Beyond informed consent

Although a relatively recent phenomenon, the role of informed consent in human research is central to its ethical regulation and conduct. However, guidelines often recommend procedures for obtaining informed consent (usually written consent) that are difficult to implement in developing countries. This paper reviews the guidelines for obtaining informed consent and also discusses prevailing views on current controversies, ambiguities and problems with these guidelines and suggests potential solutions. The emphasis in most externally sponsored research projects in developing countries is on laborious documentation of several mechanical aspects of the research process rather than on assuring true comprehension and voluntary participation. The onus for the oversight of this process is often left to overworked and ill-equipped local ethics review committees. Current guidelines and processes for obtaining informed consent should be reviewed with the specific aim of developing culturally appropriate methods of sharing information about the research project and obtaining and documenting consent that is truly informed. Further research is needed to examine the validity and user friendliness of innovations in information sharing procedures for obtaining consent in different cultural settings.     

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。     

《中国计划生育学杂志》论文中医学伦理意识的调查与思考

目的:从科技论文角度探讨我国计划生育科研工作中存在的医学伦理学问题。方法:查阅2005～2009年《中国计划生育学杂志》发表的学术论文,统计作者自述"通过伦理委员会审查""研究对象知情同意"情况。结果:5年间共出版60期(月刊),发表了以人为研究对象、前瞻性研究论文681篇,其中论文说明研究"经过伦理委员会审查"仅4篇(0.59%),"研究对象知情同意"49篇(7.20%)。结论:本次调查论文有关医学伦理学阐述的比例很低,反映出计划生育科研论文作者和编辑者的伦理学意识相当薄弱,与国外生物医学期刊差距较大。提示科技管理部门应重视对科研人员伦理学知识的宣传教育,加强计划生育科研工作伦理学规范。通过完善期刊编审程序,加强科研伦理学审查提高论文质量,促进我国人口和计划生育科学研究健康持续发展。     

Ethics review of COVID-19 human challenge studies: A joint HRA/WHO workshop

This report of a joint World Health Organization (WHO) and United Kingdom (UK) Health Research Authority (HRA) workshop discusses the ethics review of the first COVID-19 human challenge studies, undertaken in the midst of the pandemic. It reviews the early efforts of international and national institutions to define the ethical standards required for COVID-19 human challenge studies and create the frameworks to ensure rigorous and timely review of these studies.This report evaluates the utility of the WHO’s international guidance document Key criteria for the ethical acceptability of COVID-19 human challenge studies (WHO Key Criteria) as a practical resource for the ethics review of COVID-19 human challenge studies. It also assesses the UK HRA’s approach to these complex ethics reviews, including the formation of a Specialist Ad-Hoc Research Ethics Committee (REC) for COVID-19 Human Challenge Studies to review all current and future COVID-19 human challenge studies. In addition, the report outlines the reflections of REC members and researchers regarding the ethics review process of the first COVID-19 human challenge studies. Finally, it considers the potential ongoing scientific justification for COVID-19 human challenge studies, particularly in relation to next-generation vaccines and optimisation of vaccination schedules.Overall, there was broad agreement that the WHO Key Criteria represented an international consensus document that played a powerful role in setting norms and delineating the necessary conditions for the ethical acceptability of COVID-19 human challenge studies. Workshop members suggested that the WHO Key Criteria could be practically implemented to support researchers and ethics reviewers, including in the training of ethics committee members. In future, a wider audience may be engaged by the original document and potential additional materials, informed by the experiences of those involved in the first COVID-19 human challenge studies outlined in this document.     

Key criteria for the ethical acceptability of COVID-19 human challenge studies: Report of a WHO Working Group

This report of the WHO Working Group for Guidance on Human Challenge Studies in COVID-19 outlines ethical standards for COVID-19 challenge studies. It includes eight Key Criteria related to scientific justification, risk-benefit assessment, consultation and engagement, co-ordination of research, site selection, participant selection, expert review, and informed consent. The document aims to provide comprehensive guidance to scientists, research ethics committees, funders, policymakers, and regulators in deliberations regarding SARS-CoV-2 challenge studies by outlining criteria that would need to be satisfied in order for such studies to be ethically acceptable.     

Views of US researchers about informed consent in international collaborative research

Informed consent poses challenges in all settings. Challenges may be particularly great in international collaborative research, where cultural perspectives may differ, and where education levels and language may be barriers to participant understanding. We conducted a written survey and focus groups with US health researchers doing research in developing countries, asking about informed consent and other ethical issues in their research. We present here both qualitative and quantitative data relevant to informed consent. Qualitative data revealed that researchers' experiences and beliefs about informed consent fell into three paradigms: regulatory, community, and individual. The regulatory paradigm refers to researchers' views and practices relating to informed consent requirements of institutional review boards and other oversight bodies. The community paradigm refers to researchers' approach to the content and methodology of informed consent in the context of long-term relationships between research teams and study communities. Researchers emphasized the importance of these relationships for creating and maintaining communication fundamental to the informed consent process. Finally, the individual paradigm refers to researchers' views about individual participants' understanding and decision-making process regarding research. Researchers described community-level influences on participants' decision-making, but stressed the need for individual comprehension and voluntary participation. While these paradigms are distinct, they also are intertwined. Quantitative data supported the existence of these three paradigms in respondents' characterization of informed consent. Researchers frequently stated that legal language on the consent forms was meaningless (52%). Forty-four percent of researchers had consulted with community leaders, and 23% believed the consent process focuses too much on the individual, rather than on family or community. Most researchers (82%) reported that the consent process was an important means of educating participants about the study. Fifty-four percent of researchers believed participants did not understand placebos. Further research is needed to understand how culture and relationships affect research participation, and to provide information and dialogue among researchers, oversight bodies and community representatives about appropriate ways to approach informed consent in international research.     

医学期刊对涉及人的研究论文进行伦理审查的原则及实践路径

【目的】提高国内医学期刊的伦理规范意识,促进医学期刊发挥正确的伦理学导向作用。【方法】采用文献分析法,通过分析医学期刊对涉及人的研究论文进行伦理审查的意义,探讨其伦理审查的原则及实践路径。【结果】医学期刊作为坚守科研道德阵地的最后防线,对涉及人的研究论文进行伦理审查具有重要的时代意义,应坚持维护受试者利益、科学性、知情同意等原则,并通过完善投稿须知或稿约、把好审稿关等相关路径予以实现。【结论】医学期刊对涉及人的研究论文进行伦理审查具有重要意义,应坚持有关原则进行审查,并通过相关实践路径实现规范有序的伦理审查。     

Version française des recommandations de la déclaration d'Ottawa sur la conception et la conduite éthique d'essais randomisés en clusters,dans le contexte législatif français

IntroductionThere is growing evidence on the ethical challenges raised by cluster randomized trials. This specificity is not reflected in the legal texts regulating research, which creates difficulties for researchers implementing these experimental designs. The Ottawa Statement (Weijer et al. 2012) aims to provide detailed guidance on the ethical design, conduct and assessment of cluster trials. More broadly aims to help research stakeholders and decision-makers to make informed ethical decisions regarding the particularity of these experimental designs. It seems that this international statement, written in English, is not sufficiently accessible to all of the French professionals involved in health research. The aim of this article is to provide these professionals with a contextualized and illustrated French translation of the "Ottawa statement".Method. The "complex design" working group of the RECaP network (Research in Clinical Epidemiology and Public Health), carried out this work. A first version was discussed by the authors in several meetings. It was completed by contextual explanations and examples of French studies currently conducted by the authors. The final version was obtained by consensus and validated by the group.Results. This work reports 15 recommendations grouped into 7 key questions: How to justify cluster design? How to submit an article to an ethics committee? How to identify research participants? How and when to obtain informed consent? Who are the gatekeepers? How to assess benefits and harm? How to protect vulnerable participants? Each of these recommendations is specific to cluster trials. The recommendations are explained and detailed through concrete examples.ConclusionWithout interfering with current French laws, this work provides a framework for the organization, conduct and ethical assessment of cluster randomized trials in France. In the present-day context, it is essential that all concerned groups can base their decisions on recommendations in line with the elementary principles of health research ethics.     

Compliance, conscious participation, and informed consent in tumor screening programs

Compliance and coverage are supposed to be indicators of effectiveness in screening activities. Yet effectiveness is a necessary but not sufficient condition for a screening programme: adverse effects are intrinsic to screening practice; to persuade to comply to screening programme should imply that the advantages overwhelm the disadvantages; if at community level the balance is in favour of the screening, it is not possible to predict the weight for each individual of any potential harms. To accomplish individual values is fundamental from ethical point of view: we must avoid non responsible participation or uninformed refusal, through a reliable information on screening benefits and harms to the invited population. Therefore the concept of compliance should be abandon: "participation" should be used instead. The consequence of a different approach to participation in screening evaluation should be appreciated: new indicators and standards have to be defined. The following ones are proposed: prevalence of informed target population; prevalence of consent to invitation within the informed population; ratio consent/refusal to invitation; prevalence of participation in the invited group. It is unrealistic to expect an informed participation, to screening programme, from all population but incorporation of patient values and preferences is seen as the next frontier in attempts to devise valid practice guidelines. Research is needed to develop instrument on risk communication and informed consent, taking into account the current organisation of screening programs.     

Conducting research in developing countries: experiences of the informed consent process from community studies in Peru

This article discusses the process for obtaining genuine informed consent for the participation of human subjects in research in developing countries. We discuss the consent process in the light of recently published guidelines, the experience of nutrition and health research projects, and the ethics review process of the Instituto de Investigacion Nutricional with peri-urban and rural populations in Peru. We discuss the cultural context in relation to (i) who should be involved in the decision for participation, especially for research in children and in community settings; (ii) when to use written or verbal consent; (iii) the format and presentation of the consent form to ensure understanding by the target population; and (iv) the process of how and by whom information is given and consent is obtained. Common concerns of participants with regard to their involvement in research studies are presented, as well as aspects that participants find difficult to understand. Some specific concerns of conducting research with Indigenous Peoples are discussed. We recommend future research to further understand and implement informed consent processes to assure genuine and voluntary consent in different developing country contexts.     

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.     

医学期刊对学术论文伦理审查和处理方式的调查及分析——以重庆市医学期刊为例

【目的】 了解医学期刊编辑部对医学伦理规范的知晓度,调查其如何处理违背医学伦理的论文, 并针对其出现的问题提出对策。【方法】 采用自制问卷调查重庆市23种医学期刊编辑部对国内外主要医学伦理规范的知晓度,在审稿中主要审查的医学伦理内容,如何处理违背医学伦理的论文,已出版的论文中是否存在违背医学伦理的情况及如何处理。【结果】 重庆市医学期刊对医学伦理规范知晓度比较高,95.65%的编辑部对医学伦理审查有要求,在日常工作中主要审查的内容包括人体试验是否经过伦理委员会审批(100.00%)、是否获得患者知情同意(95.45%)、是否保护患者隐私(81.82%),但对动物实验的伦理审批和对临床试验注册的审查有待加强。编辑部在审稿时发现有违背医学伦理的情况时,处理方式比较符合国内外规范。但是对于已发表的论文,如果存在违背医学伦理的情况,并没有相应的处理措施。【结论】 编辑部应进一步加强对医学伦理的审查,对于出版前和出版后的医学论文存在违背医学伦理的情况,都应有相应的处理措施及流程,以促进我国的医学研究符合医学伦理要求。     

A model designed to enhance informed consent: experiences from the HIV prevention trials network

HIV prevention research in developing countries has resulted in increased attention to and discussion of ethical issues, particularly the issue of the quality of informed consent. We present a conceptual framework for an enhanced informed consent process, drawing on experiences garnered from domestic and international studies conducted by the HIV Prevention Trials Network, funded by the National Institutes of Health. This framework guides the development of an informed consent process designed to help ensure initial and continued comprehension of research participation, with an emphasis on HIV prevention research. Attention is focused at the individual and community levels and on 3 study phases: preenrollment, enrollment, and postenrollment.     

Indications and requirements for the use of prerandomization

Background and ObjectiveAlthough in effectiveness studies, the conventional randomized trial, in which informed consent is obtained before randomization, is the first choice, this design is not the panacea for all research questions. To counter contamination problems, prerandomization designs might be an alternative. Prerandomization implies that the randomization takes place before seeking informed consent, and because of this, prerandomization designs are controversial among ethicists, health lawyers, methodologists, and clinicians. However, in the Netherlands, these designs are becoming more accepted since the Dutch State Secretary of Health, Welfare and Sport decided that, under certain circumstances, prerandomization is admissible and not in conflict with the law.ResultsBased on well-defined indications and requirements, guidelines for the optimal application of prerandomization designs are presented. Designs in which prerandomization is used are outlined; methodological considerations useful when conducting trials using conventional designs or prerandomization designs are discussed, in addition to ethical and judicial aspects.ConclusionIn certain situations, prerandomization designs have an essential contribution to achieve evidence-based medicine. Banning prerandomization a priori implies that information about the effectiveness of numerous public health and medical interventions will not be forthcoming. Therefore, every design should be based on a balance between maximizing the potential for patient autonomy and minimizing the bias caused by contamination. This balance cannot be reached by formulating general rules, but an independent group of experts, like members of research ethics committee (REC), should decide whether this balance is acceptable.     

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.     

Informed consent in clinical trials

A review is provided in this paper on the empirical literature on informed consent from 1979 to 1995 referring to information disclosure and trial participation in clinical trials. Articles being reviewed focus upon information disclosure, reactions to disclosure and recall, features of consent and perceptions of informed consent, both in hypothetical and in real life situations. It is concluded that further research is needed to study the process of informed consent in clinical trials, to obtain a better insight into the myth and reality of informed consent in daily practice. Future studies should come forward on the limitations of previous empirical research on informed consent. Additional research should focus on the perspectives of patients who accept or decline trial participation.     

Children in medical research: Australian ethical standards

Summary This paper examines standards for the use of children as research participants in medical research which are relevant to Australia and relates the standards to pivotal ethical issues. The standards include the National Health and Medical Research Council's NHMRC Statement and Supplementary Notes, professional codes of ethics, international human rights conventions, United Kingdom and United States codes of ethics, and statute and case law. The key ethical issues of potential risk and benefit to the child, and consent to research participation are discussed. Suggestions for the improvement of the NHMRC Statement are made.     

When people matter: The ethics of qualitative research in the health and social sciences

When research involves people, ethics are fundamental. In the health and social sciences, when qualitative methodologies are used, in addition to ensuring an ethical process approved by the ethics review board, it is also necessary to guarantee an ethical practice capable of responding adequately to the complex questions and dilemmas which arise as the study progresses. This theoretical article analyses some of the most sensitive issues involved in qualitative research and discusses the following questions: (a) How should ethics be approached when working with vulnerable groups? (b) Is informed consent enough? (c) Should we rethink anonymity? (d) What is the difference between confidentiality and anonymity? (e) What exactly do we mean by relational ethics? (f) How can we avoid hurting people, yet remain honest? In the conclusions, we discuss some basic aspects for ensuring ethical studies. This paper, therefore, may be of interest to all health and social researchers concerned about ensuring that their studies comply with ethical principles which recognise, protect and respect participants’ rights.     

A qualitative study of subject recruitment for familial cancer research

PURPOSE: Familial epidemiological studies of cancer raise familiar ethical issues relating to informed consent and recruitment of participants. When the family is the unit of study, however, additional complexity arises. Educating and recruiting participants must be tailored to the relatives', as well as the proband's needs. An understanding of the prospective participants' concerns will aid the development of strategies for recruitment and will facilitate informed and voluntary consent. In the present study, qualitative methods were used to investigate these issues. METHODS: Focus groups with cancer patients, relatives of cancer patients, and individuals from the general population were separately conducted to identify issues that concern people who are asked to participate in family studies. RESULTS: Many of the issues which arose in the course of the focus group discussions were similar to those in any study. Yet, some of the themes emerging from the discussions were specific to familial research. In particular, participants expressed that the study should be endorsed by a trusted and familiar source; group discussions might facilitate the consent process; the benefit of the research should be clear and personal, as well as benefit the participants' family members; risks of participation should be explicit (e.g., insurance discrimination); and education about the disease and its familial nature would maintain commitment to the study. Finally, participants expressed concerns about being approached by programs to facilitate the identification and recruitment of other family members for research on family health issues. CONCLUSIONS: Findings from this study will aid future familial studies in developing a protocol that both adequately informs potential participants of the nature of familial research and maximize participation.     

Informed consent in China: quality of information provided to participants in a research project

AIMS: A study was carried out of informed consent strategies in an epidemiological project approved by the regional research ethics committees in Sweden and China and conducted in three areas south-west of Shanghai. METHODS: All participants in the epidemiological project (EP) were included in the research ethical study (RES), which was conducted as a questionnaire-based interview survey in the three areas. Answers were collected by five field interviewers. RESULTS: All participants included answered the questionnaire. Almost all perceived the information provided as rather good or quite good. However, a majority (on average 76%) had the impression that the EP was part of routine healthcare measures, and not a research project. Almost all participants felt free to abstain from participation although 38% in area II stated that they had not been informed about freedom to abstain from participation. A large proportion of participants did not fully understand the nature of the EP. However, almost all participants stated that they would agree to participate in a similar study in the future. CONCLUSION: Although informed consent procedures are supposed to be internationally applicable our study illustrates that it is not always easy to convey information and obtain consent in the present study setting.