COVID-19 (SARS-CoV-2) and Human Subjects Research FAQ

Amendment requests are NOT REQUIRED if you are halting, rescheduling, or delaying study enrollment UNLESS those actions are at the request of the funding agency, study sponsor, or data & safety monitoring group.

Amendment requests are REQUIRED and IRB approval must be obtained before you change study procedures for new or existing participants that could impact the safety of participants, the integrity of the data, or participants’ willingness to continue participation.

There are some limited exceptions to the requirement for an amendment: For IRB-approved applications that do not specify whether a procedure is remote versus in-person, you do not need to submit an amendment. If the revised deviation is minor (does not impact the safety of participants, the integrity of the data, or participants’ willingness to continue) and due to COVID-19 disruptions, these may be implemented and documented in the deviation log

Check with the OHRPP Office if you have questions. Be sure to include the following information in your amendment application:

• Potential impact on subject safety and protections
• Potential impact on scientific integrity and/or benefits of the study
• Plan for how existing subjects will be notified (if their participation will be affected by the Modification)
• Number of existing participants affected by the proposed change (if any)
• Date of proposed change implementation

Post Approval Reports (PARs) are NOT REQUIRED for halting, suspending, re-scheduling or delaying procedures for current participants except for studies with ALL of the following characteristics:

• The study involves an Intervention (i.e., not observational or no contact), and
• The study involves more than minimal risk to the participants (i.e., it was initially reviewed by the full convened IRB instead of minimal risk “expedited” review), and
• The suspension potentially has an impact on safety monitoring or the study’s scientific integrity

Post Approval Reports (PARs) are REQUIRED when you:

• Have had to implement changes to study procedures (including halting, delay, or revision of monitoring procedures) to prevent an immediate apparent hazard to one or more participants and did not have time to obtain prior IRB approval, or
• Are halting, suspending, re-scheduling or delaying procedures for current participants in studies with ALL of the following characteristics:
  • The study involves an Intervention (i.e., not observational or no contact), and
  • The study involves more than minimal risk to the participants (i.e., it was initially reviewed by the full convened IRB instead of minimal risk “expedited” review), and
  • The suspension potentially has an impact on safety monitoring or the study’s scientific integrity

Conduct a short screening by phone, email or other remote method, for exposure to the novel coronavirus COVID-19 or symptoms of illness before any study-related visits and in-person interactions. Research participants with possible exposure or symptoms of illness should not participate in in-person interactions until after the time recommended by current public health recommendations. This screening procedure does not require IRB approval.

Research visits that cannot be performed remotely and are essential (provide immediate benefit) to a participant’s health and/or well-being may be performed in person, with the following additional guidance:

• Research participants should be contacted a few days prior to their visit by study personnel to be informed about measures being taken at UCLA Health to protect visitors/subjects against coronavirus:
  • Please evaluate the participant based on the CDC criteria for evaluating and reporting Persons Under Investigation (PUI). Subjects who are PUI should avoid research visits until cleared by their primary care provider.
  • If a study team encounters a study participant that they are concerned has COVID-19, they should follow the flow chart at the following web-site with regard to whether to contact the EID Physician On-Call.

UCLA Health has created an 11-member COVID-19 Scientific Prioritization and Feasibility Committee (SPFC). This committee will review studies submitted to the IRB that are COVID related that involve UCLA Health patients or health care workers and/or UCLA Health clinical research infrastructure.

Section 1.1b/Item 3.0 of the BruinIRB application is used to identify studies requiring SPFC review.

Is this a COVID-19 research proposal that falls under the following scope:

• Access to the suspected and confirmed UCLA Health COVID-19 patients.
• Access to the electronic medical record chart or data of those patients.
• Access to the remnant or research biospecimen collection of those patients.
• Planning any clinical research interventional trial (drug/device) for those patients.
• COVID Population-based studies that overlap the UCLA Health population or UCLA healthcare workers.

Applications that involve any of the above are referred to the SPFC for review prior to IRB review.

UCLA now has a part 11 compliant version of DocuSign available for electronic consent documentation of FDA-regulated research. For more information on this e-consent option, please contact UCLA Health Office of Compliance Services. For research that is not FDA-regulated, other methods of electronic consent documentation may be used (including UCLA Campus DocuSign). If the use of part 11 compliant DocuSign is not possible, FDA COVID-19 guidance affirmed by OHRP COVID-19 guidance, provides alternate methods for conducting and documenting the consent process when the participant (or parent/legal guardian or legally authorized representative) is in COVID-19 isolation. Use of alternative consenting processes must be documented in a note to file. See pages 15-16 of the FDA guidance for details on alternative consent processes.

Use of electronic/alternative methods of obtaining consent to accommodate COVID-19 isolation does not require prior review/approval by the IRB.

The criterion that the research must provide an immediate benefit to a participant's health and/or well-being must be followed if the research requires in-person visits. This is for the safety of the participant as well as the research staff. Research must also adhere to Governor Newsom's order that everyone is required to stay home except to get food, care for a relative or friend, get necessary health care, or go to an essential job. Research that can be conducted remotely can continue as long as the above criteria can be followed.

No. The memo itself does not need to be submitted.

However, if you plan to operationalize these flexibilities and they are not currently allowed in the IRB-approved application, there are four possible pathways to implement COVID-19 related changes to the protocol:

1. If you are adding COVID-19 infection-control procedures (such as telephone screening in advance of in-person research visits or temperature screening at arrival) in line with the medical center’s practices or public health authority recommendations/requirements, no submission to the IRB is needed.
2. If you are making COVID-19-related deviations from study procedures AND the changes meet all of the following conditions, you may implement the change without prior IRB approval (amendment) or submission to the IRB after the fact (PAR).
   
   1. Does not impact the safety of participants;
   2. Does not impact the integrity of the data;
      AND
   3. Does not impact participants’ willingness to continue participation.

• These deviations should be noted in the deviation log (make sure to note that these deviations are due to COVID-19).

For any other COVID-19-related changes to the protocol, please follow existing PAR guidance:

3. Submit an amendment in advance of implementing the change (preferred)
4. If there is insufficient time to submit an amendment in advance AND the change needs to be implemented in order to avoid an immediate hazard to participants, the deviation may be implemented and notification made to the IRB via PAR application within 3 working days of the deviation.

• • Please consult with the administrator for the IRB assigned to this protocol to determine the time frame for amendment review

For COVID-19-related protocol deviations that are due to Institutional policy changes, that do not impact subject safety, compromise the integrity of study data and/or affect the subjects willingness to participate in the study do not require prior IRB review and approval or reporting via PAR. These minor deviations should be noted (and flagged as COVID-19-related) in the deviation log submitted at continuing review.

Currently the IRB would require an amendment if the currently approved protocol disallows the revise procedure unless

• The changes were needed to avoid an immediate hazard or the protocol did not include such specific detail that would then necessitate a modification. The IRB is prepared to prioritize the review and approval of these amendments accordingly.

OR

• The changes are COVID-19-related, minor deviations (does not impact the safety of participants, the integrity of the data, or participants’ willingness to continue participation). These minor, COVID-19-related deviations should be noted in the deviation log submitted at continuing review (for FDA-regulated and more than minimal-risk research) or maintained in study records for minimal risks research that does not have a continuing review requirement.

Some clinical studies involve in-person study visits in order to conduct safety monitoring of the participants. For example, participants in a treatment study involving a study drug may need to have regular examinations, interviews, or laboratory tests for specific possible side effects.

Researchers should plan for alternatives to in-person monitoring visits, if possible. If appropriate for the study, this might include:

• Delay, postpone, or modify the visits
• Phone or email check-in calls
• Photos taken and delivered by cell phone (e.g., of wound healing)
• Visits to participants’ for exams or specimen collection
• Use (or establishment) of a mobile specimen collection service

These modifications to safety monitoring procedures should be approved in advance by the IRB, except when necessary to eliminate apparent hazards to a participant and there is not sufficient time to obtain IRB approval. Consult with the OHRPP staff if you have questions. If you do need to change an approved monitoring procedure to eliminate apparent immediate hazard to the participant, please report it to the UCLA IRB within 3 business days as outlined in the PAR guidance.

This does not need to be reported to the UCLA IRBs if the suspension of research is initiated in order to follow UCLA institutional policies related to COVID-19.

If a study suspension/hold is initiated by the PI for reasons other than following local institution’s COVID-19 policy or is initiated by (as applicable) the Sponsor, the study’s DSMB, or the FDA, please submit a Post Approval Report per the PAR Guidance.

Most minimal risk research is eligible for approval of a waiver of the requirement for documented (signed) informed consent. If you wish to modify your research procedures to consent participants and collect data online or through other alternate procedures to avoid in person interactions, please create an amendment application to modify your protocol. You must obtain UCLA IRB approval for the modified consent process and/or data collection procedures prior to initiating your new/modified procedures.

UCLA guidance and templates for consent without signatures:

• UCLA OHRPP Guidance and Procedure: Requesting Waivers and Exceptions to Informed Consent
• UCLA OHRPP Consent Template: Study Information Sheet (No signature)
• UCLA OHRPP Consent Template: Oral Consent Script

Tip: When the study information sheet is used for online survey research, it can be modified to include add a check box at the end of the document for participants to indicate their agreement to participate before proceeding to the online survey questions, however this is not required.

In cases of international research, it is the Principal Investigator's responsibility, working with their international colleagues, to keep up to date with policies and directives from national or local governments and from collaborating institutions and their IRBs. It is essential that these policies be followed both for the benefit of the participant and the safety of research staff. Protocol modifications will continue to require both UCLA and collaborating institutions' IRB approvals. We also recommend that UCLA's policies be shared with collaborating institutions, as they are often helpful in considering what needs to be done in various settings where the risk of COVID-19 may be higher or lower than in Los Angeles.

In cases of international research, it is the Principal Investigator's responsibility, working with their international colleagues, to keep up to date with policies and directives from national or local governments and from collaborating institutions and their IRBs. It is essential that these policies be followed both for the benefit of the participant and the safety of research staff. Protocol modifications will continue to require both UCLA and collaborating institutions' IRB approvals. We also recommend that UCLA's policies be shared with collaborating institutions, as they are often helpful in considering what needs to be done in various settings where the risk of COVID-19 may be higher or lower than in Los Angeles. Please contact the OHRPP with any questions.

Researchers are responsible for identifying and complying with all applicable University travel restrictions.

Additionally, it is essential that the PI of international studies with no international collaborating institution keep up to date about policies regarding research in those countries and comply with those policies with regard to in-person contact. This is essential for the safety of the participants as well as research staff, including the PI if that person is going to be conducting the study in international settings. PIs need to be up to date on travel policies if they will be working internationally, both in terms of what countries are allowing in terms of international visitors and the need to repatriate to the United States once the work is completed. PIs should also be up to date on the evacuation policies related to COVID-19 under the University of California travel insurance policies.

Given the potential for multiple trials and alternative therapies in completing clinical protocols, please provide in your protocol defined inclusion and exclusion criteria, clear instructions regarding how you intend to identify and recruit potential participants, how the researcher will determine to which protocol a potential participant may be enrolled, what potential alternative treatments are available, how these potential treatments are communicated to the potential participant, any potential inclusion of the treatment provider in making determinations regarding enrollment, and how enrollment into one study or another may be prioritized within a department or research group. Depending on the inclusion criteria (the stage of disease progression at enrollment), consider whether or not a potential participant may be temporarily incapacitated (for example, intubated in the ICU) necessitating the use of a legally authorized representative for consent. The IRB must review (in advance) the possible inclusion in research of adults with impaired decision-making capacity.

If you have started your research and conducted in-person procedures prior to COVID-19 related public health closures and/or plan to resume in-person procedures after COVID-19 related public health closures are lifted, do NOT remove the description of in-person procedures from your BruinIRB application. Instead, add new paragraphs and documents to describe and support your planned remote recruitment, consent, and/or data collection.

Only if you have not commenced in-person research procedures and plan to completely replace your prior research plan with a proposal for remote data collection only, should you remove in-person recruitment, consent, and/or data collection procedures from your BruinIRB application.

Please remember to describe your proposed changes both in the amendment summary page AND in the main study protocol application in order to minimize delays in IRB review of your submission. Additionally, it is recommended that you include a descriptor such as “temporary changes due to COVID-19” in your amendment title.

No, the IRB does not need to review this communication.

The IRB would typically defer to the PI/sponsor and existing inclusion/exclusion criteria. Clinical Research protocols generally allow for the PIs to withdraw their subjects for any reason. If research subjects are able to participate in a COVID-19 treatment protocol as concomitant medication without impacting the existing trial then that should be acceptable. If subjects cannot, and they need to be withdrawn from participation to seek treatment, then that should be no different than any other withdrawal. If sponsors are going to revise their study design to allow for treatment/participation in COVID-19 trial, when it would otherwise not be permissible to continue the subject’s participation, then yes the study sponsor should amend their protocol to address how this would be implemented.

All PIs and study teams should immediately develop a COVID-19 mitigation plan. The plan should include the following elements, at a minimum. These do not need to be reviewed and approved by the IRB.

• Avoid all participants with confirmed COVID-19 infection or requiring potentially aerosolizing procedures
• Decrease potential exposure for nonclinical personnel at increased risk of severe illness from COVID-19. People at higher risk include any of the following:
  • Over 60 years of age
  • With underlying health conditions, including heart disease, lung disease, or diabetes
  • With weakened immune systems
  • Who are pregnant
  • Caregivers of children with underlying health conditions
• Have a protocol for noncontact screening for active symptoms of acute respiratory infection possibly related to COVID-19 or high risk of infection. This may be accomplished by communication with participants, care providers, chart review, screening surveys, or other options prior to approaching potential research participants. Individuals with active symptoms should be avoided.
• Reduce face-to-face contact with research participants. For example, this may be accomplished by including barriers between research personnel and participants, and/or using technology (e.g., telephone, zoom, facetime, email) to conduct interviews.
• Address Personal Protective Equipment (PPE) training status for nonclinical research personnel who need to be within 6 feet of participants, if appropriate for the study. Address sources of PPE for research use. Address methods to reduce PPE usage by all personnel, including limiting requests for second blood draws and sample collections by clinical personnel.

For the most up to date information that impacts clinical research at UCLA hospitals and Clinics please visit the UCLA Clinical Translational Science Institute Research Go website.

Actions are being taken to limit potential exposure to personnel and participants, and to avoid disruption to clinical personnel responding to patient needs. It is also related to the UCLA decision to limit hospital visitors (with some exceptions) and the Los Angeles County Department of Public Health recommendation to avoid visiting hospitals and to keep six feet away from patients. UCLA Medical facilities are experiencing an increasing influx of patients seeking care for suspected and/or confirmed COVID-19. This is expected to continue in the coming weeks.

It is recognized that this will have a negative impact on research studies recruiting participants at UCLA. Communications will be broadly distributed as soon as it is safe to resume the studies. In the meantime, UCLA research administration will be happy to communicate with funding agencies and grants officers as needed.

Studies that conduct self-monitoring or that monitor participating sites should consider how to adapt monitoring procedures to occur remotely. Possibilities might include: email, conference calls or video conferencing (e.g., Zoom), or appropriately secure exchange of files and data. Any reduction in the nature or frequency of IRB-approved monitoring procedures should be approved in advance by the IRB.

The UCLA IRBs are fully operational. The Office of the Human Research Protection Program (OHRPP)/IRB has contingency plans in place to maintain continuity. BruinIRB can be accessed anywhere an individual has internet access. Similarly, the OHRPP has the capability to conduct IRB committee meetings via Zoom. We expect this to continue even if the University suspends operations for contagion control purposes. All UCLA OHRPP email addresses and voicemail continue to be monitored with the same or greater frequency However, responses to inquiries and applications that are not related to COVID-19 or its impact on research may be delayed somewhat. For any questions or concerns, contact the OHRPP office.

The differences

• Highest priority is being given to all inquiries, requests, applications, and modifications related to COVID-19, and to their impact on ongoing research.

Some studies registered at the federal site ClinicalTrials.gov are modifying their research procedures to include testing for COVID-19 and/or assessment of COVID-19 symptoms. The ClinicalTrials.gov information for the study should be updated to include these new procedures, if they are done for research purposes. If they are being added as public health surveillance activities in coordination with public health authorities, the registration information does not need to be modified. The federal requirement about modifications is that any research-related changes that are communicated to the subjects (past, ongoing, future) must be added to the study’s ClinicalTrials.gov registration with 30 days after IRB approval of the modification.

The procedure for Single Patient Emergency Use of an experimental drug or device remains the same during the COVID-19 situation. Please contact the OHRPP office for any questions.

In some cases, IRB approval may not be required for COVID-19-related activities. For example, the activities may consist solely of public health surveillance activities, clinical care, or diagnostic testing for which an FDA emergency authorization has been obtained. UCLA OHRPP can assess the circumstances, provide advice, and issue determination letters (if warranted).

For all UCLA COVID-19 clinical research. Contact Dr. Arash Naeim at aneim@mednet.ucla.edu  who is coordinating efforts on behalf of the CTSI, Dean’s Office, and Division of Infectious Disease.

For specific issues related to research involving any UCLA Medicine facilities or patients. Contact Arash Naeim MD PhD, Chief Medical Officer for Clinical Research, at anaeim@mednet.ucla.edu.

For biospecimen guidance for study participants with COVID-19 exposure/concern please follow standard universal precautions for all patient samples.  Please refer to the following links for changing guidance:

• UCLA Health
• UCLA Pathology & Laboratory Medicine

Studies may not be able to meet their participant enrollment goals because of COVID-19-related issues. This should be described in a study’s Continuing Review application (i.e., “Status Report”). The IRB will be mindful of the circumstances when conducting its review.

You do not need to submit anything to UCLA IRB unless you are:

• Changing the PI
• Changing the IRB
• Closing the study
• The non-UCLA IRB has requested that you contact UCLA for guidance

However, if a non-UCLA IRB approves changes to the protocol, you are required to submit the new approval as an amendment to the UCLA IRB.

Each non-UCLA IRB may have different policies for what to report about suspending enrollment, activities, etc. However, in most cases if you are changing study procedures or moving from paper-based consent to e-consent, you will need to modify the study.

For multi-site studies, you may need to work with the coordinating center, lead study team, sponsor or CRO as part of implementing changes.

Some study participants may not be able to come to hospitals, clinics, or other study locations because of infection, self-isolation, travel restrictions, facilities restrictions, or being in a COVID-19 high risk group. Study teams should plan for this possibility and submit a Modification for any alternatives. These might include (but are not limited to):

• Phone calls, including use of telemedicine options.
• Use of digital technology to record symptoms (e.g., cell phone photo of a healing surgical wound).
• Visits from appropriately screened and trained study staff, visiting nurses, home health aids, etc., to conduct study procedures.
• Providing study medications through an appropriate home delivery mechanism. You should first consult with the entity providing the medication (e.g., UCLA Pharmacy; study sponsor) to find out about applicable state and federal laws.