Purpose
The purpose of this guide is to provide guidance to the research community for developing protocol-specific risk mitigation plans to ensure the safety and welfare of research participants and maintain compliance with ethical and regulatory standards during emergencies or disasters (EOD) that disrupt normal research operations.
There are different types of EODs that might affect the ability to continue with a research study as approved. These include natural disasters (hurricanes, floods, earthquakes), man-made disasters (chemical spills, civil unrest, terrorist attacks), public health crises (infectious disease, pandemics), and infrastructure failures (power outages, IT system failures, supply chain disruptions). EODs may lead to challenges such as inability to administer drugs and devices, continuation of in-person study visits, disrupted communication between study team members and/or participants, management of study records, and maintenance of specimens.
Scope
The information provided applies to all research involving human subjects, including clinical trials, behavioral studies, and observational research, regardless of funding source or location.
Regulatory Considerations
Both the Common Rule (45 CFR 46) and FDA regulations (21 CFR 56) require “prompt reporting to the IRB of proposed changes in a research activity, and for ensuring that investigators will conduct the research activity in accordance with the terms of the IRB approval until any proposed changes have been reviewed and approved by the IRB, except when necessary to eliminate apparent immediate hazards to the subject [emphasis added]. In addition, the FDA (21 CFR 108) regulations permit a delay in submitting amendments to IND or IDE applications when changes are related to an EOD but are required to be reported at a later time.
Applicability
Not all research studies will be affected depending on the type of EOD that occurs. In general, if any of the following are true, development of a protocol-specific risk mitigation plan for research may not be needed as long as institutional and HRP level guidance is being followed:
- The study is able to continue without interruption due to its nature (e.g. does not involve in-person interaction or can be modified to utilize a remote option).
- The external sponsor of the study already has a protocol-specific risk mitigation plan in place.
- The study would be placed on hold for recruitment and/or research related procedures with the exception of safety visits that must be completed.
Considerations for Developing a Study-Specific Emergency Risk Mitigation Plan
There are a number of considerations when developing a study-specific emergency risk mitigation plan.
Communication
To ensure ongoing communication between the research team, as well as between the research team and participants, the following steps should be taken:
- Maintain Updated Contact Information
- Keep an up-to-date list of all research subjects with complete contact details.
- Provide participants with remote contact information for study personnel.
- Update and Distribute Staff Contact Lists
- Ensure the contact list for all study staff is current and share it with every team member.
- Store a copy of these lists in a secure off-site location, as well as creating a physical copy
As informed consent is an ongoing process, investigators should consider how changes due to EOD situations will be communicated to participants who are active or in follow up. A research participant communication plan describing the study-specific modifications being made to ensure the ongoing safety of research participants may need to be developed for implementation with all current (and where applicable, prospective) research participants. This plan should include:
- What information will be communicated to current (and where applicable, prospective) research participants;
- Who will communicate the information;
- When the information will be communicated; and
- How the information will be communicated.
Recruitment and Enrollment Processes
Consider whether any of the following are appropriate:
- Temporary pause of study recruitment procedures.
- Temporary hold of enrollment of new research participants.
- Additional or revised screening procedures for research participants that will be completed prior to recruitment and enrollment (e.g., for infectious disease outbreaks).
- Alternate locations for enrollment and screening (e.g., at local clinics or conducted remotely)
Plan for Alternate Operations
- Identify and coordinate an alternative site for study visits, if feasible. For example:
- In the case of technology failures, modify study visits to take place in person rather than virtually.
- In situations where participant visits cannot take place in person, modify study visit procedures so that visits can be completed via phone, virtually, or at participants’ local lab, clinic or imaging center.
- Develop a pre-arranged plan with the study sponsor for securing study samples, investigational products, and research data.
Unblinding and Drug Access
- Establish a process to unblind studies in case of an EOD and ensure investigational drugs can be provided for treatment purposes.
- Confirm clear procedures for securing and accessing investigational drugs and devices during an emergency including verifying with the sponsor and/or the Investigational Drug Service whether drugs can be shipped directly to the subjects in an emergency situation.
- For any investigational products that can be self-administered, modify the protocol to allow for this alternative secure delivery method.
- For any investigational products that are normally administered in a healthcare setting, consult FDA review divisions on plans for alternative administration (e.g., home nursing or alternative sites by trained but non-study personnel).
Build Collaborative Partnerships
- Partner with other academic institutions to create collaborative emergency sites.
- Ensure approval is in place to use local laboratories for subject safety labs.
- Work with the Human Research Protection staff to establish reliance agreements as needed to rely on another institution’s (or a commercial) IRB.
- Identify alternate locations for monitoring if planned on-site monitoring visits are no longer possible.
Secure Research Records and Equipment
- Protect all clinical trial records (both paper and electronic) and document the process.
- Provide information to the study team about the location of all documents.
- Back up electronic records and ensure they are retrievable from a remote location.
- Store paper records in a safe, dry location to prevent water damage.
- Secure any sponsor-provided or study-specific equipment.
Additional Adaptations to Minimize Risk to Participants
- Consider any that are appropriate for the research:
- Withdraw some or all current research participants from the research.
- Modify the timing and scope of specific study visits to account for essential versus nonessential study procedures.
Research Record and Study Documentation
The following are additional considerations for investigators when maintaining research records and /or specimens that reflect study modifications made to ensure the continuation of research and ongoing safety of research participants in EODs. For protocol wide study restrictions or modifications necessitated by the EOD, documentation related to any of the following elements are included in the research record where applicable and appropriate to the research:
- Changes in study conduct
- Duration of those changes
- Which trial participants were impacted
- How those trial participants were impacted
- Other relevant actions that were taken.
Where there are individual instances when efficacy endpoints are not collected, the research record includes documentation related to the reasons for failing to obtain the efficacy assessment (e.g., identifying the specific limitation imposed by EOD leading to the inability to perform the protocol-specified assessment). Specific information in case report forms explains the basis of any missing data, including the relationship to the EOD for missing protocol-specified information.
Where changes in the protocol include any of the following, the research record includes documentation that changes were made in consultation with the applicable FDA review division where feasible and appropriate:
- Amendments to data and/or specimen management
- Amendments to statistical analysis plans
- Alternative administration of investigational products that are normally administered in a healthcare setting (e.g., home nursing or alternative sites by trained but non-study personnel)
- Protocol modifications for the collection of efficacy endpoints, such as use of virtual assessments, delays in assessments, and alternative collection of research-specific specimens
IRB Notification and Approval
One of the following pathways must be followed:
- If a change of the research is necessary to eliminate an apparent immediate hazard to a participant, take action and notify the IRB via an exception request within five business days. OR
- For all other study modifications made to ensure the ongoing safety of research participants throughout an ongoing EOD, submit a study amendment to the IRB prior to implementation.
11/24/2025