Risk Assessment of therapeutic agents under consideration to
treat COVID-19 in Pediatric Patients and Pregnant Women
Jeffrey S. Barrett, PhD, FCP
Critical Path Institute
1730 East River Road
Tucson, Arizona 85718-5893
jbarrett@c-path.org
Phone: 215-595-6014
What is already known about this subject:
- Coronavirus disease (COVID-19) is caused by the SARS-Cov-2 virus that
can spread from person to person. While people of any age who have
serious underlying medical conditions may be at higher risk for more
severe illness, both pregnant women and children are still at risk for
both catching and transmitting the virus.
- Various treatment modalities (single agents, drug combinations and
vaccines) are currently being researched and clinically evaluated.
Given the time-dependent changes in physiologic parameters and
dynamics of both populations, evaluating the risk of treatment for
various treatment options is a critical step in evaluating their
suitability for pregnant women and children.
- Many (but not all) of the current modalities under investigation
represent repurposed drugs and vaccines that have been studied
previously for either related or unrelated indications. Given that
these agents have been studied previously, it is possible to evaluate
risk and preliminary dosing guidance in pediatric and pregnant
populations.
What this study adds:
- A risk assessment of the repurposed drugs and vaccines currently under
consideration for treating COVID-19 specifically focusing on
pregnant women and children.
- Considerations for choosing certain agents, dosing and/or adjustments
that may be warranted in pregnant women and children in general and
specific to the repurposed drugs currently under consideration for
treating COVID-19.
- A recommendation for more prospective integration of real-world data
(RWD) from pregnant women and children with repurposed drug risk
assessment and M&S tools to highlight readiness in the wake of future
pandemics.
ABSTRACT – 250-word limit (299)
Aim. Repurposing strategies to address the COVID-19 pandemic
have been accelerated in the hope that one or more of these options can
be available quickly. As both pregnant and pediatric patients are likely
to be excluded from the majority of planned investigations, the list of
repurposed options in light of the COVID-19 disease progression and the
available data on these drugs and vaccines provides a baseline risk
assessment and identifies gaps for targeted investigation in these
populations should mainstream clinical trials look promising.
Methods. Clinical trials have been searched and reviewed;
twenty-three repurposed drugs and drug combinations and 9 candidate
vaccines have been assessed regarding the availability of relevant data
in pediatrics and pregnant women and to make a preliminary evaluation of
any expected or unanticipated risk.
Results. Thirteen of the repurposed drugs or drug combinations
are indicated for use in pediatrics in some age category (2 exclusively
in Japan, 1 exclusively in the EU) albeit for indications other than
COVID-19; 10 of these are indicated for use in pregnant women (1
exclusively in Japan). Even in cases where these drugs are indicated in
the populations, source data from which safety and or dosing could be
extrapolated for use in COVID-19 in sparse. Vaccine trials are ongoing
and generally exclude pregnant women; only in a few instances have
pediatric subgroups been planned for enrollment. Data from individual
case studies and RWD may suggest that subpopulations of both pediatric
patients and pregnant women may be more at risk, particularly those in
an increased inflammatory state.
Conclusion. In conjunction with more prospective collaboration
and data sharing, plans are evolving to ensure that we will be better
prepared to address similar situations especially in pediatrics and
pregnant women where experience is often limited and actual practice
relies heavily on leveraging data from other populations and
indications.