OHRP Issues Guidance on the Conduct of Research During COVID-19 Public Health Emergency

April 23, 2020 Alerts and Newsletters

The U.S. Department of Health & Human Services Office for Human Research Protections (“OHRP”) issued guidance, dated April 8, 2020, on the application of Common Rule requirements to research being conducted during the COVID-19 public health emergency. In the guidance, OHRP encourages the research community to prioritize public health and safety and also reassures institutions and investigators that it will use “available flexibility” in interpreting the regulations with respect to actions necessary to protect public health, while still appropriately protecting research subjects. Although OHRP does not grant any specific exemptions or waivers from Common Rule requirements in the guidance, the agency highlights existing regulations that are likely to be implicated when responding to COVID-19 and provides relevant examples to help guide the research community.

Additionally (and perhaps most notably), in its guidance, OHRP endorses the recent guidance issued by the U.S. Food & Drug Administration (“FDA”) titled Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Public Health Emergency (“FDA’s Clinical Trial Guidance”) stating that it views such guidance to be consistent with the Common Rule, even if the research is not also regulated by FDA (see our alerts on FDA’s original guidance document here and its appendix with questions and answers here and here). FDA’s Clinical Trial Guidance addresses criteria for determining whether to continue or suspend ongoing clinical trials, operational considerations and regulatory requirements that apply when transitioning to remote, or other alternative, clinical trial activities (including alternative processes for obtaining informed consent), and suggested actions for protecting the integrity of data and results arising from trials conducted during COVID-19. FDA’s Clinical Trial Guidance has continued to evolve, with additional questions and answers added periodically, but it is unclear whether OHRP will indicate whether it endorses new iterations of the guidance (including the most recent iteration of April 16, issued after OHRP’s guidance).

OHRP’s guidance addresses the application of the following Common Rule requirements to the conduct of research during COVID-19.

  • Activities performed for public health surveillance purposes (including any required sharing of results) are excluded from the definition of “research” under the revised Common Rule and, therefore, do not require institutional review board (“IRB”) approval before implementation. For example, if a public health authority authorizes screening for COVID-19, and requests that test results be shared with the authority so that it may identify, monitor, assess or investigate the COVID-19 outbreak, an investigator may incorporate these activities into an existing research study visit and share the results with the authority as requested without prior IRB approval, without running afoul of the terms of a Certificate of Confidentiality and notwithstanding any inconsistency with the study’s informed consent form. Even though a formal amendment to the informed consent form is not required, OHRP suggests that investigators inform subjects of the required reporting of results. There are two important limitations to the application of the “public health surveillance” exclusion that researchers should be aware of during this time. First, if the results from COVID-19 screening tests are to be used for research purposes (for example, to inform a new research objective), they would no longer be excluded “public health surveillance” activities and a protocol amendment would be required. This limitation was articulated by the FDA in its clinical trial guidance discussed above. Second, OHRP flagged that FDA regulations continue to apply to any screening procedures that involve use of an investigational in vitro diagnostic device. This is the case even though the research itself is not regulated by the FDA.
  • Investigators may implement changes to approved research that are necessary to eliminate apparent immediate hazards to subjects prior to IRB review and approval. In the COVID-19 context, such changes may include cancelling or postponing non-essential study visits or conducting phone visits instead of in-person visits to reduce COVID-19 transmission risks. OHRP advises that such changes still should be reported to the IRB when possible. FDA has a substantially equivalent regulation allowing for implementation of protocol changes necessary to eliminate apparent immediate hazards to the human subjects without prior IRB review and approval, as discussed in FDA’s Clinical Trial Guidance.
  • Investigators may submit any proposed changes to previously approved research to the IRB at any time. For minor protocol changes, the IRB may use an expedited review procedure to review and approve those changes. OHRP does not give any COVID-19 related examples for what types of proposed changes would be considered more than minor, requiring prior review by a fully convened IRB. FDA’s Clinical Trial Guidance has not addressed this issue to date either.
  • If an investigator or an institutional official suspends or terminates an approved research study (including for the purpose of reducing risk to subjects due to COVID-19), they need not notify OHRP – suspensions and terminations are reportable to OHRP only when initiated by the IRB. Likewise, FDA’s regulations require notice to the FDA in the event that an IRB suspends or terminates approval of a clinical trial. FDA’s Clinical Trial Guidance further clarifies that pausing enrollment to decrease potential exposure to COVID-19 generally would not necessitate submission to the FDA of a protocol amendment for clinical trials conducted under an investigational new drug (IND) application.

One important area that OHRP does not address in its guidance is whether the public health emergency itself presents a material change to the risk/benefit ratio of on-going studies or otherwise results in new information relevant to approval criteria that would require IRB review, and whether the public health emergency would now rise to the level of a research-related risk regarding which participants should be informed and to which participants should consent. This is not a change to the research requiring analysis of whether it is minor or more than minor; rather it is new information related to the research that may impact the risk analysis (akin to new literature that is published during the course of a research study on the risk profile of a drug being used in the study that must then be evaluated to determine if it changes the baseline risks imposed by participation and the material information about which subjects should be informed). For example, the continuation of in-person visits in the context of the public health emergency itself, or the continuation of the use of an investigational drug with immunosuppressive qualities, could be factors that an IRB would weight differently in light of COVID-19. Institutions may wish to consider ways in which the IRB can communicate its expectations to the researcher community regarding how existing policies and procedures (such as requirements for investigators to consider and report new information to the IRB) may apply to issues arising in the context of the pandemic.

In its guidance, OHRP also references its prior guidance titled “Effects of Disasters on Human Research Protections Programs” of May 14, 2018 (the “Disaster Guidance”), saying that the guidance “may be applicable” to research being conducted during the COVID-19 public health emergency. The Disaster Guidance focuses on facilitating research where IRBs, investigators, and research records may not be available in specified affected areas (in the event of a natural disaster, for example). The Disaster Guidance addresses continuation of research following a lapse in IRB approval due to the disaster in certain limited circumstances and also provides mechanisms for collaborating with other investigators and institutions to carry aspects of research that cannot be performed by an affected institution. These mechanisms may not be practicable in the near term, however, given the national (and global) reach of this pandemic.

OHRP suggests contacting the agency with questions about the application of Common Rule requirements to actions being taken or planned in response to COVID-19. OHRP is available by telephone at 240-453-6900 or 866-447-4777, or by email at [email protected]. For assistance, please contact Sarah V. Ferranti, Emily Chi Fogler, Kate Gallin Heffernan, Andrew P. Rusczek, Sarah L. Trautz, or your regular Verrill attorney.