The COVID-19 pandemic is impacting human subjects research in unprecedented ways. On March 23, PRIM&R hosted a forum to provide an opportunity to hear from HRPP leaders representing universities, academic health care systems, and an independent IRB on the key issues and strategies HRPPs should be considering and implementing in the face of the COVID-19 pandemic. The recording is available to view for free here.
After the webinar, the speakers responded to attendee questions time didn’t permit us to address live. We’re pleased to share those responses with readers of Ampersand.
What are institutions doing with respect to post-approval monitoring (e.g., postponing, for-cause only, etc.), particularly if paper files are not available or cannot be digitized?
In general, all monitoring/auditing by internal programs has been converted to remote only procedures. This includes providing researchers with checklist and self-audit tools that they may use to remotely monitor their own records and documents during this time when research teams may have reduced workload due to disruptions in recruitment and conduct of research. In some cases it may be necessary to conduct for-cause audits, but only in circumstances of significant concern and only in areas where it would not violate institutional, local, or state mandates regarding requirements for remote work or stay-at-home requirements. Monitoring/auditing by sponsors is being limited to remote only via access to the electronic medical record. If FDA decided to conduct a visit, we would of course be required to comply.
Do you have anything in place that addresses possible deviations for out-of-window visits, etc.?
The policy of the IRB of record must govern whether a change or event needs to be submitted as a deviation (minor or major) or as an amendment. Each IRB needs to decide how they will handle changes necessary to accommodate disruptions in research due to COVID-19. The IRB should clearly define which changes are considered minor, major, or those that would fall into the area of changes made to eliminate immediate hazard to human subjects. IRBs need to consider whether their research is regulated by federal regulations including FDA in making these decisions. Some IRBs are choosing to allow researchers to make changes such as completing some activities remotely without submitting an amendment. Instead researchers would document this as a minor deviation for each subject that would be reported to the IRB at a later time point such as at Continuing Review. However, it would be expected that such minor deviations would not impact subject safety or the integrity of the research study. Researchers would also need to consider whether changes need to be approved and/or reported to the sponsor or regulators. The FDA has recently released guidance that may be helpful to IRBs and researchers: FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic.
We are trying to develop a plan for dispensing investigational products to a subject already signed up for a clinical trial. Is there any guidance you can suggest?
You will need to consider local and state requirements and relevant sponsor and regulatory requirements.The following two guidances may be helpful in understanding dispensing options:
- CTEP guidance
- FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic
Will you require amendments to undo the changes made during the outbreak once things can return to normal practice?
Typically, most changes implemented in response to the pandemic will be temporary deviations to the protocol and are not intended to be permanent changes or modifications to the study itself. Therefore, no modification or change would be needed to “undo” the process changes.
When research was determined to be halted/suspended, did each principal investigator (PI) receive an individual letter following individual determination by the IRB?
Since this action is typically an organizational action and not a formal IRB suspension, a letter from the IRB to each individual PI would be neither necessary nor expected. The organization should have mechanisms in place for communicating the restrictions on research activities to all investigators.
Did you create a submission form for investigators to request an exception to broad-based restrictions?
Options may include the following:
- A text note through an application system, followed by phone or video conference if needed. This helps to maintain some (relatively) human contact with investigators. For large programs, a form would likely be more efficient.
- A regular amendment form. If this option is used you may want to have research teams create a separate document to attach to the application that describes the likely temporary COVID specific changes rather than making changes to the actual protocol document.
- Use of a reportable event or other event form already in use in the system, particularly for single-patient exceptions.
For remote meetings, how do you handle recusals? Especially since so many systems are overwhelmed and having a hard time joining.
The member still needs to remove themselves from the meeting by muting the conversation and walking away from any video, or leaving the meeting completely. Use of a text message to their phone to tell them when they can return would be another notification option. You could also use a system like Slack or email in tandem with the system you are using to conduct the remote meeting to communicate with the recused IRB member as to when they may return.
Can you provide any guidance on whether your IRB is requiring revisions to informed consents to inform subjects of changes in the research due to COVID-19; or have you determined that a letter or telephone call with patients is sufficient? Also, are you approving a waiver of documentation to accompany the letters?
A revised consent is only required when the fundamental consent of a participant is impacted by the change. Minor changes in study visits like changing to remote visits where procedures may still be conducted likely do not rise to that level and can be communicated by way of a letter without the need for a signed document.
How do you “prioritize strongly-constructed protocols to minimize IRBs getting bogged down with poorly written protocols" without angering the deprioritized PI's?
One strategy may be to create an independent review committee that is charged with considering issues of scientific merit and impact, priority, feasibility and ability to implement the research in the proposed environment, whether clinical or community-based. This review should occur prior to IRB review, as it may help high-priority research to be processed efficiently by the IRB and provide important guidance for researchers who need assistance in developing their research protocols.
What about phone consenting?
Telephone consenting has always been an option if appropriate in a study. This is an excellent choice for minimal risk research where documentation of consent can be waived. Even if not previously waived, the IRB may consider waiving a signature on a consent in minimal risk research, particularly if it contributes to reducing risk to the subjects (and the research staff). Whenever possible, it is still useful to provide subjects an information sheet that includes the elements of consent, but this could be mailed, emailed, or provided by other electronic means.
For studies that are more-than-minimal risk, the FDA’s FAQ found in their recent guidance guidance may be helpful. Note that for this type of research there must be documentation that the individual received the written informed consent and there was a consent process that involved discussing the required elements of consent. A signed consent should be obtained via email, fax, or scanned document.
Can anyone share ideas on how to remotely monitor sites?
The Advarra FAQ page has detailed information on remote monitoring of sites.
If the institution suspends research, does the institution need to report this to the IRB? If so, does the IRB have to report this to OHRP? Do we have to document anything in writing to the institution or to the PI?
Some organizations and/or their investigators have halted the research; not the IRB. In this situation, because the IRB did not halt the research, the organization could take the position that reports to OHRP and FDA are not necessary. However, because someone other than IRB halted the research, the IRB should be notified. As an organization it still may be appropriate to notify regulatory and sponsoring/funding entities (e.g. NIH or other agencies as well as industry sponsors) of the organization’s response and its impact on research. Researchers may have reporting requirements to regulators and sponsoring/funding entities and in particular those acting as sponsor-investigators should be reminded of their reporting responsibilities in this role.
Many industry sponsors are requiring that PI's submit planned deviations to the IRB. Is it acceptable to simply acknowledge these? Is there anything else we should do?
If an industry sponsor requires formal IRB acknowledgement of plans to deviate from the protocol temporarily, acknowledgement would be appropriate. However, IRBs should encourage study teams to share local policies related to reporting these deviations with industry sponsors to ensure reports are not submitted unnecessarily.
Reporting suspending or terminating research—minimal risk research typically SBER type. We do not have to report to OHRP? As long as HRPP office documents? Is this acceptable?
Generally, since organizational restrictions on human subjects research activities will not constitute a formal IRB suspension of the research, reporting to federal oversight agencies will not be required. However some organizations are proactively sharing their organizational approaches with oversight entities to keep them informed.
My institution doesn't seem to be taking COVID-19 very seriously and says that it can assume that "everything will change, so tell the PIs to let us know when they can...." Is this an acceptable approach?
While many areas have not yet experienced a significant incidence of COVID-19 cases, organizations should be prepared for the possibility that local circumstances may evolve quickly and should have a contingency plan prepared. As it is an organizational obligation in addition to an individual investigator obligation to ensure human participants are protected, an organizational strategy is strongly recommended.