Introduction
Modifications to clinical trial protocols to accommodate covid-19-related restrictions
Removal of covid-19-related restrictions
Best practices for conducting clinical trials during ever-evolving covid-19 pandemic
Comment
From health services to education, the covid-19 pandemic has demanded flexibility and agility in every sector. Clinical trials are no exception. In the early days of the pandemic in March 2020, the Food and Drug Administration (FDA) published guidance discussing how to conduct clinical trials during the covid-19 pandemic. It has updated that guidance periodically thereafter.
In its most recent update to the guidance (Conduct of Clinical Trials of Medical Products During the COVID-19 Public Health Emergency: Guidance for Industry, Investigators, and Institutional Review Boards) on 30 August 2021, the FDA addressed 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 remain in effect only for the duration of the covid-19 public health emergency. This article highlights the significant takeaways from the 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 modified protocols approved by the Institutional Review Board (IRB) first, then either file a protocol amendment with 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 those that were originally approved.
Most importantly, the FDA stressed that trial participants should be informed of any changes that affect their participation. Further, the FDA has emphasised the importance of keeping detailed and specific records regarding modifications, missing data and the covid-19 status of trial participants.
Removal of covid-19-related restrictions
In the wake of loosening covid-19-related restrictions, the FDA has 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 whether 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 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, as follows:
- record-keeping – sponsors and investigators should:
- 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 – sponsors and investigators should:
- as the situation changes, keep reassessing not only whether more modifications are necessary, but also whether existing modifications are viable. Pertinent questions include how to minimise contact without sacrificing safety, whether trial participants are able to access investigational products and investigations sites, whether there are sufficient staff and equipment to carry out in-person protocols, whether temporal or locational adjustments impact product stability and whether there is sufficient storage or transport to accommodate modifications, where necessary;
- determine the breadth, urgency; and impact on patient safety caused by each modification; and
- communication – sponsors and investigators should promptly notify trial participants of any changes to the protocol that affect them.
Despite the 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)
The landscape of clinical trials has likely been altered forever. The flexibility that the FDA has exercised during the pandemic has enabled those in the clinical research industry to capitalise on new opportunities for technological innovation and to reach a broader patient base geographically. Although a wider geographic reach means that there may be more supply chain and technological complications, this wider reach is consistent with the FDA's efforts to increase diversity (eg, of sex, age, race and ethnicity) in clinical trials.
For further information on this topic please contact Khelin N Aiken, Tiffany Humphries or Roberta Turner at Baker McKenzie by telephone (+1 202 452 7000) or email ([email protected], [email protected] or [email protected]). The Baker McKenzie website can be accessed at www.bakermckenzie.com.
Endnotes