Bioethics Forum Essay
Fear of Doing Too Much Too Soon or Too Little Too Late: Research on Covid-19
The Covid-19 pandemic has significantly affected the practice of clinical research. Researchers have felt an urgency to respond more quickly than usual to test possible interventions. Institutional review board staff and research administrators have prioritized rapid approval of important Covid-related research. “Research on COVID-19: Stories from IRB Members, Research Administrators, & Investigators,” a symposium in the current issue of Narrative Inquiry in Bioethics, explores the challenges—and successes—of conducting and reviewing research during the pandemic.
Symposium editors, Ana Iltis and Gianna McMillan, highlight an overriding tension in reviewing and conducting research during the pandemic: “the fear of doing too much too soon—or too little too late.”
Westyn Branch-Elliman and Paul A. Monach, clinical researchers and members of their institution’s IRB, discuss the landscape they navigated early in the pandemic when designing and implementing a trial to test possible treatments:
“In March , faced with a deadly disease descending upon our city and our hospital, there was an urge to be able to offer our patients ‘something’ beyond the under-appreciated supportive care,” they write. “Clinicians widely acknowledged that no available drug had sufficient evidence to support indiscriminate use in a purely clinical setting. The question was whether to use medications off-label based on limited anecdotes or to conduct a clinical trial—the first of many ethical issues we have confronted in the half-year since then. There was a desire by many, both among research leaders and some clinicians, for a ‘clinical trial’ banner, so that patients would be appropriately informed about the potential for a lack of benefit—and potential for harm—associated with almost any COVID-19 intervention.”
Under normal circumstances, the time from conception to implementation of a clinical trial could take months, but Branch-Elliman and Monach received IRB approval in six days and enrolled their first patient four days later. Their experience underscores the commitment of the researchers and the IRB professionals to rapid design and approval of important Covid-related research. Read their essay here.
Stefanie Juell writes that her IRB office at an academic medical center in New York City understood that its “ability to quickly respond to questions from clinicians about the use of experimental drugs might very well be the difference between life and death for patients in need of such treatments.” She even goes as far as to say, “I felt personally responsible for the lives of patients I never saw.” Juell worked “seven days per week, 10-to-12 hours per day and late into the evenings,” responding to investigator questions, updating an institution-wide FAQ page with common questions and responses, and rapidly reviewing Covid-related research to fulfill this sense of personal responsibility.
Despite the desire of many researchers to quickly test possible treatments and the efforts of IRBs to rapidly review this research, investigator Todd Seto notes that “the bureaucracy of research regulation and compliance, built over decades to minimize institutional risk and maximize human subjects protection, was poorly suited to match the rapidly evolving clinical milieu of the early pandemic.” The IRB approval process can often be seen as what IRB chair Jennifer Randles describes as “a dreaded but necessary institutional hoop” or, even worse, as a “potential obstruction to conducting research.”
IRB staff and those working in research oversight also felt this tension. Symposium commentator McMillan, an IRB member, describes this tension as “acting too quickly to be safe or, conversely, too slowly to save lives.” IRB chair Walter Dehority warns of deliberation “sacrificed on the altar of speed and efficiency,” while Stefanie Juell ponders the difference between “following the rules” and “doing the right thing.” Dehority and Juell continued to ask necessary questions about scientific validity and participant protection when reviewing studies, trying to balance hope and flexibility with warranted caution.
The long-held practice of obtaining in-person informed consent was challenged during the pandemic. Lack of personal protective equipment and personnel prompted researchers to explore alternative ways to effectively obtain participant or surrogate consent, such as obtaining consent remotely. Now, many researchers and participants appreciate the benefits of remote consent, such as reducing the need for additional clinic visits or recruiting rural participants who may not live near the study center. Some researchers have even begun to collect some data over the phone or using telehealth platforms, thus further changing the research landscape. However, these practices also raise equity concerns, as some patients may not have access to the necessary technology (computer, internet, etc.). To address these concerns, symposium authors tried to recruit diverse participants and provide technological access when possible.
In her commentary, Iltis reminds us that “conflating ethical obligations with practices used to meet those obligations can make it difficult, if not impossible, to adapt to changing circumstances or even to meet the needs of different participants.” For example, a traditional face-to-face consent process may not be the best way to protect participant autonomy or ensure equitable access to research opportunities. These narratives show that flexibility in informed consent or other traditional research practices may be warranted without sacrificing the ethical intent behind the practice, but careful scrutiny is still needed to ensure fair and equitable access to research and results.
Questions and concerns remain about the lasting impact of the pandemic on the landscape of research regulations. Should changes to research protocols be adopted permanently? What, if any, are the dangers of permanently adopting Covid-era protocols such as remote consent or data collection? As commentary author Sumit Mohan observes, “With approaches to clinical research evolving, the SARS-CoV-2 pandemic may be the catalyst needed to make sustainable improvements to our research processes, roles, and goals.”
A concurrent project by researchers in the Bioethics Research Center at Washington University aims to better understand the ethical, oversight, and regulatory barriers of doing Covid-related research during the pandemic. This project surveyed symposium participants about their views on the above questions with the goal of offering recommendations on ways to improve the process of research during pandemics in the future.
But perhaps, as McMillan writes, “the answer is not to invent new strategies, but to wield, with confidence, the tools that have already stood us good stead.” The founding principles of respect for personhood, beneficence, and justice may be, as Randles aptly notes “the best guide” for not only how to navigate this crisis or future crises, but also how to improve current approaches to clinical research. While the tension between doing “too much too soon or too little too late” remains, these narratives highlight the ability of researchers and IRB professionals to work together—balancing the steadfast commitments of scientific validity and participant protection with flexibility—to improve the scientific and ethical quality of clinical research.
Annie Friedrich, PhD, is a staff scientist in the Bioethics Research Center at Washington University School of Medicine in Saint Louis.