In this article I will argue first that if ignorance poses a problem for valid consent in medical contexts then framing effects do too, and second that the problem posed by framing effects can be solved by eliminating those effects. My position is thus a mean between two mistaken extremes. At one mistaken extreme, framing effects are so trivial that they never impinge on the moral force of consent. This is as mistaken as thinking that ignorance is so trivial that (...) it never impinges on the moral force of consent. At the other mistaken extreme, framing effects are so serious that their existence shows that consent has no independent moral force. This is as mistaken as the idea that ignorance is so serious that its existence shows that consent has no independent moral force. I will argue that, instead of endorsing either of these mistaken extreme views, we should instead endorse a moderate view according to which framing effects sometimes pose a serious challenge for the validity of consent, just as ignorance does, but one which we can solve by eliminating the effect, just as we can solve the problem of ignorance by eliminating it. (shrink)

Subjects enrolled in studies testing high risk interventions for incurable or progressive brain diseases may be vulnerable to deficiencies in informed consent, such as the therapeutic misconception. However, the definition and measurement of the therapeutic misconception is a subject of continuing debate. Our qualitative pilot study of persons enrolled in a phase I trial of gene transfer for Parkinson disease suggests potential avenues for both measuring and preventing the therapeutic misconception. Building on earlier literature on the topic, we developed and (...) tested an interview guide that focuses on how the subjects decided to participate, emphasizing the integration of subjects’ various statements that are relevant to assessing the therapeutic misconception, rather than evaluating them as isolated statements. The results indicate that a subject’s understanding of the purpose of research is best explored in juxtaposition to the subject’s motivation for participating. (shrink)

Informed consent in clinical research is widely regarded as broken, but essential nonetheless. The most recent attempt to reform it comes as part of the first revisions to the Common Rule since it became truly “common” in 1991. This change, the addition of a “key information” requirement for most consent forms, is intended to support and promote a reasoned decision-making process by potential subjects. The key information requirement is both promising and problematic. It is promising because it encourages clarity and (...) honesty about research participation, creativity in information disclosure, and mutual learning through the investigator-subject relationship. It is problematic because those goals — which have remained aspirational since the beginning — may be difficult to achieve in what has become an excessively compliance-oriented regulatory regime. (shrink)

Research Ethics Committees (RECs) play a critical gatekeeping role in clinical trials. This role is meant to ensure that only those trials that meet certain ethical thresholds proceed through their gate. Two of these thresholds are that the potential benefits of trials are reasonable in relation to risks and that trials are capable of producing a requisite amount of social value. While one ought not expect perfect execution by RECs of their gatekeeping role, one should expect routine success in it. (...) This article reviews a range of evidence showing that substantial numbers of ethically tainted trials are receiving REC approvals. Many of the trials are early phase trials that evidence shows have benefits that may not be reasonable compared with their risks and many others are later trials that evidence shows may lack sufficient social value. The evidence pertains to such matters as methodologically inadequate preclinical studies incapable of supporting the inferences that REC members must make about the prospects for potential benefit needed to offset the risks in early phase trials and sponsorship bias that can cause improperly designed, conducted, analysed and reported later phase trials. The analysis of the evidence makes clear that REC practices need to be strengthened if they are to adequately fulfil their gatekeeping role. The article also explores options that RECs could use in order to improve their gatekeeping function. (shrink)

Genetic research attracts significant attention from the popular press, and often these representations are less than ideal, skewing toward hyperbole and promises of near-future benefits. Indeed, revolutionary language has permeated public discourse since the start of the Human Genome Project in the early 1990s. If the near constant parade of enthusiastic headlines is to be believed, we have been in the midst of a "genetic revolution" for over three decades, yet, the promised revolutionary changes never fully materialize, at least not (...) to the extent envisioned by the proselytizers. The revolution is always just around the corner. Moreover, the nature and impact of the promised revolution is... (shrink)

A non-inferiority design accepts the possibility of some efficacy loss, as part of a “successful”, statistically significant result. That loss may be excessive when the non-inferiority threshold is lenient. However, even stringent significance thresholds and safety monitoring may fail to adequately protect study participants when the primary outcome is death. The OPTIMAAL trial, a large randomized clinical trial performed in high-risk patients, is discussed as an example, using the Belmont Report principles as an ethical frame of reference. OPTIMAAL compared losartan, (...) a new drug, to captopril, a drug known to reduce the risk of death in patients with heart failure after a myocardial infarction. Serious ethical challenges occurred in that study. Firstly, subjects had to tolerate captopril to participate, meaning that participation implied the possibility of higher risk of death if randomized to the losartan arm, as compared to the standard of care. Additionally, the stopping rules had to ensure enough powe... (shrink)

Subjects enrolled in studies testing high risk interventions for incurable or progressive brain diseases may be vulnerable to deficiencies in informed consent, such as the therapeutic misconception. However, the definition and measurement of the therapeutic misconception is a subject of continuing debate. Our qualitative pilot study of persons enrolled in a phase I trial of gene transfer for Parkinson disease suggests potential avenues for both measuring and preventing the therapeutic misconception. Building on earlier literature on the topic, we developed and (...) tested an interview guide that focuses on how the subjects decided to participate, emphasizing the integration of subjects’ various statements that are relevant to assessing the therapeutic misconception, rather than evaluating them as isolated statements. The results indicate that a subject’s understanding of the purpose of research is best explored in juxtaposition to the subject’s motivation for participating. (shrink)

Published research findings are sometimes refuted by subsequent evidence, says Ioannidis, with ensuing confusion and disappointment.

Clinical research has at least three problematic features: it tends to be redundant, secretive, and isolated.1 Research with these features not only wastes resources and causes harm, it also fails to meet a basic ethical requirement of research: scientific validity. As bioethicists, we should be asking why, if research with these three features is ethically unjustified, it has been so routinely approved by research ethics committees over the past half century. In what follows, I provide one answer to this question. (...) The first section of this paper outlines empirical evidence for the redundant, secretive, and isolated nature of much contemporary clinical research. Next, I argue that a lack of clarity .. (shrink)

: "Therapeutic misconception" has been misconstrued, and some of the newer, mistaken interpretations are troublesome. They exaggerate the distinction between research and treatment, revealing problems in the foundations of research ethics and possibly weakening informed consent.

Unrealistic optimism is a bias that leads people to believe, with respect to a specific event or hazard, that they are more likely to experience positive outcomes and/or less likely to experience negative outcomes than similar others. The phenomenon has been seen in a range of health-related contexts—including when prospective participants are presented with the risks and benefits of participating in a clinical trial. In order to test for the prevalence of unrealistic optimism among participants of early-phase oncology trials, we (...) conducted a survey with patients over 18 years of age who were enrolled in a phase I, phase I/II, or phase II clinical cancer trial in the New York City area between August 2008 and October 2009. Participants in our study were asked to compare their own chances of experiencing a range of risks and benefits related to the trial they were enrolled in with the chances of the other trial participants. We found a significant optimistic bias in their responses. Respondents tended to overestimate the benefits of the trial they were enrolled in and underestimate its risks. In addition, we found no significant relationship between respondents’ understanding of the trial’s purpose and how susceptible they were to unrealistic optimism. Our findings suggest that improving the consent process for oncology studies requires more than addressing deficits in understanding. (shrink)

The “therapeutic misconception” describes a process whereby research volunteers misinterpret the intentions of researchers and the nature of clinical research. This misinterpretation leads research volunteers to falsely attribute a therapeutic potential to clinical research, and compromises informed decision making, therefore compromising the ethical integrity of a clinical experiment. We review recent evidence from the neurobiology of social cognition to provide a novel framework for thinking about the therapeutic misconception. We argue that the neurobiology of social cognition should be considered in (...) any ethical analysis of how people make decisions about participating in clinical trials. The neurobiology of social cognition also suggests how the complicated dynamics of the doctor-patient relationship may unavoidably interfere with the process of obtaining informed consent. Following this argument we suggest new ways to prevent or at least mitigate the therapeutic misconception. (shrink)

A predominant ethical view holds that physician‐investigators should conduct their research with therapeutic intent. And since a physician offering a therapy wouldn't prescribe second‐rate treatments, the experimental intervention and the best proven therapy should appear equally effective. "Clinical equipoise" is necessary. But this perspective is flawed. The ethics of research and of therapy are fundamentally different, and clinical equipoise should be abandoned.

The revised Common Rule adopts the reasonable person standard to guide research disclosure. Some members of the research community contend that the standard is confusing and ill-suited to the research oversight system. Yet the revised rule is not as radical as it might seem. During the 1970s, judges started using the standard to evaluate negligence claims brought by injured patients who said doctors had failed to obtain informed consent to the harmful procedures. In its influential Belmont Report, the National Commission (...) recommended application of a “reasonable volunteer standard” to guide IRBs evaluating research disclosures. Evidence also suggests that IRBs often invoke the reasonable person standard in deliberations about consent forms. But past application of the standard has been informal and uneven. Robust application of the reasonable person standard will require researchers and IRBs to learn more about what ordinary people want and need to know about the studies they are invited to join. Input from people with personal experience as study participants could be particularly useful to this effort. (shrink)

:Academic Medical Centers offer patient care and perform research. Increasingly, AMCs advertise to the public in order to garner income that can support these dual missions. In what follows, we raise concerns about the ways that advertising blurs important distinctions between them. Such blurring is detrimental to AMC efforts to fulfill critically important ethical responsibilities pertaining both to science communication and clinical research, because marketing campaigns can employ hype that weakens research integrity and contributes to therapeutic misconception and misestimation, undermining (...) the informed consent process that is essential to the ethical conduct of research. We offer ethical analysis of common advertising practices that justify these concerns. We also suggest the need for a deliberative body convened by the Association of American Medical Colleges and others to develop a set of voluntary guidelines that AMCs can use to avoid in the future, the problems found in many current AMC advertising practices. (shrink)

Commentators tout the societal benefits of research to conclude that people have a civic duty to participate in it. A review of several problems in research demonstrate the contrary and reveal why claims we are duty-bound to participate in research deter urgently needed efforts to tackle multiple entrenched deficiencies in it.