From health services to education, the COVID-19 pandemic has demanded flexibility and agility in every sector. Clinical Trials are no exception. The FDA has published guidance discussing how to conduct clinical trials during the COVID-19 pandemic, beginning March 2020 in the early days of the pandemic, and updating that guidance periodically thereafter. In its most recent update of August 30, 2021 to its guidance Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency: Guidance for Industry, Investigators, and Institutional Review Boards, the FDA addresses important considerations for the safety of clinical trial participants during the COVID-19 pandemic with an appendix providing answers to questions the agency has received from stakeholders. The guidance will only remain in effect for the duration of the COVID-19 public health emergency.

Below we highlight the significant takeaways from FDA's guidance:

Modifications to clinical trial protocols to accommodate COVID-19-related restrictions

The FDA’s initial guidance was aimed at helping sponsors determine when and how protocols may be modified to accommodate COVID-19-related restrictions, while still maintaining compliance with good clinical practice and upholding the integrity of the clinical trial process. Depending on the urgency of the modification and the scope of the change, sponsors may implement IRB approved modified protocols first, then either file a protocol amendment with the FDA or report the deviation to the FDA. Any amendment should be consistent with the protocol given the circumstances and should specify why the change was made and how it is likely to impact the study. Standard COVID-19 screening is not considered a protocol amendment.

Potential modifications may impact trial participation, assessments, and the practical logistics of carrying out the study. An individual’s participation in a study may be extended or abbreviated, depending on the situation. A sponsor may opt to halt recruitment for a study. A sponsor may also need to use modified methods of obtaining consent. Safety or efficacy assessments that are typically done in-person and on-site may need to be modified to take place virtually or by telephone, if such a modification is not detrimental to the safety of the trial participants. COVID-19-related restrictions may require that assessments be delayed or that trial participants access investigational products using different methods than originally approved.

Most importantly, FDA stressed that trial participants should be informed of any changes that affect their participation. Further, the FDA has emphasized the importance of keeping detailed and specific records regarding modifications, missing data, and COVID-19 status of trial participants.

Removal of COVID-19-related restrictions

In the wake of loosening COVID-19-related restrictions, the FDA updated its guidance to address whether clinical trials should proceed using its pandemic-modified protocols or revert to pre-pandemic protocols. As with the initial modifications discussed above, the determination of whether pre-pandemic protocols should be observed is a fact-intensive inquiry that should be assessed on a case-by-case basis. The sponsor should evaluate modified monitoring protocols to determine if there were increased instances of data errors, protocol violations, or attrition rates using the modified monitoring protocol. If so, the sponsor should consider following up with on-site visits.

Best Practices for Conducting Clinical Trials during the Ever-Evolving COVID-19 Pandemic

To keep pace with the rapidly changing COVID-19 public health emergency, sponsors and investigators should establish a routine of keeping detailed records, continuously reassessing protocols, and communicating with trial participants:

  • Record-keeping
    • Describe in detail not only how the pandemic modifications are different, but why they were implemented.
    • Be specific with any gaps in information both on an individual trial participant basis and on a datum-by-datum basis.

  • Reassessment
    • As the situation changes, keep reassessing not only whether more modifications are necessary, but also whether existing modifications are viable.
      • How can you minimize contact without sacrificing safety?
      • Are trial participants able to access investigational products and investigation sites? Are there sufficient staff and equipment to carry out in-person protocols?
      • Will temporal or locational adjustments impact product stability? Is there sufficient storage or transportation to accommodate modification, if necessary?
    • For each modification, determine the breadth, urgency, and impact on patient safety caused by the modification.

  • Communication
    • Trial participants should be promptly notified of changes to the protocol that affect them.

Despite FDA's acknowledgement that sponsors must be nimble and may need to adjust trial protocols quite quickly, any protocol amendments that are not required to prevent imminent risk to the safety of clinical trial participants must still be submitted to FDA and the IRB consistent with the FDA's protocol amendment requirements.1

What happens after COVID-19?

The landscape of clinical trials has likely been altered forever. The flexibility that FDA has exercised during the pandemic has created opportunity for those in the clinical research industry to capitalize on new opportunities for technological innovation and to reach a broader patient base geographically. Although a wider geographic reach means there may be more supply chain and technological complications, this wider reach is consistent with FDA's efforts to increase diversity (sex, age, race and ethnicity) in clinical trials.

How can Baker & McKenzie help?

Our team assists clients with navigating all aspects of the R&D process, including clinical trial regulatory requirements, agreements (CRO, steering committee, data coordinating center agreements), informed consent, pharmacovigilance, and Part 11 compliance. Our team of experienced attorneys brings years of in-house executive experience and government regulatory experience to our work with counseling clients in the R&D space. Some of our representative matter include:

  • Assist with identification of key records to retain and systems for retention to determine what protocol changes have been made as a direct result of the pandemic, including any explanations of missing data.
  • Draft agreements that take supply chain interruptions into account and provide solutions for such occurrences.
  • Counsel clients regarding how to navigate changes in protocol, which typically cannot be implemented before review and approval by the Institutional Review Board/International Electrotechnical Commission, and in some cases, by FDA.
  • Assist sponsors in navigating state laws regarding direct to patient delivery of investigational products.
  • Assist clients in navigating the legal implications (e.g., liability) of remote patient monitoring.
  • Assist clients with identifying and capitalizing on opportunities to create or acquire new digital health tools.

1 See 21 CFR 312.30(b)(2).

Baker McKenzie's North America Food & Drug Practice

Our regulatory team has extensive experience in navigating the complex regulatory landscape of the retail, cosmetics, nutritional, pharmaceutical and medical device, generic products, and food and consumer packaged goods sectors. We advise and represent startups to multi-national corporations serving as key strategic advisors for domestic issues and assist them in navigating regional, global and cross-jurisdictional issues. We are forward thinking and vigilant, staying abreast of applicable laws and regulations to provide clients current and forward-thinking advice and counsel across a broad range of issues. We work with clients in transactional due diligence and post-acquisition support for their growth and restructuring strategies including investments, M & A and divestitures. In addition, we work extensively on compliance matters including audits, navigating notices from regulatory agencies, proactive compliance programs and cross-border issues for clients and regulatory issues in other jurisdictions.

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