"When science takes man [sic] as its subject, tensions arise between two values basic to Western society: freedom of scientific inquiry and protection of individual inviolability."1 - Jay Katz
The Institutional Review Board (IRB), a committee of scientists and nonscientists, is responsible for protecting the rights and welfare of human subjects, people who participate in scientific experiments or research. The IRB conducts a prospective review of proposed research and monitors continuing research in order to safeguard the rights and welfare of human subjects. The term institutional refers to the traditional location of the IRB, within the academic research institution or hospital. Local IRBs are geographically close to research sites, to scientists who conduct the research, known as investigators, and to communities of potential human subjects. Human research, however, also takes place beyond the walls of academia and hospitals, and may not be affiliated with such institutions. As a result, there are also IRBs that exist independently of academic research institutions and hospitals and that are not located near the investigators, the research sites, or the human research subjects.
This paper posits that an institutionally based IRB, or local IRB, is ideally situated to create a local culture based on trust and shared responsibility for the ethical conduct of biomedical or social-behavioral research. The first part of the paper will outline the history of local IRB review. The second part will illustrate how local IRB review encourages direct institutional responsibility for and community involvement in the conduct of research. The third section will address whether the current federal regulations provide adequate guidance for local review and whether institutions effectively apply both the letter and spirit of the regulations. For the purposes of this paper, the National Institutes of Health (NIH) definition of clinical research, which includes both biomedical and social-behavioral research, will be used in order to refer without distinction to all research involving human subjects.2 The actions of the local IRB are governed by ethical codes of conduct, federal regulations, local law, and institutional policies. Federal regulations give an IRB the authority to approve, require modification to, or disapprove all research activities that fall within its jurisdiction. Research that has been reviewed and approved by an IRB may be subject to review and disapproval by officials of the institution. However, those officials may not approve research if it has been disapproved by the IRB.3 Ultimately, a local IRB functions within a system of self-regulation and oversight on the part of the institution, the investigators, and the Board. A system of self-regulation and oversight requires a highly evolved sense of trust and responsibility from all participants. We trust professionals every day with our health, life, family, money, and property. We also trust scientists to be truthful and ethical in their conduct of research. To trust is to rely on the character, ability, strength, and truthfulness of someone or something. Trust also requires confidence in the truthfulness and accuracy of the information given by an individual or entity. In order to trust individuals or entities we must be assured that they will act responsibly. Therefore, to take responsibility for something makes that person or entity accountable. When we trust an individual, that person becomes responsible for upholding our trust. A discussion of local IRB review, ethical scientific conduct, and the ability to protect the rights and welfare of human subjects requires that we address the ideas of trust and responsibility as essential components of research.
The IRB system has proven so successful as to set an international standard for monitoring clinical research.4 Successful IRB review balances the interests of three distinct but inter-related social and political entities: scientists, society, and the individual human subject. The IRB, however, does not balance these interests alone. The IRB functions in a dynamic relationship with federal agencies, research sponsors, institutions hosting research, investigators, and the public. The dynamic relationship balances the competing interests of all parties and it facilitates the continued conduct of human research in an ethical and collegial environment. As a result, the local IRB is not the sole party responsible for the protection of the rights and welfare of human research subjects. An effective system of protections is a collective responsibility that requires a collaborative effort from federal agencies, the sponsors, the IRBs, the institution, and the investigators. When all parties acknowledge their shared ethical responsibilities at both the local and national level, and a balance of interests is met, they create a culture of trust that allows for their effective collaboration with the public and the research subjects.
"The public has [a] role in monitoring research with human subjects in two distinct areas. The first concerns the selection of particular fields for research programs. These are difficult choices, but with both government money and research charities the public has helped direct research into some fields at the exclusion of others. It is difficult to justify a radical departure from present methods as most important discoveries are made by chance, although by researchers with trained and open minds. The second role of the public concerns representatives serving on medical ethical committees. Increased representation of lay members on ethical committees is highly desirable."5 - W. E. Waters
The history of IRBs reveals that local review grew out of two major components: 1) ad hoc institutionally based peer review committees that preexisted any systematic notion of human subjects protections, and 2) the federal governments requirement that grantee institutions take responsibility for the ethical conduct of their research. An in depth history of human subject research review is outlined in many texts.6 Robert Levine, writing for the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research (National Commission), noted that the first documented suggestion of peer review for research may have originated with Thomas Percival in 1803.7 Though Percival may have seen the future, there is no evidence that his suggestion resulted in widespread adoption of his ideas for the next 150 years.
Prior to 1938, human experimentation was performed without federal restrictions in the United States. Such experiments were self-regulated by professional standards and guidelines such as the Hippocratic Oath of do no harm, and a cultural bias that relied upon and trusted the expertise of professionals. The subsequent regulation of human research in the United States consisted of a series of responses to crises rather than a proactive attempt to assure the ethical conduct of research or the protection of the subjects. Essentially, public outcry and political response led to a system of local review and governmental oversight and regulation of human experimentation.
The federal system for the protection of human research subjects developed primarily through major federal agencies, such as the Food and Drug Administration (FDA), the NIH, and the Public Health Service (PHS), all within the Department of Health Education and Welfare (DHEW), now the Department of Health and Human Services (DHHS). The National Cancer Institute (NCI), established in 1937, provided the first extramural research grants awarded on a competitive basis to medical researchers in the United States. The PHS was later given the power to fund research at universities and private institutions, and it administered these programs through the NIH.8 The federal Food, Drug and Cosmetic Act of 1938 required the FDA to oversee new drugs and devices for diagnosis, treatment, and prevention of disease unless they were shown to be safe. The Act, the first in the United States requiring labeling of new products intended for use with humans, was a response to public outcry over the reported death of more than 100 consumers from Elixir of Sulfanilamide. The elixir was tested only for flavour, appearance, and fragrance prior to marketing. The legislation, however, exempted regulatory oversight of the experimental use of drugs by qualified scientists9 and only required that they carry a label: Caution-New Drug-Limited by Federal Law to Investigational Use.10 Twenty-five years later another drug, thalidomide, was suspected of public harm. As a result of the thalidomide scandal, the FDAs authority was expanded to encompass oversight of the use of experimental products, including requirements for human testing, and the consent of the human subject.
It appears that the concept of local IRB review grew out of hospital based scientific peer review committees that operated on an ad hoc basis to address difficult ethical patient care issues. The peers were other physicians or experts within the institution. By 1953, Jack Masur, Clinical Research Center Director at the NIH, instructed each NIH institute to establish a disinterested committee of scientists called the Clinical Research Committee to review human research that involved unusual hazard. The committees would review and approve intramural research conducted at the NIH, with normal volunteers. The policy also required that normal subjects give informed consent.11, 12 Control subjects at the NIH were typically conscientious objectors to military service.13 Recipients of extramural NIH funding were exempted from creating such committees due to the perceived potential interference with the doctor-patient relationship, as well as a reluctance to interfere with scientific freedom and judgment of researchers and their institutions. Instead, the NIH relied on professional standards, local laws governing the practice of medicine, and the hope that research institutions would follow the federal lead to assure the ethical conduct of research.14 During this time, there was little differentiation made between research and therapy, between the physician and investigator, and between the patient and subject. Charles McCarthy observes that NIH investigators referred to human research subjects as patients and research was generically referred to as patient therapy. Given that environment, it is not surprising that the NIH had no policy of protections for patient/subjects involved in research.15 In the introduction to an NIH symposium Thomas Malone observed, It is unfortunate but true that much of the current progress in protecting the rights of patients and subjects resulted from abuse.16 The implementation of policies requiring committee review of the ethics of proposed federally funded research was prompted by several crises. Between 1958 and 1968 the country confronted revelations about transplantation of a sheep heart and chimpanzee kidney into humans, radiation experiments on prisoners,17 injection of live cancer cells into unknowing, chronically ill, indigent elderly patients at the Jewish Chronic Disease Hospital, introduction of hepatitis into severely cognitively impaired children at the Willowbrook State School, a placebo controlled crossover study of an oral contraceptive agent where ten women without knowledge of the dummy pill became pregnant and were not allowed to seek abortion due to legal restrictions,18 and Henry Beechers famous article in the New England Journal of Medicine listing cases of unethical research.19 Some scientists were acutely aware that continued ethical problems in the conduct of human experiments could lead to withdrawal of public support with a concomitant loss of public funding followed by regulation.20 NIH Director James Shannon, concerned about the problems, met with the National Advisory Health Council in September 1965, and proposed an impartial prospective peer review system to address the risks of the research and of the adequacy of protections of the rights of subjects.21 The Council accepted his proposal. On the heels of the change in NIH policy, Surgeon General William H. Stewart issued the first comprehensive federal policy for the protection of human subjects in February 1966. The policy required institutions to create local committees to prospectively review new, renewal, supplemental, and continuing grant applications for federally funded biomedical human research. The Surgeon General defined the composition of the committees as staff, or consultants to your institution who are at the same time acquainted with the investigator under review, free to assess his judgment without placing in jeopardy their own goals, and sufficiently mature and competent to make the necessary assessment. It is important that some of the members be drawn from different disciplines or interests that do not overlap those of the investigator under review. They would provide prior review of the judgment of the principal investigator or program director by a committee of institutional associates. The local institutions were henceforth responsible for applying wisdom and sound professional judgment [to] determine what constitutes the rights and welfare of human subjects in research, what constitutes informed consent, and what constitutes the risks and potential medical benefits of a particular investigation.22
Within five months, the Surgeon Generals policy was amended to require from individual grantee institutions an assurance of compliance with NIH human research policies. The assurance meant that, in order to receive federal research funds, the grantee institutions had to accept responsibility for the review and ethical conduct of human subjects research. By December 1966, the policy had undergone further revision. Its jurisdiction was expanded to include social and behavioral research and it now required committee deliberations in accordance with the laws of the community in which the investigations are conducted and [with] due consideration to pertinent ethical issues.23 The amended policy was the first acknowledgment that responsible ethical conduct of research required not only an institutional assurance of human subject protections but also consideration of community standards.
An NIH analysis in 1968 revealed that 73 percent of 142 institutional committees had membership comprised exclusively of scientific peer groups.24 The revised and expanded PHS guidelines of May 1969, formally required institutions to address community acceptance of proposed research. The modification of the guidelines made local institutions responsible for convening committees of sufficiently diverse membership to address scientific issues, local law, institutional policy, and community concerns for the protection of the rights and welfare of human research subjects.25 The DHEW stipulated in 1971 that an IRB should possess the professional competence to review specific activities, the committee should [also] be able to determine acceptability of the proposal in terms of institutional commitments and regulations, applicable law, standards of professional conduct and practice, and community attitudes. The committee may therefore need to include persons whose primary concerns lie in these areas rather than in the conduct of research, development, and service programs of the types supported by the DHEW.26
The Tuskegee Study of Untreated Syphilis in the Negro Male marks the dawning of consciousness in the United States regarding ethical obligations in the conduct of human research and a reassessment of the role of peer review in the protection of subjects. The PHS sponsored experiment began in 1932, lasted 40 years, and involved 600 African-American men, 399 with syphilis and 201 who did not have the disease. The subjects were not informed that they had syphilis or that penicillin was available when it was shown to be an effective treatment for the disease in 1947. As a result of the deception, the men lived with the disease and some unknowingly infected their partners. There was no evidence that researchers had informed the men of the study or its real purpose. In fact, the men had been misled and had not been given all the facts required to provide informed consent.27 The comments of John Heller, PHS Director of the Venereal Disease Unit, highlighted a lack of ethical obligation on the part of the PHS toward the participants in the syphilis study: The mens status did not warrant ethical debate. They were subjects, not patients; clinical material, not sick people.28 Subsequently, spokespeople for the PHS readily acknowledged that the peer review system failed29 to address fundamental ethical issues. They noted that the syphilis study was not a secret, but rather the subject of numerous reports in medical journals, and it was openly discussed at professional conferences. An official told reporters that more than a dozen articles had appeared in some of the nations best medical journals, describing the basic procedures of the study to a combined readership of well over a 100,000 United States physicians.30 In 1972, the Associated Press broke the story of the syphilis study. The ethical crimes committed by the federal government against the citizens of Tuskegee, Alabama required deep reflection on the part of bioethicists and the research community. The Advisory Committee on Human Radiation Experiments (ACHRE) later noted: While a slowly increasing number of investigators reflected on the ethical treatment of human subjects during the 1950s, it was not until the 1960s and a series of highly publicized events with names like Thalidomide, Willowbrook, and Tuskegee that it became apparent that a professional code, whether it originated in Nuremberg or Helsinki, did not provide sufficient protection against exploitation and abuse of human subjects in research.31 Within one year, congressional committees convened hearings to examine human research in the United States.
The National Research Act became law in 1974. It outlined protections for human subjects involved in biomedical and behavioral research, it required the DHEW Secretary to promulgate regulations requiring IRB review for all federally funded biomedical or behavioral research, and it impaneled the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research.32 The National Commission was charged to assess the state of protections for human subjects around the country and to provide guidance for institutions and investigators when confronting the ethical issues of human subject research. The Commission authored several reports including a document examining IRBs, and in 1979 it issued the definitive American declaration on the ethical conduct of human research, the Belmont Report.33 Following the public revelations of the syphilis study, membership requirements for IRBs were expanded again by the DHEW in regulations issued in 1974. The new regulations emphasized the importance of considering research in the context of community standards. The regulations defined the composition of an IRB as having a minimum of five members and that it should include persons whose primary concerns lie in the areas of legal, professional, and community acceptability rather than in the conduct of research, development, and services programs supported by the HEW.34 In order to ensure a diversity of opinion when considering protocols, membership on an IRB could not come from a single professional or lay group. Furthermore, the regulations now protected against an implicit institutional bias and conflict of interest by mandating that a legally convened meeting must include at least one member not otherwise affiliated with the institution.
The Commission believes that the rights of subjects should be protected by local review committees operating pursuant to federal regulations and located in institutions where research involving human subjects is conducted. Compared to the possible alternatives of a regional or national review process, local committees have the advantage of greater familiarity with the actual conditions surrounding the conduct of research. Such committees can work closely with investigators to assure that the rights and welfare of human subjects are protected and, at the same time, that the application of policies is fair to the investigators. They can contribute to the education of the research community and the public regarding the ethical conduct of research. The committees can become resource centers for information concerning ethical standards and federal requirements and can communicate with federal officials and with other local committees about matters of common concerns.35
In 1983, revised DHEW regulations further delineated and refined the broad IRB membership categories described in 1974 by requiring representation of both male and female members and by defining nonscientists as, for example: lawyers, ethicists, members of the clergy.36 The 1991 revision, which is the most recent iteration of the federal regulations, removed the examples for nonscientific members without publication of related or guiding comments.
By 1993, the concept of local IRB review was firmly entrenched for institutions that receive federal funds.37 The NIH/Office for Protection from Research Risks (OPRRs)38 1993 Protecting Human Research Subjects: Institutional Review Board Guidebook explains the concept of local review, and advises institutions that an IRB:
The federal regulations further require that if an IRB regularly reviews research that involves a vulnerable category of subjects, such as children, prisoners, pregnant women, or handicapped or mentally disabled persons, consideration shall be given to the inclusion of one or more individuals who are knowledgeable about and experienced in working with these subjects.40
Since 1966, institutions have been required to provide an assurance of compliance to the federal government. The document assures the federal government that the institution will take responsibility for the ethical and legal conduct of human research done under its auspices. Currently, institutions that receive federal funding for human research must provide the OPRR with an assurance of compliance with ethical codes of conduct and the federal regulations. A Single Project Assurance (SPA) is required for institutions that periodically perform federally funded research. Research proposals and SPAs are reviewed on case by case bases by the OPRR Assurance Branch. Institutions awarded numerous federal research grants and contracts are encouraged to file a Multiple Project Assurance (MPA) with OPRR. The MPAs are negotiated by the institutions and OPRR; they allow institutions to demonstrate responsibility for the ethical conduct of research by creating an IRB responsible for the review and approval of affiliated research. The MPA outlines the types of projects required to undergo IRB review, the responsibilities of the administration at the institution, the reporting lines within the institution, the responsibility of the IRB and investigators, the review process, and the oversight process.
The MPA stipulates that local IRB review of human research will comply with federal regulations and the ethical principles outlined in the Belmont Report: respect for persons, beneficence, and justice. In spite of past and recent problems in the conduct of human subject research, society continues to allow investigators to engage in human research because specific parameters are in place to ensure the protection of the participants. The privilege of conducting human research depends on the ability of the government, sponsors, institutions, IRBs, and investigators to effectively collaborate and ensure the on-going protection of the rights and welfare of the subjects.
The system of assurances for local IRB review is based on trust. The public has entrusted the federal government with its well-being as it relates to human subjects research. The federal government trusts the research institution to impanel an appropriate IRB to review its own research. The trust is based on the acknowledged institutional responsibility for instituting effective mechanisms for the protection of human research subjects. The institution creates an IRB and entrusts it to review research responsibly according to the federal regulations, community standards, and ethical guidelines in order to maximize the protection of the human subjects, and to negotiate the conditions of approval with investigators in a collegial manner. The local IRB review engages the scientist in a dialogue that ensures that the conduct of research is in compliance with the federal regulations and ethical guidelines and is performed according to the agreed upon IRB conditions of approval.
The subject entrusts the investigator with the protection of his or her rights and welfare beyond any research objectives. The collective trust is built through institutional support of local IRB review and compliance with federal regulations. Without the many levels of trust working together, the system of human subject research and protection falls apart.
"To leave the decision entirely to the individual researcher himself, or to a group of his colleagues, would seem to us to violate seriously what some political scientists term the principle of shared or countervailing force. The researcher and his colleagues represent a party at interest the scientific party: And there is good reason to believe that any party at interest is likely, more often than not, to give himself the benefit of the doubt. Whether he does or not, the public generally thinks or suspects that he does. And in our democracy, both theoretically and pragmatically, the views of the public must be recognized as of paramount importance."41 - H.S. Conrad
As outlined above, the concept of local IRB review evolved over the last 50 years from a peer review system to one of community participation. Since most research was performed at academic institutions and hospitals, it appeared reasonable to ask such institutions to institute review and monitoring mechanisms. The peer review system, solely consisting of scientific membership and thus insular and isolated, included a potential for the promotion of scientific self-interest. For example, though the syphilis study received multiple reviews at the national level and there were widely published accounts in the scientific literature, scientists did not question the ethics of the study design, which allowed the subjects disease to progress without consent and which withheld easily available treatment. Instead, public outcry and a congressional investigation stopped the research. In order to create a more just and representative system, the peer review model was discarded in favor of the local institutionally based IRB system, which includes nonaffiliated or community and nonscientific membership and directly engages the local research institution. It is important to note that, though the local IRB system grew out of earlier peer review programs, it is not a peer review system. As a result, the federal regulations do not recognize the IRB as a peer review committee, nor do they require a majority of scientific experts. Instead, the IRB is an open system that includes members with varying backgrounds to promote complete and adequate review of research activities commonly conducted by the institution.42 Ultimately, the federal government achieved sophisticated goals: predicating a research institutions receipt of research funding on a commitment to ensure both the ethical design of the research and the ethical conduct of its faculty through local IRB review. Such requirements hold an institutions proverbial feet to the fire regarding responsibility for the review and the ethical conduct of research.
The National Commission believed local IRB review offers a distinct advantage over regional or national committee oversight in the review of human research. The local IRB is in a superior position to interact with the institution, the investigator, and the community of potential research subjects, and to assure that the proposed research fulfills the three ethical principles of the Belmont Report: respect for persons, beneficence, and justice. Former OPRR Director Gary Ellis echoed the National Commissions recommendations and affirmed the importance of local review:
"We embrace the local IRB at the research site as the cornerstone of the American system of protection of human subjects. IRB review is both prospective and a continuing review of proposed research by a group of individuals with no formal interest in the research. It is local review by individuals who are in the best position to know the research at the site, the resources at the institution, the capabilities and the reputations of the investigators and staff, the prevailing attitudes and ethics of the community and most importantly, the likely subject population."43
Implicit in Ellis statement is the view that local IRB review provides institutions with an opportunity to demonstrate responsibility and to build a culture of trust and ethical conduct in the performance of human research. The institutions commitment to local review is manifested through its ethical obligation to provide educational opportunities for investigators, the IRB, and staff, to provide adequate personnel and resources for the IRB, and to ensure oversight of approved research with participation of both the local scientific community and the community of potential research subjects. The institution thereby demonstrates accountability for the conduct of research and the application of regulations and ethical principles that assure the protection of the rights and welfare of the human subjects.
The requirement that each federally funded institution engaged in human experimentation constitute a local IRB encourages the institution to promote an environment that supports the highest ethical standards for the review and conduct of research performed under its auspices. Francis Moore highlighted the importance of the intellectual and ethical climate of the institution. Such a climate is difficult to regulate or standardize, difficult at times even to recognize or describe. Yet it is more important than any other single consideration in protecting the willing patient from unwise, inexpert, or ill-advised therapeutic innovation.44 Moores 1969 comments on the importance of institutional culture remain largely true today. Most importantly, the imprimatur of the institution makes the local IRB an agent of the highest ethical standards embraced by the institution itself, rather than a foreign agent of the government or an adversary of research. The institution, therefore, is uniquely situated to take responsibility for various aspects of human research, such as:
- creation of an institutional culture that promotes and upholds the highest ethical standards in the conduct of human research,
- education and mentoring of the research community and provision of sufficient resources and staff to support the educational mandate of the IRB,
- involvement of all interested parties in the review process including open communication and interaction with the community (the source of potential research subjects),
- oversight of the research, and
- awareness of local resources and standards that may impact proposed research.
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"The institution should be prepared at all times to question the conduct of research, even though previously approved by both the institution and the [PHS]. The safety and welfare of the subject are paramount."45 - U.S. Public Health Service: Protection of the Individual as a Research Subject
The MPA makes the local IRB review more than just a prospective evaluation of proposed research. By compelling institutions to accept responsibility for more than just the economic management of research funds, the MPA extends their responsibility to the ethical conduct of the research. It holds the institutional official, the institutional signatory to the MPA, responsible and accountable for the actions of the investigators and the IRB. The presence of a local IRB is an acknowledgement that the institution plays a vital role in creating and maintaining a culture of ethical behavior among its investigators and staff. An institution that cultivates ethical behavior and demonstrates intolerance for unethical behavior ensures a culture of collective responsibility for the protection of the rights and welfare of human subjects and preserves the public trust. The MPA encourages a collective responsibility for the ethical conduct of research by predicating receipt of federal funding for research on the ability of all parties, i.e., the institution, the IRB, and investigators, to comply with the federal regulations. A finding of significant noncompliance can jeopardize the ability of all stakeholders to conduct research. Ultimately, the entire institution is responsible for upholding the MPA and the regulations. The entire research enterprise is balanced on the good conduct of each participant within the institution. The highest level official at the institution, therefore, should sign the assurance and serve as the institutional official, i.e., the person responsible for assuring that all parties acknowledge and carry out their ethical responsibilities in the conduct of research. The assurance thus engages all levels of the institution in a collective commitment to uphold the highest ethical standards.
Local IRB review gives the institution an opportunity to demonstrate a commitment to the highest standards of ethical conduct in human research and to create a community that supports such standards. The research institution is uniquely situated to create a culture where ethics are valued and the importance of IRB review is honored. Levine noted that in order to function most effectively, the IRB must not only be, but also must be perceived to be, an agent of its own institution.46 To achieve Levines goal, it is incumbent upon the institutional official to use his/her moral and academic authority to require the highest ethical conduct from the faculty and staff. The institution should develop and implement local policies and procedures that reflect the ethical principles of the Belmont Report and the federal regulations to create an internal standard of acceptable behavior. Institutional policies and procedures translate into a demonstration of philosophical and practical support for the autonomy and authority of the IRB, while facilitating a fair, timely, and collegial review of proposed research. An institutional ethos that highlights the importance of ethical principles will also insist upon well-conceived and properly executed research. The requirement should be evident in written institutional policies, in the actions and communications of institutional officials, and the IRB. Research that is designed or conducted so poorly as to be unethical or invalid exposes subjects and the institution to unnecessary risk. The institutional standard for well-conceived and properly conducted research minimizes the potential for conflicts between the IRB and the research community, facilitates local review, and assures the protection of the rights and welfare of the human subjects.
Investigators will perceive such internal standards as an expression of a communal commitment to ethical behavior rather than as an intrusion into academic research by a colonizing federal authority. The IRB is thus perceived by the research community as an expression of its own commitment to human subjects protection, and as the expression of an institutional mandate and policy, rather than as an alien and disembodied review process. As noted by the National Commission, such an environment demystifies the review process and builds the trust of the research community and the public.47 The institution underscores the importance of ethical conduct by convening IRBs with a respected membership that reflects the highest level of scientific expertise and community participation and support. An IRB that has the respect of the research community is better able to fulfill its principal charge as outlined by the National Commission, i.e., education of the research community. The institutional official recognizes that the Board can only carry out its regulatory, educational, and ethical functions when there are sufficient resources and high level support staff to communicate effectively with the research community and to ensure adequate protections of subjects through oversight, including continuing review and monitoring of approved research.
An institution that takes responsibility for the review and conduct of human research positions itself to engage the trust and support of the scientific community, it attracts additional financial support for research because it can assure ethical conduct and safety, and it creates an environment for successful collaboration with the community of potential research subjects. The responsibility of local review obliges all institutional parties to acknowledge a collective responsibility for the creation of a culture of intra and extramural community participation, mentoring, and accountability. The local system of review is most effective when the institutional official sets the highest ethical standards for the research community and insists upon an institutional culture that demonstrates support for the charge of the IRB, namely, respect for human dignity.
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Education and Mentoring
"The most effective protection for all concerned depends upon a recognition and an understanding of the various aspects of the problem."48 - Henry Beecher
As previously noted, the local review and conduct of human research is a collective ethical responsibility. The efficacy of the system is predicated on the ability of the institution, the IRB, and the investigators to collaborate in an environment of mutual trust and support to facilitate a common goal: the safe and ethical conduct of research. In order to accomplish this goal, the federal government, the institutional official, the IRB and its support staff, as well as investigators, should view their principal collective charge as educational in nature. An effective system of review and protection requires each party to accept the role of educator and to demonstrate ethical leadership. An institution that accepts responsibility for the review of human research is uniquely situated to demonstrate a commitment to the letter and spirit of the guiding ethical principles and federal regulations by engaging both the scientific and lay community in a shared educational dialogue. The ACHRE highlighted the importance of education: The historical record makes clear that the rights and interests of research subjects cannot be protected if researchers fail to appreciate sufficiently the moral aspects of human subject research and the value of institutional oversight.49 An academic research institution such as a university or a research hospital has three responsibilities: to conduct research, educate, and to serve the surrounding community. Education is the foundation for a local culture of trust and shared responsibility. The institution is responsible for ensuring the effective education of its scientists, faculty, staff, and IRB, in the ethical conduct of human research.50 The National Commission highlighted the contribution the local IRB can make to the education of the research community and the public about the ethical responsibilities of human research. An effective education program deepens the awareness of all stakeholders regarding their obligations to protect the rights and welfare of human subjects, it trains them in the regulatory and legal requirements, it promotes ethical conduct, and it builds an institutional culture of shared responsibility that creates trust among all parties. It also builds a participatory process that acknowledges the expertise of all participants, i.e., the IRB, the investigators, the lay community, and the institutional official. An acknowledgement of shared expertise engages the participation of all stakeholders in the creation of policy, in the IRB process, and in the ethical conduct of human research.
The research institution has the resources and the faculty to compose an IRB of respected members from the campus and the community-at-large that will promote respect for its advice and counsel.51 By naming senior research faculty members and respected community members to the IRB, the institution reinforces the importance of the IRB process as well as its own commitment to a successful and ethical human research program. Senior scientific experts on the local IRB play two important roles with respect to institutional goals and IRB responsibilities: they serve as scientific and ethical mentors to their colleagues, and they bring their research expertise to the deliberations of the IRB. In addition, the local IRB is a source of information concerning ethical standards and federal requirements, and it facilitates a close working relationship with investigators. The inclusion of faculty and local nonaffiliated lay community members on the local IRB creates a participatory democracy where all stakeholders have a direct voice in the research and review process and control of their own destiny.52
Many investigators view the human research review process as bureaucratic or mysterious. The local IRB demystifies the review process and creates an environment of collegiality. The local IRB offers investigators the opportunity to attend meetings and to directly discuss with the Board issues regarding specific research projects. Contact with the IRB provides an opportunity to directly address specific concerns of the Board or the investigator, to educate the IRB members and the investigator, and to open the review process to each stakeholder. The direct participation of investigators in the local IRB process empowers both the investigator and the Board. For example, an investigator, in response to requests for ethical justification of a study design, can attend an IRB meeting to clarify the issues. Attendance at an IRB meeting provides both the Board and the investigator with an opportunity to engage in a dialogue about their concerns. The IRB is no longer a disembodied entity making judgements on an investigator and his or her proposed research. Instead, the Board is revealed to be composed of the investigators mentors and respected scientific colleagues; ethical questions take on a newly recognized gravity and the IRB has an opportunity to collegially discuss the concerns with the researcher. As a result of direct engagement with the researchers, the IRB is demystified, and both the IRB and the investigators are educated.
A traditional educational paradigm that employs rote memorization may not lend itself to the successful education of an IRB or investigators. A rote memorization of guidelines, principles, and regulations, absent the ability to apply such concepts in practical situations will not ensure the protection of the rights and welfare of human subjects. An effective human research education program, therefore, should also include a dialogue among all stakeholders regarding the application of ethical principles and regulations in the practical research context. The promotion of dialogue among all parties avoids the perception that IRBs claim imperious authority in ethics, regulation, and research standards. Such perception will lead to adversarial relationships between the IRB and the research community, resulting in a breakdown of trust.
Education occurs in the dynamic collaboration between the IRB and the research community. An education program that acknowledges collective expertise among the IRB, the scientific community, and the lay community, and that encourages and supports an engaged dialogue among all parties, prevents adversarial relationships. An institution that adopts a collaborative educational approach draws on collective institutional expertise and knowledge which facilitates an engaged partnership by all parties in the goal of ethical research. Furthermore, the dynamic exchange of experience and knowledge creates an institutional culture that builds awareness of the regulations and sensitivity to collective responsibilities in conducting research with human subjects, and it also enlists all parties in open communication, thereby eliminating any need for conflict resolution or an appeals process outside of the IRB. For example, the institutional official may convene subcommittees of scientific and lay members of the IRB, investigators, and legal counsel to examine issues of concern to the research community for the purpose of creating institutional policy that will guide the actions of the IRB and the investigators. Subcommittees investigate, discuss, and make recommendations to the IRBs, the institutional official, and the research community, on institutional policy regarding such issues, as research with human genetic and biological material, or requirements for ensuring the privacy and confidentiality of human subjects both during recruitment and over the course of the research.
An institutional commitment to IRB review includes a responsibility to supply enough highly educated support staff and resources, such as meeting space, locking files, and computerization, to support the charge of the Board.53 To facilitate the review process, a knowledgeable local IRB staff communicates with the contract and grant administration, the institutional administration, sponsors, investigators, research staff, federal regulators and agencies, and other IRBs. The local IRB staff is an extension of the Board and is a ready and professional source of information for the research community about regulations, current national trends regarding human subject protections, and local laws. It also maintains the IRB memory in order to assure consistency in the review of like proposals, and for institutions with multiple IRBs, it assures consistency in the review of like projects among the IRBs.
Some universities have created human subject research education programs administered by faculty, IRB members, and staff to educate the research community. Professional, educated staff in collaboration with IRB members and faculty provide educational sessions for investigators, on-line tutorials, and manuals that advise investigators on the regulations and ethical standards, and guide them in the mechanics of adequate completion of IRB applications.54 Such educational tools help investigators address significant ethical and regulatory issues prior to IRB review and thus facilitate the review process for all parties. Some IRBs use correspondence, generated as part of the review process, as a way to educate investigators.55 Local educational programs encourage ethical behavior by providing a historical context for the shared regulatory responsibilities of all stakeholders, they sensitize researchers to cultural and community concerns, and they inform investigators of institutional policies to ensure the protection of the human subjects.
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Community and Participatory Democracy
"Appeals to the principle of respect for persons are often viewed with suspicion not only because they appear to remove people from time but also because they appear to remove people from their communities."56 - James Childress
In this section I will discuss the participation of the nonaffiliated community member as a nonscientist.57 A recent NIH IRB survey noted that most nonaffiliated members are nonscientists. The federal regulations require that an IRB include at least one member who is not affiliated with the institution commonly known as the community member or lay member, and one nonscientific member.58 The nonaffiliated membership on the IRB provides a voice for the community of research subjects during the review of research. OPRR suggests that the nonaffiliated member should come from the local community-at-large.The person selected should be knowledgeable about the local community and be willing to discuss issues and research from that perspective.59 The OPRR guidance implies that the nonaffiliated members charge is to represent community concerns and by extension the concerns of specific subject populations. Recognition of both the implicit scientific bias in the traditional peer review system and the need for community participation in the ethical evaluation of human research, coincides with a societal shift in emphasis from the individual to the social environment in which individuals exist. Through community representation, the IRB is able to acknowledge and address such important issues as the social context and impact of research, the heterogeneity of our society, the impact of scientific paternalism on notions of autonomy, beneficence and justice, the recognition that, in addition to physical risk, scientific inquiry includes potential social, psychological, and economic risk for subjects, and the need to engage the potential subject populations in the decision making process regarding research in their community.
Paul McNeill commented, The assumption that society (or the community) should have a voice on ethics committees is based on a notion about the role of the lay member.60 The regulations do not privilege scientific expertise over community participation on the IRB. Instead, the regulations reserve an adequate number of chairs at the IRB table for both scientific expertise and community representation and note that the IRB should be sufficiently qualified through the experience and expertise of its members, including consideration of race, gender, and cultural backgrounds and sensitivity to such issues as community attitudes, to promote respect for its advice and counsel in safeguarding the rights and welfare of human subjects.61 The National Commission endorsed a balance of scientific, individual, and community concerns on IRBs in order to guard against scientific self-interest and to demonstrate an awareness and appreciation for the various qualities, values and needs of the diverse elements of the community served by the institution or in which it is located. A diverse membership will enhance the local IRBs credibility as well as the likelihood that its determinations will be sensitive to the concerns of those who conduct or participate in the research and other interested parties.62
Community, however, consists of several distinct and sometimes intersecting groups, such as the community of potential research subjects, people located in a specific geographical area, people with similar interests, work, culture, or religious, racial, or ethnic background. The letter and the spirit of the National Commission IRB report and the federal regulations require sufficient scientific, cultural, and community expertise, and therefore, appear to support representative or democratic IRB membership, one that includes the participation of representatives of potential subject populations on the IRB. The federal regulations recognize that research is a social act involving particular social relationships. Such awareness underscores an important aspect of the spirit of the regulations and the intent behind local review, that is, the democratic constitution of a local IRB in order to balance the interests of science, society, and the individual. Though a nonscientific community member serves an important purpose on the local IRB, it is important to distinguish between such independent members and community members who are representative of or who directly advocate for subject populations. Representatives of subject populations should have a right to participate in the review process in order to protect and advance their own interests.63,64 The local IRB thus realizes and promotes a form of participatory democracy where culture [is recognized] as the essence of human endeavor, expressed in respect, recognition of differences, and inclusion.65 The first principle of the Belmont Report, respect for persons, underscores the importance of autonomy and finds its expression in the process of individual informed consent. Autonomy is derived from the Greek autos or self and nomos or rule, governance, or law. Autonomy means that an individual has the right to self-determination or self-governance. The abstract ideal of autonomous existence is a long cherished principle of American freedom. Our idea of autonomy, however, is not necessarily actualized in the real world. It is difficult to view individuals as isolated beings living outside any social context because our complex social settings do not permit us to act in an isolated way or in a purely autonomous fashion. Our actions intrinsically link us to other people in a complex web of social interactions and dependencies. The nomos or governance, therefore, is expressed through social, political, and professional interactions. James Childress reminds us, People are not as distinct and as separate as some interpretations of the principle of respect for persons appear to suggest. This point not only suggests that no man is an island because actions have so many effects on others; it also implies that an individuals wishes often reflect the social context in ways that are sometimes overlooked.66 Celia Fisher critiqued the common understanding of autonomy through the lens of relational ethics which conceives personhood and autonomy as social constructions which best can be respected through mutual understanding and dialogue between scientist and subject.67 The principle of respect for persons, therefore, requires us to balance the abstract concept of autonomy with the functional reality of lived relationships and community.
The local IRB balances respect for individual autonomy, through requirements for individual informed consent, with respect for the individuals social context, through the participation of community representatives of possible subject populations in the review process. The 1996 revised joint FDA/NIH regulations for waiver of informed consent in emergency research reveal a paradigm shift in our concept of respect for persons, traditionally expressed through individual informed consent. The revised regulations reflect a more nonindividualistic interpretation of autonomy that involves the community of the potential subject population. The regulations effectively allow a community to consent for individuals who participate in emergency room research, such as research on traumatic brain injury.68 The radical shift in emphasis from the primacy of individual autonomy to group consent embodied in the regulations is predicated on the presumption that such research would not be reviewed by regional or central IRBs.69 Instead, the regulation requires the local IRB and investigator to discuss implementation of the waiver of informed consent for specific projects within the community of the potential subjects. Annette Dula suggests the important role community plays in local IRB review when noting that the majority of emergency research performed under the waiver of informed consent regulations will include disproportionate numbers of African-American, Latina/o, and poor subjects, because of the location of trauma centers and because of the disproportionately high rate of certain kinds of trauma and a large proportion of trauma centers are located in public hospitals in or near inner cities.70 The importance of community participation in the local IRB process was also illustrated during a national FDA human research meeting on implementation of the waiver rule. High level FDA representatives underscored the importance of community participation in the IRB process: if the community response reveals substantial concerns, the [IRB] should ask for a redesign of the study, and if that is impossible, the research may not be appropriate for that community.71 The role of community members on local IRBs evolved out of concern that a committee comprised exclusively of institutional representatives would be biased toward research and the interests of the institution. The membership requirements were expanded in order to address such issues as relevant local law and community acceptance of the research. The local IRB is uniquely situated within the community of the proposed research to be able to provide potential subject populations with sufficient seats at the table to represent effectively their interests and inform the Board of prevailing attitudes and issues in the community. Community agencies, local advisory counsels, and other groups can serve as resources of information about their members concerns, they can advocate for subjects, and they can open channels of communication with the institution and the IRB by serving as Board members. A local IRB can maximize interaction with and access to community representatives and organizations in order to adequately reflect the concerns of potential research populations and cultures, and ensure that they are treated with respect and justice during the review and ultimately during the conduct of the research. The inclusion of community members who are representative of the potential subject populations can help assure the safety of the subjects by providing a window onto the local culture. They can help educate the IRB, the investigators, and the institution to the unique needs of the community, to the social and cultural implications of the research, and to local cultural nuances that will permit investigators to recruit subjects more successfully.72, 73 Community members, therefore, bring an expertise to IRB deliberations. Their collaboration with the scientific community helps the IRB identify areas of concern in the community and helps to construct a scientific enterprise based upon mutual respect, accommodation, and trust with the potential subject population.74 Adequate community representation ensures that the IRB is able to address local cultural, religious, and language issues, and to make provision for respectful and understandable informed consent, privacy, and confidentiality. Federal regulations require that an investigator provide subjects with legal, written informed consent except in specifically delineated exceptions. The consent process, including the informed consent document, must be in a language understandable to the subject.75 OPRR advised investigators and IRBs to safeguard the consent process and to promote open and free communication between the researcher and the participants. Investigators and IRBs must seek to understand cultural nuances and types of foreign languages inherent in the populations to be enrolled.76 Consideration of local language and cultural differences play a significant role in the IRB review of the scientific design of proposed research, in the assessment of the risks and benefits of the proposed research, and in the application of principles such as respect for persons and justice. Consider the population of Los Angeles. The Los Angeles Unified School District identified 80 different language groups in its student population. The largest groups with non-English language backgrounds are those that speak Spanish, Armenian, Korean, Cantonese, Vietnamese, and Russian.77 Los Angeles represents a community of diverse and highly distinct cultural groups with different community practices and needs beyond translated consent documents. The local IRB, through community awareness and by virtue of its local setting, is better able to ensure that an investigator is sensitive to cultural differences that will affirm the dignity, as well as the rights and welfare of the subject population.
Leslie J. Blackhall and colleagues noted that examining a family-centered decision-making style does not mean abandoning our commitment to individual autonomy or its legal expression in the doctrine of informed consent. Rather, it means broadening our view of autonomy so that respect for persons includes respect for the cultural values they bring with them to the decision-making process.78 Community membership on the IRB can help the investigator address different cultural paradigms such as family centered decision making and consent. In order to assure safety and autonomy, a local IRB with knowledge of the local community can also address specific safety concerns, such as how socio-economic factors including hunger or food insecurity may affect health related behavior and priorities,79, 80 the risks of combining traditional remedies with experimental drugs for populations who may access herbal medicine when participating in clinical trials,81 the inability of certain subject populations to obtain basic palliative pain relief from their local pharmacies due to societal racial inequities or alienation from the health care system,82, 83 suspicions and fears resulting from cultural and historical abuses and racial factors in mental health care,84 genetics,85 and language barriers and requirements for translated consent documents and informational materials. Additionally, the broad membership of a local IRB can address the cultural differences in beliefs and values, language and communication difficulties, issues of transportation and immigration status, and lack of familiarity with the United States health care system.86 An IRB without adequate representation from the potential subject population may fall prey to the misconception that it can generalize decision making processes, social and psychological risks, and the rights and welfare of research subjects based on a paradigm of a homogenous society. In order to create a system of human subject protection that honors and respects differences among cultures and groups, the local IRB can include representatives from research populations and provide them with an opportunity to participate in the decision making process. For example, investigators may note that the geographical location of a woman with breast cancer is irrelevant to IRB deliberations about their participation in research. This type of comment reveals a world view that sees subjects as members of a homogenous population. It also reveals an ignorance of the scope of concerns besides diagnosis and treatment that a subject and an IRB may have, including consideration of the social, psychological, and economic risks that may be involved with identification, contact, and recruitment of the potential subject, as well as from the subjects ultimate participation in research. The Jewish newspaper, Forward, illustrated the point in an article about how orthodox Jewish women, fearful of stigmatization resulting from community knowledge of having the BRCA1 genetic link for breast cancer, were travelling far from home for treatment and disguising their hospital stays as out-of-town visits, lest the news of their affliction poison the marriage prospects of their daughters. Some people in the orthodox Jewish community also expressed concern about the potential social ramifications of the discovery of the BRCA1 gene and its impact on Ashkenazi Jews.87 The article articulates concerns held by orthodox Ashkenazi Jewish women that may be different from those of other women and which require, therefore, different consideration by the local IRB and the investigator in order to ensure the respect and dignity of the subject and to minimize risk.
It is important to remember that the definition of risk includes physical, social, psychological, and economic risks.88 Human research may involve minimal physical risk, but significant potential social, psychological, and economic risks may result from a breach of confidentiality or an invasion of privacy. Research on the conditions of industrial workers, for example, may pose nonphysical risks to subjects that IRB members who do not live or work in the area may never contemplate. A national or regional IRB may not have ready access to sufficient expertise in local management/labor issues, workplace relations, etc., in order to adequately assure the protection of the subjects. A local IRB with membership from the labor community has the expertise to take the necessary steps to secure the protection of the rights and welfare of worker subjects that may not be readily apparent to the investigator, scientific members, or nonworker members. Such expertise could determine whether the scientific design of the study increases the risk to workers by linking identified individuals with specific job conditions, hazards, and adverse health effects, thus potentially disqualifying the subject from his or her job, limiting access to medical or life insurance, or excluding the worker/subject from other careers or trades. The inclusion of worker representatives on IRBs that review workers studies helps IRBs balance societal benefits against personal risks to the participants.89 Additionally, minority, immigrant, and poor populations may be vulnerable to risks that are not readily apparent to faculty at academic institutions or to members of an IRB located thousands of miles from the community of subjects. Therefore, the ivory tower may pose very real dangers for research subjects and must be a concern for an IRB reviewing the adequacy of protections for the rights and welfare of research subjects.
Jason Karlawish posited that community participation represents a basic point of justice:
It is a maxim of research ethics that a poorly or improperly designed study is unethical. The claim that a trial is potentially beneficial ought to rest upon a consensus that the trial measures benefits that the community values and acceptably balances potential risks and benefits. Clinical research needs to be responsive to the needs and values of the community that will participate in the clinical trials and use of drugs. This community comprises not just physicians and industry, but also patients. This is a basic point of justice that should govern right reason in the republic of science, and it is an agenda for bioethics research.90
Robert Fullilove suggested that the principle of beneficence may also require an IRB to examine and balance community interests. Fullilove compared a proposed epidemiological study on the frightening excess mortality rates reported for Harlem residents with a 1990 study that reported the life expectancy of black males in Harlem [as] approximately 49 years. He noted that community members expressed antipathy towards the new study and indicated that the community needed doctors and not research. Fullilove wondered whether IRBs should ask investigators proposing to work with minority communities to demonstrate how their work will have benefits (or create risks) for the community at the same time that they are describing the risks and benefits that such research will pose for participating individuals.91 Many communities approach research with skepticism due to past inequities. Some communities express concern about colonization and appropriation of their culture for research purposes without concomitant benefit to the community.92, 93 The Native American community, for example, highlights complaints about participation in research that may resonate with many other communities, such as participation in research without fully understand[ing] the risk to their health and safety, miscommunication that results in potential subjects feeling obligated to participate in research, research conducted without respect [for] the basic human dignity of the individuals or their religious and cultural beliefs, demeaning the dignity of individuals and communities due to the supposed purity of their gene pool, researchers [pursuing] issues of importance to the larger society but of marginal interest to Indian people, and manifesting a disinterest in problems of more urgent concern to the Indian community.94 The local IRB, with sufficient representation from potential subject groups, can sensitize both its own members and the investigator to issues regarding local fears, attitudes, problems, concerns, and practice. The local IRB that functions as a participatory democracy will apply the principles of the Belmont Report within a community context to ensure respect, beneficence and justice for all research subjects.
David Hayes-Bautista noted that previous conceptions of majority and minority populations are quickly changing. He outlined that California in the 1940s, was 89.9 percent European-American, and California of the 1990s, as a result of rapid and unprecedented demographic changes, reverse[d] the traditional demographic structure and [has] a minority Anglo population. Similar demographic trends exist in Texas, New York, Arizona, New Mexico, Florida, and the Chicago area. The changing demographic trends challenge us to question assumptions of minority versus majority as well as homogenous European-American value systems that may not be applicable to communities of color.95 The recognition that American society consists of multiple value systems requires that the IRB understand and honor subjects, their cultures, and preferences. By including community representatives on the Board, the research institution can ensure that the local IRB consistently and adequately applies the principles of respect for persons. It is important to acknowledge that we live in a country with a history of profound social inequity and that an individuals conception of the society is informed by variables, such as race, culture, ethnicity, and class. The local IRB, working with the institution, the sponsor, and the investigator is positioned to provide representational participation in the review process and to allow communities to have an impact on decisions regarding their needs and concerns, and their individual and collective welfare as research subjects.
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"The ultimate goal of any institutional commitment to monitoring of research must be the education of its research staff. An effective institutional monitoring program should be coupled with an institution wide program to educate researchers and other staff about the proper and ethical conduct of research. A monitoring program can help an institution develop an educational program that is responsive to its own needs, to fill in the gaps."96 - Charles Weijer, et al.
The authority of the local IRB to review, approve, require modification to, or disapprove research is founded on the institutional mandate described in its MPA, on the acceptance by the scientific community of the tradition of peer review, and on the applicable regulations. The ACHRE noted, the IRB is the enforcing agent of federal protections that is situated closest to the conduct of the research.97 The local IRB, in collaboration with investigators and the institutional official, is responsible for the adequate review of research protocols. In addition, it must ensure appropriate conduct of the informed consent process, that the research design includes adequate monitoring of the safety and data, any additional safeguards necessary to protect the welfare of particularly vulnerable subjects, and the continuing review of research at intervals appropriate to the degree of risk.98 The institution plays a vital role in ensuring adequate oversight or monitoring and review of research activities. Weijer and his colleagues proposed four categories of research monitoring:
- continuing review;
- monitoring of the consent process;
- monitoring for adherence to [the] protocol; and
- monitoring of data integrity.99 Such monitoring coupled with a human research education program ensures the responsible conduct of research.
The research institution has a vested interest in maintaining a culture of compliance. An institution that cannot demonstrate adequate protection of human subjects is at risk of losing its MPA, of incurring the suspension of all federally funded research, and of losing the trust of the community. In order to assure compliance, the institution may wish to make use of various existing committees, including the local IRB, to proactively monitor approved research. Whatever committee or mechanism the institution or the IRB employs should report directly to the IRB to ensure adequate, on-going protection of the subjects.
Biomedical institutions typically have more than one committee engaged in the review and oversight of research with human subjects. An institution may have a radiation safety committee, responsible for the review of proposals that use radiation producing machines and radioactive isotopes; institutional biosafety committees, who oversee the use of biohazardous material and recombinant DNA products, hospital or discipline quality assurance committees; and various scientific peer review committees, such as those required by the NCI for Comprehensive Cancer Centers. The institutional official can assure active collaboration and collegial relations amongst the various committees and with the IRB in order to effectively ensure the protection of the subjects. Collaborative review and monitoring by different institutional oversight entities brings diverse expertise to bear on the goal of protecting subjects.
The IRB responsibility for continuing review of approved research, if it is both thorough and substantive, is the easiest form of monitoring.100 IRBs may approve research for less than one year or require periodic reports regarding the research. An IRB that requests periodic reports from an investigator within an approval period may serve as its own Data and Safety Monitoring Board (DSMB). Some local IRBs go further and actively monitor approved research. The UCLA IRB has created Independent Safety Monitoring Boards to monitor data and the informed consent process for specific projects. At least two institutions were mandated by OPRR to create a DSMB to monitor the rights and welfare of cognitively impaired subjects enrolled in research. The DSMBs report directly to the local IRB, which may request clarifications or modifications of the research as a result of the reports.101 The UCLA IRB has trained consent monitors to serve as subject advocates and to observe the consent process. They ensure adequate communication between the researcher and the subject upon presentation of the consent form. The Department of Health and Human Services/Office of Inspector General (DHHS/OIG) report, Institutional Review Boards: Promising Approaches, outlined several approaches, other than the regulatory requirement for continuing review, to monitor the rights and welfare of subjects. One institution assigns a post-informed consent research intermediary for all subjects in psychiatric research. The research intermediary discusses the consent form with a subject after the form has been signed to ensure that the subject understood its terms and that upon reflection the [subject] continues to want to participate in the research. The research intermediaries report to the IRB every few months about subjects concerns.102 The federal regulations require that the legally effective written informed consent document provide a subject with contact information should a subject have questions about their rights.103 Local oversight includes the responsibility to follow-up on inquiries or complaints from subjects or other concerned parties about the conduct of the research. For local IRBs, the contact person is commonly the IRB administrator or the IRB chair. The IRB administrator or chair can conduct an initial inquiry, provide information to the IRB, request clarifications from the investigators, and respond to the concerns. As a result of an inquiry or complaint, the local IRB may initiate investigations into the conduct of research and engage in educational and corrective actions to ensure an ethical research environment. The availability of a local contact person, such as an IRB administrator, is a demonstration to subjects of institutional accountability and responsibility for the research and sensitivity to the surrounding community.
Some investigators, claiming a right to academic freedom, have challenged the authority of an institution or their IRB to monitor or suspend human research. A federal court, however, determined that the conduct of human subject research is a privilege and not a right, such as the right of intellectual inquiry embodied in academic freedom. The court ruled that human subject research is a privilege granted by the institution to individuals who are willing to work within the federal guidelines and state law.104 An institution that suspends an investigators privilege to conduct human research sends a message to the entire research community that anything less than the highest ethical standards in the conduct of human research will not be tolerated.
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Local Resources and Standards
The local IRB is ideally situated to know the available resources for the conduct of human research. The local IRB is well acquainted with institutional standards, such as hospital policies and procedures, it can adequately assess the scientific design of a proposal in light of those standards, and it can ascertain how the availability of resources or lack thereof, may impact potential subjects. The local IRB is familiar with the qualifications of the members of the research community and is able to assess their ability to perform research procedures. The local IRB is also able to assess the adequacy of proposed protections for the privacy and confidentiality of the subjects.
Many academic institutions and hospitals are close-knit communities where very little happens that is not common knowledge. The communal nature of such institutions allows the local IRB to have an intimate knowledge of institutional resources and standards. Members of the local IRB will know whether the institution has the facilities to conduct the research, such as sufficient beds in the clinical research center, or whether investigators have access to certain procedures, such as PET imaging. Members of a hospital IRB are intimately familiar with the procedures for engaging emergency response teams in case of serious adverse events. Some institutions have buildings spaced across a large campus. Such geographical problems play a role in the local IRB review. For example, at one institution affiliated medical buildings are across the street from the university hospital. If a subject experiences an adverse event in the affiliated medical building, it is well known to the IRB that a city ambulance service is required to move the subject from the research site across the street to the hospital. A delay on the part of the city ambulance may place the subject at undue risk. The local IRB, therefore, commonly requests that investigators conduct certain types of research in the hospital in order to secure the safety of their subjects.
The IRB is required to ensure that the investigator has the qualifications to perform the proposed research. To the local IRB the qualifications of an investigator are more than a paper curriculum vitae. Members of the local IRB have personal knowledge of the investigators capabilities, training, and reputation. The local IRB is also in a good position to make decisions about appropriate personnel, administration of experimental agents, and responsibility for assessing side effects. Because of lack of familiarity with the research setting a nonlocal IRB may allow unqualified staff to monitor symptoms and side effects which could place subjects at increased risk.105 The IRB must ensure the protection of privacy and confidentiality of research subjects. Medical record review is commonly used to identify potential research subjects, but it may also compromise a subjects confidentiality or privacy and violate local law. The local IRB with its intimate knowledge of institutional policy and local law can assess the adequacy of proposed protections for the privacy of subjects and the confidentiality of student or medical records. Additionally, the local IRB is familiar with local standards and policies regarding systems of patient referral for research, and can avoid invasions of privacy. Because of its knowledge of local standards and practice the local IRB can help the institution create systems to facilitate the ethical use of research tools, such as medical records, while ensuring the protection of patient confidentiality. IRB members typically participate in institutional discussions regarding the creation of data systems that can effectively and prospectively de-identify medical records for the purposes of health services and epidemiological research.
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Part III: The Status of Local IRBs
"Regardless of whether one believes that the ultimate justification for government policies is the goal of promoting welfare and minimizing harms or respect for self-determination, one can agree that policies represent commitments to action and hence generate obligations."106 - Advisory Committee on Human Radiation Experiments
Local IRB review is a self-regulating system that depends on the honesty and integrity of the participants, namely, the institution, the researchers, and the IRB. The efficacy of the system is predicated on the ability of the institution, IRB, and investigators to work together in a supportive environment of mutual trust towards a common goal: the safe and ethical conduct of research. The system works when each stakeholder trusts the others to act responsibly in their respective roles. The design of the local IRB system holds the research institution responsible for the conduct of human research and the creation of a culture of trust and responsibility in order to achieve the goals of science. The public and the federal government rely on institutional responsibility and accountability, and its support of the local IRB review, to ensure the protection of human subjects. The system is designed to ensure a fair review by a disinterested committee that includes the participation of the scientific and local lay community. Its single purpose is to protect the rights and welfare of the research subjects by creating a healthy and ethical research environment. The system also ensures that all parties receive adequate education to perform their ethical duties, that mechanisms are in place to assess available resources to conduct the research, to assess the qualifications of investigators, and to embrace community involvement. Yet, recent events and reports highlight questions about the efficacy of the system. Problems in the implementation of the recommendations of the National Commission, the federal guidelines, as well as the letter and spirit of the federal regulations have hampered local IRBs and prevented them from achieving their full potential.
The ability of the local IRB to assure human subject protection is predicated on four factors: 1) institutional support, 2) appropriate composition of the Board, 3) education, and 4) engagement of investigators. The IRB alone cannot create a culture that recognizes the importance of human subject protection. The responsibility for creating a culture of respect for the regulations and the research review process rests in the collaborative efforts of the institutional officials, the community of investigators, and the IRB. Recent OPRR review of several academic institutions during 199899 noted systemic institutional deficiencies in human research protection programs that resulted in suspension or restriction of institutional assurances. Furthermore, three recent unrelated reports by independent groups highlighted that an IRB working without both moral and economic support from the institution cannot ensure the protection of research subjects. The General Accounting Office (GAO) reported in 1996, that IRBs are overworked and vulnerable to pressure. The problems include pressure to mute concerns about multicenter trials, pressure to recruit subjects that can lead IRBs to overlook informed consent deficiencies, and the pressure of volume: the sheer number of studies necessitates that IRBs spend only 1 to 2 minutes of review per study.107 The DHHS/OIG made similar findings in June 1998, reporting that expanded workloads, resource constraints, and extensive federal mandates contribute to a rushed atmosphere where sufficient deliberation often is not possible.108 In December 1998, the Journal of the American Medical Association published a report by the Human Research Ethics Group which noted, Many IRBs are overburdened by the quantity and the complexity of proposals they review and by the oversight demands of federal agencies.If current trends continue, there is a distinct danger that IRBs will be considered as little more than protection against legal liability. Ultimately, the authors warned that research institutions and especially sponsors of research must accept the expenses of human subjects review as part of the cost of doing business. The burden on IRBs could be reduced if sufficient staff could be recruited. A system of recognition and rewards for IRB service should be implemented by local institutions. Work on the IRB should be recognized as the invaluable professional activity it is.109 The Human Research Ethics Group reflected the concerns of the National Commission and the DHHS/OIG, noting that IRB service may be a thankless job with a tremendous workload and no recognition or compensation.
All three reports came to the same conclusion: there is insufficient institutional support for local IRBs and their function. The reports implicitly state that systemic institutional problems exist throughout the country and that these problems threaten the IRB system and, by extension, threaten the ethical conduct of research. An objective observer could view the systemic problems as a lack of institutional commitment to the importance of IRB review and oversight of research. This lack of commitment can be interpreted as a sign of institutional disrespect for the IRB process, the investigators, and the rights and welfare of subjects; disrespect that ultimately places the system of protection and the ability to conduct human research at undue risk.
IRB Membership, Participatory Democracy, and the Balance of Influence
"We commit to increase our community involvement so that we may begin restoring lost trust. The study at Tuskegee served to sow distrust of our medical institutions, especially where research is involved. Since the study was halted, abuses have been checked by making informed consent and local review mandatory in federally funded and mandated research."110 - William Jefferson Clinton
The IRB system was developed from the peer review model. The National Commission warned that it is important when constituting an IRB to guard against self-interest influencing or appearing to influence IRB determinations. To this end, according to the National Commission, no more than two-thirds of the IRB members should be scientists, including members of the disciplines in which research is customarily reviewed by the IRB.111 The National Commissions recommendations were widely ignored and not incorporated into the federal regulations, the OPRR IRB Guidebook, or the FDA Information Sheets112 for IRBs. The result of this rejection is that many IRBs still reflect the peer review model with only a nod to community membership that could balance the influence of scientific expertise.113 The federal regulations define a legally constituted IRB as a minimum of five members, with at least one nonscientist and at least one nonaffiliated member. Interestingly, the regulations require the attendance of a nonscientist in order to vote on human research proposals, but not the attendance of the nonaffiliated member. That regulatory loophole effectively allows for exclusion of a nonscientist community representative from IRB decisions.114 In order to satisfy the regulatory requirement for a legally convened IRB meeting, some institutions rely on an IRB administrator, institutional lawyer, or contract and grants officer to serve the role of nonscientist. The OPRR submits that the nonaffiliated member should come from the local community-at-large.The person selected should be knowledgeable about the local community and be willing to discuss issues and research from that perspective.115 The OPRR language implies that the nonaffiliated member should be a nonscientific community representative. Many institutions comply with the OPRR recommendation and the regulations through a common practice of simultaneously fulfilling the requirements for the nonscientist and nonaffiliated member by engaging one or more individuals from the community, known as the community or lay member.
The lasting influence of the peer review paradigm continues today to affect the membership of IRBs, where little recognition is given to the importance of community participation. The NIH-sponsored James Bell and Associates 1998 IRB survey clearly indicates that IRBs still reflect the peer review model without adequate voting representation from the local nonscientific community. A 1995 national IRB survey indicated IRB membership was 66 percent male and 90 percent white, nonHispanic.116 The Bell survey also showed little change in the composition of IRB membership with 92 percent white and 58 percent male. Institutionally affiliated members comprised 83 percent of IRB membership.117 IRBs based in large academic institutions in some cases have three to four times the minimum required membership, leaving one nonscientist community member to fend for him/herself.118 The statistics reveal that institutions have largely ignored the IRB membership expectations of the National Commission, i.e., community representation of subject populations, and the spirit of the regulations.
The disparity of nonaffiliated lay members to affiliated employees and scientists presents many community members with an imbalance of influence or power during IRB meetings. Mildred K. Cho and Paul Billings outlined issues of power within the IRB structure and indicated that many of the shortcomings in the function of IRBs have been attributed to the imbalance of power among its medical/scientific and lay members. The composition of IRBs heavily favors biomedical scientists over social scientists and research oriented professionals over lay people. Such a composition often results in a deference to medical expertise and social-behavioral scientific knowledge, which may lead the IRB process away from ethical or social questions and create an inherent bias in favor of scientific activities for their own sake.119 An IRB composed of a large majority of scientists, academic scholars, and ethicists may, therefore, apply federal and professional guidelines, abstract moral principles, and values situated within the cultures of academia, institutionalized medicine, or science.120 It is important to question whether such an imbalance of influence maximizes the local IRBs potential to serve as an advocate for the community and to demonstrate a commitment to justice and respect for the public as well as for scientists.121 The IRB membership regulations imply at least a 4:1 ratio of affiliated scientists to non-affiliated community members. The authority of scientific expertise may be difficult to overcome even with a more broad interpretation of the regulation, e.g., a 3:2 ratio of scientific to nonscientific/nonaffiliated members. As a parallel to democratically constituted IRBs, McNeill notes that management representatives are not allowed to exceed the number of employee representatives on occupational health and safety committees.122 George Annas recently proposed a more complete democratization of the IRB process by requiring a majority of community members and by opening all meetings to the public.123 The concern of Annas and Cho and Billings resonates with the experience of many lay community members who can feel quite overwhelmed or intimidated discussing research from a lay perspective with an IRB that includes a majority of scientific experts.124 Some commentators question whether the inclusion of nonaffiliated members on an IRB is prompted by a genuine desire [on the part of the institution] to incorporate a community perspective, or only serves to address the letter of the regulations. The comment is not intended to dismiss the contribution of such members on IRBs but rather to highlight that a nonaffiliated member does not necessarily represent the interests of specific or general research subject populations.125 The Bell survey also noted that respondents suggested a top priority should be strengthening the IRB membership through additional ethnically and racially diverse community representatives, thus suggesting a need for fundamental community consultation by the Boards.126 The survey revealed an imbalance of power favoring scientific expertise over community participation. This is consistent with the OPRR Common Findings and Guidance, that IRB membership lacks both sufficient knowledge of the local research context and sufficient diversity of its membership with respect to gender, race, and cultural backgrounds to sensitively and effectively address community attitudes.127 The DHHS/OIG saw the need for more extensive representation of community members on IRBs as a vital matter, noting that individuals not associated with the institution or with the research enterprise can provide a valuable counterbalance to pressures that threaten IRB independence.128 The concept of participatory democracy suggests human research review should include representatives of subject populations in sufficient numbers to balance the spheres of influence on an IRB. Subjects might thereby protect and advance their own interests.129 There is precedent for the inclusion of subject advocates on IRBs. For example, the federal regulations require an IRB to include a prisoner representative among its members when it reviews research with prisoners.130 At least two large biomedical institutions were required by OPRR to include subject representatives on their IRBs when reviewing research that includes cognitively impaired subjects.131 Many institutions created AIDS/HIV community advisory groups that participate in discussions of the scientific design of proposed research. Some federal human research peer review panels, such as those at the Department of Defense and the NIH, successfully include patient advocates.132 This is a form of participatory democracy. That is, the subject population is given an opportunity to voice its interests in any discussion of research that will impact it. Rebecca Dresser notes, Representation of affected groups can reduce improper bias in planning and conducting research [with] human subjects.133 Institutions could approach community advisory groups when seeking appropriate community representatives for the IRB. They should be careful not to assume, however, that scholars or community leaders selected to represent a particular group can speak for the local subject populations. Fisher provides the example of the NIH Violence Initiative where a panel of African-American leaders was appointed to review a scientific protocol on the effects of pharmacologic interventions on urban violence. The appointed group, however, did not include community representatives who would have been affected by the research, i.e., African-American men and women living in impoverished ghetto communities, whose sons, based on current statistics, have a devastatingly high probability of entering the juvenile justice system before they reach adulthood. She wonders how advocates from the community of subjects may have addressed such issues as group stigmatization and how their concerns might have better ensured the protection of vulnerable subjects as well as community support for the research.134 Dula warns that the exclusion of community representatives from decision making results in paternalistic decisions made for the good of the powerless. At worst, it victimizes the powerless.135 The federal regulations and guidelines clearly require an IRB to be sensitive to community attitudes and to promote respect for its advice and counsel through membership with diverse racial, gender, and cultural background. The regulations, however, give the institution broad flexibility in their choice of IRB members and they give no interpretation of who, scientists or lay people, may best fulfill the requirements. Such flexibility and lack of definitions may have resulted in diminishing community participation and may have ultimately created an imbalance of power on IRBs. The lack of diversity among IRB members may diminish the ability of the Board to achieve its educational charge. Disparity of power and inadequate community membership limits the IRBs ability to engage in a free exchange of ideas where different points of view and expertise are honored and respected.
Henry Beecher, President Clinton, ACHRE, and the DHHS/OIG emphasize that an education program is important for assuring the protection of the rights and welfare of human subjects. An institution can only assure the protection of human subjects through an effective education program for IRBs, investigators, and staff that includes sufficient training regarding their ethical responsibilities. Nevertheless, the DHHS/OIG notes that training of IRB members and investigators is minimal and they face significant obstacles which include not only sufficient resources, but the reluctance of many investigators, especially experienced ones, to participate. The report also identifies the specific need to train community members in order to increase their participation and effectiveness in IRB deliberations.136 A common compliance concern noted by OPRR is insufficient education of the IRB, staff, and investigators.137 As discussed above, the local IRB is uniquely situated to contribute to the education of all stakeholders regarding the ethical conduct of research. A well-educated faculty, administration, staff, and IRB is key to a successful human subject research program. A 1995 survey of IRBs indicates that one quarter of Category 1 universities (those graduating at least 30 doctorally prepared individuals in three unrelated disciplines each year) offered no training to their IRB members. Of those institutions that offered training, 84 percent offered four hours or less, while 26 percent of the institutions provided less than one hour of training for their members. Training covered the scope of Board functions, IRB responsibilities, the process of group decision making, or other issues.138 The survey did not specify who was responsible for the training. Interestingly, the Bell and Associates survey did not assess whether respondents felt that the institutional administration or individual officials required more education about human subject protections. Most studies have focused only on the education of IRBs and have ignored the responsibility to educate the institutional administration and investigators.
Who is responsible for training the local IRB, investigators, and institutional officials, and for offering ongoing guidance on the nature of their charges? Neither the regulations nor the OPRR guidelines give specific direction on how to educate the institutional parties regarding their mandate or the appropriate execution of their charge. The ACHRE report leans towards making the education of all members of the scientific community a shared responsibility between federal agencies and institutions.139 An institutional commitment to education is the responsible approach for ensuring a safe research environment where all parties acknowledge their responsibilities and are aware of their shared and individual obligations.
IRB members are commonly chosen for their research expertise and not because they are knowledgeable about the federal regulations, the ethics of human research, or IRBs. Some institutions have proactively addressed the educational needs of their community by creating staff positions for human research education as well as programs that apply a spectrum of educational approaches, such as orientation and training for all IRB members, and web based training, didactic sessions, manuals, and guidebooks for investigators and research staff. Some IRBs allow time during meetings for educational sessions on current topics of concern or distribute relevant articles to the membership. Some institutions budget annual funds to allow IRB staff, IRB members, both affiliated and nonaffiliated, and investigators to attend national and regional meetings sponsored by OPRR, FDA, and national organizations such as Public Responsibility in Medicine and Research (PRIM&R) and Applied Research Ethics National Association (ARENA). IRB members and staff who attend such meetings then return to their institution and serve as educators of their own community. An institutional commitment to education helps create an open forum where all parties can share their collective expertise and can educate each other, thereby reinforcing the importance of protecting human dignity.
Staff and Resources
The most common compliance citations issued to research institutions by OPRR include: 1) overburdened IRBs; 2) inadequate resources, including lack of space and privacy for administrative staff sufficient to conduct sensitive IRB duties; and 3) lack of professional educated IRB support staff.140 The OPRR findings mirror the DHHS/OIG report calling for increased human resources, computerization, and other elements essential to an efficient and effective IRB.141 Federal regulations require that the institution provide sufficient infrastructure, space, and staff to carry out the charge of the IRB.142 The Bell report notes, Additional staff, both professional and clerical, was the resource most commonly mentioned.143 OPRR cited at least five institutions in the last two years for systemic deficiencies in their human research programs, including inadequate staff and resources to successfully implement a protection and review program.144 In order for the IRB to successfully fulfill its charge, it must have a sufficient staff of educated professionals. The DHHS/OIG reports that increasing IRB workloads have not resulted in increasing staffing levels and budgets in support of the Board. A lack of institutional support can negatively impact an IRBs ability to adequately perform its charge: With limited personnel and few resources, IRBs are hard pressed to give each review sufficient attention.145 One institutions post-OPRR site visit evaluation of its human subject protection programs resulted in a 300 percent increase in staffing and budget in order to address deficiencies effectively. The institution acknowledged that too few people understood the regulations, that the administrator responsible for the effective management of the IRB operations was overburdened, that there was too much administrative presence on the IRB, and that insufficient participation in national/regional IRB workshops resulted in problems.146 Without sufficient infrastructure and professional level staff, an IRB for a large academic institution or hospital is isolated, paralyzed, and cannot carry out basic functions, such as creating appropriate letters of condition to investigators, tracking and reviewing adverse event reports, addressing complaints from subjects, conducting appropriate annual review, and receiving guidance regarding changing interpretation of regulations.
The institution should also consider the burdens of IRB membership on affiliated members. The National Commission recognized that IRB membership requires a significant commitment of time and energy. The Commission called on institutions and the government, with little response, to allow direct costing of an IRB, to provide at least a portion of the salary of the IRB chair[person] or of the cost of administrative support for the IRB. Recognition of IRBs by providing earmarked funds for their operation would complement compliance and education activities of the DHEW in promoting quality performance by IRBs.147 There is a need to compensate IRB members for their commitment and work. IRB meetings may last three to seven hours per meeting, one to four times per month. The time spent in meetings does not include additional effort devoted to reading protocols, analyzing adverse event reports, conducting expedited reviews, creating letters of condition for investigators, among other responsibilities.148 Affiliated members are also responsible for their own clinical activities, research, teaching, and generating departmental income.149 In order to maintain adequate scientific representation on the local IRB, it is imperative that an institution implement a just system for the recruitment of members to ensure the equal distribution of the burden of service. Additionally, membership on an IRB should be honored and respected in a way that maximizes benefits for the member and demonstrates an institutional commitment to the best possible human protection program.
Institutional Influence and the IRB
The institution must create mechanisms that assure that mandates other than maintaining the protection of the rights and welfare of human subjects do not interfere with the enduring independence of the local IRB. The DHHS/OIG reports that research is an important revenue source for most academic health centers. For decades, under the fee-for-service system research expenditures were subsidized by patient-care revenues; under managed care, however, traditional financial support for research activities has been diminishing. In the process, commercial sponsorship has become increasingly important.150 Annas notes that medicine ...is currently faced with a new dominate ideology the ideology of the marketplace, which puts profit-making (sometimes denoted by its method, cost-containment) as its highest priority....Both scientific truth and the best interests of patient-subjects can often find themselves sacrificed in the name of the bottom line....To do science you need money, but to raise money competitively you need to project illusions that are the antithesis of science.151 Cho and Billings explain that interference by IRBs with large or well-funded projects may be perceived by others in the institution as adverse to the institution and therefore inappropriate....IRBs have a large and direct impact on an institutions ability to obtain funding for its research activities.152 The above comments clearly suggest that the institutionally based IRB plays an integral role in the search for research funding. The regulations require IRB review and approval before an institution can initiate a clinical trial or accept federal funding for human subject research. As a result, IRB decisions potentially affect millions of dollars in research funds at an institution. The institutions commitment to scientific inquiry and to the quest for extramural funding for research may create a conflict between the institutions obligation to promote the ethical conduct of research and its need to attract research funds. That conflict may ultimately impact the charge of the IRB. It may pose serious questions regarding the protection of research subjects, and it may prove a fundamental challenge to the autonomy of the IRB process.153 The local IRB may struggle under overt and covert institutional pressure to approve research. The OPRR warns that the IRB must be and must be perceived to be fair and impartial, immune from pressure either by the institutions administration, the investigators whose protocols are brought before it, or other professional and nonprofessional sources.154 The selection of the institutional official is crucial to the success of a local IRB program and to its ability to address internal and external pressures, as well as assuring the protection of the rights and welfare of the research subjects. The regulations, however, do not specify the necessary qualifications of the institutional official, the person responsible for ensuring the independence of the IRB, its support, and its standing within the institution. Clearly, the institutional official should have enough authority within the institution to ensure the proper support and respect for the IRB. The OPRR guidelines describe the institutional official as a person who has the legal authority to act and speak for the institution, and should be someone who can ensure that the institution will effectively fulfill it research oversight function. The official, however, may delegate the authority to the director of research and development, a dean or assistant dean, or hospital administrator.155 Bell and Associates noted that 35 percent of IRBs reported directly to a provost or vice president for research, with only 7 percent reporting to the highest level official such as a president or the next highest level such as an executive vice chancellor.156 Yet, reasoned consideration of the concerns expressed by federal agencies, professional groups, Annas, Cho, and Billings requires one to question whether an individual who is directly involved and responsible for research funding, such as a director of research and development, is immunized against financial pressures; and whether an assistant dean or a hospital administrator has sufficient authority to avoid institutional conflicts and to ensure that an IRB is given the necessary respect and authority. An institution that successfully addresses such conflicts and supports the independence and authority of the IRB can avoid the common systemic problems found by OPRR in 1999. For example, OPRR expressed concern that the placement of the IRB at a relatively low [institutional] level contributes to the diminished status and support of the system for the protection of human subjects. The Office strongly recommended elevation of the IRB to a higher level within the institutional hierarchy in order to demonstrate a greater institutional commitment to human subject protections.157 The Bell report indicates that IRBs continue to try to do their jobs without institutional support, staffing, resources, and education. In spite of the perceived conflicts and pressures on local IRBs, the NIH-funded Bell Report indicates that local IRBs are not approving research without due consideration of scientific and human protection issues. Bell and Associates found that in 73 percent of IRBs, one-quarter or fewer protocols were approved as submitted. In fact, 34 percent of IRBs did not approve any (zero) protocols as submitted in 1995. They noted four categories of protocol deficiencies: 1) consent form, 2) consent process, 3) risk/benefit, and 4) scientific design. IRBs could not approve protocols as submitted due to informed consent document deficiencies such as technical language, understatement or omission of the risks and benefits, and omission of cost information and alternatives. Additionally, IRBs reported problems with the proposed consent process where comprehension was not promoted and did not ensure voluntariness, with scientific and ethical justification for the placebo control design, and with the adequacy of provisions for the protection of privacy and maintenance of confidentiality.158 The Bell report findings are consistent with OPRR site visit letters indicating that, by and large, local IRB chairpersons, members, and staff are sincerely committed to their charge: the protection of the rights and welfare of human research subjects. The Bell statistics also indicate the inadequacy of research proposals submitted to the local IRB and, probably more profoundly, a lack of communication and education within the institutions about the requirements for the protection of the subjects. These findings, as well as reports from the DHHS/OIG and the GAO, lead to the conclusion that there is too little institutional support for the protection of the rights and welfare of human subjects.
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Part IV: Conclusion
"When so much can be accomplished medically for those who are ill, it would be tragic if the patient could not be completely confident that his [sic] welfare was the physicians only concern."159 - Herman L. Blumgart
The principles that inform and guide local IRB review engage the trust and require the responsible behavior of all parties involved in human subject research. Guidelines, ethical principles, and federal regulations create a system of human subject protection that, when responsibly implemented, addresses the concerns of all stakeholders: the government, sponsors, research institution, the investigator, the IRB, the community, and the human subjects.
The application of democratic principles to the composition of local IRBs and the review of human research acknowledges, as noted by Lawrence Gostin, that genuine respect for human dignity requires deeper understanding of the patients values, culture, family, and community.160 The system of local IRB review represents a fundamental societal and regulatory shift from reliance on scientific expertise and self-interest as represented by peer review, to acknowledgment of the expertise in ethical matters that is held within the community of research subjects. The local IRB provides the community of potential human subjects with a venue where it can actively contribute to the research review process.
The efficacy of the system of local IRB review is predicated on improved federal guidance on the role of the institution and the institutional official, and on the inclusion of community. Institutional responsibility requires more than compliance with the letter of the regulations; it also requires a willingness to apply the ethical principles that are the spirit of the regulations: to educate the research community and to create an institutional ethos that governs the actions of all stakeholders in the protection of human subjects. The research institution with support from the federal government has the authority and the responsibility to create a culture that is sensitive to the ethical imperative of protecting the rights and welfare of human research subjects. As noted by the National Commission, the local IRB, with support from its institution, is perfectly situated to ensure collegial interactions, the effective review and oversight of research, the participation of the scientific community and the community of potential research subjects in the education of all stakeholders. A system that encourages education, participation, and dialogue and calls on all parties to uphold the highest ethical standards will earn trust and support for its enterprise.
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I owe many thanks to Marina Moevs for her support, time, and commitment to this project as well as to Judith L. Brookshire, John Dreyfuss, and Christian Moevs for their insight, comments, and assistance.
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