Planning for Emergencies

• Identify critical data and specimens, where they are stored, and who is responsible for maintaining them by role.
• Plan for loss of specimens – Describe protections measures in the protocol. Identify what actions are needed if data or specimens are lost or damaged.
• Confirm that freezers and other critical equipment are maintained. Confirm that backup arrangements are being used and are understood.
• Plan for privacy or confidentiality breaches - Make sure privacy and confidentiality protections are adequate and described in the protocol.
• Identify alternative methods for collecting or accessing essential data if systems are unavailable.
• Train staff to recognize and report privacy breaches, loss of data or specimens, and other reportable events according to NIH policy and study procedures.
• Know who must be notified and the applicable reporting timeframes. Keep your Sponsor informed

• Plan ahead so IRB approval does not lapse during an emergency - If the protocol requires Continuing Review, know the IRB expiration date. Submit the Continuing Review at least 6 weeks before approval expires.
• For studies using an external Reviewing IRB, know how emergency changes or deviations will be handled. Know what still needs to be reported to the NIH IRB.

• Study design - Are your visit windows able to accommodate minor delays?
• Consent – Include remote consent procedures in the study
• Screening: Can you conduct remote assessments or records review?
• Identify which procedures or assessments must continue for safety/welfare of participants or scientific integrity. Identify them in the protocol Schedule of Activities so study staff can easily identify them during an emergency.
• Identify which procedures or assessments can be delayed or take place at outside facilities without impacting scientific integrity or participant safety.
• Enrolled participants: Can you conduct remote visits?
• Disease outbreaks: Will additional safety procedures be needed? Is this addressed in the protocol?
• Multisite studies: Determine whether another site could see participants. Who do you need to notify if the NIH site is affected? Assess whether the disruption could affect other sites.
• Withdrawal or closure: Consider what is needed if the study must temporarily halt or close. Prioritize participant safety and indicate what safety procedures or monitoring may be required for these participants. What is needed for safe discontinuation of test articles?
• Monitoring: If an emergency is prolonged, does the monitoring plan permit remote monitoring? Work with the Sponsor and IC QA/QI staff as needed to ensure the monitoring plan allows both onsite and remote monitoring when appropriate.
• Participant communications: Develop a plan for communicating with affected participants if normal operations or communications are unavailable. Work with the Sponsor to ensure participant needs are met.
• Safety Visits: Identify participants who may require additional safety visits if procedures are missed or delayed.

• Learn the Pharmacy emergency plan, particularly if the test article is compounded or prepared locally.
• Determine in advance what permissions would be needed from the Sponsor, Manufacturer/Supplier and Pharmacy. For example, to ship the test article directly to participants, or to another site.
• Plan for storage, temperature monitoring, backup storage, relocation, preparation, administration, and accountability.
• Learn what permissions you need to make changes in an emergency. Identify who has the authority to approve changes to storage, preparation, administration, shipping or accountability of the test article. Know who to work with if changes are needed.
• For studies that permit the test article to be shipped, ensure that proper shipping materials are available. For example, controlled temp boxes, TempTales, use of a specific courier, etc. Consult Pharmacy if needed.
• If the test article may be shipped to participants - establish accountability tracking and other oversight procedures. Consult with CRO/Sponsor and/or IC QAQI staff to ensure staff are adequately trained for this task.
• Determine what actions are needed if storage conditions are compromised or the test article is adversely affected. Include the chain of communication and identify who is responsible for communicating.
• Identify how test article accountability will be maintained during and after the emergency.
• If the protocol permits test article shipment to patients, ensure each patient is properly educated on how to properly receive and store the test article. For example, determine whether participants will need instructions on storage, administration, disposal, accountability or use of a medication diary. Prepare and submit participant-facing materials for IRB review in advance when possible.

• Maintain an operational emergency contact list and update it annually. Include the study team, lab/branch chief, IC leadership, IC Privacy Coordinator, IRB, other sites/Coordinating Center, Sponsor/Manufacturer, Pharmacy, FDA when applicable, monitors, and safety monitoring committee. Assign responsibility by role for updating and maintaining the emergency contact list.
• The IND/IDE Sponsor must be kept apprised of any changes impacting the test article.
• Maintain active participant contact information, including participants in long-term follow-up. Determine if you need a backup contact. Confirm contact information annually.
• Know who must give permission when study conduct needs to change: IRB, Sponsor, Manufacturer/Supplier, Pharmacy, FDA, or others as applicable.
• Know where new operating instructions will come from during an emergency, such as the Clinical Center, IC, IRB, NIH, HHS, FDA, or Sponsor.
• Issue emergency wallet cards to participants that identifies the research study, and a study contact who emergency providers can contact.
• Cross-train study staff so essential functions can continue if a team member is unavailable.
• Conduct a study-team tabletop exercise at least annually and when changes are made to the emergency plan.
• Identify critical vendors, contractors, couriers, technology platforms and other external resources. Note any alternatives or contingency arrangements that are available.

Once you have identified key steps to be taken in case of an emergency, consider if you need to develop a brief emergency response plan specific to your protocol. Here are some examples of what you might include:

• Leadership and key roles: Understand who is responsible for emergency decision making. Delegate an experienced individual besides the PI who is responsible for emergency decision making if the PI is unavailable. Delegate staff for key roles and assign back-up staff.
• Identify safety-critical procedures: Which procedures, lab tests, safety assessments and study activities must continue. Which are safe to pause or delay? Provide criteria used to assess status of the protocol and status of active participants to determine if the study should continue or be paused or delayed. For actively enrolled participants, identify which participants are undergoing study interventions or require time-sensitive safety assessments versus those who are in follow-up.
• Identify permissible alternative procedures: such as telehealth, remote consent, communication methods, remote monitoring. Identify permissions needed to use alternative procedures.
• Test article contingencies: What will happen if storage, supply, preparation, administration, shipping, or accountability is disrupted? Identify who must be contacted before changes are made.
• Essential data and specimens: Identify alternative methods for collecting or accessing essential data if systems are unavailable. Methods for recording key study information. Identify key specimens, how they will be protected and needed contingencies.
• Emergency Communications: Who must be contacted, including participants, the IRB, Sponsor, Manufacturer/Supplier, Pharmacy, study sites, and institutional contacts. Identify how the team will communicate if normal systems are unavailable. When communicating with participants, prioritize order of communications based on need.
• Emergency Documentation and notification: Specify who is responsible for documentation by role. Identify who is responsible for identifying that the emergency has ended. Identify who is responsible for reporting after the emergency has ended.
• Activation/Deactivation: Define criteria for activating the Emergency Response Plan. Identify who may activate it and deactivate it. Consider what issues must be escalated and to whom e.g., leadership, Sponsor, Manufacturer/Supplier, IRB, FDA.

• Make any immediate changes necessary to eliminate hazards to participants.
• Determine whether the study can continue, whether recruitment or enrollment should pause, or whether the study should temporarily halt or stop.
• Identify which safety or critical procedures must continue and which activities can be delayed or performed through an approved alternative.
• For actively enrolled participants, identify which participants are undergoing study interventions or require time-sensitive safety assessments versus those who are in follow-up.
• Assess staffing, data and specimen systems, test article access, and monitoring impacts.

• Review emergency operating instructions from the Clinical Center, IC, IRB, NIH, Pharmacy, HHS, FDA and Sponsor, as applicable.
• Use the emergency contact list to notify the study team and other parties who need to know, including IC leadership, Sponsor, Manufacturer/Supplier, Pharmacy, the IRB, other study sites/Coordinating Center, FDA when applicable, monitors or independent monitoring committee, and the IC Privacy Coordinator when needed.
• Notify Pharmacy immediately if there are any ancillary supply changes that may affect test article preparation or administration.
• Communicate with affected participants. Provide clear instructions about study visits, safety monitoring, etc. Provide instructions for the test article, including storage, administration, handling, disposal or accountability, as applicable.

• Notify the IRB when a change is made to eliminate an immediate hazard to participants (this is considered to be a major deviation) and submit any required Reportable New Information (RNI) reports. Follow the requirements of 3014-801 Reporting Research Events and your study protocol.
• Submit needed protocol modifications, consent documents or consent addenda, and a re-consent plan when needed. For example, any emergency related changes. Tell the IRB if the changes are temporary or permanent.
• Provide the IRB with the information needed to understand the emergency: how the study is affected, study status, numbers of active participants and participants in follow-up, how participants are affected, and steps already taken or planned for their safety and welfare.
• Submit participant letters, scripts, diaries, training materials, and other participant-facing materials for IRB review and approval as needed.
• When changes affect a test article, work with the Sponsor, Manufacturer/Supplier and Pharmacy. Submit an RNI to inform the IRB if needed.
• When monitoring is affected, work with the Sponsor and/or IC QA/QI staff.

Document:

• Permissions sought and granted by the IRB, Sponsor, IC, FDA, or others as applicable.
• The individual(s) responsible for coordinating the response.
• The basis for determining whether the study can continue, activities that should be modified, paused or whether the study should be halted.
• What changes were made and why, the duration of the changes, which participants were affected and how, and other important impacts on the study.
• Emergency-related deviations, missed or modified visits, monitoring disruptions, and participant communications.
• Test article: any impacts to storage, preparation, shipping, administration and accountability
• The date normal study activities resume.