United States: What To Know About New FDA Informed Consent Guidance

This article by partners Mark Barnes and Gregory Levine and associates Abram Barth and David Peloquin was published by  Law360 on August 11, 2017.

On July 25, 2017, the U.S. Food and Drug Administration issued a guidance document1 announcing its intention not to object to an institutional review board's (IRB) waiving or altering of the informed consent requirements for an FDA-regulated clinical investigation that presents no more than minimal risk and involves adequate human subjects protections. The guidance, which takes effect immediately, will align the FDA's policy on waiving informed consent with the "Federal Policy for the Protection of Human Subjects" (the Common Rule) (45 C.F.R. part 46, subpart A), which since 1991 has permitted an IRB to waive informed consent requirements for minimal-risk research in certain circumstances


Members of the research community have expressed frustration that the FDA's regulations on human subjects protection have not contained a provision permitting the waiver of informed consent for minimal-risk research, in contrast to the waiver provision contained in the Common Rule.2 FDA regulations govern clinical investigations: (1) subject to FDA's investigational product application requirements (either an investigational device exemption under 21 U.S.C. § 360j(g) or an investigational new drug application under 21 U.S.C. § 355(i)); or (2) the results of which will be submitted to the FDA in support of a product application or held for inspection by the FDA.3 In contrast, the Common Rule applies to research conducted by or supported by most federal government departments or agencies.4

For research subject to FDA regulations and for research subject to both FDA regulations and the Common Rule,5 sponsors and their funded sites and investigators have been able to conduct clinical investigations only if express informed consent from the human participants has been obtained, regardless of the importance of the research, the risks posed by the research, and the feasibility of obtaining consent. That has marked a sharp distinction from research subject only to the Common Rule, for which IRBs can grant a waiver of consent for certain minimal-risk research, such as registry studies and observational research. One aspect of commonality in recent years has been an FDA enforcement discretion policy announced in 2006 that allowed for FDA-regulated clinical research on "leftover" de-identified specimens to be conducted without informed consent.6 But for other types of clinical research, the distinction between FDA-regulated and non-FDA-regulated investigations has persisted.

Prior to the guidance, the inability under FDA regulations for sponsors and researchers to obtain from an IRB a waiver of informed consent had prevented potentially valuable, low-risk clinical research. For example, retrospective research involving identifiable medical records or biospecimens not subject to the FDA's policy on leftover de-identified specimens has required informed consent from the human sources of the medical information or biospecimens, in order for the results to be accepted by the FDA in support of an application. Now, with an increasing emphasis on "real world evidence" for use in FDA regulatory determinations and with greater scientific value of results from "big-data" studies — many of which are typically infeasible without an IRB's waiver of consent — the need for FDA regulations to allow waiver of consent for certain minimal-risk research has become more apparent and more pressing

Indeed, in 2014 and again in 2016, the U.S. Department of Health and Human Services Secretary's Advisory Committee on Human Research Protections (SACHRP) recommended to the HHS secretary that the FDA harmonize its regulations with the Common Rule regarding waiver of informed consent. Congress, as part of a larger effort to promote harmonization between FDA regulations and the Common Rule, addressed the issue in December 2016 when it included a provision in the 21st Century Cures Act7 amending the Federal Food, Drug, and Cosmetic Act (FDCA) to permit the HHS secretary to allow a waiver of informed consent for research involving no more than minimal risk to human subjects, assuming appropriate safeguards to protect the rights, safety and welfare of subjects. This provision of the 21st Century Cures Act requires the FDA through regulation to describe and define the conditions under which an IRB can waive informed consent for FDA-regulated minimal-risk research.

New FDA Policy on Waiver of Informed Consent

The FDA has taken the interim step of promulgating its new guidance, which immediately permits an IRB overseeing a clinical investigation subject to FDA regulations to waive or alter the informed consent requirements under circumstances that mirror those currently found in the Common Rule at 45 C.F.R. § 46.116(d). Specifically, an IRB may waive informed consent if it finds any documents that:

  • The clinical investigation involves no more than "minimal risk" to subjects;8
  • The waiver or alteration will not adversely affect the rights and welfare of the subjects;
  • The clinical investigation could not practicably be carried out without the waiver or alteration; and
  • Whenever appropriate, the subjects will be provided with additional pertinent information after participation.

Notably, revisions to the Common Rule that were issued on Jan. 19, 2017, and that are expected to take effect on Jan. 19, 2018, revised the requirements for a waiver of informed consent to include an additional criterion, i.e., that "if the research involves using identifiable private information or identifiable biospecimens, the research could not practicably be carried out without using such information or biospecimens in an identifiable format." Currently, the FDA guidance does not include this additional criterion, but the FDA will consider including this new criterion in any waiver provision that it adopts as it revises its regulations to harmonize with those of the Common Rule.

The FDA intends to revise its human subjects protection regulations to permit waiver or alteration of informed consent, but issued the guidance to announce immediately its policy of enforcement discretion in regard to such waivers. The FDA plans to withdraw the guidance after it promulgates regulations permitting waiver or alteration of informed consent for research that presents no more than minimal risk and involves adequate human subject protections.

Takeaways for Companies and Institutions Conducting FDA-Regulated Research

Companies and institutions conducting FDA-regulated research may begin immediately to rely on the policy announced in the guidance. Unlike other areas of FDA enforcement discretion that could be reversed or modified substantially based on revised internal FDA or HHS policies or a change in administration, the basis of this policy is codified in the FDCA. However, the FDA may, through notice and comment rulemaking, tweak the appropriate safeguards that must be satisfied for an IRB to waive consent. But any modification to the substance of the guidance, including the criteria for waiver, would not have retroactive application to IRB determinations already in effect.

The FDA's new policy is expected to facilitate pharmaceutical, biotechnology and medical device companies in collecting real world evidence and data from low-risk research activities, such as observational or retrospective studies or registries, and using those results to support regulatory submissions to the FDA. The FDA's announcement also is expected to benefit in vitro diagnostic device manufacturers (including developers of genomic testing software) that develop and validate assays by allowing for research using biospecimens to be conducted without consent when the risks to subjects are no more than minimal and appropriate waiver of consent has been obtained from an IRB.

Although this guidance is immediately in effect, the FDA will consider all comments received and will revise this guidance when appropriate. Companies and institutions should review carefully the content of the guidance document and determine whether any changes to the criteria should be proposed based on the nature of its FDA-regulated clinical research.

1 FDA guidance, IRB Waiver or Alteration of Informed Consent for Clinical Investigations Involving No More Than Minimal Risk to Human Subjects (July 2017), available at https://www.fda.gov/downloads/RegulatoryInformation/Guidances/UCM566948.pdf.

2 See 45 C.F.R. § 46.116(d).

3 See 21 C.F.R. §§ 50.1 and 56.101.

4 However, on Jan. 19, 2017, the U.S. Department of Health and Human Services, together with 15 other federal departments and agencies, issued a final rule to revise and modernize the Common Rule. As part of the rulemaking, HHS issued an administrative notice that HHS will be eliminating the option for a research institution with a federalwide assurance to commit voluntarily to comply with the Common Rule for its nonfederally funded research.

5 See 45 C.F.R. § 46.116(e), stating that the informed consent requirements in the Common Rule "are not intended to preempt any applicable federal, state, or local laws which require additional information to be disclosed in order for informed consent to be legally effective."

6 FDA guidance, Informed Consent for In Vitro Diagnostic Device Studies Using Leftover Human Specimens that are Not Individually Identifiable (April 25, 2006), available at https://www.fda.gov/RegulatoryInformation/Guidances/ucm078384.htm. Under the policy, FDA would not require informed consent for an in vitro diagnostic device investigation when the study: (1) meets the IDE exemption criteria at 21 C.F.R. § 812.2(c) (3); (2) uses leftover specimens, that is, remnants of specimens collected for routine clinical care or analysis that would have been discarded; (3) uses specimens that are not individually identifiable, i.e., the identity of the subject is not known to and may not readily be ascertained by the investigator or any other individuals associated with the investigation, including the sponsor; (4) involves individuals caring for the patients who are different from and do not share information about the patient with those conducting the investigation; and (5) has been reviewed by an IRB in accordance with 21 CFR Part 56, except as described in Section 7 of this guidance document.

7 See section 3024 of Pub. L. 114-255.

8 "Minimal risk" is defined in the FDA regulations to mean that the "probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests" (21 C.F.R. §§ 50.3(k) and 56.102(i)). The Common Rule contains the same definition of "minimal risk" (45 C.F.R. § 46.102).

The content of this article is intended to provide a general guide to the subject matter. Specialist advice should be sought about your specific circumstances.

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