Informed consent, therapeutic misconception, and clinical trials for Alzheimer's disease

Autor: James M. Wilkins, Brent P. Forester
Rok vydání: 2020
Předmět:
Zdroj: Int J Geriatr Psychiatry
ISSN: 1099-1166
0885-6230
DOI: 10.1002/gps.5262
Popis: A cornerstone of research ethics is the principle of respect-for-persons, by which people who enroll in research trials are supplied with the necessary information so that they can make an informed and voluntary decision regarding their enrollment in the trial.1 This concept of respect-for-persons has been formalized in the process of informed consent: prior to enrolling in a trial, potential research participants review an institutional review board-approved consent form describing the purpose of the study, risks, benefits, etc. and have the opportunity to ask research staff clarifying questions.2 If a potential research participant does not possess the capacity to make an informed decision (e.g., children, incapacitated adults), a legally authorized representative can provide informed consent for enrollment in the trial.3 The process of informed consent is generally achieved via research staff providing adequate information to a person with decision-making capacity and then that person using an understanding of the information to make a voluntary and rational decision about enrollment in the trial.2 Concern has been raised, however, that some research participants confuse participation in research trials with routine clinical care. This concept has been described as the “therapeutic misconception” and was first articulated by Appelbaum and colleagues in the 1980s.4 As patients, people expect a level of personal care where their physicians primarily address the patients’ particular needs with a goal of providing individually optimal care.2 Such optimal care may involve treatment recommendations based on a person’s individual circumstances (e.g., past treatments, family history, idiosyncrasies of person’s history), dosage adjustments based on individual responses (e.g., dose increase if suboptimal response, dose decrease if intolerable side effects), maintenance of treatment when regimen proves satisfactory, and treatments with relatively well established efficacy and safety profiles.1,4 Research trials, however, are not designed to provide individualized care; the goals are always scientific with an aim of producing generalizable knowledge.5 Indeed, the protocols of research trials may be directly at odds with the clinical expectation of personalized care: research participants may be assigned to treatment arms randomly, not necessarily based on what treatment may be best suited to their needs; the trial may be double-blinded so that neither researcher or participant are aware of what the participant is receiving; dosing of study medication may be set by the protocol, not the individual participant’s response; concomitant medications may be restricted; study medications may be discontinued at the completion of trial, regardless of whether the participant has benefitted; and placebo may be used to improve the scientific assessment, not the participant’s condition.1,2,6 Although there has been controversy regarding a consensus definition, therapeutic misconception is then thought to include beliefs that research protocols will be individualized to the personal needs of the participant, unrealistic expectations of personal benefit through participation in the research trial, and a failure to understand that the primary goal of research is pursuit of generalizable knowledge, not personal care.5,7 Therapeutic misconception has been evaluated and confirmed in a variety of clinical trial settings, with some studies evidencing therapeutic misconception in greater than 50% of trial participants.8 Using close-ended and open-ended questioning as well as qualitative and quantitative analyses, evidence for therapeutic misconception has been found in phase I to phase III trials in diverse research populations ranging from depression to heart disease to cancer.9–11 For example in an interview-based study of 220 participants enrolled in 84 varied clinical trials (36% hematology/oncology, 18% psychiatry, 46% other), 25% of participants demonstrated therapeutic misconception with respect to individualization of the research protocol, 35% with respect to expected benefit of participation in the trial, and 15% with respect to primary purpose of the study as helping study participants (overall evidence for any therapeutic misconception was 51% of study participants).12 Factors associated with higher levels of therapeutic misconception include advancing age, less formal education, severity of illness, severity of cognitive deficits, and poor prognosis.10,13,14
Databáze: OpenAIRE
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