- If trial participants are not able to come to the investigational site for visits, what are some alternative methods for safety assessments?
a) Phone contact
b) Virtual visit
c) Alternative location for assessment, including local labs or imaging centers
- Do Covid-19 screening procedures that are mandated by healthcare system in which a clinical trial is being conducted need to be reported as an amendment to the protocol if done during clinical study visits?
No, unless the sponsor is incorporating the data collected as part of a new research objective.
- If I must implement alternative processes regarding the protocol, what items should I include for documentation?
a) The reason any contingency measures were implemented
b) How the restrictions related to COVID-19 led to changes in study conduct and duration of those changes
c) Indicate which trial participants were impacted and how those trial participants were impacted
- Do I need to document changes in study visit schedules, missed visits, or patient discontinuations, (which may lead to missing information) in the case report forms?
Yes, it is important to capture specific information in the case report forms that explains the basis of the missing data, including the relationship to COVID-19 for missing protocol-specified information.
- If a trial is impacted by the COVID-19 pandemic, what items must be addressed in the clinical study report (or in a separate study-specific document)?
a) Contingency measures implemented to manage study conduct during disruption of the study
b) A listing of all participants affected by the COVID-19 related study disruption by unique subject number identifier and by investigational site, and a description of how the individual’s participation was altered
c) 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.
- Do I need to still submit IND or IDE annual reports to FDA during the COVID-19 pandemic?
Yes, you should continue to submit annual reports to the FDA during this time.
- Should I notify FDA prospectively that I have suspended enrollment due to the COVID-19 pandemic?
No, expedited reporting of suspension enrollment is required if participant safety is compromised due to the study intervention.
- How should sponsors manage protocol amendments to ongoing trials during the COVID-19 pandemic?
For a study-wide change in protocol conduct, protocol amendments that are necessary to prevent imminent hazards to 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 or IDE.
Protocol amendments that are NOT required to prevent imminent safety risks to patients can be implemented once they are submitted to FDA and IRB approval has occurred.
- If a change in protocol results from challenges related to the COVID-19 pandemic, what does the FDA require?
For IND studies, the sponsor should submit a formal amendment to its IND, with the following information added to the cover letter in the subject line:
PROTOCOL AMENDMENT – COVID-19
TITLE OF PROTOOL
In the cover letter, sponsors should summarize the major changes made to the protocol related to COVID-19. Sponsors should provide the FDA with a clean and tracked changes of the protocol and the consent (if applicable)
For IDE studies, the sponsor should submit a supplement to its existing IDE, with the following information added to the cover line in the subject line:
CHANGE IN PROTOCOL SUPPLEMENT – COVID-19 or NOTICE OF IDE CHANGE – COVID-19, as applicable
TITLE OF PROTOCOL
In the cover letter, sponsors should summarize the major changes made to the protocol related to COVID-19. Sponsors should provide the FDA with a clean and tracked changes of the supplement and the consent (if applicable)
- Why do I need to send submissions to IIS instead of sending directly to FDA?
The FDA communicates directly with the Sponsors of IND and IDE applications and holds these communications confidential. Hence, the FDA does not include or copy the University on these communications. However, the University of Pittsburgh is potentially liable for the actions of its faculty members, thus necessitating that the University be engaged in the communications. The University must be involved in the oversight and must also ensure appropriate monitoring of the progress and appropriate conduct of this type of clinical trials.
- If there is a change in Investigator for an IND, how soon should the FDA be notified?
For a change in Investigator, the FDA must be prospectively notified within 30 days of the investigator being added. For sub-investigator changes, prospective notification is not necessary; however, this information should be included with the next Annual Report and the Form FDA 1572 should be updated in the regulatory file.
- When submitting protocol modifications, should I first submit to the IRB or the FDA?
It is recommended that you first submit to the IRB. Upon IRB approval, you should then submit to the IIS office and we will forward to the FDA. Please note: All FDA submissions must include a signed and dated Form FDA 1571.