Research stands alongside many of the global activities that have been constrained
because of the COVID-19 pandemic. Physical distancing policies to mitigate viral spread
have banned or restricted in-person contacts for hundreds of thousands of clinical
trials as well as other types of human subjects’ research, not to mention the temporary
shutdown of many laboratory studies. The suspension of scientific investigations that
are in progress can invalidate or dramatically influence the quality and interpretation
of study results, a ramification magnified in proportion to the moratorium duration.
Few people question the necessity of restricting human contacts as much as possible
during the outbreak of a novel infectious agent to safeguard human health and to preserve
critical health care resources. Now nearly a year into the pandemic, research procedures
are only one among many institutional and societal policies requiring regular re-evaluation
based upon viral surges that ebb and flow. Even when COVID-19 eventually abates, lessons
learned from the current mitigation efforts will hopefully inform strategies regarding
research during future regional, national, or global crises.
McDermott and Newman have articulated strategies for maintaining the integrity of
clinical trials during the mandatory pandemic-related bans on in-person contacts.
1
Their pragmatic suggestions include (a) informing study participants of study adjustments
that may temporarily affect the study assessments or intervention; (b) modifying evaluations
or treatments, when possible, to a method that may be administered remotely by telephone
or web-based technologies; (c) for study procedures that cannot be conducted remotely,
resume assessments and interventions after the in-person ban is lifted; (d) accounting
for and reporting the interrupted subgroup of affected participants in the methods
and analysis sections of the manuscript; (e) maintaining or even increasing study
activities that do not require in-person contact, such as determining study eligibility
as well as enrolling and consenting participants. Others have highlighted similar
as well as additional pandemic-related accommodations.
2, 3
Complementing these highly useful recommendations, we provide some additional suggestions
in Table 1. These apply to all types of human subjects’ research necessitating in-person
or virtual contacts, including clinical trials and epidemiological studies as well
as community-engaged, health systems, and translational research. The two major clinical
research activities most affected by restrictions on in-person contacts are participant
assessments and intervention delivery. These activities are affected differentially
by where along the study timeline a participant is situated, i.e., whether proximal
to the baseline assessment or an intervention that has not yet begun vs. follow-up
assessments and ongoing interventions. Whereas challenges are clearly greatest with
the latter group, potential strategies for dealing with these different circumstances
are proffered. Pandemic-related constraints on basic science research have been qualitatively
different but nonetheless substantial. Although the number of unique human contacts
may be fewer for bench than for clinical studies, it is typically not feasible to
conduct laboratory experiments remotely using telephone or other virtual technology.
Table 1
Strategies for Continuing a Clinical Research Study When In-Person Contacts Are Restricted
Study component
Potential strategy
Baseline assessment
1. Convert if possible to virtual (remote) assessment by audio (if only patient-reported
outcomes are required) or video (if patient observation or performance is required)
2. If study cannot convert to remote assessment, delay baseline assessment until in-person
contacts are permitted
Follow-up assessment
1. Same as strategy #1 for baseline assessment
2. If study cannot convert to remote assessment and has assessments at multiple time
points, drop one (or more) of the assessments for these participants. Repeated measures
or imputation strategies can deal with missing assessments.
3. If near the end of the in-person ban period, delay the assessment if possible to
do so within a reasonable time window
Intervention—subject has not yet started
1. Delay intervention until in-person ban has been lifted (and decide if study needs
to re-do eligibility interview at that time)
Intervention—subject has started
1. Convert if possible to a virtual (remote) intervention delivery
2. If study cannot convert to remote delivery, suspend for several months until the
in-person contact ban is lifted. Then pick up where study left off. For example, if
study delivered sessions 1–3 of a 6-session intervention, finish sessions 4–6 after
in-person ban is lifted
3. If study cannot pick up where it left off, consider restarting the intervention
after in-person ban is lifted (a downside is a subgroup of participants will get a
“double dose” for repeated sessions).
Other issues
1. Try to avoid dropping enrolled subjects if at all possible
2. Clear major study changes with IRB and study sponsor
3. Enroll a larger number of participants if possible to compensate for the pandemic-related
subgroup should the latter affect the results
4. Use secondary analytic strategies (e.g., analyzing study results with and without
pandemic-related participant subgroup; adjusting for pandemic subgroup as a covariate;
etc.)
Besides the primary purpose of maintaining the integrity of research, there are secondary
benefits to sustaining studies until the pandemic wanes and face-to-face engagement
resumes. First, study participants currently isolated from their usual interactions
at work, at school, and in the community may value the human contact with members
of the research team. Second, research staff remain employed, a non-trivial issue
when many businesses and jobs are being jeopardized by the pandemic. Anything that
counters the economic fall-out, even to a modest degree, is consequential. Third,
keeping study participants involved allows them to contribute to something meaningful
and important while their usual daily activities, like jobs, may be curtailed. Fourth,
clinician-scientists who are able to keep their research active may experience a temporary
and welcome respite from the pressures of pandemic-related clinical activities. Fifth,
continuing research may help preserve a sense of normalcy for investigators, staff,
and study participants. Sixth, enormous amounts of monies have been committed to ongoing
studies by the federal government and other sponsors, and honoring these contractual
obligations to the extent possible, while still prioritizing control of the pandemic,
benefits not only science but also the study participants and research staff.
It may be helpful to reflect on a different, historical crisis to create some emotional
space while at the same time examining the impact on both science and individual scientists.
During World War II, some scientists were drafted while others had to decide whether
to enlist for service or continue their research during the war. A survey was sent
to 122 academic zoologists to examine their attitudes regarding research during the
war.
4
Of 41 respondents, only 6 were in favor of discontinuing research, whereas 27 favored
continuing their current research, 5 for continuing it in their spare time, and 3
for redirecting research to war-related problems.
A related albeit not identical decisional dilemma confronts researchers during the
current pandemic. Some clinician-scientists are putting research studies on hold not
only due to barriers imposed by physical distancing but also because of increased
clinical duties necessitated by the pandemic. Senior clinician-scientists either no
longer involved in patient care or at greater risk if exposed to the virus are wondering
how they can assist the pandemic efforts in ways other than front-line clinical care.
5, 6
Both clinical and basic scientists whose principal activities are not focused on COVID-19
have debated whether they should re-direct (pivot) their skills to pandemic-related
research or assist in research temporarily set aside by their clinician-scientist
colleagues whose patient care responsibilities have increased. While wrestling with
these decisions, the varying rather than uniform attitudes among scientists during
previous crises such as World War II signify that there is unlikely to be one right
answer.
Major events such as contagion, war, and natural disasters will inevitably disrupt
research to a greater or less degree. The impact may be local (circumscribed disasters),
regional or continental (wars or more widespread disasters), and with the current
pandemic even global. The disruptive impact will vary with not only the geographic
extent but also the type of event.
7
For example, research challenges in the aftermath of Hurricane Katrina included locating
displaced participants, establishing alternative clinical sites and laboratory facilities,
and securing specimens and data storage.
7
Nonetheless, infectious diseases, wars, and disasters will share some common detrimental
impacts on research. These include diversion of funds, people, and other resources
to more urgent priorities; physical or geographic obstacles to continuing scientific
studies; decisional dilemmas for many individuals regarding where and how to devote
their time and skills; and negative feelings that can temporarily dampen energy or
enthusiasm for research, such as worry, fear, exhaustion, burnout, and even existential
concerns. We also may have to be nimbler and more flexible in how research is approved,
funded, and conducted during times of crisis.
8
Finally, it is important that the preferences of research participants already enrolled
in studies be considered in weighing the risks and benefits of continued participation.
9
What we do and learn during COVID-19 and its aftermath will not only help sustain
research during the pandemic but in future crises as well. It is our hope that research
and unanticipated societal disruptions may co-exist rather than be mutually exclusive.