Please see the table below.  

Federal Regulations permit changes to the approved protocol if the changes are necessary to immediately eliminate or reduce an apparent hazard to the safety of research participants or others.

Such changes may be initiated without prior IRB approval. A report must be submitted to the IRB/HRPP within 10 working days of initiation on a protocol violation/incident report form.

Note: Temporary pauses in recruitment or other study activities implemented in conformance with UCSF policy that do not alter risks to participants do not need to be reported to the IRB, but should be noted when submitting the next modification or continuing review submission. You do not need IRB approval to communicate with research participants to inform them of a pause in recruitment or changes to study activities. Make a note to your study files to document these communications.

Guidance on what forms to complete when considering implementing a deviation that may impact participant risks in response to COVID-19:

​1. Are the proposed changes necessary for protecting a research participant from COVID-19?

In your opinion is the change truly a result of COVID-19? If no, the subsequent questions do not apply to your circumstance. Complete an Ask Andy form to obtain guidance from the HRPP.

2. Are the changes being made to comply with current UCSF policy or local ordinances?

3. Is the change for one participant or multiple participants?

If the change is projected to be long term, impacting multiple participants, a Modification form should be submitted. If the change is short term, impacting multiple participants also submit a modification form.

If the change will affect only 1-2 participants in a unique circumstance, see the “Exception” instructions at the bottom of this column.

4. Will the change be a longer term or short-term change?

If the change is long term (foreseeable future) or for multiple participants a modification should be submitted prior to implementation.

 

Tip: consider developing flexible protocols that include contingency plans up front, reverting back to the initial protocol when possible.

5. Has the sponsor provided guidance regarding the proposed protocol deviation?

If so, is there sponsor documentation to support the deviation?

Note: If the sponsor has provided guidance this documentation should be submitted for IRB acknowledgement on a reporting form.

If your study has a specific requirement for signed consent as the only acceptable form of consent for some or all of your participants, you must continue to obtain signed consent from subjects enrolled remotely. Studies without a specific requirement for signed consent and that are not FDA-regulated may consider using other electronic methods. 

UCSF has two electronic platforms that can be used for signed research consent and HIPAA research authorization: DocuSign and REDCap. Each of these platforms has a regular/standard version and an FDA-compliant version. Studies not regulated by the FDA are encouraged to use an FDA-compliant version for extra protection, but it is not required. FDA-regulated studies are required use an FDA-compliant version. In addition, the Eureka Research Platform (a UCSF-hosted resource) can be used to deliver a Docusign consent form in the context of a digital/online research study. 

If you are considering use of any other software for collecting e-signatures for non-FDA-regulated studies, you must obtain approval from the IT Security Risk Assessment team.

Information about the standard (not FDA-compliant) versions of each platform can be found at:

• DocuSign
• REDCap
• Eureka Research Platform

Information about the FDA-compliant versions of Docusign and REDCap:

• DocuSign: Submit an access request to use the FDA-compliant version of DocuSign. If you have questions or need assistance, contact [email protected]. Instructions for signatories are available here.
• REDCap Premium: The FDA-compliant version of REDCap is available at https://redcap-prem.ucsf.edu/. If you have questions or need assistance, contact Academic Research Systems Support.

Not sure which platform is the best fit for your study? Contact Academic Research Systems Support to discuss.

Note for VA research: eConsent by DocuSign must be requested and approved through the VA Central Office of Research and Development (ORD), not the San Francisco VA facility research office. Read through the IRB’s VA DocuSign guidance for information on requesting and using VA DocuSign. Additional guidance can be found on the VA's Human Research page. 

If you are approved by ORD to use DocuSign, please forward the approval notification to [email protected] and include it as an “Other Study Document” attachment to your IRB submission when requesting IRB approval for use of DocuSign.

If your study is FDA-regulated:

Here is a summary of the FDA’s regulation at 21 CFR Part 11, UCSF’s position on using the standard versus FDA-compliant versions of DocuSign and REDCap, and guidance for researchers of FDA-regulated studies:

• FDA compliance: The FDA has a set of regulations (commonly referred to as “Part 11”) that outlines specific criteria that must be in place for an electronic signature to be considered valid and reliable. The criteria involve more rigorous system protections and security safeguards than is offered by the more generic versions of DocuSign and REDCap.
• Pre-pandemic use of “regular” versions of DocuSign and REDCap: Until recently, UCSF only had regular versions of DocuSign and REDCap, which do not meet the Part 11 criteria and therefore are not compliant with FDA regulations. As such, UCSF did not allow use of DocuSign or REDCap for collecting electronic research signatures for FDA regulated studies. This changed with the onset of COVID-19.

• Pandemic use of “regular” versions of DocuSign and REDCap: Due to the immediate need to conduct study activities remotely as a direct result of COVID-19 physical distancing precautions, UCSF issued two memoranda (May 28, 2020 and September 29, 2020) stating that all studies involving signed consent— including FDA-regulated trials— could use the non-FDA-compliant (“regular”) versions of DocuSign and REDCap for electronic signed consent during the public health emergency. These memos may be shared with Sponsors. It is unknown whether the FDA will exercise enforcement discretion regarding the use of UCSF’s non-FDA-compliant versions of DocuSign and REDCap to document consent during the COVID-19 public health emergency. However, HRPP deems it unlikely, given recent FDA guidance referenced below, and assuming adherence to proper remote consent procedures and documentation described below.
• March 2021 update: As of late-March 2021, an FDA-compliant version of DocuSign is available to researchers conducting FDA regulated studies. An FDA-compliant version of REDCap is being piloted with a limited number of studies and will be made available to campus once the pilot phase is complete.
  • If you have been using a regular (non-FDA-compliant) electronic consent version: FDA-regulated studies that are still enrolling participants should begin using the FDA-compliant versions of DocuSign or REDCap once they are widely available at UCSF. The HRPP understands that the transition from the regular version to the FDA-compliant version may not be immediate in all cases, as it may take some time to set up your materials on the new version, and availability might be limited at first. See above for contact information for each system, and make an effort to transition to an FDA-compliant version as soon as possible. Please note: Already-enrolled participants do not need to be reconsented on the FDA-compliant version.
• Additional FDA Guidance: Please study these guidance documents about remote & electronic consent of FDA-regulated research
  • Use of Electronic Informed Consent in Clinical Investigations-Questions and Answers (Dec 2016)
• If you have access to a different CFR Part 11 compliant platform for obtaining electronic consent that you wish to use, please contact the HRPP to discuss.

How do I know if my study is FDA-regulated (requiring use of the Part 11 compliant DocuSign or Redcap? Your research is regulated by the FDA if either of the following are true:

• It receives funding from the FDA. Not sure? If the “Funding” section of your IRB application lists FDA as a funding source, your research is FDA-regulated.
• It involves the study of a drug, device or biologic. Not sure? If your application includes a “Drugs and Devices” section and there are items listed within that section, your research is FDA-regulated.
• Still not sure? You can contact UCSF’s FDA Regulatory Support team at [email protected] for help with this determination.

Update (December 1, 2020)

These third-party platforms are Part 11 compliant and may be used to obtain electronic consent and HIPAA signatures. SecureConsent: This consent platform may be made available by the study sponsor when it is a requirement for specific FDA-regulated multicenter studies. Questions? Contact your study sponsor. FDA COVID MyStudies: Investigators conducting studies with an IND or IDE may ask the FDA for permission to use this platform to obtain consent using a mobile device. Investigators interested in using the COVID MyStudies app should contact the CDER Real-World Evidence Program at [email protected] and reference their pre-IND or IND numbers if applicable. FDA plans to prioritize requests to use the app, taking into account agency resources. In addition, this third-party platform is fully Part 11 compliant and may be used as a comprehensive platform for all electronic study documents management: REDCap Cloud: This system offers a comprehensive platform for managing e-consent and all other electronic records. It is currently being made available to researchers requiring a fully FDA-compliant electronic records management solution. Questions? Contact the UCSF Office of Research. Additionally, UCSF endorses the use of DocuSign for signing and transmitting FDA-regulated documents requiring signatures, such as Form FDA 1572 and financial disclosure forms.

Documentation Requirements:

All expectations for informed consent documentation still apply when conducting consent remotely (45 CFR 46.117 and 21 CFR 50.27), in particular:

• Signature of the Person Obtaining Consent: The person who has oriented and obtained consent must sign and date the consent document after the participant has signed. Electronic platforms (DocuSign and REDCap) may be used to first route the document to the participant for signature then route to the person obtaining consent. This process may be followed for non-electronic consent processes as well such as mail-in or fax consenting procedures.
• Copies: You must provide a copy of the consent to the participant via mail, secure email or secured fax.
• Identification: Researchers are advised to make a record of the additional steps they take to remotely verify the identity of the person signing study documentation (i.e., by asking security questions or viewing some form of official identification). Also document that use of electronic consent at a remote visit is in compliance with the Interim UCSF Policy.
• Questions: If researchers will not be available via live chat, video conferencing or telephone (see suggestions in “Risk Mitigation,” below) at the time when the participant is asked to sign their consent and authorization forms, the participant must be provided with information about how to contact the study team with questions about the research and their rights as a participant.
• Confidentiality: Researchers must advise participants against the use of public computers when completing consent and HIPAA forms electronically.

Risk Mitigation:

In using virtual tools, including electronic consenting, UCSF researchers are strongly advised to adopt as many of the following risk mitigation measures as possible to protect research participants and the University:

• Use of video calls to permit better assessment of participant comprehension, answer questions, and verify identity; if video calls are not possible due to technology limitations, phone calls are preferred to communicating exclusively via email with participants. To ensure that patients are approached in a consistent fashion, a standard process should be used that will accomplish the following:
  • Identification of who is on the call
  • Review of the informed consent with the patient by the investigator (or their designee) and response to any questions the patient may have
  • Presence of an impartial witness to the consent process (Note: The HRPP strongly advises, but does not require, the use of a witness). If an impartial witness is involved, obtain confirmation by the witness that the patient’s questions have been answered.
  • Confirmation by the investigator that the patient is willing to participate in the trial and sign the informed consent document while the witness is listening on the phone
  • Verbal confirmation by the patient that they agree to participate in the trial and that they have signed and dated the informed consent document that is in their possession
  • Note: Verbal confirmation alone does not constitute written documentation/eSignature (see below for more information on verbal consent).

• Include additional fields in the signature section that more closely approximate Part 11 requirements (the form should already include fields for the participant’s signature and date of signature):
  • Time of signature (time stamp)
  • Typed/printed name of signer (in addition to signed name)
  • Reason for signing (for example: “I agree to participate in the study and authorize use of my health information”)
• Sponsors and clinical investigators should document how restrictions related to COVID-19 led to the changes in study conduct, the duration of those changes, and indicate which trial participants were impacted and how those trial participants were impacted. For example: “In response to the COVID-19 public health emergency, the University of California San Francisco has issued an Interim Policy on Human Subjects-Related Research Visits outlining the conduct and location of research visits. For the safety of research participants and investigators, the vast majority of consenting procedures are taking place remotely. Remote consenting was implemented on [date] and impacts all participants after that date. The policy is in place until further notice from the UCSF Office of Research.”

Verbal Consent:

• Verbal consent means that the individual obtaining consent reads/explains a verbal version of a consent form (i.e., an information sheet or a script), and subjects give their verbal consent in place of written consent to participate (i.e., there is no “wet ink” or electronic signature).
• If you are currently approved to obtain signed consent but want to obtain verbal consent only from participants remotely (i.e., no longer obtain a written signature), modification and prior IRB approval is required (see “Scenario C” in FAQ #1, above). In this case, submit a modification to the IRB in order to determine whether your study qualifies for a “waiver of signed consent.” The modification must receive IRB approval before you implement this change.

For more information, visit the guidance regarding waiver of signed consent.

HIPAA Authorization:

DocuSign and REDCap can be used for studies requiring HIPAA Authorization for the use of PHI (except for VA studies unless additional requirements can be met). Refer to https://www.hhs.gov/hipaa/for-professionals/special-topics/emergency-preparedness/notification-enforcement-discretion-telehealth/index.html

No. When changes necessary to eliminate apparent immediate hazards to participants are adopted prior to IRB review, no new consent is required unless the change fundamentally alters or negates what the participants initially consented to. Instead, participants should be informed of changes in the research study.

No. Research teams should carefully consider the risks of participants attending in-person study visits in light of the factors discussed in this document.

Not as it relates to risks of contracting COVID-19. However, any study changes adopted during the COVID-19 outbreak that may have resulted in increased risk to study participants should be reported as part of the continuing review.

Yes. Submit updated sponsor protocols/sponsor protocol amendments via the iRIS modification form as you normally would.

Submit any sponsor notification that is related to subject safety (e.g. changes in study drug dispensation or treatment)

Yes. The Office of Research has developed “Guidance for Screening of Research Participants by Clinical Research Staff.” There are additional guidance documents available at the UCSF Coronavirus site and at the UCSF Health Hospital Epidemiology and Infection Prevention site. 

No. The PI and research teams should follow applicable hospital or occupational health policies for managing and reporting COVID-19 infections.

Federal regulations from OHRP require the IRB to ensure that investigators promptly report "any unanticipated problems (UP) involving risk to subjects or others." The IRB/HRPP reviews the reports and determines whether they meet the institutional definition of a UP.

Yes. The FDA will need to be notified as soon as feasible.

No. The procedure for Emergency Use and Compassionate Use of Experimental Drugs and Devices currently remains the same during the COVID-19 outbreak.

Yes. All new studies are still being reviewed. If your study involves in-person contact, please note that procedures will either need to be performed remotely, or postponed, until the UCSF Interim Policy research restrictions are lifted. COVID-19 research studies are given review priority given the urgency of the evolving outbreak worldwide.

Yes. The IRB will continue to review and approve these submissions. If your study involves in-person contact, please note that procedures will either need to be performed remotely, or postponed, until the UCSF Interim Policy research restrictions are lifted.

Yes. IRB meetings and review agendas are proceeding as scheduled.

It depends. The requirements apply to research conducted at UCSF locations in the City and County of San Francisco and are based on the situation in the Bay Area. External research sites may have different requirements based on the local situation. As the IRB of Record for research conducted at the external research site, we require the UCSF Lead PI to assess whether the study can continue under the following conditions:

• The PI is available to maintain appropriate oversight
• There are adequate supplies available including the treatment itself and all additional supplies to administer and monitor the study treatment
• Procedures essential to the safety of subjects can be continued (labs, etc.)
• There are a sufficient number of trained study staff to support conduct of the study considering staff workloads and any requirement to work remotely or to cover other responsibilities at their health care facility or institution

Yes. The Interim Policy and requirements regarding research restrictions applies to all research conducted in our UCSF locations in the City and County of San Francisco, regardless of the IRB that oversees the ethical and regulatory conduct of these studies. Continue to follow the IRB of Record’s reporting guidelines.

How to report an enrollment pause: (1) If your study requires annual renewal (i.e. study has an IRB expiration date): Report the enrollment pause in the Continuing Review form, at the time of your next continuing review. (2) If your study does not require annual renewal (i.e. no IRB expiration date): You do not need to report the enrollment pause to the IRB. How NOT to report an enrollment pause: Please do NOT submit a Modification form, Protocol Violation/Incident Report, or Reporting Form to the IRB to report a pause in enrollment due to COVID-19. 

Yes. You should follow the requirements of the IRB that oversees your research regarding reporting changes and whether any reviews or approvals will be needed prior to resumption of study procedures.

Yes. Please email Joanne Mickalian ([email protected]) and Cheri Etter ([email protected]), and include “COVID-19” in the subject line for COVID-19 related protocols.

Please see the guidance titled “New Consent Form Statement for COVID-19 Countermeasures” on our page titled Submitting COVID-19 Research to the IRB (New Studies & Modifications).

Please email Joanne Mickalian ([email protected]) and Cheri Etter ([email protected]), and include “COVID-19” and your IRB study # in the subject line for COVID-19 related protocols. Please also consult the guidance on our page titled Submitting COVID-19 Research to the IRB (New Studies & Modifications).

Yes. The IRB help desk is available at (415) 476-1814, [email protected], and Ask Andy.

Yes. The IRB has created an information sheet for COVID-19 screening and two assent/consent form addendums for RT-PCR COVID-19 testing. These forms are specifically designed to be used when screening and/or testing are being done for the sole purpose of adhering to the UCSF Guidance for Onsite Clinical Research Activities, which requires that research participants be screened for COVID-19 prior to onsite visits and must be tested if their visit involves aerosolizing procedures.  The language from these forms can also be adapted and added to consent forms for studies in which these screening and testing procedures are being done for study purposes, i.e., the results of the screening and/or testing will be used as study data.  Visit COVID-19 Screening and Testing Forms to access these forms and to read the guidance about when and how to use them.

The UCSF Office of Research provides guidance about clinical monitoring.