Proposed Updates to the Common Rule:
Addressing a Changing Research Landscape and Its Effect on the Process of Informed Consent
Research involving human participants is an integral part of advancing our knowledge of the biomedical sciences in order to understand and treat human disease. The immense value that research participants provide through their involvement in clinical research underlies the need to protect their basic human rights and well-being. The “Common Rule,” also known as the Federal Policy for the Protection of Human Subjects1, was codified into Subpart A of 45 Code of Federal Regulations (CFR) 46 by the Department of Health and Human Services (DHHS) in June 1991 and is the basic policy that governs all federally-supported research conducted today. The Common Rule draws heavily on the ethical principles established in The Belmont Report – respect for persons, beneficence, and justice – and provides a framework upon which the protection of research participants can be built.
Twenty-five years have passed since the Common Rule was codified, and since that time, much has changed, particularly when it comes to technological advancements that make areas like research genomics, bio-imaging, and informatics possible. With each of these new advancements come new challenges and responsibilities in making sure that research participants continue to be protected from harm and treated with respect. The Notice of Proposed Rulemaking (NPRM) published in the Federal Register in September 20152 represents the most recent effort of the U.S. Federal Government to address the new challenges and responsibilities that come with clinical research conducted in the 21st century.
Historical Foundations for the Protection of Human Research Subjects in the U.S.
Although the protection of human research subjects is generally considered to be well-defined today, this was not always the case. In fact, it was not until the early 1970s that intense human research protection efforts were pursued in the U.S. as a result of a number of highly publicized abuses in research, most notably the Tuskegee Syphilis Study3. In this study, rural African-American men living in Alabama were included in a research study to document the natural progression of untreated syphilis without their consent. They were not only misled about the purpose of the research, they were also not given adequate treatment for their disease once effective treatment had become widely available. Senate committee hearings on this study and other alleged abuses sparked a number of major advancements in the development of public policy, beginning with the formation of the National Commission for the Protection of Human Subjects in Biomedical and Behavioral Research. This commission, which functioned from 1974 – 1978, fulfilled its charge in identifying the basic ethical principles that should underlie the conduct of biomedical and behavioral research subjects when it issued The Belmont Report in 19794. That same year, the Department of Health, Education, and Welfare (which eventually became the DHHS) began revising the existing federal regulations for the protection of human subjects. Revisions were completed and approved in 1981 for research conducted or supported by the DHHS, and in June 1991, the Common Rule was officially codified in separate regulations by 15 federal departments and agencies as part of an effort to promote uniformity, understanding, and compliance in human subject protection across federal departments and agencies. The DHHS regulations, 45 CFR Part 46, include subpart A (also known as the Federal Policy or the “Common Rule”), subpart B (additional protections for pregnant women, human fetuses, and neonates), subpart C (additional protections for prisoners), and subpart D (additional protections for children).
NPRM 2015 – Proposed Revisions to the Common Rule
The revisions proposed by the 2015 NPRM were generally designed with the intention of upholding the ethical principles upon which the Common Rule is based, while addressing the social, cultural, and technological aspects of clinical research conducted in the U.S. today. The following list encompasses the most significant changes to the Common Rule proposed in the NPRM5:
- Improving informed consent to better assure that participants are appropriately informed,
- Requiring informed consent for secondary research and de-identified biospecimens,
- Mandating that research sites engaged in cooperative research rely on a single institutional review board (IRB),
- Eliminating continuing review in certain circumstances,
- Extending the Common Rule to cover all clinical trials conducted in U.S. institutions receiving funding from a Common Rule agency, regardless of the funding source for the trial itself,
- Requiring new privacy standards to strengthen data protection and minimize information risks,
- Excluding from coverage under the Common Rule certain types of activities that are deemed not to be research, to be inherently low risk, etc., and
- Creating revised categories of exempt research and better calibrating the level of review to the level of risk.
If made effective in a final ruling, these changes would affect all aspects of research involving human research participants, including how informed consent documents (ICDs) are written.
Proposed Changes to Informed Consent Documents
The primary purpose of the ICD changes outlined by the NPRM is to enhance the content and overall format of these documents to better inform, and thereby, protect, research participants while continuing to build public trust. Despite a protocol team’s best efforts, modern ICDs are often considered to be long and complicated, full of legal language designed more or less to protect the people responsible for conducting the research rather than to facilitate an individual’s decision to participate. One specific way that the 2015 NPRM proposes to address this issue is by simplifying the ICD to focus more on core information that a reasonable “everyday” person would want to know. Functionally, this would involve presenting the most relevant information in a core consent (i.e., information directly relating to the required elements of informed consent), and making additional information available to participants in the form of appendices to the main document. Other format changes proposed to enhance the utility of written ICDs include:
- Treating Health Insurance Portability and Accountability Act (HIPAA) authorization information as a required element of informed consent,
- Adding an emphasis to the necessity of addressing basic elements of informed consent in a user-friendly format,
- Adding a new basic element of informed consent to better ensure that participants are informed of the possibility that de-identified data may be used for secondary research studies, and
- Adding three new additional elements of informed consent to address issues that have become relevant in recent years: use of biospecimens for commercial profit, disclosure of clinically relevant research results, and future contact relating to the current study or future studies.
According to a summary of the NPRM Public Comment presented at a meeting of the Secretary’s Advisory Committee on Human Research Protection (SACHRP) in May 2016, the proposed informed consent changes received a mostly positive response during the public comment period following the NPRM’s announcement. However, there are some critics of the changes who have urged that additional regulatory guidance, rather than more regulatory requirements, might be more appropriate. One of the leading criticisms is that relocating “non-essential” information to appendices would not necessarily result in an improvement in the overall length and complexity of ICDs, but simply serve to rearrange them. Another concern is that limiting information in the core document to only include the required elements of informed consent may not be sufficient in all cases to enable an informed decision. When put into practice, the proposed changes also present logistical challenges. For example, will common template details (such as sponsor information) be allowed in the main consent document? What will the expectations be for IRB review of material in the appendices? Now that the public comment period has ended, it will remain to be seen how these questions and concerns will be addressed in the months leading up to (and following) the announcement of the Final Rule.
The purpose of an ICD is to serve as the basis of a meaningful exchange between an investigator and a prospective research participant. Federal regulations serve an important role in establishing the standards for this exchange, and it is important that they continue to evolve to ensure that appropriate protections of research participants are maintained in an ever-changing clinical research landscape. It is the shared responsibility of all clinical research professionals to consider the fundamental principles that underlie the conduct of all human subjects research – respect for persons, beneficence, and justice – and to actively apply them to the myriad contexts in which research is conducted today, and into the future.
The Human Subject Protection (HSP) team at TRI uses a multifaceted and comprehensive approach to the application of regulations and ethical issues to support an ever-changing landscape of research sciences. Some of the services that the TRI HSP team is able to provide in support of the consent process include:
- Performing reviews of protocols and ICDs to ensure compliance with federal regulations, International Conference on Harmonisation (ICH)-Good Clinical Practice (GCP), and applicable local laws and/or institutional policies,
- Creating client-specific templates and/or training manuals to aid in the consent process, and
- Planning and conducting training on informed consent issues, including ways to facilitate comprehension of informed consent processes, increase site compliance, and promote a positive participant experience.
Helping others in promoting best practices in the consent process is just one small way that TRI helps to support an innovative and productive health sciences sector. To learn more about what else makes TRI a Full Service CRO+, please visit us at https://www.tech-res.com/.
While this article was going through final editing in preparation for the Winter 2017 TRIbune release, the Department of Health and Human Services published a press release online to announce the final revisions to the Common Rule. The final rule was published in the Federal Register on January 19, 2017. Please be sure to check back with us for a follow-up article on the final changes to the Common Rule, including how the final changes compare to the proposed changes, and what implementation of the final rule will ultimately look like.
About the Author
Eva Hymel is a Regulatory Manager who specializes in Human Subjects Protection. She has more than 8 years of experience in pre-clinical and clinical research settings and her areas of expertise include bioethics, drug development, regulatory affairs, and medicinal chemistry. Please visit www.tech-res.com for more information about TRI's services.