Opinion

Promoting Data Harmonization of COVID-19 Research

VIEWPOINT
in Pregnant and Pediatric Populations

Jessica L. Gleason, The COVID-19 pandemic, while being an acute public ric populations. After the initial ranking of items and then
PhD, MPH health emergency, has produced numerous research chal- multiple rounds of voting, CDEs were narrowed down to
Epidemiology Branch, lenges and opportunities. Amid the flurry of research concise lists (≈ 20 questions) that could be added to any
Division of Population
being conducted to understand the acute and chronic im- existing or developing study. Voting “thresholds” were set
Health Research,
Division of Intramural pact of the virus and the pandemic, an initiative was at50%,withitemsbelowthisthresholddiscussedatgroup
Research, Eunice launched at the National Institutes of Health (NIH) to cre- meetings before exclusion and items above the threshold
Kennedy Shriver ate a set of common data elements (CDEs) to recom- maintainedforfurtherroundsofvoting.Asthecorelistwas
National Institute of
Child Health and
mend for use across studies of COVID-19. Common data developed, the working groups decided to further priori-
Human Development, elements are critically important in research of urgent tizeitems,votingtodividetheremainingitemsinto2“tiers”
Bethesda, Maryland. health care crises, such as the pandemic, because they of recommended CDEs. To limit participant burden in-
contribute to consistency in data collection, allow for pre-duced by lengthy questionnaires, pregnancy CDEs in tier
Robert Tamburro, MD, cision in how constructs are operationalized, and pro- 1werelimitedtothosethatshouldbeincludedinanystudy
MSc
Division of Extramural mote interoperability and collaboration in research1 across amongpeoplewhocouldbecomepregnant,knowingthat
Research, Eunice many and diverse projects. For example, a construct such no study would accept 60 additional questions. Tier 1 in-
Kennedy Shriver as COVID-19–related anxiety may be measured in mul- formation is important in these studies because people of
National Institute of
tiple ways, but data harmonization is maximized when reproductive age may become pregnant during investiga-
Child Health and
Human Development, the same scale is used to assess anxiety across studies. tionsinwhichpregnancyisnottheprimaryfocus,buttheir
Bethesda, Maryland. The Eunice Kennedy Shriver National Institute of Child information may be useful in data harmonization efforts.
HealthandHumanDevelopment,inpartnershipwithother Duringthisprocess,theworkinggrouprealizedthatalarger
Caroline Signore, MD, NIH institutes and federal agencies, convened working contribution could be made to COVID-19 research with
MPH
groupstodevelopCDEsforresearchincertainpopulations pregnancy-specificCDEs,extendingbeyondtheinitialgoal
Division of Extramural
Research, Eunice that are frequently understudied: children and pregnant oftier1items.Thus,tier2itemsweredevelopedforCOVID-
Kennedy Shriver or lactating individuals. Use of CDEs in these populations 19 studies specifically recruiting pregnant people.
National Institute of Overall, CDE use will allow all re-
Child Health and
Human Development, searchers to better study the long-term
Bethesda, Maryland. impacts of the pandemic. Using CDEs
Common data elements are critically to harmonize data across studies could
important in research of urgent health facilitate investigating rare COVID-
related conditions, such as pregnancy
care crises, such as the pandemic, complications that may be difficult to ex-
because they contribute to consistency amine in a single clinical study. For ex-
in data collection… ample, only 0.3% of pregnant people de-
velop eclampsia,4 meaning that even in
enables combining data sets for rare outcomes to increase a sample of 1000 pregnant people, there would be only
sample size and associated statistical power.2 3 cases available to use to attempt to identify potential
Two working groups were convened and followed associations with COVID-19 infection. If researchers can
similar models. The pregnancy working groups con- combine data collected across studies, total eclampsia
vened in mid-2020 and the pediatric working groups cases identified will increase, increasing the ability to de-
convened in early 2021. Representatives from perina- termine whether there is an association with infection.
tal and pediatric research networks and federal agen- To facilitate implementation, the CDE working groups
cies and primary investigators of intramural and extra- have produced 3 reports5-7 with the full list of CDEs; since
mural studies recruiting pregnant people or children the initial publication in December 2020, the reports have
were invited to participate in separate biomedical and had more than 2600 views and 4800 downloads. The
psychosocial CDE development working groups. Al- CDE working group has used the Disaster Recovery Re-
Corresponding
Author: Jessica L. though CDEs for some research areas are extensive,3 the sponse portal through the National Institute of Environ-
Gleason, PhD, MPH, early working group goals were to create a limited num- mental Health Sciences to translate the items into
Epidemiology Branch, ber of items to ensure that COVID-19 CDEs for preg- REDCap, as well as develop and implement training on
Eunice Kennedy Shriver
National Institute of nant and pediatric populations could be seamlessly in- how to use these items (video and resources are avail-
Child Health and corporated into a larger trans-NIH initiative. able at https://www.niehs.nih.gov/research/programs/
Human Development, Tothatend,usingamodifiedDelphiapproach,experts disaster/cde/index.cfm). Although most CDEs will not re-
6710B Rockledge Dr,
first identified specific topic areas or domains (Table) to quire updates, the working groups have instructed
Bethesda, MD 20892
(jessica.gleason@nih. guide the development of lists of more than 200 items rel- researchers to update COVID-19 treatment options and
gov). evant to COVID-19 research among pregnant and pediat- other items as the science evolves to ensure relevance.

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 Opinion Viewpoint

Table. Pregnancy and Pediatric CDE Domains to Recommend for Use Across Studies of COVID-19

Pregnancy CDE domains

10 Biomedical and psychosocial PASC
13 Biomedical and psychosocial COVID-19 domains and vaccine attitudes domains 4 Biospecimen COVID-19 and PASC domains
Biomedical Biomedical Biospecimens (neonate)
Baseline maternal and pregnancy characteristics COVID-19 vaccination history Biospecimens (maternal)
Maternal COVID-19 treatment Vaccine attitudes Extended specimen collection (maternal)
Maternal outcomes Postpartum Extended specimen collection (neonatal)
Obstetric and pregnancy outcomes Family planning
Neonatal characteristics
Neonatal SARS-CoV-2 testing
Early neonatal outcomes
Psychosocial Psychosocial
Socioeconomic status, housing, and emergent financial strain Pregnancy and postpartum function
Medical care Infant care practices
Impact on parenting Childcare and education
Stressful life events Attribution of symptoms
Maternal mental health Domestic violence
Health-related behaviors Access to care
Pediatric CDE domains
8 Biomedical COVID-19 and PASC domains 8 Psychosocial COVID-19 and PASC domains 3 Shared biomedical and psychosocial COVID-19
and PASC domainsa
Baseline child health Community, family, and peer factors Sociodemographics
Manifestations: clinical Social media and screen time Disability or function status
Manifestations: laboratory Well-being factors Underlying health conditions and health history
Manifestations: cardiopulmonary diagnostic assessment COVID-19 stress and worry before the pandemic
Manifestations: imaging COVID-19 attitudes, behaviors, and experiences
Diagnosis Health-related behaviors
Treatment Mental and behavioral health
Outcomes Health care
Abbreviation: CDE, common data element. information or medical history but recommend these data be collected in any
a
Pregnancy working groups did not formally endorse collection of demographic COVID-19 study.

There is the potential for the working groups to reconvene to address
major developments, as they did to expand CDEs for post–COVID-19
conditions and attitudes toward vaccines and to update vaccination
schedules. During these latter meetings, experts specifically added
questionsaboutthemenstrualcycleafterinitialanecdotalreportsfrom
individuals noting menstrual irregularities after vaccination.
Some lessons have been learned that may guide future CDE
development, including setting clear initial goals for the group
to streamline the process, balancing the number of experts in the
group, and finding creative ways to engage busy clinicians and
researchers.
The immediate goals of the working groups have been com-
pleted: developing CDEs, publishing reports, and training research-
ers in their use. The larger vision will be realized when pediatric and
pregnancy COVID CDEs are incorporated into all studies that re-
cruit these populations to promote data harmonization.

ARTICLE INFORMATION
Published Online: July 20, 2023.
doi:10.1001/jama.2023.10835
Conflict of Interest Disclosures: Dr Tamburro
reported receiving royalties from Springer
Publishing for serving as an editor on a pediatric
critical care textbook. No other disclosures were
reported.
Funding/Support: This work was supported in part
by the Division of Population Health Research,
Division of Intramural Research, Eunice Kennedy
Shriver National Institute of Child Health and
Human Development (NICHD).
Role of the Funder/Sponsor: The NICHD had no
role in the preparation, review, or approval of the
manuscript and decision to submit the manuscript
for publication.
Additional Contributions: Special thanks to the
following for their support throughout the CDE
development process: Shelli Avenevoli, PhD,
National Institute of Mental Health, Pediatric
Working Group Co-Chair; Nahida Chakhtoura, MD,
NICHD, Pregnancy Working Group Co-Chair; Aruna
Natarajan, MD, PhD, National Heart, Lung, and
Blood Institute, Pediatric Working Group Co-Chair;
and the team at Deloitte Consulting LLP for
administrative support during working group
meetings and in outlining this draft and preparing
the table: Areej Haroon, MPH, Corinne Hausmann,
PhD, and Will Shipman, MPP.
REFERENCES
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rationale for common data elements for clinical
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1097/PCC.0000000000002455
2. Cohen MZ, Thompson CB, Yates B, et al.
Implementing common data elements across
studies to advance research. Nurs Outlook. 2015;63
(2):181-188. doi:10.1016/j.outlook.2014.11.006
3. Mawji A, Li E, Chandna A, et al. Common data
elements for predictors of pediatric sepsis:
a framework to standardize data collection. PLoS One.
2021;16(6):e0253051.
4. Abalos E, Cuesta C, Carroli G, et al; WHO
Multicountry Survey on Maternal and Newborn
Health Research Network. Pre-eclampsia,
eclampsia and adverse maternal and perinatal
outcomes: a secondary analysis of the World Health
Organization Multicountry Survey on Maternal and
Newborn Health. BJOG. 2014;121(suppl 1):14-24.
5. Eunice Kennedy Shriver National Institute of
Child Health and Human Development. Promoting
data harmonization to accelerate COVID-19
pregnancy research: post-acute sequelae of
SARS-CoV-2 infection and vaccine attitudes
working group addendum. June 2021. Accessed
March 7, 2023. https://www.niehs.nih.gov/
research/programs/disaster/database/promoting_
data_harmonization_to_accelerate_covid_19_
pregnancy_research_508.pdf
6. Eunice Kennedy Shriver National Institute of
Child Health and Human Development. Promoting
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pediatric research. June 2021. Accessed March 7,
2023. https://www.niehs.nih.gov/research/
programs/disaster/database/promoting_data_
harmonization_to_accelerate_covid_19_pediatric_
research_508.pdf
7. Eunice Kennedy Shriver National Institute of
Child Health and Human Development. Promoting
data harmonization to accelerate COVID-19
pregnancy research. February 2021. Accessed July
18, 2023. https://www.niehs.nih.gov/research/
programs/disaster/database/promoting_data_
harmonization_to_accelerate_covid19_pregnancy_
research_508.pdf

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