The United States Food and Drug Administration (FDA) and National Institutes of Health (NIH) released guidance to ensure the safety of trial participants, maintain compliance with good clinical practice, and minimize risks to trial integrity during the COVID-19 pandemic. Here is what you need to know regarding conducting clinical research during the pandemic.
The pandemic will impact clinical trials due to governmental quarantines, investigative site closures, travel restrictions, and disruptions to supply chains. Recognizing that these challenges may require unavoidable protocol deviations, the FDA provides in its guidance a number of measures for trial sponsors to consider.
Safety of subjects
Sponsors should consider the impact of each circumstance and deviation on the safety of subjects, and keep subjects informed of all study changes and monitoring plans that could affect them. In consultation with investigators and IRBs, sponsors should determine whether trial subject safety requires continuance of the protocol, discontinuation of use of the study product, or ceasing participation in the study altogether.
Alternative methods for the study
In light of travel restrictions and quarantines, sponsors should evaluate whether alternative methods of safety assessments can be used in lieu of in-person visits while assuring subject safety. Such methods include:
- Phone calls
- Virtual visits
- Alternative locations for certain aspects of the trial, such as local labs or imaging centers
- For study products that are administered in a health care setting, sponsors can consult FDA review divisions on plans for alternative administration—such as home nursing or through trained but non-study personnel. The FDA stresses that regulatory requirements for the investigational drug accountability remain in place.
Additional safety monitoring for study subjects that no longer have access to the study product or site should be considered. Also consider optimizing use of central and remote monitoring programs for site oversight when on-site monitoring is no longer possible.
Processes should be adopted or modified to account for the nature of the protocol and local situation. For example, sponsors can consider whether it is appropriate that some assessments for ongoing trials be delayed, or to halt recruitment and/or withdraw study participants if the study can no longer be properly conducted. In implementing any such changes, sponsors should adhere to the protocol to the extent possible, and the reason for any contingency measures should be well-documented by sponsors and investigators, including the duration of these changes, the study subjects impacted, and the way in which they were impacted. For all changes, sponsors are encouraged to engage with IRBs as soon as possible when coronavirus-related changes are necessary or anticipated.
If COVID-19-related measures result in missing data or information, capture specific information in the case report form explaining the reason for the missing data. This information will be summarized in the clinical study report. Consult with the applicable FDA review division where protocol amendments will alter data management or statistical analysis plans. Such plans should address how protocol deviations related to coronavirus will be handled in the analyses.
Policies and procedures
Sponsors, investigators, and IRBs should consider establishing or revising policies and procedures to describe the approaches to be taken as a result of the pandemic.
Echoing the FDA, the NIH urges that safety is their primary concern. Institutions should take all steps necessary to protect the health and welfare of subjects and research staff. Examples include:
- Limiting study visits to those needed for participant safety or coincident with clinical care
- Conducting virtual study visits
- Arranging flexibilities for required laboratory tests or imaging needed for safety monitoring to occur at local laboratories or clinics
- Canceling large gatherings of 50 or more people
- Limiting or suspending unnecessary travel
The NIH guidance also allows for additional extensions to study periods beyond those already provided by policy, and notes that recipients should contact the awarding institute or center regarding the need for an extension. Additional funding may also be available where existing grants do not cover the unanticipated costs incurred as a result of the pandemic.
Clinical research is important in the response to the pandemic. At the same time subject safety is paramount. Health care sites might not be appropriate sites for research and alternative methods during the pandemic. Alternative sites or patient safety plans may be appropriate. Review current research protocols and activities and implement policies and procedures related to pandemic preparedness and response for clinical research.
For more information on the content of this alert, please contact our Coronavirus Response team