Today’s news is filled with stories about the coronavirus, but infectious diseases are part of our global landscape, demanding a regular routine of hand washing and safe sanitary practices. Finding a vaccination that can address new infectious viruses, much like we depend upon a flu vaccination each year, is important to all of us. But even the flu vaccination can miss strains of the flu and result in individuals getting sick despite following medically recommended vaccination procedures. Life is imperfect; medicine is imperfect.
But how do we develop those vaccinations? That’s where research comes in. Emerging infectious diseases can raise certain unique issues for institutional review board (IRB) review and research informed consent. The risks and benefits of any research involving human participants must be evaluated by the IRB and carefully explained in the informed consent form (ICF). But what if we don’t yet fully know the risks and benefits of a vaccination or other treatment because it is just being developed (not an unusual situation in research). At the very least, the researchers should understand the spectrum of risks and present that information in the research ICF. Disclosure is key.
Timeliness and Quality of IRB Review
While quickly completing the IRB review of research is always optimal, it becomes more critical when reviewing research aimed at preventing or treating emerging infectious diseases. The review needs to be done in a very short time frame to ensure the research can get started as soon as possible—drug development typically takes years, and emerging infectious diseases cannot wait that long. At the same time, the quality of both the research protocol and its review should not be compromised.
As soon as a protocol involving an emerging infectious disease is even likely to be submitted for IRB review, IRBs should diligently evaluate their members’ expertise early on to ensure that those with appropriate expertise are available to conduct the review. Maintaining a diverse IRB can ensure a rapid response to research that addresses a public health concern. At Advarra, we are confident in the broad and deep infectious disease expertise on our IRB, and we have given top priority to all coronavirus protocols we’ve received in recent weeks.
Inclusion and Exclusion Criteria
IRBs are cautious about including vulnerable populations in research because of historical abuses of vulnerable groups such as children, prisoners, and individuals with cognitive impairment. In the book Strangers at the Bedside, David Rothman describes how researchers in the 1940s used “incompetent and incarcerated subjects” in research involving dysentery, malaria, and influenza. When the National Commission wrote its recommendations in 1978 on the criteria for IRB review, it recommended special protections for pregnant women, neonates, children, and prisoners in response to early studies that inappropriately used these populations.
However, many populations may be impacted by an emerging infectious disease and eliminating certain groups from the inclusion criteria might skew the results of the research. Indeed, the STAT article “Who is getting sick and how sick? A breakdown of coronavirus risk by demographic factors” noted that simply being male can put you at a higher risk and that children and teens seem to be rarely impacted. At Advarra, our IRB is prepared to evaluate any unique inclusion and exclusion strategies and discuss the potential benefits and risks with the sponsor.
Reimbursement and Compensation
Reimbursement for expenses is typically provided in a protocol involving individuals with the condition that is being studied. Payment for participation is likely to be seen in a protocol that seeks to enroll healthy volunteers. A protocol that provides reimbursement to participants for travel and other expenses, but describes the reimbursement too narrowly, may result in unnecessary delays when it becomes apparent that changes need to be made to accommodate an ever-changing landscape. For research protocols involving emerging infectious diseases, the travel preferences of participants may change over the course of the study based on the local/national infection rates. A participant who typically flies to a research site may decide instead to drive and stay in hotels even though the travel is substantially longer. Advarra recommends that reimbursement provisions should be written to cover several different travel scenarios that could arise.
To the extent reasonable, appropriate, and allowed under applicable law, researchers should consider the use of digital technology as a tool for participants to report symptoms as an alternative to requiring them to come to a site for check-ups. Video technology provides a means to see and talk to a participant without the need for them to travel. At Advarra, we have reviewed dozens of virtual trials and protocols leveraging home visits. Read our blog “Are ‘Virtual Trials’ Mainstream Yet?” for more on incorporating virtual trial elements in research.
If in-person assessments are necessary, consider whether in-home evaluations with visiting medical personnel would be sufficient.
In this type of research, an IRB must be able to quickly act on changes to ensure that newly identified issues are addressed promptly and appropriately and that the safety of human participants is always at the forefront. Investigators should always submit an amendment to the IRB to obtain prior review of changes to the research (except where the changes are necessary to eliminate an immediate hazard to subject safety—only in that situation may an investigator implement changes prior to IRB review). Advarra is prepared to prioritize these submissions for rapid turnaround as needed.
Advarra is honored to provide IRB and IBC oversight for the majority of US research being conducted in response to the current coronavirus outbreak, including multiple protocols from national entities. Our experts have extensive experience reviewing and conducting research involving infectious diseases and genetically engineered vaccines. For more information on coronavirus research, read our blog “Key Biosafety Considerations for Coronavirus Research.” Need assistance with a research project involving coronavirus or another infectious disease? Contact us for support.