frequently include comments to reassure the prospective clinical trial participant. An example can be found in the National Cancer Institute's newly released booklet on clinical trial participation,3 which includes the following sentence in boldface: "Placebos are almost never used in cancer treatment trials." If researchers take to heart the recommendations of Daugherty et al, there may be more placebo-controlled trials on the horizon. Such a development has implications for patient education: is it possible to explain the scientific rationale for a placebo arm in a way that is acceptable to patients and the public? Would the availability of more placebo-controlled trials adversely affect clinical trials accrual, which is already at a low level? Increasing the numbers of protocols that use placebo arms needs to be implemented with care, and with the input of patients and members of the public. PATIENT AND ONCOLOGIST PREFERENCES It is well established that active cancer treatment is often provided under circumstances when the benefits of treatment are likely to be minimal. There are many examples that support this care pattern: little use of watchful waiting for prostate cancer where this may be an appropriate option, low use of hospice services for incurable disease, and use of multiple continuing treatment regimens in heavily pretreated patients with advanced disease. Both oncologists and patients report preferences for active treatment—any intervention with curative intent—to other alternatives, such as supportive care, or foregoing toxic treatment that has only a small and uncertain influence on survival. In one of the first studies in this area, Slevin et al4 asked solid tumor patients (N = 100) how much of a chance of cure would make a hypothetical intensive cancer treatment acceptable; the average response was 1%. A recent study in a large (N = 1895) non-North American international sample of advanced lung cancer patients provided consistent data; 60% of respondents expressed preferences for "maximum extension of survival with acceptance of high toxicity."5 It is worth noting that in both of these studies, as well as others, patients are more willing to accept high toxicity for small survival gains than are health care professionals. De Haes and Koedoot6 review this literature and conclude that in the context of advanced disease, administering intensive cancer treatment, rather than providing supportive care, may provide both the oncologist and patient with a sense of control. As they put it, "Giving treatment, even if aggressive, is a way to avoid the confrontation with the little efficacy that the physician has to offer to incurable cancer patients." It remains to be seen whether patients and oncologists will embrace randomized trials that use best supportive care as a placebo arm. Such trials may lead the way to candid discussions between oncologists and patients regarding therapeutic alternatives, limited available curative treatment options, and effective approaches for symptom management in advanced disease. PATIENT EDUCATION More widespread use of placebo-controlled designs, particularly when state-of-the-art palliative care (with or without another intervention) constitutes the placebo, will require revised patient education. For example, clinicaltrials.gov, one of the major sources of clinical trials information on the internet, defines placebo as "an inactive pill, liquid, or powder that has no treatment value",7 and the National Cancer Institute booklet states that "A placebo is designed to look like the medicine being tested, but it is not active."3 Either the definition of placebo needs to be modified, or a different term should be used when best supportive care is the nonexperimental arm. Patient communication about aspects of study design proposed by Daugherty et al1 will need careful attention—not only placebos or best supportive care controls, but also randomized discontinuation designs. Innovative approaches might be considered. For example, Strevel et al8 report that an educational DVD about phase I trials increased knowledge and satisfaction with decision making among patients considering participating in such trials. It is encouraging that the American Society of Clinical Oncology intends to develop patient materials in this area. The impact of the article by Daugherty et al1 has the potential to go beyond the goals it identifies—and possibly to influence patient and public perceptions of clinical trials, impact cancer treatment decision making, and affect the content and modality of patient communication. The social psychological context, including perspectives of patients, providers, and the general public, will be essential in the further development and implementation of placebos in cancer clinical trials. AUTHOR's DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest. REFERENCES
1. Daugherty CK, Ratain MJ, Emanuel EJ, et al: Ethical, scientific and regulatory perspectives regarding the use of placebos in cancer clinical trials. J Clin Oncol 26:1371-1378, 2008 2. Mills EJ, Seely D, Raclis B, et al: Barriers to participation in clinical trials of cancer: A meta-analysis and systematic review of patient-reported factors. Lancet Oncol 7:141-148, 2006[CrossRef][Medline] 3. National Cancer Institute: Taking part in clinical trials. Bethesda, MD, National Cancer Institute, NIH Publication No. 07-6249, 2007 4. Slevin ML, Stubbs L, Plant HJ, et al: Attitudes to chemotherapy: Comparing views of patients with cancer and those of doctors, nurses, and general public. BMJ 300:1458-1460, 1990[Medline] 5. Chu D-T, Kim S-W, Kuo H-P, et al: Patient attitudes towards chemotherapy as assessed by patient versus physician: A prospective observational study in advanced non-small cell lung cancer. Lung Cancer 56:433-443, 2007[CrossRef][Medline] 6. de Haes H, Koedoot N: Patient centered decision making in palliative cancer treatment: A world of paradoxes. Patient Educ Couns 50:43-49, 2003[CrossRef][Medline] 7. http://clinicaltrials.gov/ct2/info/understand. Accessed 11-29-07 8. Strevel EL, Newman C, Pond GR, MacLean M, Siu LL: The impact of an educational DVD on cancer patients considering participation in a phase I clinical trial. Support Care Cancer 15:829-840, 2007[CrossRef][Medline] Related Article
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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