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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.

Background:Informed consent is regarded as a contract between autonomous and equal parties and requires the elements of information disclosure, understanding, voluntariness and consent. The validity of informed consent for critically ill patients has been questioned. Little is known about how these patients experience the process of consent.Objective:The aim of this study was to explore critically ill patients’ experience with the principle of informed consent in a clinical trial and their ability to give valid informed consent.Design:11 stroke patients who had been informed about thrombolytic treatment and had been through the process of deciding whether or not to participate in a thrombolysis trial went through repeated qualitative semistructured interviews.Results:None of the patients had any clear understanding of the purpose of the trial. Neither did they understand the principles of randomisation and voluntariness. Reasons for giving or not giving consent were trust, conceptions of benefits and risks and altruism. Several patients found it immoral to involve patients in the consent procedure and argued that this was the doctors’ responsibility. Others argued that it is a duty to question patients and perceived it as a sign of being treated with respect and dignity. A majority of the patients found the consent process vague and ambiguous.Conclusions:The results indicate that the principle of informed consent from critically ill patients cannot be seen as a contract between equal and autonomous parties. Further studies are needed to explore critically ill patients’ experiences with the process of informed consent.

Background HIV prevention trials conducted among disadvantaged vulnerable at-risk populations in developing countries present unique ethical dilemmas. A key concern in bioethics is the validity of informed consent for trial participation obtained from research subjects in such settings. The purpose of this study was to investigate the effectiveness of a continuous informed consent process adopted during the MDP301 phase III vaginal microbicide trial in Mwanza, Tanzania. Methods A total of 1146 women at increased risk of HIV acquisition working as alcohol and food vendors or in bars, restaurants, hotels and guesthouses have been recruited into the MDP301 phase III efficacy and safety trial in Mwanza. During preparations for the trial, participatory community research methods were used to develop a locally-appropriate pictorial flipchart in order to convey key messages about the trial to potential participants. Pre-recorded audio tapes were also developed to facilitate understanding and compliance with gel-use instructions. A comprehension checklist is administered by clinical staff to all participants at screening, enrolment, 12, 24, 40 and 50 week follow-up visits during the trial. To investigate women's perceptions and experiences of the trial, including how well participants internalize and retain key messages provided through a continuous informed consent process, a random sub-sample of 102 women were invited to participate in in-depth interviews (IDIs) conducted immediately after their 4, 24 and 52 week follow-up visits. Results 99 women completed interviews at 4-weeks, 83 at 24-weeks, and 74 at 52 weeks (a total of 256 interviews). In all interviews there was evidence of good comprehension and retention of key trial messages including that the gel is not currently know to be effective against HIV; that this is the key reason for conducting the trial; and that women should stop using gel in the event of pregnancy. Conclusions Providing information to trial participants in a focussed, locally-appropriate manner, using methods developed in consultation with the community, and within a continuous informed-consent framework resulted in high levels of comprehension and message retention in this setting. This approach may represent a model for researchers conducting HIV prevention trials among other vulnerable populations in resource-poor settings. Trial registration Current Controlled Trials ISRCTN64716212

Though antiretroviral therapy is the standard of care for people living with HIV, its treatment limitations, burdens, stigma and costs lead to continued interest in HIV cure research. Early-phase cure trials, particularly those that include analytic treatment interruption (ATI), involve uncertain and potentially high risk, with minimal chance of clinical benefit. Some question whether such trials should be offered, given the risk/benefit imbalance, and whether those who choose to participate are acting rationally. We address these questions through a longitudinal decision-making study nested in a Thai acute HIV research cohort.In-depth interviews revealed central themes about decisions to join. Participants felt they possessed an important identity as members of the acute cohort, viewing their bodies as uniquely suited to both testing and potentially benefiting from HIV cure approaches. While acknowledging risks of ATI, most perceived they were given an opportunity to interrupt treatment, to test their own bodies and increase normalcy in a safe, highly monitored circumstance. They were motivated by potential benefits to themselves, the investigators and larger acute cohort, and others with HIV. They believed their own trial experiences and being able to give back to the community were sufficient to offset participation risks.These decisions were driven by the specific circumstances experienced by our participants. Judging risk/benefit ratios without appreciating these lived experiences can lead to false determinations of irrational decision- making. While this does not minimise vital oversight considerations about risk reduction and protection from harm, it argues for inclusion of a more participant-centered approach.

Ethical issues can arise in the design and conduct of clinical trials. Using the trials that set the stage for our current treatment of hypertension, the authors show how the changing treatment landscape raised ethical problems as these trials were undertaken. The central tenet of clinical research in humans is that participation is informed and voluntary. Participation is considered to be informed only when there are properly scrutinized protocols and when participants are fully informed of the known risks, discomforts, and inconveniences related to their involvement. 1 Across the many types of clinical investigation, the randomized, controlled trial is the key scientific tool used to measure the efficacy and adverse effects of a diagnostic or therapeutic approach. 2 Randomization, the critical element used to reduce bias, not uncommonly creates ethical quandaries, since the treating physician and the patient, by agreeing to participate in . . .

A group of physicians, bioethicists, and scholars in allied fields agrees with the Office for Human Research Protections about the informed-consent documents in SUPPORT. To the Editor: We are a group of physicians, bioethicists, and scholars in allied fields who agree with the Office for Human Research Protections (OHRP) that the informed-consent documents that were used in the Surfactant, Positive Pressure, and Oxygenation Randomized Trial (SUPPORT) were seriously inadequate. 1 The aims of the SUPPORT study were commendable, and the study addressed important clinical issues. Nevertheless, however complex and important a study may be, the consent process must be clear enough to enable informed decision making. The U.S. Code of Federal Regulations (45CFR46.116) includes the following requirements for informed consent: “A statement that the study . . .

‘Human challenge’ results suggest that such trials could be used to test vaccines when Zika incidence is low. ‘Human challenge’ results suggest that such trials could be used to test vaccines when Zika incidence is low.

Sham surgery is a controversial and rarely used component of randomised clinical trials evaluating surgical interventions. The recent use of sham surgery in trials evaluating efficacy of intracerebral fetal tissue grafts in Parkinson’s disease has highlighted the ethical concerns associated with sham surgery controls. Macklin, and Dekkers and Boer argue vigorously against use of sham surgery controls. Macklin presents a broad argument against sham surgery controls while Dekkers and Boer present a narrower argument that sham surgery is unnecessary in the specific setting of fetal tissue engraftment for Parkinson’s disease. I defend sham surgery controls against both these criticisms. Appropriate clinical trial design, sometimes including sham surgery, is needed to ensure that false positive trial results do not occur and endanger public safety. Results of a completed trial of fetal tissue grafting for Parkinson’s disease are used to illustrate the potential benefits of, and problems associated with, sham surgery controls. Sham surgery controls, however, should be employed only when absolutely necessary. I suggest criteria for appropriate use of sham surgery controls.

When a patient could be offered one of multiple established treatments, doctors should be able to offer treatment only if the patient agrees to participate in research aimed at determining which of the treatments is most effective. Making treatment conditional on research participation will help researchers complete badly needed studies.