"Reports of experimentation not in accordance with the principles laid down in this Declaration should not be accepted for publication." From Principle 27, Declaration of Helsinki1
The Declaration of Helsinki (1964 and the later iterations)1 and the Belmont Report2 stimulated the establishment of international ethical standards as they apply to human research and the principles of respect for persons, beneficence and justice. These documents affirmed that experimental procedure should be formulated in a protocol and that an independent committee should monitor and approve the protocol with informed and voluntary consent as central elements for upholding patient autonomy. Ethical review boards or institutional review boards (referred to as IRBs in the remainder of this editorial although the group may call itself whatever it wishes) is a group formally designated to review, to approve the initiation of and to conduct periodic review of biomedical research involving human subjects. In the United States (US), IRBs are mandated for all research from the Department of Health and Human Services (HHS)3 and the principle has extended to all other medical research in the US. The IRBs are themselves regulated by the office for human research protections within HHS.4 Almost all countries have their own version of this deliberative body. In addition to assuring the protection of the rights and welfare of the human subjects, the IRBs perform critical oversight functions of scientific, ethical and regulatory details.
There are general standards for the composition, operation and responsibility of an IRB as mandated by a part of the Code of Federal Regulations5 also known as "The Common Rule"6 because 17 US federal offices and agencies involved in research have agreed to follow it. It shall have at least five members with varying backgrounds; be qualified through the expertise of its members and the diversity of the members to safeguard the rights and welfare of human subjects; possess the professional competence necessary to review the specific research activities; and be able to ascertain the acceptability of proposed research. One member must not be affiliated with the institution, experts outside the IRB may be invited to assist in evaluations, and conflicts of interest among IRB members are restricted or monitored.
Originally, IRBs were committees at academic institutions and medical facilities; today many IRB reviews are performed by for-profit organizations. These independent or commercial IRBs have identical responsibilities as those based at academic or medical institutions and they are governed by the same federal regulations. Academicians debate the value of these commercial IRBs7 and there are also some nonprofit IRBs (e.g. BioMed IRB).8
Although one of the objectives of the IRB is to assess the scientific merit of the research and its methods, the issues of safety and conflict of interest seem overarching at this time and many studies with IRB approval have a faulty hypothesis, methods or insufficient planned numbers to accomplish an advance in science, as later judged by the editorial peer review process.91011
Most journals will not publish reports that are not in accordance with the Declaration of Helsinki. The International Committee of Medical Journal Editors (ICMJE) stipulates in its guidelines, the uniform requirements for manuscripts submitted to biomedical journals, that authors should describe IRB approval, which implies informed consent, in articles.1213 Most major journals alert potential authors to the journal's mandated requirement for research standards including the ethical approval of a study protocol by an IRB and informed consent from the subjects. There have been some recent reports of low rates of ethical approval in major medical journals and therefore journals may be risking the maintenance of the public trust in the publication process.141516
Some researchers may not believe that IRB approval or consent is necessary when standard treatments are being investigated and others suggest waiving IRB approval and need for informed consent in studies that will not alter patient management or outcome and have minimal risks. These researchers, however, are violating the principles of autonomy and may undermine the public's trust. With some exceptions, when a physician or researcher makes an intervention, standard or novel, on a number of patients with the intent to publish the results, the physician is performing research and, as such, the research requires IRB approval. The Belmont Report2 first delineated the distinction between ''practice'' and ''research.'' During the normal practice of medicine, clinicians occasionally use nonstandard practice in the treatment of patients and this is an acceptable practice of medicine; the intent is to improve the health of the patients. Research, however, is a systematic approach to a group of patients with intent to test or generate hypotheses. The IRBs may quibble and have different criteria as to when the situation becomes systematic but if you have developed a protocol or if you start doing the novel therapy or procedure on more than three patients and then report it, it becomes research and subject to IRB approval. Some retrospective studies and surveys may be exempt from IRB approval; however, it is up to the IRB to determine that a particular study does not require IRB approval or is exempt; the researchers/ authors should not make this decision. The history and rationale for IRB-required approval of research can be found in numerous areas of the website of the US office for human research protections.4
The IRBs are local boards that vary in ethical standards and in the effectiveness of protocol oversight, especially in some less developed countries. The authors' disclosure in the manuscript notifies the readers to these local standards which may or may not be acceptable to select journals who must in turn consider the implications of publishing research with lower ethical standards to the readers, to the public and to research-granting agencies.12 Despite wide variations in the ethical milieu and customs in various countries, as a minimum, authors should report in a manuscript dealing with humans that the research is in accordance with the standards of the responsible ethical committee and with the Helsinki Declaration. This may be a major hurdle for multinational studies and within certain countries.1718
In 1996, the US Congress passed the Health Insurance Portability and Accountability Act (HIPAA)19 which was originally conceived to ensure that people changing jobs would not lose their health insurance. During the development of the bill, insurance companies requested the Congress to add an element to this act that assists in making a more uniform process for submitting the medical bills electronically and then an element was added concerning privacy and security issues in protecting individuals' health information. With regard to the latter, under this act, in brief, a privacy rule20 was created that requires individuals' signed authorization to use or disclose their protected health information for research purposes. Although journals and IRBs are not mentioned directly or indirectly in this Act and even though there are uncertainties in the exact interpretation for IRBs, the conservative and more financially prudent (fines are substantial for noncompliance) path is for IRBs and subsequently journals, to maintain high ethical privacy standards. Therefore IRBs have established set procedures to assist researchers, albeit at what some consider tremendous cost, paperwork, bureaucracy, inconvenience and of an uncertain beneficial effect as well as evidence suggestion an inhibition of research effort.21 Although some waivers for research are possible, HIPAA further strengthens the requirement for IRB review and approval of virtually any study or report, including retrospective studies, involving humans in the US.
The extent to which HIPAA applies to international research and submissions is currently still a matter of debate;22 however, if US patients are involved in an international study, all identifying information of all the US patients must be removed and IRB approval (or IRB waiver) is required of the protocol. If a US institution is involved in maintaining or evaluating any of the data, then it may be that all patients in the study must follow HIPAA guidelines (or obtain IRB waiver).
In short, if the authors wish to publish their research, IRB should be consulted for all human studies and the medical journals should require a statement of IRB approval or affirmation that there is an IRB waiver. If there is no ethical board (unlikely now in view of several alternatives and requirements), then a statement about informed consent, conformity with local and federal laws and conformity to the Declaration of Helsinki should be required. Authors must realize that some journals require even higher standards.
1. World medical association declaration of Helsinki: Ethical. principles for medical research involving human subjects.Last accessed on 2007 Feb 4 Available from: http://www.wma.net/e/policy/b3.htm
2. The Belmont report. Ethical principles and guidelines for the protection of human subjects of research.Last accessed on 2007 Feb 4 Available from: http://ohsr.od.nih.gov/guidelines/belmont.html#ethical
3. United States Department of Health and Human Resources. Policies and regulations.Last accessed on 2007 Feb 4 Available from: http://www.os.dhhs.gov/policies/index.shtml#laws
4. United States Department of Health and Human Resources. Office for Human Research Protections (OHRP).Last accessed on 2007 Feb 4 Available from: http://www.hhs.gov/ohrp/
5. Institutional Review Boards. Code of Federal Regulations. Title 21, Volume 1, Part 56.Last accessed on 2007 Feb 4 Available from: http://www.cfsan.fda.gov/~lrd/cfr56.html
6. The Common Rule. Teaching the responsible conduct of research in humans. Available from: http://ori.hhs.gov/education/products/ucla/chapter2/page04b.htm
7. Emanuel EJ, Lemmens T, Elliot C. Should society allow research ethics boards to be run as for-profit enterprises? PLoS Med. 2007Last accessed on 2007 Feb 4:e309 Available from: http:www.doi:10.1371/journal.pmed.0030309
8. BioMed IRB. Last accessed on 2007 Feb 4 Available from: http://www.biomedirb.com/
9. Campbell EG, Weissman JS, Vogeli C, Clarridge BR, Abraham M, Marder JE, et al Financial relationships between institutional review board members and industry N Engl J Med. 2006;355:2321–9
10. Gunsalus CK, Bruner EM, Burbules NC, Dash L, Finkin M, Goldberg JP, et al Mission creep in the IRB world Science. 2006;312:1441
11. Vogt TM. IRBs: Going too far or not far enough? Science. 2006;313:1388–9
12. Rennie D, Yank V. Disclosure to the reader of institutional review board approval and informed consent JAMA. 1997;277:922–3
13. International Committee of Medical Journal Editors. Uniform Requirements for Manuscripts Submitted to Biomedical Journals.Last accessed on 2007 Feb 4 Available from: http://www.icmje.org/
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17. Lemaire F. Do all types of human research need ethics committee approval? Am J Respir Crit Care Med. 2006;174:363–4
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19. United States Department of Health and Human Resources. Office for Civil Rights - HIPAA. Medical Privacy - National Standards to Protect the Privacy of Personal Health Information.Last accessed on 2007 Feb 4 Available from: http://www.hhs.gov/ocr/hipaa/
20. United States Department of Health and Human Resources. Summary of the HIPAA privacy rule.Last accessed on 2007 Feb 4 Available from: http://www.hhs.gov/ocr/privacysummary.pdf
21. O'Herrin JK, Fost N, Kudsk KA. Health insurance portability accountability act (HIPAA) regulations effect on medical record research Ann Surg. 2004;239:772–8
22. Schachat AP. What is HIPAA and what effect may it have on our journal? Ophthalmology. 2003;110:1074–5