As healthcare providers and universities respond to the spread of COVID-19, legal counsel at these institutions should be prepared to assist their institution’s research enterprise in anticipating and reacting to any changes in research protocol or issues as a result of the coronavirus pandemic.
Many institutions are, or should be, considering healthcare delivery process changes to minimize person-to-person contact in their facilities. Also, the unavailability of healthcare personnel due to illness or redirection toward urgent healthcare delivery may impact an institution’s ability to conduct certain study-related procedures or to review study lab results in a timely manner, posing increased risks to study subjects. Research studies will necessarily be impacted by these developments, and legal counsel, principal investigators (PIs), and Institutional Review Boards (IRBs) should be considering these impacts now and planning accordingly.
IRB Approval or Notification of Study Changes
Unlike in the context of medical care, changes to IRB-approved research procedures require IRB approval before being implemented “except where necessary to eliminate apparent immediate hazards to the human subjects” 45 CFR § 46.108(a)(3)(iii); 21 CFR § 56.108(a)(4). Note that this does not apply to studies the institution deemed exempt under 45 CFR § 46.104 or its predecessor, and it also does not apply to changes that do not vary from what was described in the IRB-approved protocol (scheduling changes or COVID-19 phone screening may fall into this category), unless institutional policy states a different requirement. Institutions and IRBs should urgently consider their threshold for allowing changes prior to IRB review and communicate their interpretations to their PIs accordingly.
Examples of changes that are likely to require either prior IRB approval or IRB notification (if done to eliminate an immediate hazard) in non-exempt studies include conducting study visits by phone or at home (for simple procedures like measuring blood pressure) and shipping investigational products to study subjects.
Changes to Informed Consent Forms
Institutions’ legal counsel, together with medical leadership considering the advice of local public health authorities, will also need to consider whether research informed consent forms for studies that will still require in-person visits during the epidemic are required to disclose COVID-19 exposure risks as “reasonably foreseeable” under 45 CFR § 116(b)(2) and 21 CFR § 50.25(a)(2), as well as whether there are any new risks posed by study procedure modifications that need to be disclosed.
Contact the Appropriate Parties about Study Changes
In addition to notifying (or obtaining prior approval from) the IRB, institutions may also need to notify the following parties of changes in IRB-approved study procedures in response to COVID-19:
- The study sponsor, for industry-sponsored trials, pursuant to the terms of the clinical trial agreement or other contract governing the study.
- ClinicalTrials.gov, for studies registered there for which the institution is the “responsible party” under 42 CFR Part 11 if required by 42 CFR § 11.64, or for other studies that the institution has registered on ClinicalTrials.gov because of the funding source, Medicare reimbursement requirements, or journal publication policies.
- The FDA, for studies where the PI or institution holds the investigational new drug application (IND) or the investigational device exemption (IDE), pursuant to 21 CFR 312.30 (for drugs) or 21 CFR § 812.35 (for devices).
- The NIH (if the study is NIH-funded), depending on the change in procedures, after consulting with the institution’s grant management office and the Grants Management Officer and Program Official at the NIH awarding Institute/Center.
Some institutions or individual PIs may also consider temporary pauses in study conduct due to study staff availability, strains on hospital resources, participant safety, or for other reasons. Many of the same considerations described above for study procedure modification will apply to study pauses, although a pause in itself will not usually require IRB approval or notification. In addition, for studies involving investigational products, working closely with the study sponsor (or, for studies in which the institution or PI holds the IND or IDE, the FDA), the IRB, and any Data and Safety Monitoring Board will usually be necessary to ensure participant safety.
Finally, if your institution is considering research involving a COVID-19 vaccine or treatment, expanded access to antiretrovirals (such as is already taking place with remdesivir), or research on biological material containing SARS-CoV-2 itself, we encourage you to contact experienced counsel to discuss the unique considerations that will apply in these contexts.