Bioethics Forum Essay

National Research Act at 50: An Ethics Landmark in Need of an Update

On July 12, 1974, President Richard M. Nixon signed into law the National Research Act, one of his last major official actions before resigning on August 8. He was preoccupied by Watergate at the time, and there has been speculation about whether he would have done this under less stressful circumstances. But enactment of the NRA was a foregone conclusion. After a series of legislative compromises, the Joint Senate-House Conference Report was approved by bipartisan, veto-proof margins in the Senate (72-14) and House (311-10).

The NRA was a direct response to the infamous Untreated Syphilis Study at Tuskegee whose existence and egregious practices disclosed by whistleblower Peter Buxtun [whose death was reported on July 15, 2024] were originally reported by Associated Press journalist Jean Heller in the Washington Star on July 25, 1972.  After congressional hearings exposing multiple research abuses, including the Tuskegee syphilis study, and legislative proposals in 1973, support coalesced around legislation with three main elements: (1) directing preparation of guidance documents on broad research ethics principles and various controversial issues by multidisciplinary experts appointed to a new federal commission, (2) adopting a model of institutional review boards, and (3) establishing federal research regulations applicable to researchers receiving federal funding.

This essay reflects on the NRA at 50. It traces the system of research ethics guidance, review, and regulation the NRA established; assesses how well that model has functioned; and describes some key challenges for the present and future. We discuss some important substantive and procedural gaps in the NRA regulatory structure that must be addressed to respond to the ethical issues raised by modern research.  

Ethical Guidance

The NRA established the National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The commission was originally proposed as a permanent entity to provide ongoing ethical guidance, but, in a compromise, it was authorized for less than three years. Among other things, the 11-member commission was directed to “identify the basic ethical principles which should underlie the conduct of biomedical and behavioral research involving human subjects [and to] develop guidelines…to assure that it is conducted in accordance with such principles.”

The commission was specifically tasked with considering several contentious issues, some of which remain significant concerns. These include fetal research; psychosurgery; the boundaries between medical research and medical practice; the criteria for assessing risks and benefits for research participants; and informed consent for research involving children, prisoners, and individuals in psychiatric institutions.

The commission’s preeminent members and exemplary staff were extremely productive, and their work products were–and remain–highly influential. For example, commission reports on research with children and prisoners figured prominently in federal regulations. Its best-known work product, the Belmont Report, identified the basic ethical principles and guidelines for research with human subjects as directed by the NRA.

Working in subcommittees and consulting with bioethicists Tom L. Beauchamp and James F. Childress, the commission sought to identify the principles that would reflect the shared values of a diverse population. The commission initially identified seven principles, which later were reduced to the well-known three: respect for persons (honoring participant autonomy, privacy, informed consent), beneficence (requiring minimization of risks and maximization of benefits), and justice (entailing equal distribution of research burdens and benefits and protecting vulnerable populations).

The approach of the Belmont Report became known as “common morality principlism,” a term that has been used dismissively in several criticisms. These criticisms include that it focuses too much on individuals and not enough on communities, in short, that it is too U.S.-centric. In addition, the approach does not rank-order the principles or indicate how they should be applied, particularly when they conflict.

Despite these criticisms, the principles have endured for 50 years. The universal appeal of this approach is illustrated by its prominent place in U.S. regulations governing human subjects research and in international research ethics, and the continued reliance on the principles as valuable guideposts for research ethics analysis by researchers, bioethics scholars, and the public. Beauchamp and Childress have further explored the application of the principles through eight editions of their landmark book, Principles of Biomedical Ethics. In April 1978, as the commission was winding down its work, Willard Gaylin, co-founder and president of a nascent bioethics think tank later known as The Hastings Center, was quoted in the New York Times: “They [the commission members] deserve the compliments and gratitude of all of us in the field.”

In subsequent years, the public bioethics commission model of addressing difficult bioethics issues has been used repeatedly in the U.S. Six federal bioethics commissions or similar entities have been created to address such issues as research using stem cells, somatic cell nuclear transfer, radiation experiments, and human enhancement. However, such commissions have been ad hoc, and, since 2017, there has not been any comparable body to address the numerous problematic bioethics issues of today or the future.

Institutional Review Boards

The NRA required entities applying for grants or contracts involving biomedical or behavioral research with human subjects to demonstrate they had an institutional review board to review the research and “protect the rights of the human subjects of such research.”

Many research institutions already had local IRBs by1974, and researchers preferred local review instead of federally directed research review, a model used by many other countries. Perceived advantages of local IRBs included their knowledge of potential participant communities, researchers, institutional research, social mores, and applicable laws. The NRA formalized and expanded IRB reviews by mandating them for all federally conducted or funded research. According to a study by the Government Accountability Office, as of 2023 there were approximately 2,300 IRBs, most of them affiliated with universities or health care institutions. But there are also many independent, primarily for-profit, IRBs, which have had the largest increase in protocol reviews, a process likely accelerated by the move to single IRB review, described below.  

Traditional IRBs based at universities and health care institutions have inherent conflicts of interest because, in addition to having an interest in assuring the well-being of research participants, the institutionalso has a financial and professional interest in expeditious approval of the protocols supported by external funding. IRB members and administrators may feel pressured to approve submissions. For-profit IRBs also have conflicts of interest because repeat business depends on their being easier, faster, and presumably more favorable alternatives to university or health care IRBs.

Among the most important recent changes to IRB review, effective in 2020, NIH-funded multisite and cooperative research must use single-site (or central) IRB review. This process is designed to eliminate duplicative and sometimes inconsistent IRB reviews and to expedite the review process. It is available for all IRBs, including commercial IRBs, that are registered with the Office for Human Research Protections. It remains to be seen whether this new procedure will achieve the goals of consistency and expediency.       

Despite 50 years of experience, assessing and improving the quality of IRB reviews remains challenging. IRBs must have a minimum of five members, and large institutions typically have multiple, much larger committees. Thus, based on the GAO estimate mentioned previously, U.S. IRBs have a minimum of 11,500 members, plus professional staff. Reviews are rarely shared with IRBs outside the institution. Public Responsibility in Medicine and Research (PRIM&R), a nonprofit organization that provides educational services to researchers and research administrators, was founded in 1974. Since 1999, it has offered a certification process for IRB officials. However, IRB service is burdensome and often uncompensated, and many IRB members do not take advantage of PRIM&R education.

The Association for Accreditation of Human Research Protection Programs, an independent, nonprofit, voluntary organization founded in 2013, uses a peer-review process to accredit IRBs. It reports that approximately 60% of U.S. research-intensive universities and medical schools have been accredited or have begun the accreditation process. Although AAHRPP accreditation requires institutions to assess the quality of their reviews, there are no clear criteria for doing so. Finally, OHRP and the Food and Drug Administration conduct on-site inspections, which may be routine or for cause (e.g., in response to a complaint). According to the GAO, only a small fraction of IRBs are inspected annually. It is also not clear how effective inspections are in preventing or remediating substandard practices.

Federal Research Regulations–the “Common Rule”

The NRA directed the secretary of the Department of Health, Education, and Welfare (now the Department of Health and Human Services) to promulgate regulations necessary to carrying out IRB review. On June 18, 1991, final regulations were published in the Federal Register.  The regulations specify the composition and operations of IRBs and, incorporating the Belmont principles, the criteria for their review. The policy became known as the Common Rule because it was adopted by 15 federal departments and agencies.

Since the NRA was enacted, IRB review and compliance with the Common Rule have been mandatory only for federally funded research. This framework has proven inadequate. Although many universities and health care institutions voluntarily apply the Common Rule to research that is not federally funded, not all do. A few states, notably Maryland and Virginia, have laws that apply the Common Rule standard to all research, but there is little enforcement. Differences in other state laws may result in substantive protections for some research participants, but not others. This patchwork of voluntary compliance and state laws is not up to the task of protecting the welfare of research participants, especially now when online data is exploding, research increasingly is multisite and multistate, and research is no longer confined to universities and health care institutions.

The Common Rule has several other substantive limitations. One of them is the exclusion of deidentified information and biospecimens from protection. Increasingly sophisticated computer technology can reidentify individuals from records and specimens. Both “identifiable private information” and “identifiable biospecimens” use the standard of “readily ascertainable.” This means that if the identity of information or biospecimens is not readily apparent, then they are deemed unidentifiable and the research falls outside the scope of the regulations, even if the identity can be discovered by more complex techniques. By contrast, the Health Insurance Portability and Accountability Act privacy rule uses a much more stringent standard for deidentification and lists 18 identifiers that must be removed.

Another important limitation of the Common Rule is that it prohibits IRBs from considering “possible long-range effects of applying knowledge gained in the research (e.g., the possible effects of the research on public policy)” in assessing research risks. Thus, IRBs can only consider the direct effects of the research on participants and must ignore the larger societal implications, including the impact on groups.  A new international study of 22 countries found that the U.S. is the only country to prohibit their research ethics review bodies from considering societal implications of research.

Conclusion

On the 50th anniversary of the NRA, it is evident that the act needs to be updated.

First, there should be a standing national public bioethics body to study and report on emerging issues such as gene therapy, artificial intelligence, xenotransplants, and brain-computer interfaces would provide necessary guidance in a continuously and rapidly changing scientific environment.

Second, additional efforts are required to assess and improve IRB quality. Single IRB review may mitigate some of the unresolved conflicts of interest inherent in locating research ethics review bodies at the institutions submitting research protocols. But problems remain, since the IRB likely either will be located at the institution receiving the grant (and therefore will have an incentive to approve research proposals) or it will be a for-profit IRB (and therefore will have an incentive to expedite favorable reviews to get repeat business). In addition, there is negligible oversight of IRB decisions and operations, with accreditation and training largely by voluntary, private organizations.

Third, the Common Rule should be expanded and strengthened. There was a missed opportunity to do this in the 2018 revisions.  Although HHS initially proposed expanding the Common Rule’s to all research, the Final Rule retained coverage only for federally funded or conducted research. Arguably, such an expansion would exceed the authority afforded by the NRA. But HHS did not submit a recommendation to Congress to authorize this expansion, nor did it notify Congress that there was a problem with it that should be addressed. Similarly, despite initial proposals, the revised Common Rule failed to add any protections for minimally deidentified information or specimens, retaining a standard that is significantly less protective than the HIPAA privacy rule.

Fifty years ago, the first steps were taken to impose deliberative processes and order on American biomedical research. These actions, however, were not complete, and time and changed circumstances have increased the gap between the NRA’s regulatory system and what is needed for well-considered and coordinated research regulation. It’s time for the research ethics community, researchers, and policymakers to take the next steps to update the actions begun on July 12, 1974.     

Mark A. Rothstein, JD, is Director of Translational Bioethics, Institute for Clinical and Translational Science at the University of California, Irvine. He is a Hastings Center fellow.

Leslie E. Wolf, JD, MPH, is the Ben F. Johnson Jr. Chair in Law and Distinguished University Professor at Georgia State University. @LeslieWolfGSU, LinkedIn (25) Leslie Wolf | LinkedIn