Coronavirus Guidance

If you changed the conduct of the protocol permanently (or for an indefinite time period) due to COVID-19: Please submit an amendment to the IRB.

• This should be done in a reasonable time frame, after initiating any changes required to eliminate immediate hazards to participant safety.

If you are changing the protocol procedures temporarily due to COVID-19: No notice to Advarra is required unless there is:

• An increased risk of harm to participants, or
• The integrity of the data will be adversely impacted.

If you have not done so already, at continuing review, we ask investigators to confirm that:

• Any changes to procedures in response to the pandemic (e.g., changing from in-person visits to remote visits, obtaining consent remotely, etc.) have been documented and communicated to the sponsor;
• Any changes made to the conduct of the study that will be in place indefinitely have been submitted to the IRB for review as an amendment to the study or administrative letter;
• Any changes made to the study that are minor, temporary, and do not increase the risk of harm to participants or adversely impact the data have been documented as minor deviations; and
• Any changes made to the study that are major deviations (including changes in administration of study drug) have been submitted to the IRB for review.

When there is a change in the administration of a study agent or the shipping of a study agent, in most cases this must be reported to the IRB.

• This is because in-hospital/office/clinic monitoring will not be available to participants at their homes.

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Revised to include new information regarding OHRP sIRB exception expiration date.

Advarra has compiled the following list of regulatory guidance documents and other resources to help you remain compliant during this challenging time. Have a question about these external resources? Ask Advarra.

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The IRB has no general policy regarding individuals who get a COVID or other vaccination and research. If the protocol itself excludes anyone who gets a vaccination or who specifically gets a COVID vaccination, that is a protocol requirement and needs to be observed or changed via an amendment. If the protocol is silent as to whether prospective or enrolled participants get COVID or other vaccination, then vaccination would be deemed to be a consideration outside of the research unless the protocol was amended to include some restriction.

Enrollment

US:

• A halt or delay in enrollment does not have to be reported to the IRB, but it may need to be reported to the sponsor.
• A total suspension of a non-therapeutic trial does not need to be reported to the IRB, but it should be reported to the sponsor.
• A total suspension of a therapeutic trial should be reported to the IRB if participants are enrolled and may be at risk due to the discontinuance of study procedures. The report should include a plan for managing those risks. This suspension should also be reported to the sponsor.

Canada:

• If recruitment or enrollment is halted, sponsors should inform Health Canada using a clinical trial application notification (CTA-N).
• A temporary hold on recruitment/enrollment does not need to be reported to Advarra.

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COVID-19 cases do not need to be reported to the IRB unless:

• The research protocol requires reporting; or
• The infection is related to the research.

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Protocol deviations do not need to be reported to Advarra unless they impose an increase in the risk of harm to participants or adversely affect the integrity of the data. 

• A protocol deviation is something that applies to individuals (not the study as a whole).  

• • Example: If some individuals are not able to travel for an in-person visit because of concerns related to COVID-19, that is a minor deviation and does not need to be reported unless it impacts the risk to the participant. 

• This is Advarra’s standard reporting requirement; other IRBs’ policies may vary. 
• For more information, see section 18.3 of the Advarra IRB Handbook for Investigators, Institutions, Sponsors, and Sponsors’ Representatives (available in the Reference Materials section of the Advarra CIRBI Platform [login required]). 

US: Any change implemented to manage study conduct during disruption of the study as a result of COVID-19 control measures must be documented per FDA. 

• A listing of all participants affected by the COVID-19 related study disruption must be documented. This documentation should include unique participant number identifier, investigational site, and a description of how the individual’s participation was altered. 

Canada: If the deviations to not place participants at risk, sponsors are not required to report these deviations to Health Canada.  

• Sites should have a system in place to identify, document, assess, and report protocol deviations to the sponsor and REB. 
• Sponsors should define/identify the protocol deviations that must be reported. 

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As a result of the COVID-19 pandemic, remote visits via telephone, telemedicine, Skype, FaceTime, or other appropriate virtual communication may be substituted for a visit to an office, hospital, or clinic without prior review by the IRB.

While a substitution of a remote visit would be a protocol deviation, during the pandemic if it does not increase harm to participants it would not need to be reported to the Advarra IRB as a deviation. If however, there is a harm to participants from having a remote visit instead of an in-office visit, the study team should take whatever steps are appropriate and necessary to mitigate that harm and report those actions, in as reasonable a time frame as possible, to the IRB.

For remote visits that occur due to the pandemic, subjects may be compensated as they would have been for an in-office visit.

If remote visits will continue for an indefinite period of time, a study amendment should be submitted. We recommend that participants be advised by letter or other form of communication of the change in study visits (re-consent is not required).

Considerations when conducting visits at home:

• Will the study staff be wearing personal protective equipment (PPE)?
• What other safety protocols are needed to protect a participant from exposure when inviting study staff into their home?
• How will the health status of the study staff going into the home be evaluated prior to entering the participant’s home?
• Will the study use third-party vendors to provide home health care services?
  • If the research is federally funded, are the health care providers (HCPs) “engaged in the research” as described in OHRP guidance?
  • If the research is FDA-regulated, are the HCPs sub-investigators who should be listed on Form 1572?

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If study visits are missed due to COVID-19, and the sponsor plans to collect information on missed visits and analyze the data in order to discern the impact of COVID-19 on the research, the protocol should be modified to reflect that objective. If the impact of COVID-19 on the research is not additionally being assessed, a protocol amendment is not needed.

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Re-consent is not necessary unless the changes to the research are such that the original consent is no longer valid (e.g., re-consent is not necessary when changing from clinic visits to remote visits). Participants should be notified of changes to the research via a letter or other form of communication.

This does not need to be reported to the IRB if it is a temporary change unless the changes increase the risk of harm to participants. If the changes to the research (such as changing to remote visits) may continue for an indefinite period of time, these changes should be submitted as a study amendment.

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Revised to consolidate guidance and provide clarification on current policies.

Investigators may need to obtain informed consent from a potential trial participant or their legally authorized representative (LAR) when these individuals are unable to travel to the site where the investigator is located due to COVID-19 illness, travel restrictions, or other similar situations.

When investigators do not have electronic informed consent (eIC or eConsent) capabilities, methods of obtaining informed consent other than a face-to-face consent interview may still be acceptable if those methods:

• Allow for an adequate exchange of information and documentation, and
• Include a way to ensure that the signer of the ICF is the person who plans to enroll as a participant in the clinical investigation (or is the LAR of the trial participant).

For example, the ICF may be sent to the participant or their LAR by fax or email, and the consent interview may then be conducted by telephone when the participant or their LAR can read the ICF during the discussion. After the consent discussion, the participant or their LAR can sign and date the ICF.

Options for returning the ICF to the clinical investigator may include:

• Fax
• Photographic image sent through electronic means
• Scanning the ICF and returning it through a secure email account
• Posting it to a secure internet address

Alternatively, the participant may bring the signed and dated ICF to their next visit to the clinical site, if restrictions on traveling to the clinical trial site are alleviated, or they can mail it to the clinical investigator.

The study record for each participant must document that informed consent was obtained prior to participation in the trial, and the person signing the ICF must receive a copy of the ICF. Although FDA regulations do not require the participant’s copy to be a signed copy, FDA recommends a copy of the signed ICF be provided.

The participant or their LAR must sign and date the ICF before the investigator may conduct any study-related procedures involving the participant. Where it is not feasible for investigators to receive the signed ICF prior to beginning study-related procedures, investigators should have the prospective trial participant or LAR confirm verbally during the consent interview that the participant or LAR has signed and dated the ICF. In addition, the overseeing IRB must review and approve the planned informed consent process.

In summary, when a copy of the fully executed ICF will be returned to the study team, informed consent may be obtained by telephone. When obtaining consent by telephone, researchers must:

• Document how the ICF was transmitted to the participant /LAR (e.g., email, fax, mail, etc.).
• Document the process, including:
  • Identification of who is on the call, and
  • Review of the ICF with the participant/LAR by the investigator/designee and response to any questions the participant may have, and
  • Verbal confirmation by the participant/LAR that their questions have been answered, they would like to participate in the trial, and they have signed and dated the ICF that is in their possession.
• Document how the participant/LAR signature was obtained during the process. For example:
  • Electronic signature (e.g., Adobe Sign)
  • A scanned signed ICF emailed, faxed, or mailed back to the study team
  • A photograph of signature/signature page sent back to the study team
• A study team member enters the returned ICF into the trial records along with an attestation that states how the ICF was obtained (e.g. email, fax, mail, etc.).

Note: For FDA regulated research, the participant must also date the ICF.

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The following are acceptable methods for obtaining consent from COVID-19 patients in a containment unit or quarantined space or from a physically unavailable legally authorized representative (LAR):

Method 1: A photograph of the signed ICF can be transmitted to trial staff.

1. An unsigned ICF is provided to the patient by a person who has entered the room.
2. The investigator/designee arranges a telephone call or videoconference call with the patient (and, if desired and feasible, additional individuals requested by the patient [e.g., next of kin]).
3. To ensure the patients are approached in a consistent fashion, a standard process should be used that will accomplish the following:
   1. Identification of who is on the call.
   2. Review of the ICF with the patient by the investigator/designee and response to any questions the patient may have.
   3. Verbal confirmation by the patient that their questions have been answered, that they would like to participate in the trial, and that they have signed and dated the ICF that is in their possession.
4. The patient (or an individual in the room) takes a photograph of the signed ICF and sends it to the investigator/designee.
5. A trial team member enters the photograph into the trial records along with an attestation that states how the photograph was obtained and that it is a photograph of the ICF signed by the patient.

Method 2: A witness can attest to the signature, but a photograph of the signed ICF cannot be transmitted.

1. An unsigned ICF is provided to the patient by a person who has entered the room.
2. The investigator/designee arranges a three-way telephone call or videoconference call with the patient, a witness who is not otherwise connected with the clinical investigation, and, if desired and feasible, additional individuals requested by the patient (e.g., next of kin).
   1. Alternatively, in lieu of using a witness, a recording of the conversation can be made.
3. To ensure that patients are approached in a consistent fashion, a standard process should be used that will accomplish the following:
   1. Identification of who is on the call.
   2. Review of the ICF with the patient by the investigator/designee and response to any questions the patient may have.
   3. Verbal confirmation by the patient that their questions have been answered, that they would like to participate in the trial, and that they have signed and dated the ICF that is in their possession.
4. When using a witness, documentation of the trial records should include:
   1. A signed and dated attestation by the witness who participated in the call that the patient confirmed their agreement to participate in the trial and signed the ICF, and
   2. A signed and dated attestation by the investigator/designee stating why the ICF signed by the patient was not retained (e.g., due to potential contamination of the document by infectious material).
5. When using a recording in lieu of a witness, documentation in the trial records should include:
   1. The recording of the conference call, and
   2. A signed and dated attestation by the investigator/designee who participated in the call stating why the ICF signed by the patient was not retained (e.g., due to potential contamination of the document by infectious material).

When either method is used to document informed consent, the resulting documentation should be:

• Collected and archived, as either original paper copies or appropriately certified electronic copies (e.g., using a validated process for scanning paper copies), and
• Retained according to applicable FDA record retention requirements as part of the trial record.

If the patient is unable to provide informed consent and there is an LAR, investigators must obtain written consent from the patient’s LAR in accordance with 25 CFR 50.27.

HIPAA Considerations

Disclosures to Prevent a Serious and Imminent Threat: Health care providers may share patient information with anyone as necessary to prevent or lessen a serious and imminent threat to the health and safety of a person or the public – consistent with applicable law (such as state statutes, regulations, or case law) and the provider’s standards of ethical conduct. Thus, providers may disclose a patient’s health information to anyone who is in a position to prevent or lesson the serious and imminent threat, including family, friends, caregivers, and law enforcement without a patient’s permission. HIPAA expressly defers to the professional judgment of health professionals in making determinations about the nature and severity of the threat to health and safety. For more information, see 45 CFR 164.512(j).

Disclosures to Family, Friends, and Others Involved in an Individual’s Care and For Notification: The covered entity should get verbal permission from individuals or otherwise be able to reasonably infer that the patient does not object, when possible. If the individual is incapacitated or not available, covered entities may share information for these purposes if, in their professional judgment, doing so is in the patient’s best interest.

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When individuals cannot print and sign a paper copy of the ICF provided by the investigator/designee, they cannot electronically sign the ICF, and providing a paper copy of the ICF via mail/courier is not feasible within the timeframe for enrollment into the clinical trial, the investigator may consider using the following alternative process to satisfy FDA requirements for obtaining and documenting informed consent:

1. The investigator/designee provides the prospective participant (or LAR) with an electronic version of the ICF.
2. The investigator/designee arranges a telephone call or videoconference call with the prospective participant (or LAR), the investigator/designee, a witness who is not otherwise connected with the clinical investigation, and, if desired and feasible, additional participants requested by the prospective participant (e.g., next of kin).
   1. Alternatively, in lieu of using a witness, a recording of the conversation can be made.
3. To ensure the prospective participant (or LAR) is approached in a consistent fashion, a standard process should be used that will accomplish the following:
   1. Identification of who is on the call.
   2. Review of the ICF with the prospective participant (or LAR) by the investigator/designee and response to any questions the prospective participant (or LAR) may have.
   3. Verbal confirmation by the prospective participant (or LAR) that their questions have been answered and that they would like to participate in the trial.
4. Verbal confirmation by the participant (or LAR) that they signed and dated a blank piece of paper with a written statement that they voluntarily agree to participate in the protocol, noting both the protocol “number” and brief protocol title.
5. After signing and dating the newly created document, the trial participant (or LAR) sends a photograph of the signed and dated statement by fax, text message, or email to the investigator/designee OR returns the document to the investigator by mail at a later date or at a future study visit that might occur in person.
   1. When using a witness, documentation in the trial records includes a signed and dated attestation by the witness who participated on the call that the participant confirmed their agreement to participate in the trial and signed the document referenced above.
   2. When using a recording in lieu of a witness, documentation in the trial records should include the recording of the conference call.
6. After the signed and dated document is received by trial staff, it should be appended to a copy of the ICF that was reviewed with the trial participant (or LAR) and retained in the trial records as would normally be done for a signed ICF.
   1. Additionally, a note in the trial records should be made explaining the circumstances of why informed consent was obtained through an alternative method.
   2. The case history for each trial participant must document that informed consent was obtained prior to participation in the trial.

This alternative approach must be reviewed and approved by the IRB overseeing the trial as required by FDA regulations.

HIPAA Considerations

Disclosures to Prevent a Serious and Imminent Threat: Health care providers may share patient information with anyone as necessary to prevent or lessen a serious and imminent threat to the health and safety of a person or the public – consistent with applicable law (such as state statutes, regulations, or case law) and the provider’s standards of ethical conduct. Thus, providers may disclose a patient’s health information to anyone who is in a position to prevent or lesson the serious and imminent threat, including family, friends, caregivers, and law enforcement without a patient’s permission. HIPAA expressly defers to the professional judgment of health professionals in making determinations about the nature and severity of the threat to health and safety. For more information, see 45 CFR 164.512(j).

Disclosures to Family, Friends, and Others Involved in an Individual’s Care and For Notification: The covered entity should get verbal permission from individuals or otherwise be able to reasonably infer that the patient does not object, when possible. If the individual is incapacitated or not available, covered entities may share information for these purposes if, in their professional judgment, doing so is in the patient’s best interest.

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