Congress Should Create Commission to Examine the Protection of Human Participants in Research; Notice of Proposed Rulemaking to Revise Common Rule Should Be Withdrawn
A new report from the National Academies of Sciences, Engineering, and Medicine that examines the regulations governing federally funded research recommends that Congress authorize and the president appoint an independent national commission to examine and update the ethical, legal, and institutional frameworks governing research involving human subjects. The commission should make recommendations for how the ethical principles governing human subjects research should be applied to unresolved questions and new research contexts.
The executive branch should withdraw the Notice of Proposed Rulemaking for the “Common Rule” (formally known as the Federal Policy for Protection of Human Subjects), the report says. The regulatory structure protecting human research subjects should not be revised until the national commission has issued its recommendations and the research community, patient groups, and the public have had a chance to consider and react to them.
The report is the second part of a two-part study. Part 1, released in September 2015 and included in the new volume, concluded that continuing expansion of federal regulations on research is diminishing the effectiveness of the U.S. research enterprise and recommended actions to reduce the regulatory burden. It also recommended the creation of a public-private Research Policy Board to streamline research policies going forward.
Part 2 concludes the study’s analysis of regulations governing federally funded research. In addition to reviewing regulations on human subjects research, it also makes recommendations regarding research with select agents and toxins, export controls, and intellectual property, and discusses how the new regulatory framework proposed in the first report might be put into operation.
“Congress and the administration have an opportunity for a course correction that can yield significantly greater value to the public from the nation’s investment in research, and we hope our recommendations will guide that effort,” said Larry Faulkner, chair of the committee that wrote the report and president emeritus at the University of Texas, Austin.
Comprehensive Review Needed for Regulations Governing Human Subjects Research
Ethical principles for conducting research involving humans were laid out by a national commission in 1978 in what is known as the Belmont Report. The Belmont Report identified three principles that should guide such research: respect for persons, which requires informed consent from research subjects; beneficence, which involves maximizing benefits for research participants and society and minimizing harm to research participants; and justice, which means the fair distribution of the benefits and burdens of research.
The Belmont principles remain central to protecting human research subjects, the new report says. However, in the nearly four decades since the Belmont Report was issued, the biomedical and socio-behavioral research enterprises have grown enormously and witnessed profound changes in knowledge and technologies. Today, many developments — new research contexts and capabilities; the profusion, sharing, and accessibility of personal data; and increasing privacy concerns — raise important questions about how the principles should be applied.
In September 2015, the U.S. Department of Health and Human Services issued a Notice of Proposed Rulemaking (NPRM) as part of an effort to update the federal policy governing the protection of human subjects. The committee found that the NPRM is marred by omissions and a lack of clarity, and that it does not adequately or effectively address the breadth, depth, and import of unanswered questions and contemporary challenges related to human subjects research. Important questions about the overall impact and long-term costs of its proposed regulatory changes are also unresolved.
An example of the committee’s concern with the NPRM is its proposed expansion of the definition of human subject to include de-identified excess biospecimens. Biospecimens are materials taken from the human body and can include tissue, blood, saliva, and urine, among others. Currently, the Common Rule allows for research to be performed using previously collected biospecimens without informed consent as long as the specimens are de-identified.
The NPRM’s expanded definition of human subject means that for such biospecimens to be used in research, individuals undergoing tissue excision would need to provide written “broad” consent for future unspecified uses of their de-identified biospecimens — a significant departure from current practice. Research on excess or residual biospecimens has contributed enormously to the growth of medical knowledge for nearly a century and a half, improving human health with little evidence of harm to individuals whose biospecimens were used in this way, the report says. Moreover, implementation of the proposed rule would necessitate maintaining a link between the consent document and the biospecimens – a proposal that raises substantial risks of re-identification and loss of privacy.
Emerging scientific technologies and advances in the research enterprise since the Belmont report, together with the NPRM’s inadequacies, signal a pressing need for a comprehensive review of the nation’s ethical, legal, regulatory, and institutional frameworks for protecting human research subjects, the report says. It recommends that Congress authorize and the president appoint an independent, national commission to make recommendations regarding how the basic ethical principles governing human subjects research should be applied to unresolved questions and novel contexts, for example:
- research involving anonymous and de-identified human biospecimens
- research involving large data sets
- clinical trials where the unit of intervention is a cluster or group
- clinical studies comparing the effectiveness of different accepted interventions for a disorder to determine whether one approach may be preferable
- research aimed at clinical innovation and quality assurance and improvement
The commission should also recommend to the president and Congress where in the executive branch the regulatory authority for human subjects research should lie, and whether the U.S. should have a standing advisory committee on human subjects protections.
Reforms Needed to Regulations on Select Agents, Export Controls, Intellectual Property
The report also reviews regulations and makes recommendations on several additional topics related to federally funded research:
Research with select agents and toxins. Current regulations for keeping inventories of select agents and toxins focus heavily on tracking individual vials. But select agents are often living, self-replicating microbes that can be removed from a vial without obviously affecting the volume of material in a vial. Accounting for individual vials will not prevent the removal of material for nefarious purposes, and inventory control systems that require researchers to account for every individual vial will not ultimately offer protection against the removal of materials. The Federal Select Agent Program should develop and promulgate a reasonable inventory management system for biological select agents and toxins that takes into account the living, self-replicating nature of biological agents.
In addition, regulations should be amended to allow researchers to more readily access relevant select agents in times of public health emergencies; to increase the number of lower-virulence strains of select biological agents available to researchers; and to make more transparent the process by which materials are added to and removed from the Select Agents and Toxins list. The president should assign responsibility for regulating all microbes and toxins on the Select Agents and Toxins list to a single agency.
Export controls. Export controls restrict U.S. individuals and institutions from physically exporting certain manufactured items, software, biological agents, and technical information that could be of military use to an adversary. The report urges Congress and the administration to support a robust continuation and renewal of the Export Control Reform Initiative to improve the regulations, oversight, and ease of compliance and to seek university input at all stages of the process.
Intellectual property and technology transfer. Under the Bayh-Dole Act, institutions that conduct federally funded research must provide data to agency sponsors on inventions that result from the research – reporting that is done through the Interagency Edison (iEdison) system. This system is difficult to use and inadequately staffed and maintained, the report says. It recommends that Congress transfer responsibility for the system to the U.S. Department of Commerce and allocate appropriate resources for upgrading the system and creating a user-friendly interface for data input on inventions.
The study was sponsored by the U.S. Department of Education and the National Institutes of Health. The National Academies of Sciences, Engineering, and Medicine are private, nonprofit institutions that provide independent, objective analysis and advice to the nation to solve complex problems and inform public policy decisions related to science, technology, and medicine. The Academies operate under an 1863 congressional charter to the National Academy of Sciences, signed by President Lincoln. For more information, visit http://national-academies.org.
Download a free copy of Optimizing the Nation’s Investment in Academic Research: A New Regulatory Framework for the 21stCentury from the National Academies Press