From the Deputy Director for Intramural Research

Accreditation of NIH’s Human-Subjects Research Protections Program

BY MICHAEL GOTTESMAN, DDIR; AND LYNNETTE NIEMAN, DIRECTOR, OHSRP

From the time its Clinical Center opened in the 1950s, NIH has been a leader in conducting clinical research under a complex oversight system that reflects legal and regulatory requirements and international ethical standards. We are pleased to announce that the high quality of our human-subjects research protections program was recognized recently when the Association for the Accreditation of Human Research Protection Programs (AAHRPP) awarded full accreditation to the NIH intramural research program.

Ethical standards for research involving human participants are rooted in the Nuremberg Code, published in 1949, which reflected the verdict of the Nuremberg trial of 23 Nazi physicians who had conducted medical experiments on prisoners of war. The Code laid out 10 ethical standards that guided research involving human subjects.

In 1953, Dr. Roy Hertz admitted the first patient to the NIH Clinical Center and the Clinical Center Medical Committee codified a policy for the protection of human subjects. The policy stipulated that individuals not involved in a study should review the proposal. This review process was the forerunner of the Institutional Review Boards (IRBs) that are fundamental to the protection of human subjects worldwide today. The policy also emphasized the protection of healthy subjects who volunteered for research that was unlikely to provide personal benefit.

In 1955, Dr. Min Li, in collaboration with Dr. Hertz, administered methotrexate to a woman with advanced choriocarcinoma (a cancer that occurs in pregnancy) and achieved a cure. This amazing success was just one of many advances that have emerged from the Clinical Center. All of the studies were reviewed beforehand to ensure the protection of human subjects.

The NIH continued to play a central role in the development of human-research ethics, setting policy for extramural investigation in 1966. Federal policy was codified further in 1974, when a commission was formed to evaluate the existing system, resulting in the 1978 Belmont Report entitled “Ethical Principles and Guidelines for the Protection of Human Subjects of Research,” which has since set the standard for ethical considerations related to research on human subjects. This report led to the Code of Federal Regulations that governs all federally funded research today.

Some have asked why the NIH—with its long history of ethical treatment of human subjects and proven contributions to human health—would go through AAHRPP’s rigorous assessment process. It is worth noting the benefits of accreditation. One benefit has been to achieve a more consistent “One NIH” human-subjects protections program rather than multiple approaches at different institutes and centers (ICs).

• The NIH now has codified many existing policies into 49 standard operating procedures (SOPs), which address issues ranging from IRB composition and standards for protocol review to the protection of vulnerable subjects (including employees) and processes for extramural collaborations. The SOPs are available on the Web (http://ohsr.od.nih.gov).
• We now have a uniform process for capturing important information about protocols and for reminding investigators of federal regulations and NIH policy requirements.
• The harmonization of ICs’ policies and adoption of best practices has increased consistency and streamlined processes. This consistency will facilitate the use of the Clinical Center by extramural investigators.

As part of the accreditation process, NIH has also implemented the SOPs, consistently collaborated across ICs, and educated the entire community about human-subjects protections. At the AAHRPP site visit in early January, a team of six reviewers interviewed nearly 300 NIH staff—including NIH and IC leadership; IRB chairs, members and staff; investigators; research staff; quality-assurance monitors; and pharmaceutical development and radiation-safety representatives—at the Clinical Center; the National Institute of Drug Abuse in Baltimore; and the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina.

The site visitors were impressed with the “vigor and enthusiasm” shown by all those involved in human-subjects protections at the NIH. We are grateful for the outpouring of energy and effort from the entire NIH human-subjects research community that made accreditation possible.

To achieve continued success of our accreditation program and clinical research, NIH must stay true to its mission of improving human health. That mission has always been intertwined with consistent dedication to ethical treatment of our human subjects. As you have read on posters around the NIH, groundbreaking clinical research and human-subjects protections go hand in hand.

Lynnette Nieman is the director of the Office of Human Subjects Research Protections and a senior investigator in the Section on Reproductive and Adult Endocrinology in the Eunice Kennedy Shriver National Institute of Child Health and Human Development.