United States: Another Step Toward Harmonization: FDA Issues Proposed Rule To Waive Informed Consent Requirements In Minimal-Risk Studies

On November 15, 2018, the U.S. Food and Drug Administration ("FDA") published a proposed rule1 that would allow institutional review boards ("IRBs") to waive or alter informed consent when a clinical investigation poses no more than minimal risk to, and includes appropriate safeguards for, human subjects (the "Proposed Rule"). If finalized in its current form, the Proposed Rule would harmonize FDA consent requirements with those of the "Federal Policy for the Protection of Human Subjects," known as the "Common Rule."2


Both FDA regulations and the Common Rule have provisions to protect human research subjects, including requirements pertaining to IRB review and informed consent. FDA regulations govern clinical investigations (1) that are 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 FDA in support of a product application or held for inspection by FDA.3 Currently, FDA's regulations require investigators to obtain informed consent of clinical investigation participants, except (1) in certain life-threatening situations4 or (2) for emergency research.5

In contrast, the Common Rule applies to research conducted or supported by certain federal government departments or agencies that have adopted the Common Rule (e.g., the Environmental Protection Agency, Department of Health and Human Services, and National Science Foundation). The Common Rule allows IRBs to grant a waiver of informed consent for certain minimal-risk research (e.g., observational research).

This discrepancy in approach to informed consent has frustrated the research community for years, particularly when research is subject both to the Common Rule and to FDA regulations, in which case informed consent, even in low-risk studies such as registry studies, has been required.

In an effort to promote scientific research and harmonize the Common Rule and FDA regulations, Congress passed the 21st Century Cures Act (the "Cures Act") in December 2016. The Cures Act included a provision amending the Federal Food, Drug, and Cosmetic Act ("FDCA") to permit waiver of informed consent for research involving no more than minimal risk to human subjects, if appropriate safeguards are in place to protect the rights, safety, and welfare of subjects.6 The Cures Act provision requires FDA, through regulation, to define and describe the conditions under which an IRB may waive informed consent for FDA-regulated minimal-risk research activities.

In advance of issuing such regulations, on July 25, 2017, FDA issued a guidance document ("Consent Waiver Guidance")—described in this Ropes & Gray alert—announcing its intention not to object to an IRB's 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.7 FDA stated that it planned to withdraw this guidance upon its promulgation of relevant regulations.

The Proposed Rule

The Proposed Rule would allow an IRB to approve an informed consent process that omits or alters certain elements of informed consent8 or that waives the informed consent requirement altogether, if the IRB finds (and documents) the following four criteria, all of which are required under the Common Rule9:

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

On January 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 (the "Revised Common Rule").10 The Revised Common Rule retains the four criteria listed above, but also includes a fifth criterion for waiver of informed consent: "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."11 The Proposed Rule adopts the four criteria above from the Common Rule, but does not adopt this new fifth criterion from the Revised Common Rule—although FDA does not explain in the Proposed Rule its decision to omit this new criterion, it has invited comments on this point.

Under the Proposed Rule, if the four criteria are satisfied, an IRB may waive or alter certain required elements of informed consent, including certain statements regarding reasonably foreseeable risks or appropriate alternative procedures. However, the regulations as proposed would not permit an IRB to allow the omission or alteration of the required statement regarding posting of study information at https://www.ClinicalTrials.gov.12 In addition to requiring certain substantive elements of informed consent, FDA regulations also set forth documentation requirements for informed consent (i.e., that written consent be obtained), and provide scenarios where an IRB may waive the written consent requirement.13 The Proposed Rule states that it does not affect these provisions relating to waiver of documentation of informed consent.

Takeaways for Companies and Institutions Conducting FDA-Regulated Research

Comments to the Proposed Rule must be submitted by January 14, 2019. The Proposed Rule, once finalized, would allow investigators to engage in low-risk research without having to obtain informed consent. The Proposed Rule would also reduce or remove certain administrative burdens associated with IRB review of minimal-risk studies, as IRBs would no longer need to review informed consent forms. This could result in cost and time savings to IRBs, research institutions and industry, particularly when the research at issue must comply with both FDA regulations and the Common Rule, as IRBs and researchers will no longer need to determine compliance with different requirements.


1 See Institutional Review Board Waiver or Alteration of Informed Consent for Minimal Risk Clinical Investigations, 83 Fed. Reg. 57378 (Nov. 15, 2018), available at https://www.federalregister.gov/documents/2018/11/15/2018-24822/institutional-review-board-waiver-or-alteration-of-informed-consent-for-minimal-risk-clinical.

2 See 45 C.F.R. Part 46, subpart A.

3 See 21 C.F.R. §§ 50.1 and 56.101.

4 See 21 C.F.R. § 50.23.

5 See id. at § 50.24. FDA enforcement discretion policy announced in 2006 also allows for FDA-regulated clinical research on "leftover" de-identified specimens to be conducted without informed consent. See 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/downloads/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm071265.pdf.

6 See Section 3024 of Pub. L. 114-255.

7 See 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. See also Mark Barnes et al., What to Know About New FDA Informed Consent Guidance (August 14, 2017), https://www.ropesgray.com/en/newsroom/alerts/2017/08/What-To-Know-About-New-FDA-Informed-Consent-Guidance.

8 These informed consent elements are found at 21 C.F.R. § 50.25(a) and (b).

9 See 45 C.F.R. § 46.116(d).

10 See 82 Fed. Reg. 7,149 (Jan. 19, 2017). The changes announced in the Final Rule were originally scheduled to take effect in January 2018, but the effective date was delayed in January 2018 until July 19, 2018. More recently, the Common Rule departments and agencies issued a notice of proposed rulemaking proposing to delay further the general compliance date of the 2017 Final Rule until January 21, 2019. See 83 Fed. Reg. 17,595 (Apr. 20, 2018).

11 45 C.F.R. § 46.116(f)(3)(iii).

12 Informed consent for clinical trials requires the following statement to be provided to each study subject: "A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. Law. This Web site will not include information that can identify you. At most, the Web site will include a summary of the results. You can search this Web site at any time." 21 C.F.R. § 50.25(c).

13 See 21 C.F.R. § 56.109(c).

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.

To print this article, all you need is to be registered on Mondaq.com.

Click to Login as an existing user or Register so you can print this article.

Similar Articles
Relevancy Powered by MondaqAI
In association with
Related Topics
Similar Articles
Relevancy Powered by MondaqAI
Related Articles
Related Video
Up-coming Events Search
Font Size:
Mondaq on Twitter
Mondaq Free Registration
Gain access to Mondaq global archive of over 375,000 articles covering 200 countries with a personalised News Alert and automatic login on this device.
Mondaq News Alert (some suggested topics and region)
Select Topics
Registration (please scroll down to set your data preferences)

Mondaq Ltd requires you to register and provide information that personally identifies you, including your content preferences, for three primary purposes (full details of Mondaq’s use of your personal data can be found in our Privacy and Cookies Notice):

  • To allow you to personalize the Mondaq websites you are visiting to show content ("Content") relevant to your interests.
  • To enable features such as password reminder, news alerts, email a colleague, and linking from Mondaq (and its affiliate sites) to your website.
  • To produce demographic feedback for our content providers ("Contributors") who contribute Content for free for your use.

Mondaq hopes that our registered users will support us in maintaining our free to view business model by consenting to our use of your personal data as described below.

Mondaq has a "free to view" business model. Our services are paid for by Contributors in exchange for Mondaq providing them with access to information about who accesses their content. Once personal data is transferred to our Contributors they become a data controller of this personal data. They use it to measure the response that their articles are receiving, as a form of market research. They may also use it to provide Mondaq users with information about their products and services.

Details of each Contributor to which your personal data will be transferred is clearly stated within the Content that you access. For full details of how this Contributor will use your personal data, you should review the Contributor’s own Privacy Notice.

Please indicate your preference below:

Yes, I am happy to support Mondaq in maintaining its free to view business model by agreeing to allow Mondaq to share my personal data with Contributors whose Content I access
No, I do not want Mondaq to share my personal data with Contributors

Also please let us know whether you are happy to receive communications promoting products and services offered by Mondaq:

Yes, I am happy to received promotional communications from Mondaq
No, please do not send me promotional communications from Mondaq
Terms & Conditions

Mondaq.com (the Website) is owned and managed by Mondaq Ltd (Mondaq). Mondaq grants you a non-exclusive, revocable licence to access the Website and associated services, such as the Mondaq News Alerts (Services), subject to and in consideration of your compliance with the following terms and conditions of use (Terms). Your use of the Website and/or Services constitutes your agreement to the Terms. Mondaq may terminate your use of the Website and Services if you are in breach of these Terms or if Mondaq decides to terminate the licence granted hereunder for any reason whatsoever.

Use of www.mondaq.com

To Use Mondaq.com you must be: eighteen (18) years old or over; legally capable of entering into binding contracts; and not in any way prohibited by the applicable law to enter into these Terms in the jurisdiction which you are currently located.

You may use the Website as an unregistered user, however, you are required to register as a user if you wish to read the full text of the Content or to receive the Services.

You may not modify, publish, transmit, transfer or sell, reproduce, create derivative works from, distribute, perform, link, display, or in any way exploit any of the Content, in whole or in part, except as expressly permitted in these Terms or with the prior written consent of Mondaq. You may not use electronic or other means to extract details or information from the Content. Nor shall you extract information about users or Contributors in order to offer them any services or products.

In your use of the Website and/or Services you shall: comply with all applicable laws, regulations, directives and legislations which apply to your Use of the Website and/or Services in whatever country you are physically located including without limitation any and all consumer law, export control laws and regulations; provide to us true, correct and accurate information and promptly inform us in the event that any information that you have provided to us changes or becomes inaccurate; notify Mondaq immediately of any circumstances where you have reason to believe that any Intellectual Property Rights or any other rights of any third party may have been infringed; co-operate with reasonable security or other checks or requests for information made by Mondaq from time to time; and at all times be fully liable for the breach of any of these Terms by a third party using your login details to access the Website and/or Services

however, you shall not: do anything likely to impair, interfere with or damage or cause harm or distress to any persons, or the network; do anything that will infringe any Intellectual Property Rights or other rights of Mondaq or any third party; or use the Website, Services and/or Content otherwise than in accordance with these Terms; use any trade marks or service marks of Mondaq or the Contributors, or do anything which may be seen to take unfair advantage of the reputation and goodwill of Mondaq or the Contributors, or the Website, Services and/or Content.

Mondaq reserves the right, in its sole discretion, to take any action that it deems necessary and appropriate in the event it considers that there is a breach or threatened breach of the Terms.

Mondaq’s Rights and Obligations

Unless otherwise expressly set out to the contrary, nothing in these Terms shall serve to transfer from Mondaq to you, any Intellectual Property Rights owned by and/or licensed to Mondaq and all rights, title and interest in and to such Intellectual Property Rights will remain exclusively with Mondaq and/or its licensors.

Mondaq shall use its reasonable endeavours to make the Website and Services available to you at all times, but we cannot guarantee an uninterrupted and fault free service.

Mondaq reserves the right to make changes to the services and/or the Website or part thereof, from time to time, and we may add, remove, modify and/or vary any elements of features and functionalities of the Website or the services.

Mondaq also reserves the right from time to time to monitor your Use of the Website and/or services.


The Content is general information only. It is not intended to constitute legal advice or seek to be the complete and comprehensive statement of the law, nor is it intended to address your specific requirements or provide advice on which reliance should be placed. Mondaq and/or its Contributors and other suppliers make no representations about the suitability of the information contained in the Content for any purpose. All Content provided "as is" without warranty of any kind. Mondaq and/or its Contributors and other suppliers hereby exclude and disclaim all representations, warranties or guarantees with regard to the Content, including all implied warranties and conditions of merchantability, fitness for a particular purpose, title and non-infringement. To the maximum extent permitted by law, Mondaq expressly excludes all representations, warranties, obligations, and liabilities arising out of or in connection with all Content. In no event shall Mondaq and/or its respective suppliers be liable for any special, indirect or consequential damages or any damages whatsoever resulting from loss of use, data or profits, whether in an action of contract, negligence or other tortious action, arising out of or in connection with the use of the Content or performance of Mondaq’s Services.


Mondaq may alter or amend these Terms by amending them on the Website. By continuing to Use the Services and/or the Website after such amendment, you will be deemed to have accepted any amendment to these Terms.

These Terms shall be governed by and construed in accordance with the laws of England and Wales and you irrevocably submit to the exclusive jurisdiction of the courts of England and Wales to settle any dispute which may arise out of or in connection with these Terms. If you live outside the United Kingdom, English law shall apply only to the extent that English law shall not deprive you of any legal protection accorded in accordance with the law of the place where you are habitually resident ("Local Law"). In the event English law deprives you of any legal protection which is accorded to you under Local Law, then these terms shall be governed by Local Law and any dispute or claim arising out of or in connection with these Terms shall be subject to the non-exclusive jurisdiction of the courts where you are habitually resident.

You may print and keep a copy of these Terms, which form the entire agreement between you and Mondaq and supersede any other communications or advertising in respect of the Service and/or the Website.

No delay in exercising or non-exercise by you and/or Mondaq of any of its rights under or in connection with these Terms shall operate as a waiver or release of each of your or Mondaq’s right. Rather, any such waiver or release must be specifically granted in writing signed by the party granting it.

If any part of these Terms is held unenforceable, that part shall be enforced to the maximum extent permissible so as to give effect to the intent of the parties, and the Terms shall continue in full force and effect.

Mondaq shall not incur any liability to you on account of any loss or damage resulting from any delay or failure to perform all or any part of these Terms if such delay or failure is caused, in whole or in part, by events, occurrences, or causes beyond the control of Mondaq. Such events, occurrences or causes will include, without limitation, acts of God, strikes, lockouts, server and network failure, riots, acts of war, earthquakes, fire and explosions.

By clicking Register you state you have read and agree to our Terms and Conditions