This article previously appeared in its entirety in the Journal of Clinical Research Best Practices, Vol. 14, No. 12, December 2018. Read the full article at FirstClinical.com
In clinical research, consent forms must state that the study’s purpose is to expand general knowledge, not to provide clinical care to the participant. This requirement addresses the therapeutic misconception, the concept that potential research participants might confuse joining a clinical trial with receiving medical benefits. Regulations that govern the ethics of clinical research require that the informed consent process make clear this distinction between research and treatment, but current trends and recent events suggest that society no longer accepts this dichotomy. Instead, current social values might be leaning toward expecting that clinical research should provide some direct benefit to study participants.
At the very least, the traditional division between pure research and routine medical care might be blurring. Industry publications increasingly call for considering clinical research as part of treatment: “clinical research as a care option (CRAACO).” The possibility of returning research results, once dismissed out of hand, is becoming a basic expectation. If these developments represent a shift in societal norms toward expecting benefits from clinical research, does it follow that we should alter our ethical approach to the therapeutic misconception?
Preventing Therapeutic Misconception
For decades, medical ethicists have insisted on a clear distinction between clinical care and clinical research. The purpose of clinical treatment is to cure a patient or to alleviate suffering: “First, do no harm.” The primary aim of clinical research, on the other hand, is to scientifically explore new treatments, not to provide personal medical care to study participants. Our ethical guidelines about therapeutic misconception require that we hold those two pursuits as distinct, with potentially conflicting goals. Psychiatrist Paul Appelbaum and others have shown that people are predisposed to seeing clinical research as a kind of treatment, even in a placebo-controlled study of an experimental treatment with no proven benefit. A potential consequence of this misconception is that people might act against their own best interest, such as enrolling in a study with very unlikely benefit and real health risks. The ethical requirement, therefore, has been to ensure that the informed consent process explains that participating in a trial will not provide any medical benefit, even when such possible benefit might actually exist. In addition, any stipends for participation also cannot be portrayed as a benefit.
A countercurrent, however, is also present: What if participating in a clinical trial does provide some benefit to its participants? An experimental treatment might provide some relief or cure of a condition even before it is approved. In fact, the whole point of clinical research is to assess a potential health benefit. Should we, therefore, not be surprised when study participants ignore our disclaimers and assume there is, in fact, a good chance they will obtain a health benefit? Studies of why participants agree to join (or decline to join) clinical trials suggest this is the case. In 2002, the ECCRI Health Technology Assessment Information Service conducted a review of past studies on this topic and found that, on average, 45% of study participants cited a potential health benefit as a reason for volunteering. Another study, in 2016, found that just over half of participants in oncology trials volunteered because they believed the trial offered the best available treatment.
In addition, participating in a trial could provide someone with knowledge about his or her condition, provide better care and monitoring than he or she would have received otherwise, or just offer hope during a very trying time. Our ethical standards usually prevent us from presenting these possibilities as benefits. As one paper on therapeutic misconception puts it, “The presence of concomitant clinical care and the potential for benefit associated with trial participation should not be confused with the fundamentally scientific goals of clinical trials.” But what if general society feels differently?
In 2007, a workshop about therapeutic misconception asked attendees to consider the true purpose of research. A survey question posed the following choices about a typical research study’s purpose:
The purpose of the study is to help:
- Only patients enrolled in the study, or
- Only patients in the future, or
- Both patients enrolled in the study and patients in the future.
While many said that only (2) can be true, others — including some attendees at that workshop — argued that (3) is also a valid choice. Not only does research benefit the patients of the future, but it also can provide some benefit, or the chance of benefit, for those who enroll in a study today.
The same workshop ended by presenting a common definition of therapeutic misconception:
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.
This definition might hold, but only if everyone agrees that it is fundamentally misleading to suggest that a clinical study could provide any benefit whatsoever to its participants. Going further, what if our societal norms are shifting and society expects clinical studies to provide benefits to participants? If such is the case, an updated definition of therapeutic misconception might be as follows:
Depending on the situation, therapeutic misconception exists when individuals do not understand that (a) the sole purpose of a clinical study is to produce generalizable knowledge, with no possible benefit to the subjects, or (b) the sole purpose of a clinical study is to produce generalizable knowledge, regardless of any possible benefit to the subjects, or (c) the primary purpose of a clinical study is to produce generalizable knowledge, with only the possibility of benefit to the subjects.
This definition prompts a corollary, and potentially contentious, question: Is it ever possible for therapeutic misconception to not exist? To say “yes” suggests that the risks and benefits of joining a clinical trial could be indistinguishable from the medical care a person receives otherwise. But even in a research study that compares two approved treatments, the choice of treatment depends on the protocol, not on what a physician might decide is best for the individual patient. This, combined with the risks that can come with participation in any research, suggests that the potential to confuse research for treatment will always exist. At the same time, for diseases without a cure or effective treatment — such as terminal cancer — the risks of research and the unknown chance of benefit might seem equivalent to the limited effectiveness of an existing treatment. In such extreme cases, some argue, the therapeutic misconception should not be a concern.
Are Societal Norms Shifting?
Societal norms can change over time, and so can the actions we consider ethical. For example…
The full article continues in the Journal of Clinical Research Best Practices, Vol. 14, No. 12, December 2018. Read the full article at FirstClinical.com.