RESEARCH CONTINUITY: IRB & HUMAN RESEARCH PROTECTIONS PROGRAM (HRPP)

Access to UCI research facilities is limited to UCI personnel and registered students. Human research participants may not be physically present at any UCI research facilities excepted for clinical research as provided for below in the clinical research matrix:

Yes, if your study site is located in space that is not owned or controlled by UCI and the entity that controls the site is permitting or will permit access for conducting human subjects research.  UCI personnel should follow the site’s guidelines and precautions, provided that doing so does not cause them to violate UCI policy. If a site does not have published guidelines and precautions, UCI personnel should follow UCI guidance and policies.  Delay research activities until a later phase if circumstances at a site may prevent personnel from either following the site’s guidelines and precautions or UCI’s guidance and policies

When LRs implement physical 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 before implementing the change.  LRs should include such changes as part of the next modification. Please see related listserv posting:  SARS-CoV-2/COVID-19 Related IRB Modifications – Points to Consider

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.

There are other prerequisite UCI committee reviews that may be required that may impact IRB review and approval. Please review the Other UCI Required Reviews Chart (PDF) to verify whether any ancillary committees apply.  

For Human Research involving COVID-19, please consider the following ancillary committees.   

INSTITUTIONAL BIOSAFETY COMMITTEE  (IBC)

The IBC reviews research procedures involving infectious agents and human materials when the work that is done at campus laboratories and UCIMC building 55 research laboratories. Use of all human materials (whether it is COVID-19 positive or not) require IBC approval at Biosafety level.

The IBC ensures that research involving these agents or materials is conducted in a manner that complies with all applicable regulations, policies and standard and does not endanger the researcher, laboratory worker, human research subjects, the public or the environment.

For additional information about the IBC please visit: Institutional Biosafety Committee (IBC) 

For applicable research, IBC approval must be provided to the IRB for final IRB approval to be granted. Securing IBC approval for biosafety issues (e.g., blood draws, specimens transferred from clinic to UCI lab, etc.) is the responsibility of the LR and is required before clinical research procedures are initiated. 

EPIDEMIOLOGY AND INFECTION PREVENTION (EIP) COMMITTEE

EIP review is required when the human research involves conducting a trial of devices or biologic or infectious agents (e.g. live vaccine, probiotic) at UC Irvine Health facilities.  Please review the Epidemiology & Infection Prevention Screening Form to determine whether EIP approval is required for this study.

This committee provides oversight for all infection prevention and control issues related to UC Irvine clinical areas. Focus of the review will be on adequacy of protocols to ensure patient and healthcare worker safety and prevent transmission. For example, review components may include cleaning and disinfection protocols, discarding infectious waste, use of personal protective equipment, and personnel training on infection prevention procedures, among others.

For additional information about the EIP please visit: Epidemiology and Infection Prevention (EIP) Committee  

EIP approval will not impact final IRB approval. However, securing EIP approval is the responsibility of the LR and is required before clinical research procedures are initiated. 

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

Studies involving in-person interactions in UCI space must exceed physical 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:

• Remote Clinical Research Guidelines During the COVID-19 Public Health Emergency
• 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 Physical 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)

COVID-19 Testing at UCI Non-CLIA Certified Clinical Laboratories:

• The study PIs will be responsible for referring to the research subjects to a physician/CLIA certified lab if the result is suspicious.
• Every laboratory completing non-CLIA certified testing should have a physician that can place orders for CLIA testing
• All the UCI laboratories at UCI, which are testing research subjects for COVID RNA or antibodies, should be registered with our UCI clinical laboratory, and have an SOP in place in case positive results are identified.

FDA - FAQs on Testing for SARS-CoV-2

HHS Laboratory Developed Tests FAQ

Department of Health and Human Services

• Memorandum on Interim Guidance for Clinical Trial Activities Affected by the Novel Coronavirus
• Additional Guidance Regarding Alternative Procedures for Clinical Trials Supported by the NCI Cancer Therapy Evaluation Program (CTEP) and NCI Community Oncology Research Program (NCORP) Affected by the Spread of the Novel Coronavirus

Food and Drug Administration

• FDA has created the Coronavirus Treatment Acceleration Program (CTAP), intended to accelerate review of protocol submissions for trials studying treatments for Covid-19
• FDA issued new guidance regarding use of non-invasive remote monitoring devices that measure or detect common physiological parameters and that are used to support patient monitoring during the COVID-19 public health emergency (listed below).
  The guidance directs that FDA does not intend to object to limited modifications to FDA-cleared non-invasive remote monitoring devices used to support patient monitoring during the declared public health emergency without prior submission of a premarket notification where the modification does not create an undue risk in light of the public health emergency. Examples may include wearable, hand-held, stationary in-home monitoring and digital interfaces. These non-invasive monitoring devices have the potential to be connected to a wireless network through Bluetooth, Wi-Fi, or cellular connection to transmit a patient’s measurements directly to their health care provider or other monitoring entity. Some of these devices also have the potential to apply algorithms to transform a patient’s physiological parameters into a novel index or alarm that may aid a health care professional in the diagnosis of a particular condition or disease state/severity.
• FDA Guidance Documents on Plasma to Treat Covid-19
  • Investigational COVID-19 Convalescent Plasma Guidance for Industry
  • Investigational COVID-19 Convalescent Plasma - Emergency INDs
  • Investigational COVID-19 Convalescent Plasma - Emergency INDs Frequently Asked Questions

• Additional FDA Guidance
  • Assessing COVID-19-Related Symptoms in Outpatient Adult and Adolescent Subjects in Clinical Trials 
  • COVID 19: Developing Drugs and Biological Products for Treatment or Prevention
  • Guidance on Conduct of Clinical Trials of Medical Products during the COVID-19 Pandemic
  • Postmarketing Adverse Event Reporting for Medical Products and Dietary Supplements During a Pandemic
  • COVID-19: Developing Drugs and Biological Products for Treatment or Prevention: Guidance for Industry
  • COVID-19 Public Health Emergency: General Considerations for Pre-IND Meeting Requests for COVID-19 Related Drugs and Biological Products : Guidance for Industry and Investigators
  • Policy for Coronavirus Disease-2019 Tests During the Public Health Emergency (Revised): Immediately in Effect Guidance for Clinical Laboratories, Commercial Manufacturers, and Food and Drug
    
  • IRB Review of Individual Patient Expanded Access Requests for Investigational Drugs and Biological Products During the COVID-19 Public Health Emergency
  • Supplements for Approved Premarket Approval (PMA) or Humanitarian Device Exemption (HDE) Submissions During the Coronavirus Disease 2019 (COVID-19) Public Health Emergency

On April 9, 2020, OHRP issued “OHRP Guidance on COVID-19.” The guidance responds to questions OHRP received from the research community regarding how the Department of Health and Human Services (HHS) human subjects protection regulations (45 CFR part 46) apply to actions taken by institutions and investigators in response to the COVID-19 outbreak.

OHRP offers guidance on the following topics: (i) Public Health and Clinical Activities; (ii) Excluded Public Health Surveillance Activities; (iii) Legally Required Reporting; (iv) Research Changes to Eliminate Apparent Immediate Hazards; (v) Proposing and Reviewing Study Changes; and, (vi) Whether Suspensions of Research Must be Reported.

The guidance document can be accessed at: https://www.hhs.gov/ohrp/regulations-and-policy/guidance/ohrp-guidance-on-covid-19/index.html

Should you want to review additional resources on the PREP Act and this Declaration, they are available here:

• COVID-19 - Medical Countermeasures (effective February 4, 2020)
  • Amended April 10, 2020 to add countermeasures pursuant to the CARES Act
  • OGC Advisory Opinion on PREP Act Declaration

On March 17, 2020, HHS issued a Declaration, under the Public Readiness and Emergency Preparedness Act (PREP Act), providing immunity to certain covered persons against any claim of loss caused by, arising out of, relating to, or resulting from the manufacture, distribution, administration, or use of drugs, biologics, diagnostics, devices, and vaccines used to treat, diagnose, cure, prevent, or mitigate COVID-19. The product must be used under an FDA-approved mechanism – i.e., EUA, IND, IDE, etc. The Act enables individuals (patients, representatives, and estates) to seek compensation from HRSA under the CICP Program for serious injuries resulting from the activities described above. Compensation may include unreimbursed medical expenses (expenses that health insurance did not cover), lost employment income, and the survivor death benefit.

If a study involves the use of drugs, biologics, diagnostics, devices, and vaccines used to treat, diagnose, cure, prevent, or mitigate COVID-19 and the product used is under an FDA-approved mechanism, please include this language:

"If you are injured as a result of being in this study, the University of California will provide necessary medical treatment. The costs of the treatment may be billed to you or your insurer just like any other medical costs, or covered by the study sponsor or another entity, depending on a number of factors.

Due to the coronavirus public health crisis, the federal government issued a Declaration under the Public Readiness and Emergency Preparedness (PREP) Act. If the Declaration applies, it limits your right to sue and recover for losses from the researchers, healthcare providers, any study sponsor or manufacturer or distributor involved with the study, including the University of California, while participating in this COVID-19 clinical study. However, the federal government has a program that may provide compensation to you or your family for certain claims if you experience serious physical injuries or death and these costs are not covered by other payors. To find out more about this “Countermeasures Injury Compensation Program” go to https://www.hrsa.gov/cicp/about/index.html or call 1-855-266-2427."

Add the following text for COVID-19 research as applicable:

“HIV / Hepatitis / COVID-19 testing:  Being tested may make you feel nervous or anxious about the test results. Receiving positive results may make you very upset.  If other people learn about your positive test results, you may have trouble obtaining insurance or employment. To the extent permitted by law, the researchers will keep your test results confidential and will not release them to anyone without your written permission. If you test positive, California law requires health care providers and clinical laboratories to report the test results with your personal identifying information to the local health department.”

Template – Information Letter for Current Participants (Covid-19)