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Ethical Practices: Institutional Oversight and Enforcement
Ethical Practices: Institutional Oversight and Enforcement Sophia F Dziegielewski, College of Health and Public Affairs, University of Central Florida (UCF), Orlando, FL, USA; and Merritt Island, FL, USA Ó 2015 Elsevier Ltd. All rights reserved. This article is a revision of the previous edition article by R.J. Levine, volume 7, pp. 4770–4774, Ó 2001, Elsevier Ltd.
Abstract This article provides an overview of the history, development and regulations, composition and performance, hopes and hindrances related to the committees in the United States charged with the protection of human subjects in research studies. Often referred to as Ethical Review Committees, Ethical Review Boards, or the Institutional Review Board, the roles of these risk-management committees are explored, with an emphasis on contemporary issues and concerns as well as the power they have in requesting modifications to scientific protocol and in making the ultimate decisions for approval.
Lessons from the Past and Development of Regulation Most researchers are bound to a professional code of ethics and operate within ethical guidelines. Simply defined, in clinical practice ethics are rules to help professionals distinguish between what is right and wrong. When ethical practice becomes research, however, the focus switches slightly to focusing on minimizing the risks of those who participate while conducting scientifically valid research. The fluid nature of ethical conduct, by definition, is a continuous process (Fujii, 2012). Ethical practice, with its inherent decision-making principles, needs constant updating and reexamination to ensure that environmental and technological advancements are included. Therefore, there is rarely a simple response or check-box answer that will ensure that all human subjects are protected. Ethical decision-making is a complex task, and it can also be somewhat elusive. The rights and welfare of human subjects have not always been considered; at times individuals have been used with no concern for their autonomy or safety. Many professionals are familiar with the Nazi medical experiments of the 1930s and 1940s where brutal mutilative surgery was performed in the name of science. Following World War II (1946–49), tribunals were held in the Palace of Justice in Nuremberg, Germany to review the travesties that were reported. These tribunals recommended a set of research ethics termed ‘The Nuremberg Code.’ The Nuremberg Code of 1947 outlined 10 principles related to ethical conduct. This Code was the first to emphasize the importance of protecting research participants by means of informed consent with the absence of coercion and properly designed experimentation that minimizes risk and maximizes benefits. In the 1960s, the issue of human participant rights was further highlighted by the Declaration of Helsinki formulated by the World Medical Association in Helsinki, Finland. This document went beyond the Nuremberg Code by focusing primarily on ethical principles related directly to medical research and is often considered an overarching precursor to the guidelines practiced today in the United States. The Declaration of Helsinki provided the basis for an international standard that recognized the importance of biomedical research involving human subjects and that mandated that each research protocol
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be reviewed by a specially appointed Ethical Review Committee (ERC) (World Medical Association, 2000: Article 13). The horrors uncovered in the Nuremberg tribunals, were brought closer to home when the American people were alerted to the Tuskegee Syphilis Study. This shocking violation of human dignity still ripples through the hearts and minds of a previously trusting public. This study first began in 1932 when the U.S. Public Health Service (USPHS) started a 40-year clinical study of the effects of untreated syphilis on black males. Over 600 low-income study subjects were promised free health care by the government, along with meals and burial rights. When a cure for the disease was discovered in 1940s (penicillin), the participants were not told and some were actually prevented from receiving treatment. In May 1997, President Clinton issued a formal apology to the survivors of the Tuskegee study and their families. In addition, a second study, from 1946 to 1948, also supported by the USPHS, in collaboration with Guatemalan health authorities, deliberately infected prisoners with sexually transmitted diseases such as syphilis. The Guatemalan prisoners were provided treatment, however, this was all done without their informed consent. After the discovery and exposure of the Guatemala study in 2010, the President of the United States issued an apology to the Guatemalan people in general because those individuals who were actually harmed could not be found (NIH, Fact Sheet, n.d.). Given the misuse of research subjects in the past it became clear that a set of guidelines was essential if research ethics were to be put into practice. The National Research Act was signed into law by the U.S. Congress on 12 July 1974. This Act authorized the creation of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. This commission identified basic ethical principles and in 1978 released a document entitled The Belmont Report. The Belmont Report identified three major principles: (1) respect for persons; (2) beneficence and ‘do no harm’; and (3) justice (The Belmont Report, 1979). For researchers in the United States, this effort culminated with what is usually referred to as the ‘Common Rule.’ This regulation is advanced by the Office of Human Research Protections (OHRP) which is responsible for safeguarding the rights, welfare, and well-being of research subjects in the
International Encyclopedia of the Social & Behavioral Sciences, 2nd edition, Volume 8
http://dx.doi.org/10.1016/B978-0-08-097086-8.11014-1
Ethical Practices: Institutional Oversight and Enforcement
conduct of federal research. To ensure compliance OHRP, supported by the U.S. Department of Health and Human Services (HHS), oversees biomedical and behavioral science research institutions ensuring compliance with HHS regulations as described in Title 45, Part 46, Code of Federal Regulations (45 CFR 46). The Common Rule defines research as a systematic investigation designed to develop or contribute to generalizable knowledge. This includes research, testing, and evaluation on human subjects. The Common Rule further defines human subjects as any living individual where data about the individuals are obtained either through intervention or interaction or includes private, identifiable data [45 CFR 46.102(f)]. “Thus, according to the Common Rule, as currently written, research involving material from deceased individuals (e.g., autopsy material) or the use of specimens that are completely anonymous (i.e., a link to subject identity does not exist), would not be subject to the Common Rule, although state and local regulations and policies may apply” (Bledsoe and Grizzle, 2013: p. 324). When looking specifically at nonbiomedical research, effective and efficient application of the Common Rule requires: 1. an Institutional Review Board (IRB) that has sufficient expertise in social and behavioral research; 2. an IRB that understands and utilizes the flexibility in the Common Rule; and 3. investigators who understand the potential for social and psychological risk in their research.
The Health Insurance Portability and Accountability Act The importance of those in clinical practice as well as researchers gaining access to a participant’s health-related information is coupled with a need to protect the privacy and ensure the consent of all research participants. This need to control a patient’s identifiable information provided the impetus for the creation of the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule in 1996, (Health Information Privacy, 2014). Based on previous incidents of researcher misconduct and the public fear that private information would be used or misused without proper informed consent, guidelines were put in place to control access to both health and mental health-related information. Designed to protect the consumer, this Act identified and clearly defined what constitutes a participant’s Protected Health Information (PHI). At times PHI may need to be released and this Privacy Rule allows for the release of such disclosures for treatment or other purposes with the expectation that certain protections be put into place. In practice today, HIPAA has carried over into research activity and when PHI is collected, a detailed plan for outlining what will be collected and analyzed, how it will be retrieved, who will have access, how it will be securely stored, and when it will be destroyed will be a necessary part of the participant’s awareness requiring consent. The researcher must explain and justify his or her reasoning when requesting a waiver of participant, such as when the study is minimal risk, the waiver will not adversely affect the rights and welfare of the
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subjects, and the research would not be practicable if consent were required.
Ethical Oversight in the United States: The Formulation of the IRB The Nuremberg Code and the original Declaration of Helsinki were helpful in formulating the basis for ethical conduct of research, but made no direct statement as to the importance of formulating an ethical review panel. Historically, the expectation for ethical research was placed on the investigator with little, if any, system of checks and balances. In the United States, the first federal document requiring committee review was issued on 17 November 1953. This document and its guidelines applied only to research conducted at the newly opened Clinical Center at the National Institutes of Health (NIH) (Lipsett et al., 1979). The first mention of committee review from an international perspective was in Tokyo with a revision of the Declaration of Helsinki (World Medical Association, 1975). Learning from the mistakes of the past, all research-savvy institutions in the United States that conduct research involving human subjects have access to an IRB. In some cases, the IRB may be viewed as an independent ethics committee or referred to as an Ethical Review Board (ERB) or Research Ethics Committees (REC). In countries other than the United States, the term REC is most common, whereas in the United States the most common term is IRB. In Canada, the term Research Ethics Board (REB) has been used with similar authority to approve or disapprove research proposals (Medical Research Council of Canada, 1987). In the United States, one significant pronouncement that can be seen as a forerunner for today’s IRB came on 8 February 1966, from the Surgeon General of the USPHS. The Surgeon General issued the first federal policy statement requiring research institutions to establish the committees which subsequently became known as RECs and ultimately IRBs (Curran, 1970). Focusing on USPHS grant funded research, the grantee’s institution, in cooperation with the investigator and his or her institutional associates, were expected to be responsible for the oversight of projects involving human subjects. The conception of IRB oversight rests in three important concepts. (1) These boards serve as the official designated guardians of the rights and welfare of the participants that serve in research studies under their purview. As central units, it is clear that these boards have the responsibility and are empowered to review and monitor the research activities and ultimately have the ability to approve or deny the research protocol being submitted. (2) As the scope of research extends far beyond traditional expectations, an updated systematic review is needed that takes into account participant awareness, consent, and safety, but also balances federal regulation with ethical expectations in research conduct. Lastly (3), the IRB is expected to ensure that the research is conducted in a transparent and scientifically feasible way while evaluating whether it is ethically sound, thereby protecting the rights of all human subjects involved. Defining vulnerable subjects can be problematic. In its simplest definition ‘vulnerable’ includes individuals who, in
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Ethical Practices: Institutional Oversight and Enforcement
health care or research are at the greatest risk of being harmed or have greater susceptibility to being harmed (Hurst, 2008). Protecting human subjects who are most vulnerable rests at the heart of ethical conduct. This type of protection requires additional attention to any structural or systematic bias and introduces a subject surrogate that serves as an expert in the area. For example, related to the unique and vulnerable role of prisoners, DHHS regulations require that an REC/IRB member regularly review research that involves this vulnerable category of subjects. This board representative is specifically assigned to review any research related to this population. This reviewer scrutinizes these protocols to ensure that the rights of vulnerable populations have been addressed. Other vulnerable groups include children, pregnant women, and those that are considered mentally incompetent.
Ensuring Ethical Conduct: The CFR Today, in the United States it is clear to all that human participant research must be conducted in compliance with federal regulations. The Division of Education and Development provides guidance to individuals and institutions conducting HHS-supported human subjects’ research. The Division of Policy and Assurances administers the Federal-wide Assurance (FWA) of compliance and registration of IRBs. When an IRB is formed a FWA is completed with the HHS, and, therefore, must meet all the HHS regulations. All riskmanagement reviews need to be conducted with subsequent approval required by law. All research-related activities carried out under the institution’s auspices that are supported by federal funds are subject to regulation by the Food and Drug Administration. Often referred to as ‘checking the box,’ in addition to the legal requirements for federally funded research, many institutions also voluntarily extend the requirement for IRB review to all research involving human subjects. Once an IRB is established (as published in the Federal Register on 15 January 2009), it must be registered. IRB registration falls under (74 FR 2358), 21 CFR Part 56, IRBs, and amended with regard to IRB registration (21 CFR 56.106). HHS monitors and updates this Internet-based registration system for federally funded research. In addition, an assurance document is generated between the institution and HHS that the institution will comply with federal guidelines for the protection of human subjects and adhere to regulations [45 CFR part 46] with the assurance mechanism described in 45 CFR 46.103. Understanding how membership of this committee is established is an important first step in ensuring that it can complete its important tasks. IRB membership must include at least five appointed members. It is expected that every effort should be made to create a culturally and professionally diverse committee taking into account race, gender, and cultural backgrounds, as well as affiliation. There is no regulation that says that members cannot be compensated. In addition, at least one of the members should be from the scientist area and one must be a nonscientist. There should also be at least one appointed member that has no connection with the institution apart from committee membership, although absence of this
member can still constitute a quorum for decision-making. There are many professionals that can serve on the committee and depending on the types of research reviewed, composition can vary. It is important to note that IRB members do not need to cover every discipline or research area; when needed the IRB can and should obtain information and guidance from outside consultants as they make their research determinations.
Establishment of the IRB: Basics for Structure and Functioning For many institutions the IRB is located in the facility and remains an integral part of its research activities. For others, the activities of the IRB may be outside of the institution, often referred to as central review boards. Regardless, the oversight of the studies conducted by either affiliated or nonaffiliated researchers is their purview. The purpose of the IRB, ERB, or the ERC is clear in that it is designed to protect the rights of human subjects that participate in research-related activities. The goal of these boards is to ensure that research involving human subjects is designed to conform to relevant ethical and legal standards while safeguarding the rights and welfare of individual research subjects, ensuring informed consent, and minimizing risks while maximizing any anticipated benefits. Originally, these committees were created to provide oversight for biomedical research; however, today their domain has been extended to also cover research in the social and behavioral sciences. To complete this task, these boards are expected to perform a type of risk–benefit analysis that ensures all research conducted with its oversight will be performed ethically and legally within expected compliance standards. When research is conducted in the United States, every precaution needs to be taken to ensure that regulations designed to address the needs of participants are followed. Membership of the IRB should contain an interdisciplinary group of professionals made up of diverse professionals such as doctors, nurses, lawyers, scientists (including those skilled in the biomedical area and behavioral scientists such as psychologists and social workers) as well as clergy that bring professional expertise to the review process. These professionals under the leadership of a Chair utilize a jury model that incorporates a risk-management strategy capable of confirming scientific merit as well as ethical conduct always reflecting common sense principles of reasonable expectations.
Avoiding Conflicts of Interest Although incredible gains in knowledge and human understanding and betterment may result from research findings, how they were obtained and what was done to human subjects to achieve them remains a core issue. Secondary gain and whether the researcher may personally benefit from the research study requires careful consideration. To help avoid the potential for ‘conflict of interest,’ all studies, especially those that are deemed to be more than minimal risk require the diverse membership of a board of
Ethical Practices: Institutional Oversight and Enforcement
scientists and nonscientists that oversee the process. In addition, it is expected that at each meeting – prior to starting protocol reviews and the risk-management discussions – that members should identify any conflicts of interest. Once identified, the member should absent him or herself from discussions and abstain from voting on any relevant protocols. The Chair of the IRB is responsible for ensuring this is done at each meeting and if the Chair has a conflict, a substitute Chair for the proceedings should be appointed.
Mission Creep and Criticisms of the IRB IRB leadership and participation is not for the squeamish and it should come as no surprise that this type of work rests heavily on all involved. Historically, complaints about the IRB overstepping its bounds are nothing new. Concerns related to the development of ethical guidelines, codes, or sets of procedures concerning the ‘conduct of research’ prevailed in the medical research community (Curran, 1970). Furthermore, in the 1970s biomedical scientists and social behavioral scientists alike remained harshly critical of the role of the IRB and its risk-assessment practices (Levine, 1988). The social behavioral researchers felt strongly they were far less likely to harm human subjects, when compared to a biomedical scientist, and they questioned whether they should be held to the same rules. The behavioral scientists believed that because they did not complete medical procedures or gather tissue from participants and only spoke with them that equivalent regulations were an unconstitutional constraint on their freedom of speech (Levine, 1988). Similar to earlier objections, concerns are still voiced regarding many areas of research oversight, including community-based participatory research. These complaints from investigators related to oversight of their research activities are not uncommon and at times the assumption is they fall upon deaf ears (Wolf, 2010). At the root of this controversy is whether the REB/REC/IRB really has the skill and expertise to approve or disapprove the scientific design of research protocols (Levine, 1988). After all, who knows better the scientific design than those who created it? This requires that REB/REC/IRBs identify what constitutes a strong and comprehensive design with the intention of providing oversight and awareness of what also meets ethical requirements designed to protect human subjects. Moreover, they argue, the IRBs obligation to determine that risks to subjects are reasonable in relation to anticipated benefits necessarily relies on a prior determination that the scientific design is adequate, for if it is not, there will be no benefits and any risk must be considered unreasonable. Just by virtue of the power vested in their review, guidance, monitoring, and approval power it is clear why some researchers are wary of the IRB and the potential for mission creep. Mission creep defined simply is when the power vested in the IRB extends its bounds and goes beyond what is covered in the federal regulations. This type of extension, in its worst case scenario, is conflict driven and not directly related to the protection of human subjects. It therefore may be directly related to institutional legal concerns and protecting the university or in pushing the self-interest of board members or
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others in institutional leadership positions. It is clear that there is often a fine line between ensuring a subject’s rights, institutional liability, and balancing what might be termed overarching yet limited federal guidelines – all of which rarely provide direct guidance for every situation. For those serving on the IRB, as well as the scientific investigators, should not this always be a test for weight and balances? Should federal law be adhered to the letter even when situations are not fully addressed by the general guidelines provided? Yet, who monitors the IRB and how is their work overseen? Although no comprehensive answer is provided, steps along the corrective path include: Continuing education for board, investigators, and the community; and, regulation of IRBs by an independent body such as Association for the Accreditation of Human Research Protection Programs. This independent accreditation body can work to protect the rights of human subjects and foster clear guidelines for institutions, selfassessment, peer-review of all policy and procedures, and education. When continuation for RECs and IRBs are required, this type of training needs to be updated regularly and reflective of changing technologies in research methods as well as public policy initiatives (Wolf, 2010). Most IRBs already have such policies and procedures in place but clear budgeting and allowances for such updating are vital. This includes budgeting for attendance at conferences where the sharing of the latest information and exchange of ideas with those familiar with IRB requirements and activities is essential. For those on the board, required training should take place at each meeting as well as through a systematized fashion on a cycle of renewal. In addition, there are certificates and additional training that can make board members aware of how to best apply the federal guidelines and any subsequent changes that occur. In turn, the scientific investigators should also receive updated training. To have investigators aware of the latest rules makes it a win–win for all in terms of review, modifications, and subsequent approvals. Lastly, the human subject, now generally referred to as the participant in the study, clearly can benefit from learning more about informed consent and what to or not to expect in any research study, not just the one he or she is invited to participate. An educated public helps to avoid confusion and can empower participants to ask the questions they have not thought to ask before. This requires that continuing education remain rich with updated policies and procedures essential for the success of any IRB.
Conclusions: Pulling It All Together After the lessons learned in the past, some researchers continue to question the IRBs role in the protection of human subjects in clinical and behavioral science research. With the gains made through regulation, some professionals continue to wonder whether there are still gaps that occur in study conception and implementation (Slade et al., 2012). This is complicated by federal regulations that are written in vague language in contrast to the clearer direction provided for protecting subjects’ rights. A board composed primarily of professionals may be more scientifically curious than those with less training in the lay public. Such a board could be more
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Ethical Practices: Institutional Oversight and Enforcement
likely to vote in favor of proposals that may be considered of higher risk based on the potential for the gain of scientific knowledge. Lastly, as is true in any group process, a gathering of the minds can lead to group think where members of the group are influenced by a charismatic leader. Gaining approval of the IRB has never been more persuasive when increasingly academic settings require faculty to conduct research and publish the results to advance the profession. Similar, to publish these research findings and contribute to the literature, academic, and rigorous journals will not publish the information gathered if it has not had prior IRB review and approval. This makes escape from IRB oversight almost impossible if one wishes to contribute scientific information to the literature. Pressure on IRBs to meet unrealistic deadlines and expectations that go beyond federal regulations can lead to ‘mission creep,’ a concept that only slows the process and discourages a professional collegial and supportive relationship between the researcher and the board (Saleem and Khalid, 2011). Furthermore, are we really drawing a line in the sand when we try to separate out research from clinical practice? Can one really be distinct from the other? If so, then applying different rules makes sense. If not, trying to apply different rules and oversight of certain aspects of practice by calling it research may mislabel and subsequently misrepresent clinical inquiry (Anderson, 2010). When the potential for mission creep is mixed with a blurred definition of what is clinical practice and what constitutes research, the lines between the two heighten the existence of the other. The more blurred the definitions, the greater the mission creep and the more complicated decisions become. Contemporary considerations and global connections make the situation even more complicated. When scientific investigations that are funded by U.S. enterprises such as pharmaceutical companies extend into developing countries, the need for control with limited red tape becomes even more evident (Saleem and Khalid, 2011). How does one truly stop the seductive benefits of secondary gain filled with researcher bias? Also, with changing technology problems continue to evolve related to ensuring consent to storing data in the cloud. As scientific and technological advances continue, the usual conflicts related to the varied professional interpretations of what constitutes ethical conduct designed to protect human subjects will make disagreements and differences in opinion unavoidable. Research regulations and the work of the IRB committee remains at the heart of risk-management review. These activities, however, will continue to fall short if this responsibility is not assumed deep in the core activities of the principal investigator and his or her research colleagues. In closing, this leads to one primary assumption, IRBs can help provide risk-management assessment, but the true ethical imperative to safeguard the participant must always rest with the individual investigator and his or her colleagues. Few would disagree that the use of human subjects in research has led to significant scientific and medical advancements and equally few would question the need to protect research subjects from the potential for abuse (Bledsoe and Grizzle, 2013). In fact the rights and welfare of human subjects should always be considered first because it is the only way to ensure participant autonomy and safety.
See also: Common Rule: US Regulatory Protections for Human Research Participants; Ethical Dilemmas, Research, and Access to Treatment; Ethics for Biomedical Research Involving Humans: International Guidelines; Objectivity of Research: Ethical Aspects; Privacy of Individuals in Social Research: Confidentiality; Research Ethics, Cross-Cultural Dimensions of; Research Ethics: Research.
Bibliography Anderson, J.A., 2010. Clinical research in context: reexamining the distinction between research and practice. Journal of Medicine and Philosophy 35, 46–63. Bledsoe, M.J., Grizzle, W.E., 2013. Use of human specimens in research: the evolving United States regulatory, policy and scientific landscape. Diagnostic Histopathology 19 (9), 322–330. Curran, W.J., 1970. Government regulation of the use of human subjects in medical research: the approaches of two federal agencies. In: Freund, P.A. (Ed.), Experimentation with Human Subjects. George Braziller, New York, pp. 402–454. Fujii, L.A., 2012. Research ethics 101: dilemmas and responsibilities. Political Science and Politics 45 (4), 717–723. Health Information Privacy, Updated 2014. U.S. Department of Health and Human Services. From: www.hhs.gov/ocr/privacy/ (retrieved 30.03.14.). Hurst, S.A., 2008. Vulnerability in research and health care: describing the elephant in the room. Bioethics 22 (4), 191–202. Levine, R.J., 1988. Ethics and Regulation of Clinical Research, second ed. Yale University Press, New Haven, CT. Lipsett, M.B., Fletcher, J.C., Secundy, M., 1979. Research review at NIH. Hastings Center Report 9 (1), 18–21. Medical Research Council of Canada, 1987. Guidelines on Research Involving Human Subjects. Medical Research Council of Canada, Ottawa, Canada. NIH: Fact Sheet on 1946–1948 U.S. Public Health Service Sexually Transmitted Diseases (STD) Inoculation Study. HHS.Gov: US Department of Health and Human Services. From: http://www.hhs.gov/1946inoculationstudy/factsheet.html (retrieved 29.03.14.). Saleem, T., Khalid, U., 2011. Institutional review boards- A mixed blessing. International Archives of Medicine 4 (19). Retrieved: http://www.intarchmed.com/content/ 4/1/19. Slade, K.L., Carreau, N.A., Heald, P., 2012. Ethics of clinical trials in dermatology. Clinics in Dermatology 30, 226–230. The Belmont Report, 18 April 1979. U.S. Department of Health and Human Services. From. http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html (retrieved 29.03.14.). Wolf, L.E., 2010. The research ethics committee is not the enemy: oversight of community-based participatory research. Journal of Empirical Research Ethics: An International Journal 5 (4), 77–86. World Medical Association, October 1975. Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects (Amended), 29th WMA General Assembly, Tokyo, Japan. World Medical Association, October 2000. Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects (Amended), 52nd WMA General Assembly, Edinburgh, Scotland. http://www.wma.net/e/policy/17c.pdf.
Relevant Websites http://www.ahrq.gov/ – Agency for Healthcare Research Quality U.S. Department of Health and Human Services. From HHS.gov, retrieved from: www.hhs.gov/ohrp/about/index.html – Office of Human Research Protections About OHRP. http://www.hhs.gov/ocr/privacy/hipaa/understanding/special/mhguidance.html – HIPAA Privacy Rule and Sharing Information Related to Mental Health. http://www.hhs.gov/ocr/privacy/hipaa/understanding/special/mhguidance.html – HIPAA Mental Health Privacy Rules. http://www1.va.gov/oro/ – VA Health Care: Office of Research Oversight.
Abstract This article provides an overview of the history, development and regulations, composition and performance, hopes and hindrances related to the committees in the United States charged with the protection of human subjects in research studies. Often referred to as Ethical Review Committees, Ethical Review Boards, or the Institutional Review Board, the roles of these risk-management committees are explored, with an emphasis on contemporary issues and concerns as well as the power they have in requesting modifications to scientific protocol and in making the ultimate decisions for approval.
Lessons from the Past and Development of Regulation Most researchers are bound to a professional code of ethics and operate within ethical guidelines. Simply defined, in clinical practice ethics are rules to help professionals distinguish between what is right and wrong. When ethical practice becomes research, however, the focus switches slightly to focusing on minimizing the risks of those who participate while conducting scientifically valid research. The fluid nature of ethical conduct, by definition, is a continuous process (Fujii, 2012). Ethical practice, with its inherent decision-making principles, needs constant updating and reexamination to ensure that environmental and technological advancements are included. Therefore, there is rarely a simple response or check-box answer that will ensure that all human subjects are protected. Ethical decision-making is a complex task, and it can also be somewhat elusive. The rights and welfare of human subjects have not always been considered; at times individuals have been used with no concern for their autonomy or safety. Many professionals are familiar with the Nazi medical experiments of the 1930s and 1940s where brutal mutilative surgery was performed in the name of science. Following World War II (1946–49), tribunals were held in the Palace of Justice in Nuremberg, Germany to review the travesties that were reported. These tribunals recommended a set of research ethics termed ‘The Nuremberg Code.’ The Nuremberg Code of 1947 outlined 10 principles related to ethical conduct. This Code was the first to emphasize the importance of protecting research participants by means of informed consent with the absence of coercion and properly designed experimentation that minimizes risk and maximizes benefits. In the 1960s, the issue of human participant rights was further highlighted by the Declaration of Helsinki formulated by the World Medical Association in Helsinki, Finland. This document went beyond the Nuremberg Code by focusing primarily on ethical principles related directly to medical research and is often considered an overarching precursor to the guidelines practiced today in the United States. The Declaration of Helsinki provided the basis for an international standard that recognized the importance of biomedical research involving human subjects and that mandated that each research protocol
48
be reviewed by a specially appointed Ethical Review Committee (ERC) (World Medical Association, 2000: Article 13). The horrors uncovered in the Nuremberg tribunals, were brought closer to home when the American people were alerted to the Tuskegee Syphilis Study. This shocking violation of human dignity still ripples through the hearts and minds of a previously trusting public. This study first began in 1932 when the U.S. Public Health Service (USPHS) started a 40-year clinical study of the effects of untreated syphilis on black males. Over 600 low-income study subjects were promised free health care by the government, along with meals and burial rights. When a cure for the disease was discovered in 1940s (penicillin), the participants were not told and some were actually prevented from receiving treatment. In May 1997, President Clinton issued a formal apology to the survivors of the Tuskegee study and their families. In addition, a second study, from 1946 to 1948, also supported by the USPHS, in collaboration with Guatemalan health authorities, deliberately infected prisoners with sexually transmitted diseases such as syphilis. The Guatemalan prisoners were provided treatment, however, this was all done without their informed consent. After the discovery and exposure of the Guatemala study in 2010, the President of the United States issued an apology to the Guatemalan people in general because those individuals who were actually harmed could not be found (NIH, Fact Sheet, n.d.). Given the misuse of research subjects in the past it became clear that a set of guidelines was essential if research ethics were to be put into practice. The National Research Act was signed into law by the U.S. Congress on 12 July 1974. This Act authorized the creation of the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. This commission identified basic ethical principles and in 1978 released a document entitled The Belmont Report. The Belmont Report identified three major principles: (1) respect for persons; (2) beneficence and ‘do no harm’; and (3) justice (The Belmont Report, 1979). For researchers in the United States, this effort culminated with what is usually referred to as the ‘Common Rule.’ This regulation is advanced by the Office of Human Research Protections (OHRP) which is responsible for safeguarding the rights, welfare, and well-being of research subjects in the
International Encyclopedia of the Social & Behavioral Sciences, 2nd edition, Volume 8
http://dx.doi.org/10.1016/B978-0-08-097086-8.11014-1
Ethical Practices: Institutional Oversight and Enforcement
conduct of federal research. To ensure compliance OHRP, supported by the U.S. Department of Health and Human Services (HHS), oversees biomedical and behavioral science research institutions ensuring compliance with HHS regulations as described in Title 45, Part 46, Code of Federal Regulations (45 CFR 46). The Common Rule defines research as a systematic investigation designed to develop or contribute to generalizable knowledge. This includes research, testing, and evaluation on human subjects. The Common Rule further defines human subjects as any living individual where data about the individuals are obtained either through intervention or interaction or includes private, identifiable data [45 CFR 46.102(f)]. “Thus, according to the Common Rule, as currently written, research involving material from deceased individuals (e.g., autopsy material) or the use of specimens that are completely anonymous (i.e., a link to subject identity does not exist), would not be subject to the Common Rule, although state and local regulations and policies may apply” (Bledsoe and Grizzle, 2013: p. 324). When looking specifically at nonbiomedical research, effective and efficient application of the Common Rule requires: 1. an Institutional Review Board (IRB) that has sufficient expertise in social and behavioral research; 2. an IRB that understands and utilizes the flexibility in the Common Rule; and 3. investigators who understand the potential for social and psychological risk in their research.
The Health Insurance Portability and Accountability Act The importance of those in clinical practice as well as researchers gaining access to a participant’s health-related information is coupled with a need to protect the privacy and ensure the consent of all research participants. This need to control a patient’s identifiable information provided the impetus for the creation of the Health Insurance Portability and Accountability Act (HIPAA) Privacy Rule in 1996, (Health Information Privacy, 2014). Based on previous incidents of researcher misconduct and the public fear that private information would be used or misused without proper informed consent, guidelines were put in place to control access to both health and mental health-related information. Designed to protect the consumer, this Act identified and clearly defined what constitutes a participant’s Protected Health Information (PHI). At times PHI may need to be released and this Privacy Rule allows for the release of such disclosures for treatment or other purposes with the expectation that certain protections be put into place. In practice today, HIPAA has carried over into research activity and when PHI is collected, a detailed plan for outlining what will be collected and analyzed, how it will be retrieved, who will have access, how it will be securely stored, and when it will be destroyed will be a necessary part of the participant’s awareness requiring consent. The researcher must explain and justify his or her reasoning when requesting a waiver of participant, such as when the study is minimal risk, the waiver will not adversely affect the rights and welfare of the
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subjects, and the research would not be practicable if consent were required.
Ethical Oversight in the United States: The Formulation of the IRB The Nuremberg Code and the original Declaration of Helsinki were helpful in formulating the basis for ethical conduct of research, but made no direct statement as to the importance of formulating an ethical review panel. Historically, the expectation for ethical research was placed on the investigator with little, if any, system of checks and balances. In the United States, the first federal document requiring committee review was issued on 17 November 1953. This document and its guidelines applied only to research conducted at the newly opened Clinical Center at the National Institutes of Health (NIH) (Lipsett et al., 1979). The first mention of committee review from an international perspective was in Tokyo with a revision of the Declaration of Helsinki (World Medical Association, 1975). Learning from the mistakes of the past, all research-savvy institutions in the United States that conduct research involving human subjects have access to an IRB. In some cases, the IRB may be viewed as an independent ethics committee or referred to as an Ethical Review Board (ERB) or Research Ethics Committees (REC). In countries other than the United States, the term REC is most common, whereas in the United States the most common term is IRB. In Canada, the term Research Ethics Board (REB) has been used with similar authority to approve or disapprove research proposals (Medical Research Council of Canada, 1987). In the United States, one significant pronouncement that can be seen as a forerunner for today’s IRB came on 8 February 1966, from the Surgeon General of the USPHS. The Surgeon General issued the first federal policy statement requiring research institutions to establish the committees which subsequently became known as RECs and ultimately IRBs (Curran, 1970). Focusing on USPHS grant funded research, the grantee’s institution, in cooperation with the investigator and his or her institutional associates, were expected to be responsible for the oversight of projects involving human subjects. The conception of IRB oversight rests in three important concepts. (1) These boards serve as the official designated guardians of the rights and welfare of the participants that serve in research studies under their purview. As central units, it is clear that these boards have the responsibility and are empowered to review and monitor the research activities and ultimately have the ability to approve or deny the research protocol being submitted. (2) As the scope of research extends far beyond traditional expectations, an updated systematic review is needed that takes into account participant awareness, consent, and safety, but also balances federal regulation with ethical expectations in research conduct. Lastly (3), the IRB is expected to ensure that the research is conducted in a transparent and scientifically feasible way while evaluating whether it is ethically sound, thereby protecting the rights of all human subjects involved. Defining vulnerable subjects can be problematic. In its simplest definition ‘vulnerable’ includes individuals who, in
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health care or research are at the greatest risk of being harmed or have greater susceptibility to being harmed (Hurst, 2008). Protecting human subjects who are most vulnerable rests at the heart of ethical conduct. This type of protection requires additional attention to any structural or systematic bias and introduces a subject surrogate that serves as an expert in the area. For example, related to the unique and vulnerable role of prisoners, DHHS regulations require that an REC/IRB member regularly review research that involves this vulnerable category of subjects. This board representative is specifically assigned to review any research related to this population. This reviewer scrutinizes these protocols to ensure that the rights of vulnerable populations have been addressed. Other vulnerable groups include children, pregnant women, and those that are considered mentally incompetent.
Ensuring Ethical Conduct: The CFR Today, in the United States it is clear to all that human participant research must be conducted in compliance with federal regulations. The Division of Education and Development provides guidance to individuals and institutions conducting HHS-supported human subjects’ research. The Division of Policy and Assurances administers the Federal-wide Assurance (FWA) of compliance and registration of IRBs. When an IRB is formed a FWA is completed with the HHS, and, therefore, must meet all the HHS regulations. All riskmanagement reviews need to be conducted with subsequent approval required by law. All research-related activities carried out under the institution’s auspices that are supported by federal funds are subject to regulation by the Food and Drug Administration. Often referred to as ‘checking the box,’ in addition to the legal requirements for federally funded research, many institutions also voluntarily extend the requirement for IRB review to all research involving human subjects. Once an IRB is established (as published in the Federal Register on 15 January 2009), it must be registered. IRB registration falls under (74 FR 2358), 21 CFR Part 56, IRBs, and amended with regard to IRB registration (21 CFR 56.106). HHS monitors and updates this Internet-based registration system for federally funded research. In addition, an assurance document is generated between the institution and HHS that the institution will comply with federal guidelines for the protection of human subjects and adhere to regulations [45 CFR part 46] with the assurance mechanism described in 45 CFR 46.103. Understanding how membership of this committee is established is an important first step in ensuring that it can complete its important tasks. IRB membership must include at least five appointed members. It is expected that every effort should be made to create a culturally and professionally diverse committee taking into account race, gender, and cultural backgrounds, as well as affiliation. There is no regulation that says that members cannot be compensated. In addition, at least one of the members should be from the scientist area and one must be a nonscientist. There should also be at least one appointed member that has no connection with the institution apart from committee membership, although absence of this
member can still constitute a quorum for decision-making. There are many professionals that can serve on the committee and depending on the types of research reviewed, composition can vary. It is important to note that IRB members do not need to cover every discipline or research area; when needed the IRB can and should obtain information and guidance from outside consultants as they make their research determinations.
Establishment of the IRB: Basics for Structure and Functioning For many institutions the IRB is located in the facility and remains an integral part of its research activities. For others, the activities of the IRB may be outside of the institution, often referred to as central review boards. Regardless, the oversight of the studies conducted by either affiliated or nonaffiliated researchers is their purview. The purpose of the IRB, ERB, or the ERC is clear in that it is designed to protect the rights of human subjects that participate in research-related activities. The goal of these boards is to ensure that research involving human subjects is designed to conform to relevant ethical and legal standards while safeguarding the rights and welfare of individual research subjects, ensuring informed consent, and minimizing risks while maximizing any anticipated benefits. Originally, these committees were created to provide oversight for biomedical research; however, today their domain has been extended to also cover research in the social and behavioral sciences. To complete this task, these boards are expected to perform a type of risk–benefit analysis that ensures all research conducted with its oversight will be performed ethically and legally within expected compliance standards. When research is conducted in the United States, every precaution needs to be taken to ensure that regulations designed to address the needs of participants are followed. Membership of the IRB should contain an interdisciplinary group of professionals made up of diverse professionals such as doctors, nurses, lawyers, scientists (including those skilled in the biomedical area and behavioral scientists such as psychologists and social workers) as well as clergy that bring professional expertise to the review process. These professionals under the leadership of a Chair utilize a jury model that incorporates a risk-management strategy capable of confirming scientific merit as well as ethical conduct always reflecting common sense principles of reasonable expectations.
Avoiding Conflicts of Interest Although incredible gains in knowledge and human understanding and betterment may result from research findings, how they were obtained and what was done to human subjects to achieve them remains a core issue. Secondary gain and whether the researcher may personally benefit from the research study requires careful consideration. To help avoid the potential for ‘conflict of interest,’ all studies, especially those that are deemed to be more than minimal risk require the diverse membership of a board of
Ethical Practices: Institutional Oversight and Enforcement
scientists and nonscientists that oversee the process. In addition, it is expected that at each meeting – prior to starting protocol reviews and the risk-management discussions – that members should identify any conflicts of interest. Once identified, the member should absent him or herself from discussions and abstain from voting on any relevant protocols. The Chair of the IRB is responsible for ensuring this is done at each meeting and if the Chair has a conflict, a substitute Chair for the proceedings should be appointed.
Mission Creep and Criticisms of the IRB IRB leadership and participation is not for the squeamish and it should come as no surprise that this type of work rests heavily on all involved. Historically, complaints about the IRB overstepping its bounds are nothing new. Concerns related to the development of ethical guidelines, codes, or sets of procedures concerning the ‘conduct of research’ prevailed in the medical research community (Curran, 1970). Furthermore, in the 1970s biomedical scientists and social behavioral scientists alike remained harshly critical of the role of the IRB and its risk-assessment practices (Levine, 1988). The social behavioral researchers felt strongly they were far less likely to harm human subjects, when compared to a biomedical scientist, and they questioned whether they should be held to the same rules. The behavioral scientists believed that because they did not complete medical procedures or gather tissue from participants and only spoke with them that equivalent regulations were an unconstitutional constraint on their freedom of speech (Levine, 1988). Similar to earlier objections, concerns are still voiced regarding many areas of research oversight, including community-based participatory research. These complaints from investigators related to oversight of their research activities are not uncommon and at times the assumption is they fall upon deaf ears (Wolf, 2010). At the root of this controversy is whether the REB/REC/IRB really has the skill and expertise to approve or disapprove the scientific design of research protocols (Levine, 1988). After all, who knows better the scientific design than those who created it? This requires that REB/REC/IRBs identify what constitutes a strong and comprehensive design with the intention of providing oversight and awareness of what also meets ethical requirements designed to protect human subjects. Moreover, they argue, the IRBs obligation to determine that risks to subjects are reasonable in relation to anticipated benefits necessarily relies on a prior determination that the scientific design is adequate, for if it is not, there will be no benefits and any risk must be considered unreasonable. Just by virtue of the power vested in their review, guidance, monitoring, and approval power it is clear why some researchers are wary of the IRB and the potential for mission creep. Mission creep defined simply is when the power vested in the IRB extends its bounds and goes beyond what is covered in the federal regulations. This type of extension, in its worst case scenario, is conflict driven and not directly related to the protection of human subjects. It therefore may be directly related to institutional legal concerns and protecting the university or in pushing the self-interest of board members or
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others in institutional leadership positions. It is clear that there is often a fine line between ensuring a subject’s rights, institutional liability, and balancing what might be termed overarching yet limited federal guidelines – all of which rarely provide direct guidance for every situation. For those serving on the IRB, as well as the scientific investigators, should not this always be a test for weight and balances? Should federal law be adhered to the letter even when situations are not fully addressed by the general guidelines provided? Yet, who monitors the IRB and how is their work overseen? Although no comprehensive answer is provided, steps along the corrective path include: Continuing education for board, investigators, and the community; and, regulation of IRBs by an independent body such as Association for the Accreditation of Human Research Protection Programs. This independent accreditation body can work to protect the rights of human subjects and foster clear guidelines for institutions, selfassessment, peer-review of all policy and procedures, and education. When continuation for RECs and IRBs are required, this type of training needs to be updated regularly and reflective of changing technologies in research methods as well as public policy initiatives (Wolf, 2010). Most IRBs already have such policies and procedures in place but clear budgeting and allowances for such updating are vital. This includes budgeting for attendance at conferences where the sharing of the latest information and exchange of ideas with those familiar with IRB requirements and activities is essential. For those on the board, required training should take place at each meeting as well as through a systematized fashion on a cycle of renewal. In addition, there are certificates and additional training that can make board members aware of how to best apply the federal guidelines and any subsequent changes that occur. In turn, the scientific investigators should also receive updated training. To have investigators aware of the latest rules makes it a win–win for all in terms of review, modifications, and subsequent approvals. Lastly, the human subject, now generally referred to as the participant in the study, clearly can benefit from learning more about informed consent and what to or not to expect in any research study, not just the one he or she is invited to participate. An educated public helps to avoid confusion and can empower participants to ask the questions they have not thought to ask before. This requires that continuing education remain rich with updated policies and procedures essential for the success of any IRB.
Conclusions: Pulling It All Together After the lessons learned in the past, some researchers continue to question the IRBs role in the protection of human subjects in clinical and behavioral science research. With the gains made through regulation, some professionals continue to wonder whether there are still gaps that occur in study conception and implementation (Slade et al., 2012). This is complicated by federal regulations that are written in vague language in contrast to the clearer direction provided for protecting subjects’ rights. A board composed primarily of professionals may be more scientifically curious than those with less training in the lay public. Such a board could be more
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likely to vote in favor of proposals that may be considered of higher risk based on the potential for the gain of scientific knowledge. Lastly, as is true in any group process, a gathering of the minds can lead to group think where members of the group are influenced by a charismatic leader. Gaining approval of the IRB has never been more persuasive when increasingly academic settings require faculty to conduct research and publish the results to advance the profession. Similar, to publish these research findings and contribute to the literature, academic, and rigorous journals will not publish the information gathered if it has not had prior IRB review and approval. This makes escape from IRB oversight almost impossible if one wishes to contribute scientific information to the literature. Pressure on IRBs to meet unrealistic deadlines and expectations that go beyond federal regulations can lead to ‘mission creep,’ a concept that only slows the process and discourages a professional collegial and supportive relationship between the researcher and the board (Saleem and Khalid, 2011). Furthermore, are we really drawing a line in the sand when we try to separate out research from clinical practice? Can one really be distinct from the other? If so, then applying different rules makes sense. If not, trying to apply different rules and oversight of certain aspects of practice by calling it research may mislabel and subsequently misrepresent clinical inquiry (Anderson, 2010). When the potential for mission creep is mixed with a blurred definition of what is clinical practice and what constitutes research, the lines between the two heighten the existence of the other. The more blurred the definitions, the greater the mission creep and the more complicated decisions become. Contemporary considerations and global connections make the situation even more complicated. When scientific investigations that are funded by U.S. enterprises such as pharmaceutical companies extend into developing countries, the need for control with limited red tape becomes even more evident (Saleem and Khalid, 2011). How does one truly stop the seductive benefits of secondary gain filled with researcher bias? Also, with changing technology problems continue to evolve related to ensuring consent to storing data in the cloud. As scientific and technological advances continue, the usual conflicts related to the varied professional interpretations of what constitutes ethical conduct designed to protect human subjects will make disagreements and differences in opinion unavoidable. Research regulations and the work of the IRB committee remains at the heart of risk-management review. These activities, however, will continue to fall short if this responsibility is not assumed deep in the core activities of the principal investigator and his or her research colleagues. In closing, this leads to one primary assumption, IRBs can help provide risk-management assessment, but the true ethical imperative to safeguard the participant must always rest with the individual investigator and his or her colleagues. Few would disagree that the use of human subjects in research has led to significant scientific and medical advancements and equally few would question the need to protect research subjects from the potential for abuse (Bledsoe and Grizzle, 2013). In fact the rights and welfare of human subjects should always be considered first because it is the only way to ensure participant autonomy and safety.
See also: Common Rule: US Regulatory Protections for Human Research Participants; Ethical Dilemmas, Research, and Access to Treatment; Ethics for Biomedical Research Involving Humans: International Guidelines; Objectivity of Research: Ethical Aspects; Privacy of Individuals in Social Research: Confidentiality; Research Ethics, Cross-Cultural Dimensions of; Research Ethics: Research.
Bibliography Anderson, J.A., 2010. Clinical research in context: reexamining the distinction between research and practice. Journal of Medicine and Philosophy 35, 46–63. Bledsoe, M.J., Grizzle, W.E., 2013. Use of human specimens in research: the evolving United States regulatory, policy and scientific landscape. Diagnostic Histopathology 19 (9), 322–330. Curran, W.J., 1970. Government regulation of the use of human subjects in medical research: the approaches of two federal agencies. In: Freund, P.A. (Ed.), Experimentation with Human Subjects. George Braziller, New York, pp. 402–454. Fujii, L.A., 2012. Research ethics 101: dilemmas and responsibilities. Political Science and Politics 45 (4), 717–723. Health Information Privacy, Updated 2014. U.S. Department of Health and Human Services. From: www.hhs.gov/ocr/privacy/ (retrieved 30.03.14.). Hurst, S.A., 2008. Vulnerability in research and health care: describing the elephant in the room. Bioethics 22 (4), 191–202. Levine, R.J., 1988. Ethics and Regulation of Clinical Research, second ed. Yale University Press, New Haven, CT. Lipsett, M.B., Fletcher, J.C., Secundy, M., 1979. Research review at NIH. Hastings Center Report 9 (1), 18–21. Medical Research Council of Canada, 1987. Guidelines on Research Involving Human Subjects. Medical Research Council of Canada, Ottawa, Canada. NIH: Fact Sheet on 1946–1948 U.S. Public Health Service Sexually Transmitted Diseases (STD) Inoculation Study. HHS.Gov: US Department of Health and Human Services. From: http://www.hhs.gov/1946inoculationstudy/factsheet.html (retrieved 29.03.14.). Saleem, T., Khalid, U., 2011. Institutional review boards- A mixed blessing. International Archives of Medicine 4 (19). Retrieved: http://www.intarchmed.com/content/ 4/1/19. Slade, K.L., Carreau, N.A., Heald, P., 2012. Ethics of clinical trials in dermatology. Clinics in Dermatology 30, 226–230. The Belmont Report, 18 April 1979. U.S. Department of Health and Human Services. From. http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html (retrieved 29.03.14.). Wolf, L.E., 2010. The research ethics committee is not the enemy: oversight of community-based participatory research. Journal of Empirical Research Ethics: An International Journal 5 (4), 77–86. World Medical Association, October 1975. Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects (Amended), 29th WMA General Assembly, Tokyo, Japan. World Medical Association, October 2000. Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects (Amended), 52nd WMA General Assembly, Edinburgh, Scotland. http://www.wma.net/e/policy/17c.pdf.
Relevant Websites http://www.ahrq.gov/ – Agency for Healthcare Research Quality U.S. Department of Health and Human Services. From HHS.gov, retrieved from: www.hhs.gov/ohrp/about/index.html – Office of Human Research Protections About OHRP. http://www.hhs.gov/ocr/privacy/hipaa/understanding/special/mhguidance.html – HIPAA Privacy Rule and Sharing Information Related to Mental Health. http://www.hhs.gov/ocr/privacy/hipaa/understanding/special/mhguidance.html – HIPAA Mental Health Privacy Rules. http://www1.va.gov/oro/ – VA Health Care: Office of Research Oversight.