IRB Guidance

Last Updated: 03-18-2020 6:42 p.m.

Effective immediately, the IRB office, located in Andrews Hall, Suite 128, will be closed temporarily. Most staff will be working remotely, but since some will be in the office the closure is to limit person-to-person contact.

Read the EVMS Policies affecting ongoing and new IRB Studies. Investigators are responsible for ensuring compliance with the information noted in the noted links.

Submission Procedures

We are waiving the need for original documents and signature on IRB items. Do not bring documents over and do not send them through the mail system. Documents will ONLY be submitted through IRBManager for acceptance, processing, and IRB reviews and outcomes. Signature pages must be signed, scanned and submitted either via IRBManager or to the Administrator handling the study. Please send only the pages showing signatures as the other pages should already be in IRBManager. If you currently owe hard copies to the office, please contact your IRB Administrator or IRB-INFO@evms.edu.

If you do not have an account in IRBManager to submit studies email IRB-INFO@evms.edu and the staff will set up an account for your use.

After a submission, wait for IRB Administrator to contact you (usually within one to two working days). This contact will provide any feedback to assist you in document preparation for the IRB and instructions on your next step.

Ongoing Clinical Trials

If you are conducting ongoing clinical trials where study procedures and visits may be affected by subjects who cannot or should not come in for study visits due to the virus, please reach out to the Study Sponsor now to obtain guidance on missed treatments/procedures/visits. Any changes to the study visits must be submitted to the IRB as an amendment.

Of note, the link on our page to Protocols Under Advarra IRB Review/Oversight has excellent suggestions on what to plan for and how to address those concerns. We strongly recommend reviewing this guidance even if your review is not through Advarra.

EVMS has set up a two-phase action plan. The second phase involves a tiered process for new and ongoing studies and direct subject interactions. Investigators must comply with this guidance effective Wednesday, March 18, 2020.

Last Updated: 03-18-2020 6:47 p.m.

In light of the COVID-19 pandemic and its emergence in the Hampton Roads area, the EVMS IRB office provides the following guidance to meet the needs of our clinical and research community.

The off-label use of currently approved drugs to treat a patient does not require IRB review unless a clinical investigator wishes to conduct that treatment, or to collect data to support the safety and efficacy of that treatment, as part of a research study. In these latter cases, review by the convened IRB may be required, with considerations for seeking an IND from the FDA.

If there is a desire to treat a patient with an investigational drug that is not currently approved by the FDA, there are various routes to this access, also known as expanded access.

• Clinicians may seek FDA approval for a single patient IND using FDA Form 3926. The FDA routinely performs expeditious reviews of such requests, and as part of their approval process can grant authorization for the clinician to use an alternative IRB review procedure. If such a request is granted, IRB review can be performed by the chair of an IRB, rather than the convened Board.
• Mechanisms for treatment of an intermediate-sized patient population as well as widespread treatment of patients, either with standalone INDs or as part of existing sponsor INDs, are available.

**Of particular note, if the sponsor(s) of such investigational drugs have already opened expanded access programs through either the intermediate-sized or widespread treatment mechanisms with a commercial or large academic medical center IRB, the EVMS IRBs are willing to enter into reliance agreements with such organizations in order to minimize the time needed to gain access to the drugs in question. These reliance agreements must be coordinated through the Research Subjects’ Protection office. Please contact the office at IRB-INFO@evms.edu or Betsy Conner at ConnerBC@evms.edu for assistance.

Additional information relating to expanded access are available at the following:

• FDA: Expanded access information for physicians
• FDA: Physicians guide to non-emergency single patient expanded access
• FDA: How to request non-emergency single patient expanded access (i.e,. “compassionate use”)

The IRBs and the office staff want to assure investigators that ongoing clinical trials or other research studies can continue for the safety of enrolled subjects and that our research partners can continue to offer novel treatments, including COVID-19 trials, expanded access, and single patient access as needed.

Last Updated: 03-18-2020 6:57 p.m.

NOTICE: The EVMS IRBs and Human Subjects’ Protections Program are operating under Phase 2 at this time.

EVMS has developed recommendations to advise the research community during the current coronavirus public health emergency.

These recommendations are being made to ensure the protection of EVMS researchers, subjects, as well as our larger Hampton Roads community from risk of infection with COVID-19. At the same time, EVMS recognizes that access to certain research activities is necessary to provide essential care to research participants.

With the exception of a screening process and disinfecting sites described below, all changes to research protocols must receive review and approval by the EVMS IRBs. Investigators are permitted to implement study changes to eliminate immediate risks to subject safety. Amendments should be submitted to the EVMS IRBs promptly, describing any changes, as appropriate, and justification for why changes were put into place prior to IRB review.

Phase 1: Business as usual with some enhanced safety precautions

1. Screening Process

Investigators need to develop a screening procedure prior to any in-person, protocol-mandated interaction. The use of this screening procedure DOES NOT require IRB approval prior to implementation. For any sponsored study, investigators should consult with the sponsor for specific guidance or requirements. Suggestions include:

• Have you traveled out of the United States in the past 14 days?
• Have you had any of the following symptoms in the past 14 days without confirmation as something other than COVID-19 (such as a positive flu test, chronic medical condition, etc.)?
  • Fever greater than 100.4 degrees Fahrenheit
  • Cough
  • Difficulty breathing
  • Sore throat
• In the last 14 days, have you lived with or been in contact with someone who has visited, cared for, or been in a room for a prolonged period of time with someone who is under investigation or has been confirmed for COVID-19?

If a participant says ‘yes’ to any of the above questions, it is recommended that study staff identify a resource to which a participant can be directed.

Disinfecting sites

Develop intensive disinfecting protocols for your research site for the safety of research subjects and research team members. IRB approval is not required.

Prepare now to ramp down all clinical research studies

We know this is inconvenient and may affect research agreements and finances, but there is a new national standard emerging from this health crisis and we have taken relevant information from multiple, high-volume research sites to help set policy. That includes giving consideration to pausing certain aspects of clinical studies for the safety of all involved.

Voluntary Remote Visits

In general, research visits for on-going research studies should be performed remotely whenever possible. Options for remote conduct of research visits may include phone, Skype, FaceTime, etc. Any changes to your protocol to allow such remote visits must be IRB approved prior to implementation. Please submit Amendments as early as possible to avoid delays.

Phase 2: Requires a pause in face-to-face interactions

At the Phase 2 stage, it is likely many operations may be affected at the Medical School. There are very few cases that will warrant direct interactions between subjects and research sites. Most cases allowing direct interactions will be those involving a life-threatening condition that requires intervention. Initiating Phase 2 means that school leaders consider the situation to have moved to a critical juncture and risks to subjects and employees should be minimized as much as possible.

Any study procedures or visits that requires in-person contact must be paused unless participation in the research study, such as a clinical trial, is essential to a subject’s health or well-being. The determination of whether or not participation in the research is essential to the health or well-being of the subject is to be made by the principal investigator however, if the decision is to continue, the PI must notify the IRB in writing and receive confirmation from the IRB that it is acceptable to continue.

Research visits that cannot be performed remotely as described above and that are not essential to the safety and well-being of a subject must be postponed until such time as these measures are no longer necessary. The determination of whether a research visit is essential will be made by the principal investigator and based on which tier the study fits.

New enrollment and follow-up visits for non-interventional qualitative studies are to be considered ‘non-essential.’

Last Updated: 03-18-2020 6:59 p.m.

EVMS is following processes put in place by UVA, Johns Hopkins and other universities to protect research subjects and research team members. The following is guidance developed at JH, which has been modified somewhat for the EVMS community.

Human Subject Research Operations Related to the Coronavirus Outbreak

With the declaration of a national emergency because of the spread of COVID-19 and the announcement of cases touching the Tidewater community directly, we are hoping to minimize risks to subjects and our community in the conduct of human subject research. Research teams could have individuals with the COVID infection or in isolation. With the work-from-home policies, research teams are already coping with fewer individuals on site.

The risk-benefit ratio drives these changes to clinical research operations. While some research teams may have already made wise decisions to reduce their research activity, EVMS is activating a more definitive policy on continuity of human subject research so that the Medical School can fairly and efficiently direct resources for support of high priority activity.

We recognize that research may define the career of many investigators and team members. Nonetheless, it is important to focus on maintaining the ability to safely and effectively conduct research. We are using an established triage framework (developed at JH) for study teams and the institution to prioritize decisions regarding continued research in a resource-limited environment.

IRB staff and boards are ready to respond to questions or changes in research related to the new policy. If the IRB is overwhelmed with amendments or other important matters due to the national emergency this policy will be evaluated and possibly modified.

Last Updated: 03-18-2020 7:05 p.m.

Effective March 18, 2020, ALL human subject research at EVMS will be divided into three tiers as outlined below—and the following actions must be implemented by researchers depending on the research tier:

Tier 1 – High Direct Benefit to Research Participants

All protocols involving COVID-19 as well as other research protocols in which serious or immediate harm could be caused to the research participants if stopped.
For example:

• Research protocols involving treatments for acute, life-threatening health conditions (e.g. some treatment trials for cancers)
• Protocols where stopping the intervention (e.g. some investigational drugs or vaccines or preventative drug regimens) could be harmful

Research in Tier 1 can continue if the Principal Investigator (PI) determines AND the IRB agrees the research can be conducted in a safe manner that protects subjects, research, and the community. PIs must immediately pause on enrolling new research participants unless there is a compelling reason. PIs must notify the IRB by March 20th of any research they currently have ongoing that fits Tier 1 or 2. The IRB will return a confirmation to the PI that the study may continue.

PIs may petition the IRB if they have a compelling reason for not following this new policy. Requests will be reviewed in order of priority. These new guidelines must be followed for studies seeking such an appeal until the appeal is approved.

If a notice is not received by the IRB that there is a study that fits Tier 1, the assumption will be the PI had no studies meeting this level and that the PI’s studies meet only Tier 2 and/or Tier 3.

Tier 2 – Moderate Direct Benefit to Research Participants

Protocols which, if stopped, may pose a risk to the research participant. For example:

• Protocols in which research participants are receiving interventions or clinical care that is very interrelated to their research participation (e.g. test results coming back that might have clinical implications for their care).
• Some protocols evaluating treatments for chronic conditions (e.g. asthma, hypertension, depression, etc.).
• Protocols involving assessment of the safety or efficacy of an intervention in which, if stopped, the potential societal benefit of the science would be significantly and adversely impacted, for example where a research assessment (blood collection or imaging study) is only valuable if collected at a very specific time. This must be measured against the risk to participants, including the risk of exposure of COVID-19.

Research in Tier 2 can continue if the PI agrees the research can be conducted in a safe manner that protects subjects, researchers and the community. PIs must pause on enrolling new research participants immediately unless there is a compelling reason. PIs must notify the IRB by March 20th of any research they currently have ongoing that fits Tier 1 or 2. The IRB will return a confirmation to the PI that the study may continue with new enrollment and/or ongoing treatment.

Tier 3 – Low Direct Benefit to Research Participants

• Cohort and natural history studies where delays in data collection have limited impact on scientific objectives.
• Protocols in which delays to starting or pausing of research do not substantively impact research objectives or the research protocol.
• Protocols in which risks to research participants are higher (e.g. potentially exposing elderly vulnerable individuals to COVID) and benefits of the study to the participants remain minimal.
• Research with healthy volunteers.
• Any minimal risk studies that require research subjects to travel, that involve undergraduate students, or that are in a community setting and require direct interaction with researchers.

Research activities in Tier 3 must not enroll new participants in studies requiring face-to-face interaction nor continue to conduct face-to-face visits. On-line visits or data collection that does not require participant interaction may continue. Otherwise, these studies must be paused until further notice.

PIs must consider each of their IRB studies and decide which tier each study matches. If they have questions, they should consult with the Human Subjects’ Protection office.

Last Updated: 03-18-2020 7:08 p.m.

Investigators with ongoing studies using Advarra must follow their guidance at: Protocols Under Advarra IRB Review/Oversight. However, we also suggest that individuals whose reviews are through other IRBs take this excellent guidance into consideration as well.

Last Updated: 03-18-2020 7:09 p.m.

Investigators with studies approved through the NCI CIRB must follow the CIRB guidelines for continuity of care, new subject enrollment, and IND studies.