Informed consent in experimentation involving mentally impaired persons: ethical issues

The problem of experimentation involving subjects whose mental condition prevents them from understanding information and providing proper informed consent has been addressed in various codes, declarations, conventions, treaties and regulations adopted by national, international and supranational institutions and authorities. This article summarizes the basic ethical criteria these documents provide and stresses the historical development from the nearly total exclusion of incapacitated subjects, established in the mid-twentieth century, to their contemporary inclusion in clinical trials on certain ethical conditions. The problem of proxy consent by legal representatives for participation in clinical trials is addressed particularly in reference to current Italian regulations. Exceptions to human experimentation requirements in emergency situations are also briefly discussed.     

从贝尔蒙报告审视医疗器械临床试验的伦理问题

医疗器械临床试验是最直接最有效地检测医疗器械性能的方式，贝尔蒙报告是对基本的道德原则及方针的陈述，用来帮助在解决涉及人体实验对象的科研中所产生的道德问题。本文从贝尔蒙报告角度来审视医疗器械临床试验的伦理问题，介绍了贝尔蒙报告产生的背景概念和医疗器械临床试验的概念及基本流程；贝尔蒙报告中的三项原则尊重个人、善行和平等公正原则在医疗器械临床试验中的体现以及针对贝尔蒙报告来解决医疗器械临床试验中产生的伦理问题的重大意义。通过知情同意的具体体现、对风险和好处的评估及受试者的选择和研究成果的分配三方面来解决临床试验中产生的伦理问题。     

Randomized controlled trials in environmental health research: ethical issues

Randomized controlled trials (RCTs) are becoming increasingly common in environmental health research. Like all studies involving human subjects, environmental health RCTs raise many ethical challenges, ranging from obtaining informed consent to minimizing risks to protecting privacy and confidentiality. One of the most important issues raised by these studies is whether it is ethical to withhold effective environmental health interventions from research subjects in order to satisfy scientific objectives. Although environmental health investigators usually do not have professional obligations to provide medical care to research subjects, they have ethical obligations to avoid exploiting them. Withholding interventions from research subjects can be ethical, provided that it does not lead to exploitation of individuals or groups. To avoid exploiting individuals or groups, investigators should ensure that research subjects and study populations receive a fair share of the benefits of research.     

Ethics of Informed Consent for Pragmatic Trials with New Interventions

Objectives: Pragmatic trials evaluate the comparative benefits, risks, and burdens of health care interventions in real-world conditions. Such studies are now recognized as valuable to the perimarketing stage of drug development and evaluation, with early pragmatic trials (EPTs) being explored as a means to generate real-world evidence at the time of regulatory market approval. In this article, we present an analysis of the ethical issues involved in informed consent for EPTs, in light of the generally recognized concern that traditional ethical rules governing randomized clinical trials, such as lengthy informed consent procedures, could threaten the “real world” nature of such trials. Specifically, we examine to what extent modifications (waivers or alterations) to regulatory consent for EPTs would be ethical. Methods: We first identify broadly accepted necessary conditions for modifications of informed consent (namely, the research involves no more than minimal risk of harm, the research is impracticable with regulatory consent, and the alternative to regulatory consent does not violate legitimate patient expectations) and then apply those criteria to the premarket and early postmarket contexts. Results and Conclusions: The analysis shows that neither waivers nor alterations of regulatory consent for premarket EPTs will be ethically permissible. For postmarket EPTs with newly approved interventions, waivers of consent will be ethically problematic, but some studies might be conducted in an ethical manner with alterations to regulatory consent.     

Why clinical trials of AIDS vaccines are premature.

Considering the current state of scientific knowledge and the fact that no relevant animal model exists for demonstrating a vaccine's probable efficacy, the fundamental prerequisites for testing experimental AIDS vaccines in human beings have not been met. The ethical obligations of informed consent, patient confidentiality, and the balancing of risks and benefits are examined in a call for more public debate on the issue before clinical trials are begun.     

Are distinctive ethical principles required for cluster randomized controlled trials?

Cluster randomized trials are increasingly used in research into health care and health services. Ethics of individual patient randomized trials have been elucidated in a number of different codes, but less attention has been given to the ethical issues raised by cluster randomized trials. I assess the challenges raised by cluster randomized controlled trials by considering three questions: What are the essential elements of ethical medical research, particularly experiments on people? What are the features which distinguish cluster randomized controlled trials from ordinary RCTs? Do the distinctive features of cluster randomized trials entail new ethical principles, or careful application of existing principles? I conclude that cluster randomized controlled trials raise new issues on the nature and practice of informed consent, because of the levels at which consent can be sought, and for which it can be sought. In addition, careful consideration of the principles relating to the quality of the scientific design and analysis, balance of risk and benefit, liberty to leave a trial, early stopping of a trial and the power to exclude people from potential benefits is required.     

医学期刊编辑对生物医学研究伦理问题的处理方式调研及建议

【目的】 探讨医学期刊编辑处理生物医学研究伦理问题的方式,为推动确立医学期刊伦理审查规范提供参考。【方法】 通过问卷星向国内医学期刊编辑发放调查问卷,对审稿时和论文出版后处理医学伦理相关问题的方式展开调研。【结果】 共回收问卷230份。调查显示:在审稿阶段,在保护患者隐私方面,英文期刊、中英双语期刊的编辑更注重要求作者提供授权同意相关证明材料;中、英文期刊以及中英双语期刊的编辑对涉及人体试验伦理问题的处理方式都比较规范。但是,对于研究是否获得患者知情同意、动物实验研究是否经过伦理委员会审查、回顾性研究是否需要伦理审查、涉及人的研究是否在临床试验注册中心注册等问题,编辑还需要进一步重视。在论文出版后,编辑发现的医学伦理问题主要是“涉及人的研究未说明是否经过伦理委员会审查”。对论文出版后发现的没有保护患者隐私和没有在临床试验注册中心注册的问题,大部分期刊缺乏相关处理方案。【结论】 编辑应加强对论文知情同意、动物实验伦理、回顾性研究伦理的审查,并审查涉及人的研究是否在临床试验注册中心注册,以推动我国医学期刊的高质量发展。     

Confusions in the equipoise concept and the alternative of fully informed overlapping rational decisions

Despite its several variations, the central position of equipoise is that subjects in clinical experiments should not be randomized to conditions when others believe that better alternatives exist. This position has been challenged over issues of which group in the medical or research community is authorized to make that determination, and it has been argued that informed consent provides sufficient ethical protection for participants independent of equipoise. In this paper I frame ethical participation in clinical research as a two-party decision process involving offering and accepting participation under informed consent. Nine conditions are identified in which it is possible that potential participants and researchers or care professionals can rationally choose divergent actions based on identical understandings of the situation. Under such circumstances, researchers or care professionals cannot ethically substitute their understanding of equipoise in the situation for the patients’ choices, or vice versa.     

Empty ethics: the problem with informed consent

Informed consent is increasingly heralded as an ethical panacea, a tool to counter autocratic and paternalistic medical practices. Debate about the implementation of informed consent is constricted and polarised, centering on the right of individuals to be fully informed and to freely choose versus an autocratic, paternalistic practice that negates individual choice. A bioethical framework, based on a principle-led form of reductive/deductive reasoning, dominates the current model of informed consent. Such a model tends to abstract the process of consent from its clinical and social setting. By flashing out the social process involved when patients and healthy volunteer subjects consent to take part in clinical drug trials, this paper attempts to address the problem arising from the current 'empty ethics' model. My arguments are substantiated by qualitative interview data drawn from a study I conducted on the process of consent as experienced by participants in clinical drug trials.     

Rights and respect. Legal and ethical issues challenge today's mental healthcare professionals

The special circumstances of patients in mental health facilities often make questions concerning patient autonomy, freedom of choice, and consent to treatment even more complex than they are in other contexts. Individual facilities need to identify the ethical issues they are likely to encounter and create policies that address them effectively. The advent of managed care has created unprecedented access problems for mental healthcare providers. In many cases patients must be proven dangerous to themselves or others before they can be admitted for emergency care; because it is difficult to prove this, many persons go without needed treatment. The high costs of care and prejudices against persons with mental illness also create ethical problems. The necessity of performing clinical evaluations raises important ethical issues as well. Care givers evaluating someone at the request of a school, employer, or court should be sensitive to the possible consequences of their evaluation. They should also restrict their diagnoses to their area of competency and inform clients of the purpose of the evaluation, its possible consequences, and the limits of its confidentiality. Mental health professionals must also respect patients' rights to informed consent and understand the issues of voluntary or involuntary admissions. In addition, care givers should be aware of the various issues created by the need to occasionally control patients' behavior. Finally, for mental healthcare facilities, it is essential to establish an ethics committee to address these issues.     

Psychosocial evaluation interview protocol for living related and living unrelated kidney donors

This article is intended to help mental health clinicians who work with kidney transplant teams enhance their understanding, abilities and skills to determine the best possible psychosocially stable living donor candidates who present for evaluation. Additionally, this article is intended to help the clinician gain a better understanding of the donor ability and willingness to give informed consent, and determine those who present for donorship which may be at high risk due to either historic or current mental health, substance use and current lifestyle issues. Finally, this article considers the rationale and goals of pretransplant psychosocial evaluation of potential kidney donors as well as the net effects on the families. The intent is to provide a clinical protocol useful in both private and public hospitals. The current protocol is currently being used at HCA: Henrico Doctors' Hospital, Virginia Transplant Center in Richmond, Virginia. Early post-transplant psychosocial problems and their management and the long-term adaptation for the donors are discussed. Additionally, ethical considerations are addressed.     

Ethical dilemmas created by the criminalization of status behaviors: case examples from ethnographic field research with injection drug users.

The criminalization of behaviors such as the ingestion of certain mood-altering drugs creates ethical dilemmas for researchers studying those behaviors. The Syringe Access, Use, and Discard (SAUD) project is designed to uncover microcontextual factors that influence HIV and hepatitis risk behaviors of injection drug users. The article presents seven ethical dilemmas encountered using ethnographic methods: issues involving syringe replacement at injection locales, risks of participants' arrest, potential disruptions in participants' supply routes, risks of research staff arrest, threats to the protection of confidentiality, issues surrounding informed consent in working with addicts, and the confiscation of potentially incriminating information by police. The article concludes with a discussion of the limitations of traditional ethical frameworks, such as utilitarianism, for resolving these dilemmas and recommends instead improving public health professionals' capacity for practical reasoning (phronesis) through the greater use of case studies in public health curricula.     

Human experimentation in historical and ethical perspectives

Prepared as background material for a World Health Organization/Council for International Organizations of Medical Sciences document, Proposed International Guidelines for Biomedical Research Involving Human Subjects (1982), this article reviews historical aspects of human experimentation and considers several current issues. It refers to early experiments, including auto-experiments by physicians; traces the history of drug trials through the pharmacotherapeutic revolution and the thalidomide tragedy; and describes the formulation of ethical requirements during the Weimar Republic in Germany. Contemporary problems discussed are the use of controls and placebos, investigators as subjects, special categories of subjects, and informed and vicarious consent. The text of the proposed WHO/CIOMS Guidelines is appended.     

刍议基于医院管理的临床试验受试者的知情同意权保护

随着临床试验在国内日渐频繁,知情同意权作为受试者的一项权利已经得到普遍认同,现在医患双方都比较注重诊疗实践中一般的知情同意,而对临床试验中受试者这一特殊群体的"知情同意"没有引起足够的重视,导致在实践中这项权利常被侵犯,为医疗纠纷埋下了隐患。医院作为临床试验的必经场所,理应肩负起保护受试者权益的重任,文章从医院管理着手通过分析目前受试者知情同意权的保护现状进而探讨保护措施。     

The informed consent aftermath of the genetic revolution. An Italian example of implementation

A great part of human genetics research is carried out collecting data and building large databases of biological samples that are in a non-anonymous format. These constitute a valuable resource for future research. The construction of such databases and tissue banks facilitates important scientific progress. However, biobanks have been recognized as ethically problematic because they contain thousands of data that could expose individuals and populations to discrimination, stigmatization and psychological stress if misused. Informed consent is regarded as a cornerstone in the protection of personal autonomy in research involving human subjects. Yet in recent years this fundamental concept has been overwhelmed by the genomic revolution. From a general overview of international literature, it seems evident that informed consent issues have come into sharp focus, in particular in relation to the twin issues of time extension (blanket versus specific/repeated consent) and personal extension (group consent). After an introduction on obtaining informed consent in the context of genetic research, this paper addresses the apparent lack of a single, universal model of obtaining informed consent among populations involved in genetic research and it argues for the need to develop an ethical framework tailored to the specific features of each project. In order to support this theory of contextualizing, the case of a private biotechnology company, SharDNA is presented. The present paper explores the management of its biobank, developed from a genetic research project carried out on isolated populations living on the Italian island of Sardinia. In particular, the paper highlights how the company is tackling the problem of informed consent and other ethical requirements for genetic research, such as the respect of individual privacy, the population approach and the existing Italian legal regulatory framework.     

'Even if they ask you to stand by a tree all day, you will have to do it (laughter)...!': community voices on the notion and practice of informed consent for biomedical research in developing countries

Ethical dilemmas in biomedical research, especially in vulnerable populations, often spark heated debate. Despite recommendations and guidelines, many issues remain controversial, including the relevance, prioritisation and application of individual voluntary informed consent in non-Western settings. The voices of the people likely to be the subjects of research have been notably absent from the debate. We held discussions with groups of community members living in the rural study area of a large research unit in Kenya. Discussions were facilitated by three research study vignettes outlining one field-based and two hospital-based studies being planned or taking place at the time. In addition to gathering general views about the aims and activities of the research unit, questions focused on whether consent should be sought for studies, and if so from whom (chiefs, elders, men/women, children), and on ascertaining whether there are any special concerns about the physical act of signing consent forms. The findings revealed the community's difficulty in distinguishing research from clinical investigations conducted in clinical settings. There was a spectrum of views regarding perceived appropriateness of consent procedures, in part because of difficulty in disentangling clinical from research aims, and because of other challenges to applying consent in practice. Debates between community members highlight the inadequacy of simplistic assumptions about community members' views on informed consent, and the complexity of incorporating lay opinions into biomedical research. Failure to appreciate these issues risks exaggerating differences between settings, and underestimating the time and resources required to ensure meaningful community involvement in research processes. Ultimately, it risks inadequately responding to the needs and values of those on whom the success of most biomedical research depends. Although compliance with community views does not necessarily make the research more ethical, it is argued that community opinions on local issues and practices should inform ethical decision-making in health research.     

Ethical issues in occupational health research

This is an overview of ethical issues in occupational health research involving human subjects. Research that requires human subjects review must be distinguished from surveillance or public health practice. Confidentiality and privacy concerns are particularly important in an occupational setting because individual participants may be identifiable through job title or other characteristics, and because there may be concerns about employment discrimination associated with participation status or results. Additional issues include notification of individual test results to the study participants, including whether the results have clinical significance and/or provide other potentially relevant information to the study subjects; consent for banking of biological specimens for future research (e.g., uses of the specimens, plans for anonymization, notification of future results); and the higher level of sensitivity of workplace studies involving genetic modifiers of risk. Many occupational studies involve no more than minimal risk. Studies that involve greater than minimal risk require the investigator to document the potential risks and attempt to minimize them.     

转化医学中利益冲突及其影响

医学、法律和伦理是相互伴生的科学.近年来,转化医学的提出及其开展,促进基础研究成果的快速的临床转化和应用,促使研究成果尽快形成市场化的产品,提高医疗诊断水平和促进健康.同时面临一些新的挑战,产生新的伦理问题,并使一些现有伦理问题更为凸显.开展转化医学具有潜在的风险和问题,利益冲突,及其对受试者权益保护和知情同意的潜在影响还没有受到应有的重视,需要伦理委员会加强审核.     

Motivating Donors to Genetic Research? Anthropological Reasons to Rethink the Role of Informed Consent

In this article we explore the contribution from social anthropology to the medical ethical debates about the use of informed consent in research, based on blood samples and other forms of tissue. The article springs from a project exploring donors’ motivation for providing blood and healthcare data for genetic research to be executed by a Swedish start-up genomics company. This article is not confined to empirical findings, however, as we suggest that anthropology provides reason to reassess the theoretical understanding of autonomy as generally defined by Beauchamp and Childress. Careful consideration of the trust expressed by donors through the act of donation, furthermore, suggests that there is reason to redirect the ethical scrutiny from informed consent to issues concerning institutional arrangements and social responsibility. In particular, we suggest that an anthropological approach could facilitate a reconsideration of the political implications of using informed consent as a regulatory practice in tissue-based research.