Editor’s note: In its inaugural issue in April 2001, IRB Advisor featured a story about the creation of the Office for Human Research Protections (OHRP), formerly the Office of Protections from Research Risks (OPRR). IRB Advisor asked OHRP to look back since its launch in June 2000 to see how human research protections has evolved. OHRP requested that its answers be attributed to an “OHRP spokesperson.”
A Time of Scrutiny
“OHRP was founded at a time when its predecessor office (OPRR) was under considerable scrutiny due to a series of widely publicized compliance actions against a number of large, prestigious academic research institutions, which involved temporary suspensions of those institutions’ research programs,” OHRP says. “While the rationale for creating OHRP was to move the office outside of the authority of NIH [the National Institutes of Health], many people believed that the creation of OHRP was intended to revise the relationship between the federal government and the regulated institutions to promote a more collaborative relationship.”
OPRR was created in 1972 and fell under the NIH. When its replacement, OHRP, was established on June 13, 2000, the agency moved under the Department of Health and Human Services’ (HHS) Office of the Assistant Secretary for Health. OHRP was designed to lead the HHS efforts “to protect human subjects in biomedical and behavioral research and to provide leadership for all federal agencies that conduct or support human subjects research under the Federal Policy for the Protection of Human Subjects, also known as the Common Rule.”1
David Satcher, MD, PhD, who was then assistant secretary, said that OHRP’s long-term goal was to develop “new, stronger, and clearer patient protection policies, with an expanded focus on performance and prevention.”2 The organizational change was intended to allow effective coordination across HHS and provide a model for other federally and privately sponsored research, he said.
The switch to OHRP came after the September 1999 death of volunteer Jesse Gelsinger in a gene therapy trial at the University of Pennsylvania. In May 1999, the U.S. government had temporarily shut down the license to conduct human research at Duke University Medical Center after investigators said the university could not ensure the safety of trial participants. Duke blamed the lapses on “administrative” issues.3 Within a year, federal investigators had halted all or some research at seven other institutions.
In 1998, the Office of the Inspector General (OIG) of HHS also published its report, Institutional Review Boards: A Time for Reform, which described IRBs being overwhelmed with demands that put their effectiveness in jeopardy.4 The report blamed scarce resources as a primary problem. An update to the report was published in April 2000. It reported expanded federal enforcement efforts but little other progress in any of the first report’s recommendations.5
“In the last decades of the 20th century, the human research subjects protections system in the United States was very de-centralized,” OHRP says. “Most research studies were conducted by single research institutions, and the regulations delegated the responsibility for human research subject protections to the institutions conducting the research. The federal office overseeing the regulations was quite small, and its auditing capacity was quite limited. This meant that the quality of compliance with the regulations was very much institution-specific. There is very little research or other information documenting the quality of research protections provided during those years.”
Scientific Advances in Research
Much has changed in scientific research since then. “Over the last 20 years, scientific advances, especially in the areas of genetic research and information technology, the increased availability of large data sets and stored biospecimens, and the integration of research into the delivery of clinical care, have contributed to changes in the human research protections system,” OHRP says. “In addition, the rise in multisite research and the role of nontraditional research sites such as community healthcare clinics, corresponded with a growth in independent IRBs and institutions’ reliance on IRBs operated by outside organizations.
“Perhaps not coincidently,” OHRP says, “this was also the period when the human research protection field became more professionalized. In 2001, the Association for the Accreditation of Human Research Protection Programs, Inc. [AAHRPP] was founded, and institutions began to seek voluntary accreditation. And in 1999, Public Responsibility in Medicine and Research [PRIM&R]began offering the Certified IRB Professional certification for individuals working with IRBs.”
AAHRPP currently lists 257 organizations on its website with full or qualified accreditation, while PRIM&R says more than 3,000 individuals have been certified since it was introduced.
One big change happened with the revision of the Common Rule, which went into effect on July 19, 2018. Changes to the rule included:
- new and revised definitions for such terms as “human subject,” identifiable biospecimen,” and “clinical trial”;
- new categories of secondary research exempt from the Common Rule;
- elimination of continuing review for minimal risk studies;
- revised informed consent requirements.6
The revised Common Rule recognized that technology has had an impact on the nature of research by including several new provisions that were designed to address this change, OHRP says. “For example, technological advances have led to a rise in secondary research using ‘big data’ and biospecimens left over from clinical procedures, which has the potential benefit of learning from large numbers of research subjects, while avoiding the physical risks posed by some interventional studies.
“To address this change and more appropriately calibrate the research protections required for such secondary research, which mainly pose informational risks to subjects, the revised Common Rule includes several new exemptions that incorporate privacy and confidentiality protections, and in some cases a new option for broad consent, but do not impose all of the same requirements that apply to higher risk interventional studies,” OHRP says.
Some in the research community wished for more guidance from OHRP and IRBs after the revision. For example, the revised Common Rule required informed consent forms to be organized and easier to understand for participants but did not specify on how to make that possible. As of 2019, OHRP has not offered guidance on the revisions, said Joy Jurnack, RN, CCRC, CIP, FACRP, in an opinion piece for the Association of Clinical Research Professionals. “IRBs want to honor the revisions and will assist the research team, but it is up to the team to complete whatever template the IRB supplies with the details required to comply with the Common Rule. IRBs will assist and edit, but the initial work is on the research team.”7
The COVID-19 Challenge
As soon as it became clear that COVID-19 was a serious and highly transmissible infection, OHRP says it began working with the Office for the Assistant Secretary of Health and its federal partners, including the Food and Drug Administration and the Centers for Disease Control and Prevention, to develop guidance that would help the research community manage and protect research participants during the pandemic.
OHRP published its guidance in response to the coronavirus for research regulated under 45 CFR part 46 on April 8, 2020. On April 28, OHRP held a live webcast to explain the guidance and answered questions from the research community. The guidance document, the archived video of the webcast, and other related resources that could help inform the research community on protecting research participants during the pandemic are available on the OHRP website (https://bit.ly/3mo4Gy3). OHRP also says it has been working closely with the team of public health and communication experts across HHS to promote the use of the resources on the About Research Participation (https://bit.ly/3gSGHpf) website to help combat the “fear, confusion, and misinformation about research and research participation in the public.”
Some of the changes that IRBs have made to research protocols from the COVID-19 guidance may remain after the days of the pandemic have passed. A May 2020 survey of clinical research professionals at the UT Southwestern Medical Center in Dallas showed a positive reaction to trial modifications, such as telehealth appointments and allowing electronic signatures. Survey respondents said that the changes positively affected patient safety; treatment efficacy; patient and staff experience; and communication with patients, investigators, and sponsors.8 More than 90% of respondents, especially those with the more professional research experience, thought some of these COVID-19-related clinical research adjustments should continue after the pandemic ends.
- HHS.gov. About OHRP. https://bit.ly/37maIdY
- Lesney MS. A new broom? Mod Drug Discov 2000;3:31-33. https://bit.ly/2WlebDi
- Weiss R. U.S. Halts human research at Duke. The Washington Post. May 12, 1999. https://wapo.st/37nXbml
- Department of Health and Human Services. Office of Inspector General. Institutional Review Boards: A Time for Reform. Publication No. OEI-01-97-00193. June 1998.
- Department of Health and Human Services. Office of Inspector General. Protecting Human Research Subjects: Status of Recommendations. Publication No. OEI-01-97-00197. April 2000.
- American Society of Clinical Oncology. ASCO in Action. New: Summary of Updates to Common Rule for Researchers. April 17, 2018. https://bit.ly/383a0Sa
- Jurnack J. Opinion: Shedding light on the impact of the revised Common Rule on the informed consent document. Clinical Researcher Dec. 13, 2019. https://bit.ly/3nmWfnX
- Gerber DE, Sheffield TY, Beg MS, et al. Experience, perceptions, and recommendations concerning COVID-19–related clinical research adjustments. J Natl Compr Canc Netw 2020; Oct. 7. doi:10.6004/jnccn.2020.7643.