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Ethical Review of Studies and Informed Consent

Ethical and Legal Considerations

Annette Flanagin

Ethical Review of Studies and Informed Consent

UPDATE: We will discontinue using quotation marks to identify parts of an article, but retain the capitalization; eg, This is discussed in the Methods section (not the “Methods” section). This change was made February 14, 2013.

To protect the safety and dignity of individuals who participate in research, academic institutions and grant agencies require that any study involving human participants be reviewed and approved by an institutional review board (IRB) or independent ethics review committee. (Note: When referring to individuals who participate in studies, the word participant is preferred to subject [see 11.1, Correct and Preferred Usage, Correct and Preferred Usage of Common Words and Phrases]. However, a number of guidelines and regulations cited herein refer to human “subjects.”)

The US National Institutes of Health (NIH) defines research as “any systematic investigation designed to develop or contribute to generalizable knowledge” and a human subject as “a living individual about whom an investigator obtains either (1) data through interaction or intervention with the individual, or (2) identifiable private information.”6 The NIH considers the following to be components of research not involving human participants: samples from deceased individuals; samples collected for diagnostic purposes only; samples or data that are available from commercial or public repositories or registries; established cell lines that are publicly available; and self-sustaining, cell-free derivative preparations (eg, viral isolates, cloned DNA or RNA).

The NIH also identifies 6 categories of research involving human participants that may be exempt from IRB review and approval provided the study does not expose participants to physical, social, or psychological risks and does not permit identifiability of individual living participants.5,6 These categories are study or collection of publicly available existing records, surveys, interviews, use of educational tests, observations of public behavior, and some types of research involving taste testing of food.5,6

In addition, the nature and purpose of all procedures and their attendant possible risks must be fully explained to potential participants in advance, and participants must fully comprehend the nature of the participation and voluntarily agree to such participation. Research protocols for studies involving human participants typically address the following minimum set of protections: risks to all participants, experimental procedures, anticipated benefits to participants (if any), anticipated number of participants, proposed consent document and process to be used, and appropriate additional safeguards if the study is to include vulnerable participants (eg, children, incapacitated adults).4,5

Journal Policies and Procedures.

In accordance with these requirements, journals should require authors of manuscripts that report studies involving human participants to state explicitly in the Methods section of the manuscript that an appropriate independent ethics committee or IRB approved the study protocol or project or determined that the investigation was exempt from such approval and why. The name of the ethics committee(s) or IRB(s) should be specified in the Methods section. If the study protocol was approved by several ethics committees/IRBs, as would be expected in a multicenter study, it is appropriate to note that review and approval were conducted by the ethics committees/IRBs of all participating centers/institutions.

Journals should also require authors to indicate in the Methods section that informed consent was obtained from all adult participants and from parents or legal guardians for minors or incapacitated adults and how such consent was obtained (ie, written or oral). If an IRB or ethics committee waived the requirement for informed consent, the author should explain the reason for such waiver.

Ethical approval for research involving animals and relevant animal-handling protocols should be reviewed and approved by independent animal care and use committees as required by national regulations, such as the NIH’s Office of Laboratory Animal Welfare requirements.18 Such review and approval or waiver should be adequately described in the Methods section of all manuscripts reporting research involving animals.

Although numerous regulations and international documents require compliance with these procedures, and groups such as the International Committee of Medical Journal Editors (ICMJE),14 World Association of Medical Editors,15 and UK Committee on Publication Ethics16 support these requirements, authors and journals continue to fail to properly report information on ethics committee review and approval and informed consent.19-22 As recommended by the ICMJE,14 specific guidelines regarding documentation of formal ethical review and informed consent should be included in a journal’s instructions for authors.

Additional Regulations and Principles.

US biomedical investigators who are subject to jurisdiction of an IRB or formal ethics review committee should follow the principles described in the Belmont Report4 and the US Department of Health and Human Services Regulations for the Protection of Human Subjects.5 Investigators outside the United States who are not subject to jurisdiction of an institutional ethics review committee should rely on and cite their relevant national regulations11; regional guidelines, such as the Council of Europe’s Convention on Human Rights in Biomedicine12; or international guidelines, such as the Council for International Organizations of Medical Science’s International Ethical Guidelines for Biomedical Research Involving Human Subjects,10 the Universal Declaration on Bioethics and Human Rights,13 or the Declaration of Helsinki.1 In addition to requiring researchers to have the protocol describing the study reviewed by a “specially appointed committee independent of the investigator and sponsor,” and to obtain study participants' “freely given informed consent, preferably in writing,” the Declaration of Helsinki specifies that reports of experimentation not in accordance with the basic principles described in the Declaration “should not be published.”1

For studies conducted in a specific country by investigators from another country, regulations from both the local (host) country and the investigator’s home (sponsoring) country should be followed, and both IRB/ethics committees that reviewed and approved the study should be cited in the Methods section of the manuscript.10,13,23,24 For studies conducted in multiple countries, relevant regulations of all host countries and any home/sponsoring countries and/or the Declaration of Helsinki1 or the Universal Declaration on Bioethics and Human Rights13 should be followed, and all IRB/ethics committees that reviewed and approved the study should be cited in the Methods section. In all multinational, multicultural studies, attention should be given to the ethical requirements for protecting the interests of the research participants, namely, acquiring informed consent, avoiding harm, attending to needs, and obligations when the study is completed.24 Each of these considerations should be addressed in the Methods section of the manuscript.

Reports of Unethical Studies.

The past publication of unethical research does not justify this continued practice. In a 1966 pioneering article on ethics and clinical research, Beecher25 identified 50 unethical studies involving human participants that were published in medical journals. Beecher concluded that “an experiment should be ethical at its inception and is not made ethical by publication” and that “failure to obtain publication would discourage unethical experimentation.”25 If the author of a report of an experimental investigation that involves humans or animals does not report in a submitted manuscript that formal ethics review and informed consent from human participants were obtained or appropriately considered and waived, the editor should ask the author why this information was not reported. The author may have neglected to report this information because of inadvertent omission or a misunderstanding. For example, an author may fail to report this information because ethics review was considered unnecessary (such as in a retrospective audit of publicly available data), or an informed consent requirement was formally waived by an IRB, or a manuscript contains a secondary analysis and the information about IRB approval and/or informed consent was reported in the primary publication.

All manuscripts, including those reporting studies in which IRB approval and/or informed consent requirements were deemed unnecessary, formally waived, or previously reported, should include details about how the ethical requirements were met or why these requirements were considered unnecessary or waived.

Even when a study has been approved by an ethics committee or IRB, the ethics of the reported research may be questioned by reviewers and editors. In such cases, editors are obliged to ask the authors to clarify the situation and respond to any concerns. Unless the authors can provide satisfactory responses and reassurance, editors may choose to reject the manuscript in question.

If an author refuses to address serious concerns about such ethical requirements, the editor may need to notify the author’s institutional or funding authority (see also 5.7.2, Confidentiality, Confidentiality in Allegations of Scientific Misconduct, and 5.4, Scientific Misconduct).

Publication of an investigation that raises ethical dilemmas may be warranted if such publication would encourage professional and public debate and reform. Such publication should be accompanied by an editor’s note or an editorial describing the ethical issues and concerns. Research that violates established ethical principles should not be published.

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