Description
You’ll imagine that you are the leader of a unit. You’ll need to write an email to your team that gives them directions about the new procedures for remote monitoring.Read question #14 in the FDA guidance(p.23).“I am a study monitor and am unable to conduct onsite monitoring visits due to the COVID-19 public health emergency. May I remotely perform the site monitoring visit? What recommendations does the FDA have for how I can remotely perform source document review?”Using a “9” concern for results and a “9” concern for people approach, draft a concise email to your team of clinical trial monitors that explains their next steps. Don’t worry if you aren’t a clinical trial expert. You can see this is a BIG change in operations, and as a leader, you must provide direction and comfort to your group. You need to help them adjust their practices and transition from onsite monitoring to remote monitoring. To complicate matters, you not only have to comply with your institutional structures and policies, but you also have to fully comply with the regulatory requirements that govern clinical trials. In this email to your team, outline how you are going to change from onsite monitoring to remote monitoring. The email is less about the technical requirements and more about your behavior as a leader. Remember, it’s what you do and say that will help comfort, guide, and unify your approach in these challenging and uncertain times.Length: 1-2 pages.Use APA (7th edition) for the citations.You must submit a Word document.
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Conduct of Clinical Trials of
Medical Products During the
COVID-19 Public Health
Emergency
Guidance for Industry,
Investigators, and Institutional
Review Boards
This guidance is intended to remain in effect until November 7, 2023, unless superseded by a
revised final guidance before that date. For further information, refer to 88 FR 15417, March 13,
2023, available at https://www.federalregister.gov/documents/2023/03/13/2023-05094/guidancedocuments-related-to-coronavirus-disease-2019-covid-19.
Contains Nonbinding Recommendations
Conduct of Clinical Trials of
Medical Products During the
COVID-19 Public Health
Emergency
Guidance for Industry,
Investigators, and Institutional
Review Boards
March 2020
Updated on August 30, 2021
For questions on clinical trial conduct during the COVID-19 pandemic, please email
[email protected].
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research (CDER)
Center for Biologics Evaluation and Research (CBER)
Center for Devices and Radiological Health (CDRH)
Oncology Center of Excellence (OCE)
Office of Good Clinical Practice (OGCP)
Contains Nonbinding Recommendations
Preface
Public Comment
This guidance is being issued to address the Coronavirus Disease 2019 (COVID-19) public
health emergency. This guidance is being implemented without prior public comment because
the Food and Drug Administration (FDA or Agency) has determined that prior public
participation for this guidance is not feasible or appropriate (see section 701(h)(1)(C) of the
Federal Food, Drug, and Cosmetic Act (FD&C Act) (21 U.S.C. 371(h)(1)(C)) and 21 CFR
10.115(g)(2)). This guidance document is being implemented immediately, but it remains
subject to comment in accordance with the Agency’s good guidance practices.
Comments may be submitted at any time for Agency consideration. Submit written comments to
the Dockets Management Staff (HFA-305), Food and Drug Administration, 5630 Fishers Lane,
Rm. 1061, Rockville, MD 20852. Submit electronic comments to https://www.regulations.gov.
All comments should be identified with the docket number FDA-2020-D-1106 and complete title
of the guidance in the request.
Additional Copies
Additional copies are available from the FDA web page titled “COVID-19-Related
Guidance Documents for Industry, FDA Staff, and Other Stakeholders,” available at
https://www.fda.gov/emergency-preparedness-and-response/mcm-issues/covid-19-relatedguidance-documents-industry-fda-staff-and-other-stakeholders, and the FDA web page
titled “Search for FDA Guidance Documents,” available at https://www.fda.gov/regulatoryinformation/search-fda-guidance-documents. You may also send an email request to
[email protected] to receive an additional copy of the guidance.
Please include the docket number FDA-2020-D-1106 and complete title of the guidance in
the request.
Questions
For questions about this document, contact us via email at [email protected].
Contains Nonbinding Recommendations
TABLE OF CONTENTS
I.
INTRODUCTION …………………………………………………………………………………………………1
II.
BACKGROUND……………………………………………………………………………………………………2
III.
DISCUSSION ……………………………………………………………………………………………………….3
IV.
ADDITIONAL RESOURCES ……………………………………………………………………………….6
APPENDIX: QUESTIONS AND ANSWERS ………………………………………………………………….7
Contains Nonbinding Recommendations
Conduct of Clinical Trials of
Medical Products During the
COVID-19 Public Health
Emergency
Guidance for Industry,
Investigators, and Institutional
Review Boards
This guidance represents the current thinking of the Food and Drug Administration (FDA or Agency) on
this topic. It does not establish any rights for any person and is not binding on FDA or the public. You
can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations.
To discuss an alternative approach, contact the FDA office responsible for this guidance as listed on the
title page.
I.
Introduction
FDA plays a critical role in protecting the United States from threats such as emerging infectious
diseases, including the Coronavirus Disease 2019 (COVID-19) pandemic. FDA is committed to
providing timely guidance to support response efforts to this pandemic.
FDA is issuing this guidance to provide general considerations to assist sponsors in assuring the
safety of trial participants, 1 maintaining compliance with good clinical practice (GCP), and
minimizing risks to trial integrity for the duration of the COVID-19 public health emergency.
This document updates the guidance of the same title issued in January 2021 (previous versions
December, September, July, June, May, April, and March 2020). The appendix to this guidance
further explains those general considerations by providing answers to questions that the Agency
has received about conducting clinical trials during the COVID-19 public health emergency.
In this document, the terms trial participant or participant are used and are interchangeable with the term subject
as used in referenced FDA regulations.
1
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Contains Nonbinding Recommendations
This policy is intended to remain in effect only for the duration of the public health emergency
related to COVID-19 declared by the Secretary of Health and Human Services (HHS) on January
31, 2020, effective January 27, 2020, including any renewals made by the HHS Secretary in
accordance with section 319(a)(2) of the Public Health Service Act (PHS Act) (42 U.S.C.
247d(a)(2)).
Given this public health emergency, and as discussed in the Notice in the Federal Register of
March 25, 2020 (85 FR 16949), titled “Process for Making Available Guidance Documents
Related to Coronavirus Disease 2019,” available at https://www.govinfo.gov/content/pkg/FR2020-03-25/pdf/2020-06222.pdf, this guidance is being implemented without prior public
comment because FDA has determined that prior public participation for this guidance is not
feasible or appropriate (see section 701(h)(1)(C) of the Federal Food, Drug, and Cosmetic Act
(FD&C Act) and 21 CFR 10.115(g)(2)). This guidance document is being implemented
immediately, but it remains subject to comment in accordance with the Agency’s good guidance
practices.
The contents of this document do not have the force and effect of law and are not meant to bind
the public in any way, unless specifically incorporated into a contract. This document is
intended only to provide clarity to the public regarding existing requirements under the law.
FDA guidance documents, including this guidance, should be viewed only as recommendations,
unless specific regulatory or statutory requirements are cited. The use of the word should in
FDA guidances means that something is suggested or recommended, but not required.
II.
Background
There is currently an outbreak of respiratory disease caused by a novel coronavirus. The virus
has been named “SARS-CoV-2” and the disease it causes has been named “Coronavirus Disease
2019” (COVID-19). On January 31, 2020, HHS issued a declaration of a public health
emergency related to COVID-19 and mobilized the Operating Divisions of HHS. 2 In addition,
on March 13, 2020, there was a Presidential declaration of a national emergency in response to
COVID-19. 3
FDA recognizes that the COVID-19 public health emergency may impact the conduct of clinical
trials of medical products. Challenges may arise, for example, from quarantines, site closures,
travel limitations, interruptions to the supply chain for the investigational product, 4 or other
considerations if site personnel or trial participants become infected with COVID-19. These
challenges may lead to difficulties in meeting protocol-specified procedures, including
Secretary of Health and Human Services, Determination that a Public Health Emergency Exists (originally issued
Jan. 31, 2020, and subsequently renewed), available at
https://www.phe.gov/emergency/news/healthactions/phe/Pages/default.aspx.
3
Proclamation on Declaring a National Emergency Concerning the Novel Coronavirus Disease (COVID-19)
Outbreak (Mar. 13, 2020), available at https://trumpwhitehouse.archives.gov/presidential-actions/proclamationdeclaring-national-emergency-concerning-novel-coronavirus-disease-covid-19-outbreak/.
4
For the purposes of this guidance, the term investigational product refers to human drugs and biological products,
as well as medical devices.
2
2
Contains Nonbinding Recommendations
administering or using the investigational product or adhering to protocol-mandated visits and
laboratory/diagnostic testing. FDA recognizes that protocol modifications may be required, and
that there may be unavoidable protocol deviations due to COVID-19 illness and/or COVID-19
public health control measures. Although the necessity for, and impact of, COVID-19 public
health control measures on trials will vary depending on many factors, including the nature of
disease under study, the trial design, and in what region(s) the study is being conducted, FDA
outlines the following general considerations to assist sponsors in assuring the safety of trial
participants, maintaining compliance with good clinical practice (GCP), and minimizing risks to
trial integrity. The appendix further explains those general considerations by providing answers
to questions about conducting clinical trials that the Agency has received during the COVID-19
public health emergency.
III. Discussion
A.
Considerations for ongoing trials:
•
Ensuring the safety of trial participants is paramount. Sponsors should consider
each circumstance, focusing on the potential impact on the safety of trial
participants, and modify study conduct accordingly. Study decisions may include
those regarding continuing trial recruitment, continuing use of the investigational
product for patients already participating in the trial, and the need to change
patient monitoring during the trial. In all cases, it is critical that trial participants
are kept informed of changes to the study and monitoring plans that could impact
them.
•
Sponsors, in consultation with clinical investigators and Institutional Review
Boards (IRBs)/Independent Ethics Committees (IECs), may determine that the
protection of a participant’s safety, welfare, and rights is best served by
continuing a study participant in the trial as per the protocol or by discontinuing
the administration or use of the investigational product or even participation in the
trial. Such decisions will depend on specific circumstances, including the nature
of the investigational product, the ability to conduct appropriate safety
monitoring, the potential impact on the investigational product supply chain, and
the nature of the disease under study in the trial.
•
Since trial participants may not be able to come to the investigational site for
protocol-specified visits, sponsors should evaluate whether alternative methods
for safety assessments (e.g., phone contact, virtual visit, alternative location for
assessment, including local labs or imaging centers) could be implemented when
necessary and feasible, and would be sufficient to assure the safety of trial
participants. Sponsors should determine if in-person visits are necessary to fully
assure the safety of trial participants (for example, to carry out procedures
necessary to assess safety or the safe use of the investigational product
appropriately); in making the decision to continue use or administration of the
investigational product, the sponsor should consider whether the safety of trial
3
Contains Nonbinding Recommendations
participants can be assured with the implementation of the altered monitoring
approach.
5
•
In some cases, trial participants who no longer have access to investigational
product or the investigational site may need additional safety monitoring (e.g., on
withdrawal of an active investigational treatment).
•
The need to put new processes in place or to modify existing processes will vary
by the protocol and local situation. For example, this assessment could include
consideration of whether it is appropriate to delay some assessments for ongoing
trials, or, if the study cannot be properly conducted under the existing protocol,
whether to stop ongoing recruitment, or even withdraw trial participants.
•
COVID-19 screening procedures that may be mandated by the health care system
in which a clinical trial is being conducted do not need to be reported as an
amendment to the protocol, even if done during clinical study visits, unless the
sponsor is incorporating the data collected as part of a new research objective.
•
Changes in a protocol are typically not implemented before review and approval
by the IRB/IEC, and in some cases, by FDA. Sponsors and clinical investigators
are encouraged to engage with IRBs/IEC as early as possible when urgent or
emergent changes to the protocol or informed consent are anticipated as a result
of COVID-19. Such changes to the protocol or investigational plan to minimize
or eliminate immediate hazards or to protect the life and well-being of research
participants (e.g., to limit exposure to COVID-19) may be implemented without
IRB approval or before filing an amendment to the investigational new drug
(IND) or investigational device exemption (IDE), but are required to be reported
afterwards. 5 FDA encourages sponsors and investigators to work with their IRBs
to prospectively define procedures to prioritize reporting of deviations that may
impact the safety of trial participants.
•
The implementation of alternative processes should be consistent with the
protocol to the extent possible, and sponsors and clinical investigators should
document the reason for any contingency measures implemented. Sponsors and
clinical investigators should document how restrictions related to COVID-19 led
to the changes in study conduct and duration of those changes, indicate which trial
participants were impacted, and how those trial participants were impacted.
•
Changes in study visit schedules, missed visits, or patient discontinuations may
lead to missing information (e.g., for protocol-specified procedures). It will be
important to capture specific information in the case report form that explains the
basis of the missing data, including the relationship to COVID-19, for missing
protocol-specified information (e.g., from missed study visits or study
See 21 CFR 56.108(a)(4), 56.104(c), 312.30(b)(2)(ii), and 812.35(a)(2).
4
Contains Nonbinding Recommendations
discontinuations due to COVID-19). This information, summarized in the clinical
study report, will be helpful to the sponsor and FDA.
•
If scheduled visits at clinical sites will be significantly impacted, certain
investigational products, such as those that are typically distributed for selfadministration, may be amenable to alternative secure delivery methods. For
other investigational products that are normally administered in a health care
setting, consulting FDA review divisions on plans for alternative administration
(e.g., home nursing or alternative sites by trained but non-study personnel) is
recommended. In all cases, existing regulatory requirements for maintaining
investigational product accountability remain and should be addressed and
documented.
•
With respect to efficacy assessments, FDA recommends consultation with the
appropriate review division regarding protocol modifications for the collection of
efficacy endpoints, such as use of virtual assessments, delays in assessments, and
alternative collection of research-specific specimens, if feasible. For individual
instances where efficacy endpoints are not collected, the reasons for failing to
obtain the efficacy assessment should be documented (e.g., identifying the
specific limitation imposed by COVID-19 leading to the inability to perform the
protocol-specified assessment).
•
If changes in the protocol will lead to amending data management and/or
statistical analysis plans, the sponsor should consider doing so in consultation
with the applicable FDA review division. Prior to locking the database, sponsors
should address in the statistical analysis plan how protocol deviations related to
COVID-19 will be handled for the prespecified analyses.
•
If planned on-site monitoring visits are no longer possible, sponsors should
consider optimizing use of central and remote monitoring programs to maintain
oversight of clinical sites.
B.
•
In general, and if policies and procedures are not already in place for
applicable trials:
Sponsors, clinical investigators, and IRBs should consider establishing and
implementing policy and procedures, or revise existing policy and procedures, to
describe approaches to be used to protect trial participants and manage study
conduct during possible disruption of the study as a result of COVID-19 control
measures at study sites. Changes to policy and procedures could address, but not
be limited to, impact on the informed consent process, study visits and
procedures, data collection, study monitoring, adverse event reporting, and
changes in investigator(s), site staff, and/or monitor(s) secondary to travel
restrictions, quarantine measures, or COVID-19 illness itself. Policy and
procedures should be compliant with applicable (regional or national) policy for
the management and control of COVID-19. Depending upon the nature of the
5
Contains Nonbinding Recommendations
changes described above, a protocol amendment may be required under the
applicable regulations. 6
C.
For all trials that are impacted by the COVID-19 public health emergency:
Sponsors should describe in appropriate sections of the clinical study report (or in a separate
study-specific document):
1. Contingency measures implemented to manage study conduct during disruption of the
study as a result of COVID-19 control measures.
2. A listing of all participants affected by the COVID-19 related study disruption by unique
trial participant number identifier and by investigational site, and a description of how the
individual’s participation was altered.
3. Analyses and corresponding discussions that address the impact of implemented
contingency measures (e.g., trial participant discontinuation from investigational product
and/or study, alternative procedures used to collect critical safety and/or efficacy data) on
the safety and efficacy results reported for the study.
Robust efforts by sponsors, investigators, and IRBs/IECs to maintain the safety of trial
participants and study data integrity are expected, and such efforts should be documented. As
stated above, FDA recognizes that protocol modifications may be required, including
unavoidable protocol deviations due to COVID-19 illness and/or COVID-19 control measures.
Efforts to minimize impacts on trial integrity, and to document the reasons for protocol
deviations, will be important.
IV. Additional Resources
For further questions on clinical trial conduct during the COVID-19 public health emergency,
please email [email protected].
Contact information for FDA’s review divisions is as follows:
CDER: https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/office-newdrugs.
CBER: https://www.fda.gov/about-fda/center-biologics-evaluation-and-research-cber/contactscenter-biologics-evaluation-research-cber#indcont.
CDRH: https://www.fda.gov/about-fda/cdrh-offices/cdrh-management-directory-organization.
See 21 CFR 312.30(b) and 812.35(a). Under applicable Federal regulations, investigators must engage with the
Drug Enforcement Administration when amending protocols for research involving Schedule I substances under the
Controlled Substances Act by requesting a modification to a site-specific investigator registration (see 21 CFR
1301.18).
6
6
Contains Nonbinding Recommendations
Appendix: Questions and Answers
Q1.
Deciding whether to suspend, continue, or initiate trials ………………………………………………8
Q2.
Deciding whether to continue administering product appearing to provide benefit ………….9
Q3.
Managing protocol deviations and amendments ………………………………………………………..10
Q4.
Submitting changes to IND and IDE protocol …………………………………………………………..11
Q5.
Conducting remote (virtual) clinic visits …………………………………………………………………..11
Q6.
Capturing data on protocol and process deviations …………………………………………………….12
Q7.
Delivering low-risk investigational products to home ………………………………………………..12
Q8.
Disposal of unused investigational product……………………………………………………………….13
Q9.
Changing site for delivering high-risk investigational product …………………………………….14
Q10. Alternative monitoring approaches ………………………………………………………………………….14
Q11. Obtaining informed consent for patients in isolation ………………………………………………….15
Q12. Obtaining informed consent from legally authorized representatives ……………………………17
Q13. Obtaining informed consent when electronic and paper forms cannot be provided ………..18
Q14. Remote clinical outcome assessments ………………………………………………………………………20
Q15. Remote site monitoring visits ………………………………………………………………………………….22
Q16. Challenges and temporary waivers for eCTDs…………………………………………………………..24
Q17. Shipping investigational product to local provider ‒ Form 1572 and accountability ………25
Q18. Use of commercial vs. investigational products …………………………………………………………26
Q19. Scheduling of meetings with review divisions …………………………………………………………..27
Q20. Use of alternative laboratory or imaging centers ……………………………………………………….28
Q21. Use of video conferencing for trial visits ………………………………………………………………….28
Q22. Postmarketing requirements for drugs, biologics, and devices …………………………………….29
Q23. Reporting serious adverse events for approved drugs used to treat COVID-19 ……………..31
Q24. Reporting serious adverse events associated with COVID-19 in a non-COVID trial ……..32
Q25. Reviewing IND safety reports …………………………………………………………………………………33
Q26. Collecting electronic signatures and Part 11 compliance …………………………………………….34
Q27. Exclusion criteria for “investigational medical products” …………………………………………..35
Q28. Re-monitoring after pandemic-related restrictions are lifted ……………………………………….36
7
Contains Nonbinding Recommendations
Q1.
What are some of the key factors that a sponsor should consider when deciding
whether to suspend or continue an ongoing study or to initiate a new study during
the COVID-19 public health emergency?
Central to any decision should be ensuring that the safety of clinical trial participants can be
maintained. Sponsors, in consultation with clinical investigators and Institutional Review
Boards (IRBs)/Independent Ethics Committees (IECs), should assess whether the protection of a
participant’s safety, welfare, and rights is best served by continuing a study participant in the
trial as per the protocol or by discontinuing the administration or use of the investigational
product or even participation in the trial. Such decisions will depend on specific circumstances,
including the nature of the investigational product, the ability to conduct appropriate safety
monitoring, the potential impact on the investigational product supply chain, and the nature of
the disease under study in the trial. As part of this assessment, sponsors should carefully
consider the following aspects of clinical trial conduct when deciding how or whether to proceed
with a clinical trial:
•
Assessing whether the limitations imposed by the COVID-19 public health
emergency on protocol implementation pose new safety risks to trial participants,
and whether it is feasible to mitigate these risks by amending study processes
and/or procedures.
•
Assessing the continued availability of the clinical investigator/sub-investigators
to provide oversight of the trial and properly assess and manage safety issues that
may emerge.
•
Assessing whether there will be sufficient clinical trial support staff given the
evolving COVID-19 situation and its impact on staff availability. Are there
appropriately trained staff that could be available to handle the expected tasks? Is
there adequate equipment and materials for clinical trial support staff?
•
Assessing whether clinical investigator sites will remain open to trial participants
for required in-person assessments or whether the clinical investigator has the
ability to provide required in-person assessments at an acceptable alternate
location(s), or whether such protocol-specified, in-person assessments can instead
be conducted virtually.
•
Assessing the continued availability of clinical trial supplies and continued
operations of vendors, especially related to supply of the investigational product
and/or to clinical trial supplies that are essential to maintaining appropriate safety
monitoring or other key trial procedures. This should include consideration of
product stability (shelf life) if the treatment schedule is revised, or if the clinical
site is unable to properly store the product for the needed duration.
•
Assessing the continued availability of, and support for, information technology
systems and any other technological tools that are needed to support the trial. Are
current contingency plans adequate for the types of disruptions that might be
8
Contains Nonbinding Recommendations
anticipated? What other plans can be put in place to minimize any potential
disruptions?
•
Assessing whether there will be continued operations of, and adequate
communications with, IRB/IEC and Data Monitoring Committee (DMC) staff, if
applicable, to support trial needs.
•
Assessing whether it is feasible to conduct the trial in light of any COVID-19
public health measures implemented by Federal and State authorities to control
the virus.
Involvement of a study’s DMC, if one has been established, can provide support for the
assessments discussed above. Since a primary responsibility of the DMC is assuring the safety
of participating trial participants, the DMC’s assessment of the impact of modifications of trial
conduct due to COVID-19 on patient safety is important to consider.
The risks and benefits of continuing a trial are likely different than a decision to initiate a trial
(other than trials intended to evaluate investigational treatments or vaccines for COVID-19).
Given the evolving situation, with likely increasing impacts on investigators, staff, and supply
chains, sponsors should carefully consider the ability to effectively mitigate risks such that
patient safety and trial integrity are assured. In addition, it is important to consider whether
initiation of the trial could interfere with public health measures implemented by Federal and
State authorities to control the virus.
Q2.
What key factors should sponsors consider when deciding whether to continue
administering or using an investigational product that appears to be providing
benefit to the trial participant during the COVID-19 public health emergency?
There may be circumstances in which an investigational product (either a drug, biological
product, or medical device) appears to be providing benefit to the trial participant. A sponsor
deciding whether to continue administering or using such a product during the COVID-19 public
health emergency should carefully consider context-dependent issues, including whether a trial
participant appears to be benefitting from treatment with the investigational product, whether
there are reasonable alternative treatments, the seriousness of the disease or condition being
treated, and the risks involved in switching to an alternative treatment if necessary. FDA
recognizes that in some circumstances it may be necessary (e.g., based on lack of product supply
or inability to administer or ensure the safe use of the investigational product) to discontinue
investigational product administration in a trial. If there are individual trial participants for
whom discontinuing the investigational product might present a substantial risk (e.g., trial
participants perceived by the investigator as having a clinical benefit from the investigational
product), the sponsor should consider amending the protocol, after discussion with the relevant
review division, to limit investigational product use to those patients with apparent benefit and
discontinue investigational product use to other participants. In all cases, if a trial participant is
discontinued from an investigational therapy, it is important that there be appropriate
management after discontinuation.
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Contains Nonbinding Recommendations
Q3.
How should sponsors manage protocol deviations and amendments to ongoing trials
during the COVID-19 public health emergency?
FDA recognizes that during the COVID-19 public health emergency, sponsors of clinical trials
may need to modify protocol-specified procedures. As is discussed in the main body of this
guidance, for protocol deviations necessitated by the impact of the current COVID-19 public
health emergency, the sponsor should document the specific protocol deviation and the reason
for the deviation. The sponsor can document protocol deviations using its standard processes, or
given the larger expected number of such deviations, use alternative documentation approaches.
For example, if visits are to be conducted by telephone/video contact rather than at the
investigational site as specified in the protocol, documentation that provides a listing of all study
visits (e.g., listing study reference number, patient ID, date of visit) that are deviations from the
protocol due to the current COVID-19 situation generally would be acceptable. Protocol
deviations should be included in final study reports and may also be included in annual reports.
For a study-wide change in protocol conduct, under the IND regulations protocol amendments
that are necessary to prevent imminent hazards to trial participants can generally be immediately
implemented with subsequent submission and formal approval by the IRB and notification to
FDA through filing a protocol amendment to the IND. 7
For studies under an IND, 21 CFR 312.30(b) specifies that sponsors must submit a protocol
amendment to the IND describing any change in a phase 1 protocol that significantly affects the
safety of trial participants or any change in a phase 2 and 3 protocol that significantly affects the
safety of trial participants, the scope of the investigation, or the scientific quality of the study.
Pausing enrollment in a trial to decrease potential exposure to COVID-19 would not generally be
expected to significantly affect trial participant safety, the scope of the investigation, or the
scientific quality of the study; therefore, submitting a protocol amendment would not be required
under the regulation for such a pause.
Protocol amendments that are not required to prevent imminent safety risks to patients can be
implemented after they are submitted to FDA and IRB approval has occurred. 8
FDA recognizes that during the rapidly evolving circumstances of the current COVID-19 public
health emergency, a sequence of changes may be needed to address those circumstances.
Clinical investigators must document as protocol deviations any modifications to protocolspecified procedures that occur prior to IRB approval and submission of the protocol amendment
implementing the modification. 9 Consolidating several protocol modifications in a single
protocol amendment would be acceptable but should be submitted expeditiously.
For studies under an IDE, 21 CFR 812.35(a) generally re
