RESEARCH CONTINUITY: UCI’S IRB AND HUMAN RESEARCH PROTECTIONS PROGRAM (HRPP)

Non-critical research has been halted, in accordance with the Vice Chancellor for Research’s shutdown message. However, all non-critical human subject research that can be performed from the homes/residences of the research team may continue.

• Social, Behavioral and Educational Studies – if a study involves in-person interactions with participants that study activity may only continue if the activity can be carried out through alternative means (e.g., over the phone or by videoconferencing, etc.).
• Non-therapeutic Clinical Research - Lead Researchers (LR) and sponsors of studies involving visits to one of UCI’s research centers must postpone site-visit recruitment immediately, and actively explore ways to continue the study using telemedicine or other forms of communication which do not involve study participant-study staff physical interaction. The UCI CCR-ICTS Clinical Research Acceleration and Facilitation Team (CRAFT) will work with LRs and sponsors to identify acceptable procedures to safely complete data accrual.

All Critical Research may continue, but social distancing guidelines must be exceeded as required by the Vice Chancellor for Research’s shutdown message.

• Social, Behavioral and Educational Studies
  
  • COVID-19 relevant studies should promptly coordinate with the CRAFT – COVID 19 committee.
  • If a study involves in-person interactions with participants that cannot be carried out through alternative means (e.g., over the phone or by videoconferencing, etc.), the LR is responsible for ensuring that research team members and participants exceed the social distancing guidelines, and that the space used for these interactions is thoroughly cleaned between each participant visit. In addition, the LR is responsible for ensuring that each participant is screened as described below.
• Therapeutic Clinical Research – Enrollment in studies that involve necessary visits to one of the UCI clinical research sites can continue if continued enrollment is deemed by the sponsor, LR and cognizant Dean (or designee) to be critical for the health of study participants. When clarification or adjudication is needed, the following procedure must be followed:
  • The LR, sponsor, or key staff may raise the issue with Drs. Bota and/or Cooper.
  • The issue will be formally discussed (notes taken, etc.) at the daily CCR-ICTS briefing.
  • If appropriate, the issue will be adjudicated by the CRAFT committee.
  • In all cases, approval of any change in the study protocol, accrual, or retention plans must be approved by the sponsor.
  • If a change in approved procedures is necessary to eliminate apparent immediate hazards to the human subjects or the study team, a formal prospective modification to the IRB is not required per 21 CFR 56.108(a)(4) and 45 CFR 46.108(a)(3)(iii). Direct questions about whether a modification meets the intent of the regulations to the HRP Staff who can coordinate with the IRB Chair/s (if necessary). Otherwise, make the change, log it in the study record and update the IRB protocol at the next necessary modification.
  • In all decisions, the safety of patients, participants and study staff (per FDA guidelines) is paramount.
  • While the above is currently consistent with policies from federal, state, UC and other authoritative bodies, such policies and directives may change overtime and will supersede local decisions where those decisions conflict with such policies and directives.

When LRs implement social distancing in lieu in-person interactions (e.g., change IRB- approved study procedures from an in-person interaction to a phone interaction, etc.), a modification is not required prior to implementation.  In an effort to facilitate research during this public health crisis, as further noted above, protocol changes to implement various methods of social distancing must be added to the protocol at the next modification.

During the declared national and statewide emergency in response to the COVID-19 pandemic, the UCI IRB is broadly allowing the use of DocuSign as well as phone consent with voice recording to document informed consent for:

1. Critical Research, as determined by the Dean or research unit director, involving human participants, and
2. Non-critical human research carried out from the homes of study team members.

About DocuSign – Use DocuSign for electronic consent when a subject has access to their own computer, tablet or smart phone.  For security reasons, they subjects should not use public or shared devices for signing e-informed consents.  For information about DocuSign, please visit: https://docusign.uci.edu/

About Phone Consent and Audio Recordings – For those researchers where DocuSign may not be an option.  If written consent is required, this process can occur over the phone, and should include an audio recording to document the consent process.  Remember that all expectations of informed consent documentation still apply (45 CFR 46.117 and 21 CFR 50.27), in particular, please be sure to provide a copy of the consent to the subject to keep either by mail, email or fax.  Please review and/or use this sample script template when developing a script for your study.

Important Things to Remember – Please discuss the use of DocuSign (because UCI’s licensed version is not compliant with 21 CFR Part 11) or phone consent with your sponsor/s and (as applicable) the IRB of Record prior to implementing.  Please do not submit a prospective modification to the IRB requesting DocuSign.  Rather, make the change, log it in the study record and update the IRB protocol at the next necessary modification.

Whether using DocuSign, phone consent or written consent, Lead Researchers must ensure there is a system to verify the subject’s identity and facilitate the subject’s understanding of the information presented to them. To help ensure the highest quality of clinical data, please review this resource on how paper and electronic source data meet ALCOA elements. Consider using RedCap to store consent documents and electronic recordings.

Federal Regulations - Before getting started with any electronic consent process, researchers and their teams should review the joint FDA/OHRP guidance on using electronic consent in FDA-regulated research:  Use of Electronic Informed Consent in Clinical Investigations – Questions and Answers.  In addition, please refer to the FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic.

HIPAA- For studies involving protected health information where the UCI IRB has required HIPAA research authorization be obtained, electronic consent may also be used.  Refer to Notification of Enforcement Discretion for telehealth remote communications during the COVID-19 nationwide public health emergency and FAQs on telehealth remote communications for more information.

Studies activities conducted in a study participant’s home must be halted immediately.

Studies involving in-person interactions in UCI space must exceed social distancing guidelines, and must include a short screening of participants to assess exposure to and symptoms of COVID-19.  A screening process for symptoms, recent travel, or exposure to confirmed cases of COVID-19 is not considered a research procedure and does not require review or approval by the UCI HRPP/IRB. The following approach is advised:

• Please call participants prior to their appointment and inform them that they should not come in for the study visit if they have a fever, sore throat, and/or symptoms of acute respiratory distress (cough, difficulty breathing, etc.). Inform them that they will be immediately sent home if they arrive for their appointment and exhibit any of these symptoms and their appointment will be rescheduled.
• Ask participants about recent travel, especially international travel to any of the CDC Level 2 - 3 countries, or whether they have been in close proximity to a person who recently returned from international travel, especially from CDC Level 2 - 3 countries. If they have, inform them that their appointment will be rescheduled.
• Ask participants if they have been in close proximity to a person with a confirmed case of COVID-19, or a person who is currently a person under investigation for COVID-19 infection (i.e., the person has been or will be tested for COVID-19). If they have, inform them that their appointment will be rescheduled.
• Reassure participants that study visit compensation (if applicable) will still be received if their visit needs to be rescheduled.
• In the event that a participant clears the above screening, but exhibits symptoms at the time of appointment, the study procedures should not be conducted, and the participant should be instructed to return home and to contact (by telephone) their healthcare provider to arrange for an evaluation and their care. The participant should also be informed that the study personnel will contact them to reschedule the appointment.
• Below is suggested screening language:
  • Within the last 30 days, have you had a fever, cough, sore throat, difficulty breathing, or any other respiratory symptoms? Do you have any of these symptoms now?
  • Have you returned from international travel within the last 30 days? If so, to what countries did you travel?  During your travel, did you pass through or lay over in any of the following countries:  China, Japan, South Korea, Iran, or Italy? (Note, this list of CDC Level 2 - 3 countries may change and should be updated with the countries on the CDC Level 2 and 3 lists at the time of screening.)
  • Within the last 30 days, have you been in close contact with someone who has a confirmed case of COVID-19 (Coronavirus), or have you been in close contact with someone who will be or has been tested for COVID-19? If so, and the person was tested, did they test positive for COVID-19?
• If study procedures include collecting biospecimens, all standard precautions and safety procedures should be followed, along with any additional safety procedures determined to be appropriate by the LR. Biospecimens should not be collected from participants who do not clear the above screening.

The clinical research enterprise at UCI (Center for Clinical Research (CCR), Institute for Clinical and Translational Science (ICTS), Chao Family Comprehensive Cancer Center (CFCCC), and Alpha Stem Cell Clinic (ASCC)) is fully committed to the safety of our research participants, staff, faculty, and our community in every aspect of clinical research and clinical trials at all times and in particular during the present uncertainty surrounding COVID-19. Our clinical research enterprises adhere fully to the specific patient and staff safety guidelines currently developed.

The following guidance is effective until further notice, and will be updated as conditions change:

• During the current COVID-19 outbreak, ensuring health and safety requires the implementation of special precautions and policies affecting UCI Clinical Research facilities. UCI CCR is working with the Office of Research (local and central IRBs) to implement regulatory changes (e.g. See the WCG communication about possible regulatory changes and their implications).
• IRB approval is not required when hazard is apparent, as per FDA and HHS regulations. Changes to the protocol (other than the addition of a COVID-19 screening process) can be added to the protocol at next modification.
• UCI Clinical Research Staff will be asked to respect the current UCI Health regulations regarding COVID-19 and will be educated on Enhanced Hand Hygiene and Social Distancing Interventions (see Box 1 on workplace rules from Dalton et al.).
• Research treatments requiring hospital/infusion room procedures for patients currently enrolled in clinical trials will continue as scheduled while observing the precautions now enforced for all UCI Health patients (please see the UCI Health Screening policy for patients and other useful protocols).
• Shipping of oral investigational products directly to research patients will be considered when allowable.
• Whenever possible and permitted per protocol, investigators are encouraged to optimize the use of telemedicine, appropriately protected social media, or video and phone conferencing using proper safeguards for research participant confidentiality.
• Clinical trial patients on follow-up after completing the active treatment period and non-therapeutic clinical trial participants might have their visits or study procedures (laboratory and imaging, etc.) rescheduled/delayed if the health system resources are limited due to COVID-19 treatments.
• Site visits (e.g. pre-site selection visits, site initiation visits, interim monitoring visits, etc.) conducted by industry partners, auditors and clinical research organizations (CROs) are encouraged to be conducted remotely when possible. When on-site visits must occur, all precautions in affect for visitors at UCI Health must be observed.

Regulatory References

• FDA: “Each IRB shall … (a) Follow written procedures for ensuring that changes in approved research, during the period for which IRB approval has already been given, may not be initiated without IRB review and approval except where necessary to eliminate apparent immediate hazards to the human subjects.” - 21 CFR 56.108(a)(4)
• HHS: “…Ensuring 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.” 45 CFR 46.108(a)(3)(iii)

• Department of Health and Human Services – Memorandum on Interim Guidance for Clinical Trial Activities Affected by the Novel Coronavirus
• Food and Drug Administration – Guidance on Conduct of Clinical Trials of Medical Products during the COVID-19 Pandemic