Informed Consent, Therapeutic Misconception, and Unrealistic Optimism.

The Belmont Report attested to the cardinal importance of informed consent for ethical research on human subjects. Important challenges to securing informed consent have emerged since its publication more than 40 years ago. Among some of the most significant of these challenges are those that highlight social psychological factors that have the potential to impair the appreciation of relevant information disclosed in the informed consent process. Responding to these challenges requires us to think harder about the content of the principle of informed consent and the demands that it imposes on investigators. This article focuses on two challenges in particular, that presented by the so-called therapeutic misconception, and that presented by the psychological bias of unrealistic optimism. After outlining an account of the principle of informed consent as it applies to the research context, the article briefly reviews the empirical literature on the therapeutic misconception and the bias of unrealistic optimism. It then relates these phenomena to the principle of informed consent, paying special attention to the ethical demands they impose on investigators. The article concludes by considering how recent trends to integrate research and clinical care affect the main points it has advanced.

A survey in Mexico about ethics dumping in clinical research.

BACKGROUND: The exportation of unethical practices to low- and middle-income countries ("Ethics Dumping") has been conceived as a prevalent practice which needs to be examined more closely. Such a practice might point towards the exploitation of vulnerable population groups. We conducted a survey among Mexican research ethics committee members to explore the issue of ethics dumping in Mexico by understanding how its existence and contributing factors and norms are perceived by these ethics committee members. METHOD: We designed an exploratory survey based on a five-point Likert scale, following an established, validated and published methodology. The questionnaire included both open close-ended questions. The aspects covered in the questionnaire were introductory questions on the existence of ethical issues; general perception on ethics dumping in Mexico; lack of voluntariness, undue inducement, and therapeutic misconception as exploitation risks; existence of exploitative practices; norms facilitating ethics dumping; acceptable levels of benefit to Mexico; boundaries of ethics dumping. The survey was administered to a sample of research ethics committee members from public and private Mexican hospitals in 2016. RESULTS: Most of the ethics committee members believed clinical trials are generally ethically sound, though almost a majority think that ethics dumping is a common occurrence and that it is a serious issue. Most agree that ethics dumping needs to be addressed. They also identified other issues such as ethical issues related to patient participation and ethics committees. Further, most committee members agree that undue inducement and therapeutic misconception affect voluntariness, and that both individuals and communities receive appropriate benefits. CONCLUSION: From the perspective of Mexican research ethics committee members, ethics dumping commonly exists in Mexican clinical trials, as well as several related issues such as ethical issues on patient participation and ethics committees, as well as voluntariness issues. Further, most members believed these issues need to be addressed. However, most were also of the opinion that clinical trials are generally ethically compliant. This points to the need for further studies on the reasons for these perspectives.

How Should Physicians Help Patients Understand Unknowns of Nanoparticle-Based Medicines?

When a patient wants to enroll in a clinical trial to gain early access to an apparently promising but unproven intervention, her physician should clarify differences between participating in research and receiving treatment to help her avoid therapeutic misconception, make a thoughtful decision, and consider relevant clinical and ethical details. These include a patient's disease and treatment experiences, needs, interests, values, the design and phase of the trial, and the nature of the intervention being studied. When an unproven intervention is a nanodrug, a physician's role is especially difficult, because though nanomedicine might offer real benefits, it can also pose unexpected or even unprecedented harms. Thus, a physician should help a patient explore possible outcomes while promoting realism, countering hype, and preserving hope.

How Should a Research Ethicist Combat False Beliefs and Therapeutic Misconception Risk in Biomedical Research?

Therapeutic misconception can be especially challenging at large research-intensive academic medical centers, where boundaries between clinical care and research can become murky. In early stage clinical trials, for example, physicians often encourage patients to enroll in a drug or an intervention study as part of a treatment plan. As a research ethicist, I have found myself having to temper researchers' enthusiasm to prevent their overemphasizing positive benefits to participants. One strategy I've used is to encourage researchers to collaborate with treating physicians and to continually engage participants in assessing risks and benefits. This strategy has been helpful not only in early stage trials but also in translational genomic studies in which research can be used in part as a means of making costly testing available to patients.

Taking Respect Seriously: Clinical Research and the Demands of Informed Consent.

There is broad agreement among research ethicists that investigators have a duty to obtain the informed consent of all subjects who participate in their research trials. On a common view, the duty to obtain this informed consent follows from the need to respect persons and their autonomous decisions. However, the nature of informed consent and the demands it places on investigators are open to dispute and recently have been challenged. Respect for persons, it has been claimed, does not require investigators to guarantee that the subjects enrolled in their trials comprehend the risk/benefit information disclosed to them or even that they appreciate the difference between research and therapy. According to this critique, the significance of defects in informed consent, like therapeutic misconception or unrealistic optimism, has been greatly exaggerated. This article reevaluates informed consent in clinical research in light of this critique. It not only rebuts the main points the critics raise, but also shows that other points they raise can be accepted by a doctrine of informed consent that resembles the common view in maintaining that autonomous authorization is central to informed consent.

The Therapeutic "Mis"conception: An Examination of its Normative Assumptions and a Call for its Revision.

Dissecting Bioethics, edited by Tuija Takala and Matti Hayry, welcomes contributions on the conceptual and theoretical dimensions of bioethics. The department is dedicated to the idea that words defined by bioethicists and others should not be allowed to imprison people's actual concerns, emotions, and thoughts. Papers that expose the many meanings of a concept, describe the different readings of a moral doctrine, or provide an alternative angle to seemingly self-evident issues are particularly appreciated. To submit a paper or to discuss a suitable topic, contact Tuija Takala at tuija.takala@helsinki.fi.

Dispelling misconceptions in the management of familial adenomatous polyposis.

Patients with familial adenomatous polyposis require surgical intervention at some point in their lives. The diagnosis is often apparent from their phenotype and family history, however, this is not always the case. Many factors can influence the surgical strategy although the polyposis burden and distribution remain the main consideration. While prophylactic removal of the rectum and colon is often required, sparing the rectum at the index surgery is safe in select patients. This article aims to dispel misconceptions in the diagnosis and treatment of patients with familial adenomatous polyposis.

Why take part in personalised cancer research? Patients' genetic misconception, genetic responsibility and incomprehension of stratification-an empirical-ethical examination.

Therapeutic misconception is a well-known challenge for informed decision-making for cancer research participants. What is still missing, is a detailed understanding of the impact of "personalised" treatment research (e.g. biomarkers for stratification) on research participants. For this, we conducted the first longitudinal empirical-ethical study based on semi-structured interviews with colorectal cancer patients (n = 40) enrolled in a biomarker trial for (neo)adjuvant treatment, analysing the patients' understanding of and perspectives on research and treatment with qualitative methods. In addition to therapeutic misconception based on patients' confusion of research and treatment, and here triggered by misled motivation, information paternalism or incomprehension, we identified genetic misconception and genetic responsibility as new problematic issues. Patients mainly were not aware of the major research aim of future stratification into responders and non-responders nor did they fully acknowledge this as the aim for personalised cancer research. Thus, ethical and practical reflection on informed decision-making in cancer treatment and research should take into account the complexity of lay interpretations of modern personalised medicine. Instead of very formalistic, liability-oriented informed consent procedures, we suggest a more personalised communication approach to inform and motivate patients for cancer research.

Cure research and consent: the Mississippi Baby, Barney Clark, Baby Fae and Martin Delaney.

Trials using children as subjects are much more problematic from an informed consent perspective than trials on competent adults, although the 'therapeutic misconception' is a central concern in both. The role of famous experiments and the use of one individual's experience to designate and justify a whole category of research have always threatened to undermine the validity of informed consent to research by making it seem to be a validated therapy. In research, the unintended consequence of 'naming' based on goals ('cure') or specific individuals (like the Mississippi Baby) tends to subvert informed consent when the famous case is a 'success', and to prematurely end a line of research if the named subject dies. Names, including the Mississippi Baby, Barney Clark, Baby Fae and even Martin Delaney, are more suggestive of fantasy than science. The word 'cure' should not be used in obtaining consent for HIV 'cure trials', and names of people involved in past experiments should be avoided in the informed consent process. These two modest proposals should reduce the risks of the therapeutic misconception in 'cure research'.

Are patients with amyotrophic lateral sclerosis at risk of a therapeutic misconception?

OBJECTIVES: To assess whether persons with amyotrophic lateral sclerosis (ALS) are at risk of a therapeutic misconception (TM) in which they misconceive research as treatment or overestimate the likelihood of its benefit. METHODS: 72 patients with ALS recruited via academic and patient organisations were surveyed using a hypothetical first-in-human intervention study scenario. We elicited their understanding of the purpose of the study ('purpose-of-research question') and then asked how they interpreted the question. We then asked for an estimate of the likelihood that their ALS would improve by participating and asked them to explain the meaning of their estimates. RESULTS: Although 10 of 72 (14%) subjects incorrectly said that the intervention study was 'mostly intending to help [me]' in response to the purpose-of-research question, 7 of those 10 thought that the question was asking them about their own motivations for participating. Overall, only one of 72 respondents (1.4%) both understood the purpose-of-research question as intended and gave the incorrect response. Subjects' mean estimate of likelihood of benefit was 31% (SD 26). This was due to 29 of 72 of respondents providing high estimates (50%-54% likelihood), which they said were expressions of hope and need for a positive attitude; among those who said their estimates meant 'those are the facts' or 'there is a lot of uncertainty', the estimates were much lower (12.6% and 18.5%, respectively). CONCLUSIONS: In this group of patients with ALS considering a hypothetical first-in-human intervention study, apparent TM responses have alternative explanations and the risk of true TM appears low.

Vulnerability, therapeutic misconception and informed consent: is there a need for special treatment of pregnant women in fetus-regarding clinical trials?

Historically, pregnant women have generally been excluded from clinical trials. One of the reasons for this exclusion has been the belief that pregnant women are vulnerable as research participants. Although this view has now largely fallen into disfavour, this article argues that in the situation where the pregnant woman is newly diagnosed with a fetal condition for which the only option, other than watchful waiting, is enrolment in a clinical trial, she should be considered a cognitively and medically vulnerable research participant. This is because she is in a highly stressed emotional state and so less able to decide completely freely whether or not to participate in the clinical trial. In other words, she is under a higher risk of therapeutic misconception and of not understanding what she is consenting to. This article suggests that in order for the consent of these women to be given freely and without emotional pressure, it has to be ensured that strategies are developed to ensure they are fully informed and actually understand the information. This surpasses the requirements of the English law of informed consent and also of General Medical Council (GMC) guidance on consent to research but such an approach would help safeguard that, despite these women's poor bargaining position, their trial participation is really free, voluntary and informed.

Therapeutic misconception in clinical trials: fighting against it and living with it / Los malentendidos terapéuticos en los ensayos clínicos: luchando contra ellos y viviendo con ellos

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El equívoco terapéutico en los ensayos clínicos: combatirlo y convivir con él / Therapeutic misconception in clinical trials: fighting against it and living with it

Un ensayo clínico busca obtener datos para el beneficio de futuros pacientes y no necesariamente para los que participan en él. Sin embargo, hay pacientes que creen que obtendrán un beneficio terapéutico directo por participar en un ensayo clínico: es el denominado «equívoco terapéutico». En este artículo se describe la naturaleza y la extensión del equívoco terapéutico, que también pueden presentar los investigadores. Su presencia es especialmente relevante en ensayos con grupo placebo y en los de fase 1 de oncología. Para intentar limitar su aparición hay que asegurar que las hojas de información para los participantes estén bien redactadas, y que los investigadores establezcan una conversación efectiva y transparente en el proceso de obtención del consentimiento informado, de forma que el paciente conozca todos los matices de su participación en la investigación y valore lo que esto significa (AU)

A clinical trial seeks information for the benefit of future patients and not necessarily for those who participate in the study. However, there are patients who believe that they will receive a direct therapeutic benefit by participating in a clinical trial, the so-called «therapeutic misconception». In this article, we describe the nature and extent of therapeutic misconception, which researchers can also experience. Its presence is especially important in phase 1 oncology trials and those with placebo group. To limit its occurrence, investigators have to ensure that participant information sheet are well written and to establish an effective and transparent discussion during the process of obtaining informed consent so that patients understand all aspects of their participation in the research and appreciate what this participation entails (AU)