3/30/2020
Recently, the Food and Drug Administration (FDA) released a finalized guidance document for conducting clinical trials during the COVID-19 pandemic. Clinical trials are facing many challenges due to site closures, travel restrictions, and investigational product supply chain interruptions. The guidance clarifies how to proceed with alternative methods of assessments that maintain subject safety and are in compliance with Good Clinical Practice (GCP), while minimizing risks to data integrity. The FDA just issued an updated document with a Frequently Asked Questions section. The FDA will continue to update the document as new questions arise in the rapidly changing environment of the COVID-19 pandemic.
Summary of the appendix FAQ:
Question 1: “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 pandemic?”
Answer Summary: Safety of subjects is the top priority. Sponsors should consult with Ethics Committees (EC) or Institutional Review Boards (IRBs) to determine whether continuing or suspending a clinical trial would be best to protect the subjects’ safety and wellbeing. An assessment of risks due to new challenges and restrictions versus the benefits should be considered when making the decision. A sponsor would need to very carefully assess increasing impacts of restrictions on the ability to conduct a clinical trial before starting a new one.
Question 2: “What key factors should sponsors consider when deciding whether to continue administering or using an investigational product (IP) that appears to be providing benefit to the trial participant during the COVID-19 pandemic?”
Answer Summary: The sponsor should consider several factors when deciding whether to continue or discontinue IP, including 1) if the subject is benefitting, 2) if there is an alternative treatment and the risk to switching to it, and 3) how serious the disease or condition being studied is. The sponsor may need to discuss the decision with the EC/IRB and amend the protocol to reflect the decision if some but not all subjects continue with the IP.
Question 3: “How should sponsors manage protocol deviations and amendments to ongoing trials during the COVID-19 pandemic?”
Answer Summary: Protocol deviations due to the pandemic need to be documented with the reason. If there are a high volume of deviations, alternative methods can be used, such as listing all study visits where the deviation occurred due to COVID-19 restrictions.
Because protocol amendments due to the pandemic are to protect the safety of subjects, they can be implemented immediately and then submitted for approval to the IRB and FDA. Other protocol amendments not due to safety should be implemented after approval as usual. Pausing enrollment to protect subjects from COVID-19 exposure would not require a protocol amendment under an IND.
Under an IDE, FDA approval is usually needed prior to implementing a change in investigational plan. Because changes due to the pandemic would be for subject safety, sponsors can implement and then inform the FDA with a 5 day Notice. Due to the unique circumstances, sponsors can combine implemented changes in 5 day Notices, and 5 day Notices and updates to the IDE should be submitted as soon as possible.
Question 4: “How should a sponsor submit a change in protocol that results from challenges related to the COVID-19 pandemic?”
Answer Summary: IND studies submit a formal amendment, and IDE studies submit a supplement to existing IDE. Specific wording of the cover letter is explained in the guidance.
Question 5: “Can a sponsor initiate virtual clinical trial visits for monitoring patients without contacting FDA if there is an assessment by the sponsor and investigator that these visits are necessary for the safety of the trial participant and it will not impact data integrity?”
Answer Summary: Until the changes are in an approved protocol amendment, these changes are acceptable to protect subjects but are still considered protocol deviations. These should be documented with the reason. For IDE, sponsors can combine implemented changes in 5 day Notices. See also question 3.
Question 6: “With the rapid changes in clinical trial conduct that may occur due to the COVID-19 pandemic, including multiple deviations to address patient safety, what is the best way for sponsors and investigators to capture these data?”
Answer Summary: The deviation for each subject should be linked to the reason, specifying if it is for COVID-19 restrictions, and documented. This information should be summarized in the clinical study report.
Question 7: “If patients are currently dispensed investigational product through a pharmacy for self administration at home, can a sponsor switch that to home delivery without amending the protocol?”
Answer Summary: If home delivery does not create any new safety risks, it could be implemented. Compliance with regulations for storage and accountability still apply and need to be documented. The protocol may need to be amended to reflect home delivery of IP, although it could be in a less urgent cumulative amendment. If home delivery is needed for only some of the subjects, protocol deviations could be an alternative to an amendment.
Question 8: “If patients are currently receiving an investigational product infusion at the clinical trial site, can a sponsor switch to home infusion?”
Answer Summary: It is recommended to consult with the appropriate FDA review division to plan for alternate infusion sites. Compliance with all IP regulations is still required.
Question 9: “Considering that there will be likely delays to on-site monitoring of clinical trials during the COVID-19 pandemic, what are FDA’s expectations in such circumstances?”
Answer Summary: Sponsors need to find alternative ways to monitor clinical trials to maintain subject safety and data integrity and quality, such as remote monitoring. Delays in on site monitoring can hinder identification of Good Clinical Practice (GCP) noncompliance. If monitors cannot gain access to or have a delay in gaining access to a site, the circumstances should be well documented. Any GCP noncompliance or protocol deviations should be documented, including if any delays in identification were due to delays in the ability to monitor due to restrictions.
Question 10: “How do I obtain a signed informed consent from a patient who is in isolation and the COVID-19 infection control policy would prevent us from removing a document signed by the patient from their hospital room?”
Answer Summary: Alternative methods should be employed, such as electronic signature or a phone call to discuss the clinical trial. If a phone or video call is used, it should include an impartial witness who can be with the subject.
Documentation should be clear as to how consent was obtained and why an original subject signed copy may not be present.
If applicable, a legally authorized representative may be used as in other circumstances where a subject is unable to consent, but not due to lack of ability to enter the room.
The Use of Electronic Informed Consent in Clinical Investigations – Questions and Answers guidance should be followed for electronic informed consent.
- The Clinical Pathways Team
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