Revamping the US Federal Common Rule

Opinion VIEWPOINT James G. Hodge Jr, JD, LLM Public Health Law and Policy Program, Sandra Day O’Connor College of Law, Arizona State University, Phoenix. Lawrence O. Gostin, JD O’Neill Institute for Global and National Health Law, Georgetown University Law Center, Washington, DC. Corresponding Author: Lawrence O. Gostin, JD, Georgetown University Law Center, 600 New Jersey Ave NW, McDonough 568, Washington, DC 20001 (gostin@law .georgetown.edu). Revamping the US Federal Common Rule Modernizing Human Participant Research Regulations On January 19, 2017, the Office for Human Research Protections (OHRP), Department of Health and Human Services, and 15 federal agencies published a final rule to modernize the Federal Policy for the Protection of Human Subjects (known as the “Common Rule”).1 Initially introduced more than a quarter century ago, the Common Rule predated modern scientific methods and findings, notably human genome research. Research enterprises now encompass vast multicenter trials in both academia and the private sector. The volume, types, and availability of public/private data and biospecimens have increased exponentially. Federal agenciesdemandedmoreaccountability,researchinvestigators sought more flexibility, and human participants desired more control over research. Most rule changes become effectivein2018,givinginstitutionstimeforimplementation. rule failed to meaningfully distinguish research from hospital oversight and public health practices. High-profile cases of unethical research heightened public mistrust. Modernizing Research Regulations The OHRP last updated the Common Rule in 2005, issuing a proposed rule in 2015 that garnered more than 2000 public comments. National Research Council3 and National Academies4 reports also proved influential. Major changes to human subject research protections are noted in the Table. The Common Rule enhances participant protections while limiting administrative burdens on research entities and investigators. It clarifies what qualifies as human subject research, exempting educational studies, behavioral assessments, public benefit program reviews, and secondary studies of stored biospecimens entailing minimal risks or conducted with “broad” consent. Genesis of the Common Rule A sad history of failed oversight of human research partici- Researchers can examine confidential data or tissue pants, exemplified by the Tuskegee syphilis study and mili- banks for prospective participants without consent. The Common Rule reduces IRB administrative retary radiation experiments, provided impetus for federal protections.The1979BelmontReportformedtheintellec- sponsibilities. Subject to exceptions, it (1) clarifies IRB tual backdrop for federal research protection, introducing proceduresforresearchapproval;(2)dispenseswithonerous reviews of grant applications, contracts, and ongoing minimal-risk studies (eg,dataanalyses);(3)requires(in3years) The Common Rule enhances participant single IRB approval and oversight of multiprotections while limiting institutionalresearch(unlesstribalorstate laws mandate additional IRB review); and administrative burdens on research (4) facilitates online tools to help IRBs entities and investigators. assess an expanded array of “exempt” or “expedited” research. ethical principles of respect for persons, beneficence, and The rule simplifies the informed consent process justice. A driving purpose of the 1991 Common Rule was to to enable participants to better understand the scope, create uniformity consistent with ethical standards in re- risks, and benefits of research. Prescribed elements of searchconductedorfundedbyfederalagencies.2 TheCom- consent forms include a concise, up-front explanation monRuledefinedhumanparticipantresearch,specifiedthe of information a “reasonable” person would desire, roleandscopeofinformedconsent,andrequiredresearch such as purposes, risks, benefits, and alternative treatoversight and compliance through institutional review ments. Investigators are empowered to seek broad boards (IRBs) at participating research entities. consent to use identifiable data or biospecimens in unspecified future research instead of requiring additional consent, IRB waivers, or data deidentification. The Changing Research Landscape The Common Rule, although an ethical landmark, was The OHRP’s decision to not reform the Common antiquated almost from its inception. Digitization of re- Rule in certain areas was just as consequential. The search data, biobanking of human tissues, and elec- rule still applies only to federally funded research. tronic health records were rapidly altering the research However, federal agencies can require enterprises relandscape. Informed consent forms, the bulwark of pro- ceiving any federal research funds to apply Common tection, ballooned to the point that many participants Rule protections to all non–federally funded invescould not fully understand the risks and benefits—the tigations. The rule also fails to mandate security forms became more a hedge against institutional liabil- measures such as encryption to safeguard personal ity than a promotion of human dignity and autonomy. data against hacking or unwarranted disclosure. In adCosts escalated as investigators strived to implement dition, it does not address compensation for researchcomplex rules and fulfill repetitive IRB requirements. The related injuries. jama.com (Reprinted) JAMA April 18, 2017 Volume 317, Number 15 Copyright 2017 American Medical Association. All rights reserved. Downloaded From: by a University of Iowa User on 01/22/2018 1521 Opinion Viewpoint Table. The Common Rule: Major Reforms Preimplementation Broadly defines human subject research to generally apply Common Rule safeguards regardless of risk level Entails lengthy and complex informed consent processes and requirements Unclear as to consent requirements for secondary uses of human biospecimens For multi-institutional studies, permits local IRBs approvals at each participating institution Fails to adequately distinguish between human participant research and public health practice Postimplementation Establishes newly defined categories of exempt or excluded research studies based on the level of risk posed to study participants Requires consent forms to include up-front concise and focused descriptions of key information, risks, and benefits of the study Requires online posting of consent forms used in applicable studies Allows investigators to obtain broad consent for use of identifiable biospecimens in future unspecified research studies Does not require consent for secondary uses of nonidentifiable biospecimens Generally requires the use of a single IRB for multi-institutional studies within the United States Federal agencies can determine that using a single IRB would not be appropriate in some multi-institutional contexts Explicitly excludes public health surveillance from human subject research Abbreviation: IRB, institutional review board. Biospecimens and Genetic Data Distinguishing Public Health Practice and Research The Human Genome Project opened new vistas for research, including genetic sequencing of stored or future biospecimens (eg, blood, tissues, cells). Launched in 2015, the Precision Medicine Initiative aims to collect genetic data from more than a million people, also examining lifestyle data to better target prevention and treatment.5 The rule supports the need to obtain informed consent for such studies. Classification of “human subjects” clearly includes living persons from whom biospecimens are obtained through intervention, interaction, or mere analysis. If existing or emerging technologies can match biospecimens to individuals, the specimens are regarded as identifiable. Public controversy has swirled around the practice of using existing biospecimens for future research without participant, parent, or family consent. In 2011, parents sued Minnesota over the health department’s collection, use, storage, and dissemination of newborn screening samples.6 A genome sequence of Henrietta Lacks’ tissue (first gathered in 1951) ignited public concern in 2015 over the fair use of an individual’s cell line.7 The question arises whether investigators have to obtain consent for all future uses of biospecimens, even if nonidentifiable. Individuals have personal and even property claims, particularly if the data can be rendered identifiable. Yet requiring future consent can prove costly and burdensome for investigators. The very process can create a sampling bias, undermining research utility. The OHRP ultimately decided thatsecondaryresearchonnonidentifiablebiospecimenscouldbeconducted without additional informed consent, including newborn sample studies. Once the Common Rule is implemented on January 19, 2018, the Newborn Screening Saves Lives Reauthorization Act of 2014 limiting such research will no longer be operational. Public health agencies have lamented failures to properly distinguish between human participant research and public health practice. Certainly, surveillance and other epidemiologic investigations gather personalinformationandcangenerategeneralizableknowledge.Yetthese activities are vital to public health, with the primary goal of safeguarding populations. Requiring IRB approval forced health departments to curtail, restructure, or discontinue important activities. Although not entirely resolved, the Common Rule clarifies the distinction between public health practice and research. In defining research, the rule explicitly exempts the newly defined classification of public health surveillance, broadly worded to include an array of public health practice activities.Asaresult,governmentalagenciesandtheircontractedpartners can undertake routine and emergency “public health surveillance activities” without IRB review and approval. ARTICLE INFORMATION Published Online: February 22, 2017. doi:10.1001/jama.2017.1633 Conflict of Interest Disclosures: The authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest and none were reported. 1522 Advancing Research, Protecting Participants Common Rule reforms strike a difficult balance between facilitating modern research while safeguarding privacy. Allowing secondary biospecimen research after obtaining an initial consent and without significant IRB oversight should generate new discoveries with fewer costs. In this sense, the rule recognizes important collective interests in science and health. Yet weighing the interests of funders, investigators, and participants still poses a major challenge. In an age of big data and cybersecurity threats, and as new technologies reveal personal identities, ethics rules become even more important. Federal oversight will remain the bulwark against unethical practices. In the end, treating human research participants with respect and fairly is essential for continuing public support of vital scientific investigations. 2. US Department of Health and Human Services. Federal Policy for the Protection of Human Subjects (“Common Rule”). https://www.hhs.gov/ohrp /regulations-and-policy/regulations/common-rule /index.html. Accessed February 10, 2017. REFERENCES 3. National Research Council. Proposed Revisions to the Common Rule for the Protection of Human Subjects in the Behavioral and Social Sciences. Washington, DC: National Academies Press; 2014. 1. Federal policy for the protection of human subjects: Final Rule. Fed Regist. 2017;82(12):7149-7274. 4. National Academies of Sciences, Engineering, and Medicine. Optimizing the Nation’s Investment in Academic Research: A New Regulatory Framework for the 21st Century. Washington, DC: National Academies Press; 2016. 5. White House. The Precision Medicine Initiative. https://obamawhitehouse.archives.gov /precision-medicine. Accessed February 10, 2017. 6. Bearder v State, 806 NW2d 766 (Minn 2011). 7. Hudson KL, Collins FS. Bringing the common rule into the 21st century. N Engl J Med. 2015;373(24): 2293-2296. JAMA April 18, 2017 Volume 317, Number 15 (Reprinted) Copyright 2017 American Medical Association. All rights reserved. Downloaded From: by a University of Iowa User on 01/22/2018 jama.com