Patients, Placebos, and Clinical Research: Making much ado about nothing

Researchers are required to furnish patients with information to enable them to make informed decisions. In medical research participants need to know: “What are the risks of participating? What are the risks of not participating? What are the possible benefits?” Providing this information is an ethical imperative.

Studies show that medical researchers are doing a poor job of respecting patients’ rights.

Medical ethicists and social scientists have long observed common confusions among research participants who are enrolled in clinical trials. They dub these confusions ‘therapeutic misconception’.[1] The term describes the misconception that the primary goal of clinical research is to provide individualized care to enrollees. This is manifestly not the priority of clinical research where the primary purpose is scientific and to improve treatments for future patients.

Findings show that therapeutic misconception is widespread. In 2009 a systematic review of studies on informed consent processes concluded that individuals only understood around fifty per cent of the information that was conveyed to them.[2] The same is true in pediatric research. For example, in a trial for childhood leukemia only one in two parents who consented to their child’s participation understood randomization.[3] Therapeutic misconception is also correlated with willingness to enroll in clinical research. In other words, there may be unintentional, implicit biases on the part of researchers to perpetuate misconceptions.

In an Analysis paper published in BMJ in 2017 placebo expert Ted Kaptchuk of Harvard Medical School, University of Southampton health psychologist Felicity Bishop, and I published an article entitled ‘Informed consent and clinical trials: where is the placebo effect?’[4]

In our paper we argued that the therapeutic misconception is likely exacerbated by failure to disclose adequate information about placebos and placebo effects.

What are placebos? Placebos in clinical research are controls used to test for the efficacy of interventions. Placebos help researchers to differentiate normal fluctuations in illness, systematic bias in reporting, regression to the mean, and placebo effects. Placebo effects are genuine, therapeutic effects that can occur in clinical contexts – through the administration of placebos or medication. A wealth of research shows that placebo effects can be significant for a range of self-reported symptoms and conditions: these include pain relief, depression, and anxiety.

Research shows that comprehensive information about placebos and placebo effects is still not routinely disclosed to patients.  For example, a recent Finnish study of 52 randomized controlled trials found that only 12 described why placebo use was necessary in the research.[5]

Medical researchers must disclose clear and comprehensible information about placebos and placebo effects to potential participants. By taking this step we argue that investigators will help eliminate misconceptions about the purpose of clinical research and to uphold the Declaration of Helsinki on the rights of patients to make informed decisions. Finally, to fulfill this professional goal medical educators must find ways to improve placebo literacy and research ethics education among students – the clinical investigators of the future.

Dr. Charlotte Blease,

Fubright Scholar and Irish Research Council-Marie Sklowowska Curie Research Fellow, School of Psychology, University College Dublin;  General Medicine & Primary Care, Beth Israel Deaconess Medical Center, Harvard Medical School

 

References:

[1] Appelbaum, P. S., Lidz, C. W., & Grisso, T. (2004). Therapeutic misconception in clinical research: frequency and risk factors. IRB: Ethics & Human Research.

[2] Falagas, M. E., Korbila, I. P., Giannopoulou, K. P., Kondilis, B. K., & Peppas, G. (2009). Informed consent: how much and what do patients understand?. The American Journal of Surgery198(3), 420-435.

[3] Kodish E, Eder M, Noll RB, Ruccione K, Lange B, Angiolillo A, Pentz R, Zyzanski S, Siminoff LA, Drotar D. Communication of randomization in childhood leukemia trials. Jama. 2004; 291(4):470-5.

[4] Blease, C. R., Bishop, F. L., & Kaptchuk, T. J. (2017). Informed consent and clinical trials: where is the placebo effect?. BMJ: British Medical Journal (Online), 356:j463 doi: 10.1136/bmj.j463

[5] Keränen, T., Halkoaho, A., Itkonen, E., & Pietilä, A. M. (2015). Placebo-controlled clinical trials: how trial documents justify the use of randomisation and placebo. BMC medical ethics16(1), 2.