Protocol Changes Due to an Emergency or Disaster

Challenges to study conduct may arise from events such as, but not limited to:

• Extreme weather
• Natural disasters
• Equipment/technology malfunctions
• Man-made disasters
• Infectious disease outbreaks

These events may lead to challenges in conducting protocol-specified procedures, including but not limited to: administering drugs and devices, adhering to protocol mandated visits and procedures, communicating with participants, and managing study records and /or specimens. 

What changes require IRB review and approval related to mitigating risk to participants during a pandemic or other health emergency?

According to IRB policy, any changes in IRB-approved research procedures must be reported to the IRB and may not be implemented prior to review and approval by the IRB, except when necessary to eliminate apparent immediate hazards to the subject. This is permitted by both the Common Rule (45 CFR §46.108(a)(3)(iii)) and by FDA regulations (21 CFR §56.108(a)(4)).

If you are changing the protocol procedures temporarily, to eliminate immediate hazards to subject safety due to an emergency or disaster, there is no need to wait for IRB approval. However, the IRB would ask that you submit documentation of the changes in HSERA within 10 business days.

NOTE: Any changes or deviations that may increase risk of harm to participants or adversely affect the scientific integrity of the data should wait for IRB review. 

When is a protocol-specific risk mitigation plan necessary? 

The Emergency Risk Mitigation Planning Guidance: Ensuring Participant Safety in Research provides investigators with general guidance for developing protocol-specific plans to modify research during an emergency/disaster situation impacting the investigator’s ability to ensure the ongoing safety of participants. 

Consent Process Options

In situations where in-person informed consent or procedures are not possible, the Penn IRB supports the use of remote consent and remote study procedures, when appropriate. However, the use of remote methods must be outlined for IRB review to ensure that risks to subjects continue to be minimized and the data integrity of the study can be maintained. The Remote Consent Guide is meant to serve as a resource to guide research teams considering the use of remote procedures for research.

Expectations for Following Local Directives and Laws During an Emergency or Natural Disaster

The IRB expects Penn research teams to follow any applicable and current guidelines and laws set forth by the country, state/ province, and city / town in which the research is taking place. Additionally, Penn research teams should follow any applicable policies in place at the University and associated Schools. Researchers should be prepared to respond to local government directives, as well as University alerts, and potential short-notice announcements that would require ramp-downs of activity in labs, floors, and buildings.

Vaccination Requirements for Research During an Infectious Outbreak

Can researchers incorporate a blanket requirement for research participants to be vaccinated against COVID-19 or another such virus? The IRB recommends this be determined on a study-by-study basis. Eligibility requirements should be carefully considered in the context of the Belmont Ethical principles and IRB Criteria for Approval, notably, the following:

1. Risks to subjects are minimized … by using sound research design… and risks to subjects are reasonable in relation to anticipated benefits

   For FDA regulated studies, FDA guidance notes that “there may be valid scientific reasons to have an exclusion criterion” [or inclusion criterion] for a medical product. These scientific reasons may include risks to an individual if they enroll or continue to participate in a clinical trial after receiving or not receiving the product, or the potential impact of the use of the product on trial objectives, such as confounding the determination of effectiveness of the product under investigation.

2. Selection of subjects is equitable

   It may be possible that requiring a vaccine for research participation could violate the ethical principles of justice and respect for persons. For example, if someone is not vaccinated, or can’t be for a particular reason (due to anaphylactic reaction), are there alternative steps/provisions that may be taken to ensure equitable subject selection while still maintaining the safety of those involved?
   
   

   Likewise, requiring vaccination for participation could also complicate the issues of vaccine hesitancy and public trust in research.
   
   

   It is also important to note the following FDA guidance in relation to Emergency Use Authorized products such as vaccines that have not yet been FDA approved: “When a medical product is being used under an EUA, it is an authorized (though not an approved or cleared) medical product for use in clinical care that has met the statutory criteria under section 564 of the FD&C Act.” Given the investigational nature of the product, when Congress granted the authority to issue EUAs, it chose to require that every individual should be allowed to decide whether or not to receive an EUA product. The FDA and CDC considered this requirement of choice important enough that they reinforced that policy decision when issuing their guidance related to the Covid-19 vaccines. This again ties back to the ethical principle of respect for persons.

Scientific or safety-based rationale for requiring vaccination (or excluding those who are not vaccinated) should be outlined in the study protocol. The IRB will evaluate the rationale in the context of the criteria for approval.

Use of a Product with an EUA in a Research Study

Congress created the Emergency Use Authorization (EUA) in the Project BioShield Act of 2004 to give the public health system access to a greater range of medical products during a declared emergency. An EUA is intended to allow for faster use of a product compared to an IND/IDE.

An EUA is not an Emergency Use IND or IDE. An EUA is a regulatory authorization from the FDA for the use of unapproved medical products (drugs, biologics [e.g., vaccines], and devices [e.g., diagnostics]) or the use of approved medical products in unapproved ways to diagnose, treat, or prevent serious diseases or conditions caused by chemical, biological, radiological, or nuclear (CBRN) agents. An EUA has its own distinct statutory and regulatory requirements.

An EUA product can be used or investigated in a research study. However, the FDA may rescind an EUA at any time if it is determined that the product is not effective. Please be aware that research studies utilizing these products may require IND or IDE, or exemption determination from FDA IND/IDE regulations if FDA rescinds approval. Penn Medicine researchers should seek guidance from the Office of Clinical Research, Sponsor Support Unit.

Requirements Surrounding the Use of COVID-19 Associated Data and Specimens

If your research involves the collection and/or processing of samples from COVID-19 positive subjects, and the samples will be processed or stored in a Penn research laboratory, please consult with a Biosafety Officer from EHRS prior to commencing research.