Mary-Tara Roth, RN, MSN, MPH
Director, Clinical Research Resources Office, Clinical and Translational Science Institute, Boston University School of Medicine/Boston Medical Center, Boston, MA, USA
Previous articles in this newsletter have discussed the significance and challenges of obtaining subjects’ informed consent in alcohol and other drug (AOD) human-subjects research.1,2 A related ethical issue that warrants further exploration in this context is therapeutic misconception (TM). This article will present some history of TM, the relevance of this ethical construct to AOD research, and measures that can be implemented to minimize the potential for TM and the consequent interference with obtaining valid informed consent.
In 1982, Appelbaum et al coined the term therapeutic misconception to describe certain subjects’ responses to questions about enrolling in psychiatric research.3 At the time, he defined the term as a “defective understanding of scientific methodology.” That is, even when subjects are presented with details of a study, both in discussion and in writing, they do not necessarily comprehend the important differences between personal medical care and research.4,5 Even though the primary objective of research (to contribute to generalizable knowledge) is different from that of individualized medical care (treating the patient with the best available care for that individual), subjects may believe that they are receiving individualized care when they are participating in a research study. For example, in one case that Appelbaum described in the article, a subject was informed that there was double-blind randomization in the assignment of participants to treatment, but the subject said that she was participating in the study because she needed help. She stated that subjects receiving the placebo would be those who “might not need medication,” suggesting that, as she understood it, the care provided to each subject in the research study would be based on his or her specific medical needs.
It should be noted that when Appelbaum published this article, basic regulations governing the protection of human subjects in research had been published not long before (1974), and these were subsequently expanded in the late ’70s and early ’80s in response to significant abuses in research.6 Since that time, the content and quality of the overall informed consent process in clinical research—and more specifically TM—have been assessed in myriad empirical research studies and scholarly papers on research ethics.
In 2007, a group of scholars proposed a concise definition of TM: “Therapeutic misconception exists when individuals do not understand that the defining purpose of clinical research is to produce generalizable knowledge, regardless of whether the subjects enrolled in the trial may potentially benefit from the intervention under study or from other aspects of the clinical trial.”7 This group further identified five dimensions that must be communicated to and understood by research participants to reduce the potential for TM. These include: scientific purpose (the purpose of the research is to produce generalizable knowledge); study procedures (the specific procedures involved in the research); uncertainty (less is known about study interventions than for clinical care procedures); adherence to protocol (a strict protocol is followed in research versus individual care); and clinician as investigator (the difference between the role of a researcher and that of a clinician providing individual medical care).7,8
TM in AOD Research and Possible Effects
Although Appelbaum coined the term therapeutic misconception in response to specific concerns about how subjects who are enrolled or enrolling in psychiatric research understand the distinction between research and individual medical care, TM carries through to many types of studies involving diverse research subject populations, including those who are not necessarily considered to be part of a “vulnerable” population.4,9 In interviews with 225 subjects from 44 studies that encompassed a whole range of diseases, Appelbaum et al found that 62 percent of subjects who were interviewed had been affected by TM.4
There is not a wealth of literature that specifically addresses the prevalence of TM in AOD research, but certain factors that are often associated with AOD populations may increase the risk of TM because they are known to pose problems with an overall understanding of research. For example, lower educational levels, occupational status, older age, and more severe disease status are issues that have been associated with the likelihood that a subject may have difficulty comprehending a study’s purpose.4,10,11 Research conducted in a hospital or clinic setting can present the potential for TM,5 especially if it takes place where the subjects typically receive their medical care; this scenario is not uncommon in AOD research. Individuals suffering from addiction may also be more likely than the general population to have a lower socioeconomic status, limited access to healthcare, belong to a marginalized population, and to have complex associated health conditions, all of which can affect the ability of the subject to understand the research.12 To the extent that these factors exist, the risk for TM could be assumed to be elevated and care should be taken to mitigate its potential impact among AOD populations.
Scholars contend that TM can impact a subject’s understanding of the overall purpose of a research study and the design and methods used to execute it. This threatens a subject’s ability to adequately evaluate the risks and benefits of participation.7,9 Thus, TM can potentially lead to an overestimation of benefits, an underestimation of risks, or an under-appreciation of alternatives to participation.7 It can also lead to unrealistic expectations and misplaced trust when subjects realize (either during or after the study) that their participation did not lead to personalized medical treatment.13 It has been suggested that TM can lead to increased rates of enrollment in a study since people are generally motivated to seek the best care for their condition; if their understanding is that they will receive this within a study, they may be more likely to take part. But these misunderstandings may lead to increased dropouts among those subjects who become aware of their TM during the study.10
What can be done?
While there is much ongoing research to determine strategies for improving the informed consent process in general—and specifically to lessen the potential for TM—there are existing measures that can be implemented by those who are conducting human-subjects AOD research:
- Understand that subjects come to the consent process with a preexisting “therapeutic bias,” meaning that they will tend to believe that health care professionals (including researchers) would only do something that would benefit the individual subject.10
- Include as part of the consent process (in writing and in discussion) details about the differences between individual medical care and research. Ensure that the subject understands HOW and WHY treatment and research are different.10
- Avoid terms that might be confusing, such as referring to the intervention as “treatment” or “therapy,” or to the research subject as a “patient.”
- Be aware that terms such as “placebo,” “randomization,” and “double-blind,” may not be well understood by research subjects and should be carefully described in lay language with examples, whenever possible.
- In addition to paying attention to terminology, be aware of what might be left out of the discussion. For example, a study by Sankar (2004) analyzed language used in consent discussions and found significant omissions that could contribute to TM.5 For example, for subjects entering a study at the lowest dose-level in a multiple-dose trial, subjects were told that “the next patient we treat will get a higher dose […] and we really think that’s likely to be effective.”5
- Avoid discussions and explanations that emphasize personal benefits to subjects participating in the study (e.g., “So far everyone has done really well in this study”).
- Make a point in research visits to continue the consent process and education about particular aspects of the study that are often related to TM. Take some time to ask the subjects questions about their understanding of the study.
- Consider including compensation for participants. Payments are never given out at regular doctor visits, so compensation for involvement in research studies may help subjects understand that the research is not about their own individual care.4
When first identified 30 years ago, TM in research was recognized as an urgent problem, yet still it persists. Its presence can be destructive to both the integrity of the study as well as the researcher-participant relationship. AOD researchers can evaluate the likelihood that their subjects may be more at risk for TM, and also ascertain whether there are aspects of the studies that might increase the risk. Taking steps to prevent TM among participants in AOD research is crucial.
1. Baedorf Kassis S, Roth MT. Obtaining informed consent for research from people with alcohol and other drug dependence. AOD Health. March–April 2012. Available at: http://www.bu.edu/aodhealth/issues/issue_mar12/feature32012.html
2. Heaton B. Ensuring subject competence to enroll and participate in addiction research. AOD Health. May–June 2013. Available at: http://www.bu.edu/aodhealth/issues/issue_may13/feature052013.html
3. Appelbaum PS, Roth LH, Lidz C. The therapeutic misconception: informed consent in psychiatric research. International Journal of Law and Psychiatry. 1982;5:319–329.
4. Appelbaum PS, Lidz CW. The therapeutic misconception. The Oxford Textbook of Clinical Research Ethics. Emanuel EJ, Grady C, Crouch RA, et al. (eds). Oxford, UK: Oxford University Press, 2008.
5. Sankar P. Communication and miscommunication in informed consent to research. Medical Anthropology Quarterly. 2004;18:429–446.
6. Office of Human Research Protections (OHRP). What is the historical basis for the current human research regulations, 45 CFR part 46? Available at: http://answers.hhs.gov/ohrp/questions/7184
7. Henderson GE, Churchill LR, David AM, et al. Clinical trials and medical care: defining the therapeutic misconception. PLOS Medicine. 2007;4(11):1735–1738.
8. Churchill LR, King NMP, Henderson GE. Why we should continue to worry about the therapeutic misconception. The Journal of Clinical Ethics. 2013;24(4):381–386.
9. Applelbaum PS, Lidz CW, Grisso T. Therapeutic misconception in clinical research: frequency and risk factors. IRB: Ethics and Human Research. 2004;26(2):1–8.
10. Lidz CW, Appelbaum PS. The therapeutic misconception: problems and solutions. Medical Care. 2002;40(9):v55–v63.
11. Roth LH, Lidz CW, Meisel A, et al. Competency to decide about treatment or research: an overview of some empirical data. International Journal of Law and Psychiatry. 1982;5:29–50.
12. Fisher CB, Oransky M, Meena M, et al. Marginalized populations and drug addiction research: realism, mistrust, and misconception. IRB. 2008;30(3):1–9.
13. Copperman C, Terry SF. Beyond genetic tests and biomarkers: what about therapeutic misconception? Genetic Testing and Molecular Biomarkers. 2012;16(9):999–1000.