Reporting Time-Sensitive Modifications
Per federal regulations, IRB review and approval is required before implementing any changes to IRB approved research (an exception exists for an immediate hazard to subjects). To assist study teams with procedures for submitting time-sensitive or urgent changes to research studies, especially as it relates to COVID-19 circumstances, the information below consolidates IRBMED guidance in a single location.
I. General Overview
The following framework outlines specific reporting mechanisms based on the type of changes:
1. To report changes that were initiated without IRB approval (to eliminate apparent immediate hazards to the subjects), see IRBMED guidance: Reporting Changes That Were Made to Eliminate an Immediate Hazard to Subjects.
2. To report time-sensitive changes that are study wide and/or permanent, submit an Amendment in eResearch by following the directions provided below (Section II).
3. To report time-sensitive changes that are one-time and/or temporary to accommodate one or two subjects (e.g., adjustment of enrollment criteria for a single participant), submit an ORIO in eResearch by following the directions provided
below (Section III).
4. All other changes that are NOT time-sensitive should be submitted to IRBMED per the standard amendment process.
Currently, IRBMED is adequately resourced to address the time-sensitive requests promptly when the corresponding eResearch submissions are submitted appropriately (by following the directions provided below). Generally, any submission received by IRBMED will be screened and triaged within 24 hours during normal business hours. During the weekend, these will be checked periodically as necessary.
Once a time-sensitive submission is submitted, the study team can also contact the staff owner of the submission (preferred method) or, the general email ID at firstname.lastname@example.org for a status update.
II. eResearch Amendment (study wide and/or permanent changes)
- Labeling: Update the Amendment Title to indicate “Time-Sensitive” or “Urgent” (or as appropriate to reflect the situation) along with any other indicators
Include adequate details in the Amendment to minimize the back and forth between IRBMED and the study team. For example:
- Explain the time-sensitive nature in the Amendment coversheet (Section 01.4 or 01.5). This will allow IRBMED to appropriately triage the submission
- Describe the proposed changes clearly in the Amendment coversheet
- Evaluate how the proposed changes will impact the current study procedures and then update the study materials (protocol, recruitment, informed consent, etc.) as applicable.
- If the consent document is being updated, evaluate, and indicate whether or not subjects will be re-consented. Also, clarify the method of re-consenting (in-person or remote).
- NOTE: See Section IV below for an alternative approach that can be utilized under some limited circumstances.
III. eResearch ORIO (one-time and/or temporary changes)
The study teams may encounter situations where the intended change is one-time and impacts only one or two subjects and is not a study wide change. For these situations, the ORIO reporting process can be utilized to obtain IRB approval. The study team should carefully evaluate whether the intended change is a one-time or a permanent study-wide change before using this ORIO process.
Example(s) of scenarios where this is permitted:
- A request to enroll a participant who does not meet the currently approved eligibility criteria:
- Lab values slightly differ from those stated in the protocol
- Participant age slightly varies from inclusion criteria (but not adding children and/or other new subject population)
- Making adjustments to the current study drug dosage (but not adding new drugs or devices)
Example(s) of scenarios where this will NOT be accepted:
- Changes to the study procedures that will impact either all or most of the subjects
- Adding a study team member
IV. eResearch ORIO (Special Process for COVID-19 Research Reactivation ONLY)
In the special circumstances associated with COVID-19 research reactivation, IRBMED will accept time-sensitive modifications that are study wide and/or permanent via the eResearch ORIO reporting mechanism if they meet the following criteria:
The standard eResearch Amendment process permits only one amendment to be in progress at the same time to assure version control of the IRB application/protocol. This may create challenges when two unrelated modifications require evaluation at the same time. When an Amendment is already in-progress and the study team wants to make additional changes that cannot be added to the currently opened Amendment, the ORIO process can be utilized in these unique circumstances, to obtain IRB approval.
Example(s) of scenarios where this is permitted :
- Changing from in-person visits to remote ‘visits’ for a group of subjects (a minor change) but this change cannot be added to the currently opened Amendment as the Amendment is currently undergoing ancillary review or is already scheduled for a convened board meeting.
Example(s) of scenarios where this will NOT be accepted:
- A standard Amendment is necessary for informed consent updates that require finalization.
- Adding study team members as they require conflict of interest and PEERRS validation.
When Submitting ORIOs per Section III or Section IV
When Submitting ORIOs per Section III or Section IV:
Study-Specific Planning for Research Reactivation
PROCEDURES FOR BEGINNING OPERATIONS DURING RESEARCH REACTIVATION:
The UMOR website (https://research.umich.edu/covid-19) provides specific details associated with research reactivation (Tier) procedures. To assure the safety of research participants, individuals accompanying them in their research participation, the research workforce, and the broader communities, research is being reactivated in four Tiers. Benefits of the research to individual participants is balanced with the risk of COVID-19 community transmission.
The following information is provided to assist the study teams in preparing their activation plans in compliance with applicable regulations, UMOR and IRBMED procedures, and best practices.
1. Contact study sponsors prior to reactivation
Contact federal, industry, or private sponsors and/or any coordinating center for any study-specific information and guidance. Ensure that guidance provided is consistent with U-M policies and guidelines. Study teams may require information and guidance on specific issues including:
Changes in reporting requirements and documentation of deviations due to COVID-19
Alternative safety assessments due to delays
Delayed or missed participant contacts/visits
How delayed or missed participant contacts/visits may impact on-going study participation (e.g. whether a missed safety assessment might impact the ability of the participant to receive the next round of therapy)
Any changes to biospecimen/sample storage and shipping requirements
Drug shortages or delays in shipping and the subsequent impact on study conduct
Changes to the study procedures requiring IRBMED approval
2. Develop study-specific plans
The type of research being conducted will determine what revisions are required to the research plan. If the research has a sponsor, formal instructions may have been provided which will simplify the study team’s need to consider all subject facing aspects of the research. If not, develop a plan for implementation which takes into account the UMOR assigned Activation Tier as well as U-M policies and guidelines.
IRB amendments will be necessary if protocol changes were not previously approved to take into account alternative procedures involving the following categories of changes. Note, however, that not all studies will require all of these type of changes.
Sponsor provided information and protocol changes (from prior section)
Remote procedures that substitute for on-site visits, such as home visits, video research visits, and remote consenting
U-M Research Pharmacy operations as applicable
Ability to conduct research interventions in current locations
Orderly withdrawal of subjects if indicated or necessary
Substantive delays in the ability of the team or participant to complete study procedures
Other treatment options for patients not able to access clinical trials (e.g., cancer, cardiac patients)
Schedule of planned communication with sponsors
Revised plans for community recruitment of participants (in the event the study remains open for recruitment)
Contact ORSP for cost/charge/effort considerations on sponsored projects
3. Prepare Plans to address resource availability and communication
Study team and clinical staff availability
Emergency communication plans within the study team
Communication with participants (i.e., participants are kept informed of research reactivation and expectations)
Compliance with UMOR social distancing and other unit or workplace limitations
4. Prepare and submit necessary IRB applications via eResearch
Prepare necessary amendments, continuing reviews, Adverse Event and ORIO reports to IRBMED. Follow the tips below and watch the IRBMED website for updates on any workflow adjustments.
Per FDA guidance, “COVID-19 screening procedures that may be mandated by the health care system in which a clinical trial is being conducted do not need to be reported as an amendment to the protocol [emphasis added] even if done during clinical study visits unless the sponsor is incorporating the data collected as part of a new research objective.”
IRBMED strongly recommends that study teams follow this FDA guidance when submitting Amendments in eResearch. Generally, an Amendment is NOT required for the mitigation procedures that are required by the University of Michigan (like hand hygiene, masks, temperature checks, screening questions, etc.) unless the study team is planning to incorporate the data collected as part of a new research objective. However, an Amendment is required for the study-specific mitigation procedures (such as remote consent or remote study procedures) that are not previously approved by IRBMED.
- New Study applications:
New study IRB applications (or, other submissions) can continue to be submitted for IRBMED review. However, along with the previously-approved research, these applications must be conducted in compliance with applicable U-M COVID-19 policies and guidelines.
Studies should be submitted to IRBMED first for review and approval, then study teams should complete the Activation Checklist.
Both approvals (IRBMED and Human Research Activation Committee) are necessary before beginning the study.
See IRBMED guidance for initiating new COVID-19 related research.
- Time-Sensitive Modifications:
Carefully assess whether it is a study-wide change that should be submitted as an Amendment (preferred) or a time-sensitive, one-time or temporary change that may be submitted as an ORIO. Review IRBMED guidance (also above) on this topic.
Label the submission appropriately (Time-Sensitive, Urgent, Activation, etc.) by editing the title when creating the submission in eR.
Include adequate details in the submission to minimize the need for additional queries from IRBMED. Instead of indicating ‘everything is remote’, provide additional details, as applicable. For example:
Clearly indicate the study procedures that will be done remotely
Indicate how many subjects will be impacted by the change (one or all)
Describe the impact of the changes on the previously enrolled subjects or to-be-enrolled subjects
Indicate how the impacted subjects be notified of changes (e.g., email or phone calls or letters or at their next visits). Provide scripts where applicable.
Indicate specific remote or electronic medium (Zoom, SignNow, REDCap, etc.) that will be used by the study team
Include the stage, phase, or cohort interaction currently taking place in the research. How many current subjects will be affected by the revisions, or if subjects are in different stages of research interaction (some in active research interaction/intervention, some only being followed for follow up surveys)
Use the categories described in section 2 of this guidance and the examples above as an outline for the study specific changes. Summarize the proposed changes in the Amendment Coversheet and use the summary to check that each change is reflected in the amendment application section and in any related support documents (the protocol, informed consent, and recruitment material.
- Upload any necessary documentation in appropriate sections to trigger appropriate reviews.
Section 15 (Drugs) uploads trigger Research Pharmacy review
Section 10-1 (Informed Consent) uploads may trigger CRAO (Billing calendar) review
- Electronic Informed Consent/Signature and Informed Consent with Documentation Waiver should be identified appropriately in the IRB application:
Example of Documentation Waiver: As part of a Qualtrics survey, the study team will provide the necessary information and ask the subjects to click a link if the subject is agreeing to participate. Completing and submitting the survey questions indicates informed consent. For this method, request for documentation waiver must be completed in Section 10-4 (by selecting the appropriate option in Section 10.1).
Example of Electronic Consent: Subjects will be required to provide their signature electronically via SignNow after reviewing the information about the study. For this, a documentation waiver is not applicable.
- Submitting Protocol Deviations:
Review IRBMED ORIO Reporting Guidance and clearly identify whether the deviation is major and should be reported via ORIO within 7 days or minor to be reported at the time of SCR.
For protocol deviations, especially related to COVID-19 procedures, the FDA urges investigators to capture specific information in the case report form that explains the basis of missing data, including the relationship to COVID-19 for missing protocol-specified information (e.g., from missed/delayed study visits or study discontinuations due to COVID-19).
EMERGENCY USE OF A TEST ARTICLE
Procedures to request emergency use of an investigational test article will remain the same. For additional information, refer to https://az.research.umich.edu/medschool/guidance/emergency-use-test-article-life-threatening-circumstances
- FDA’s 2020 Guidance: Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency
- FDA’s 2001 Guidance: Changes or Modifications During the Conduct of a Clinical Investigation
- UMOR COVID-19 Webpage: https://research.umich.edu/covid-19
- IRBMED Guidance: Initiating New COVID-19 Related Research