Evidence map›Paper›PMID 42693525›Full record

ReviewClinical pharmacology and therapeutics2026

Secondary Pharmacology Targets for Pediatric Developmental Safety Assessment of New Drugs: Clinical Pharmacology Considerations.

Gilbert J Burckart, Sherbet Samuels, Susan M Abdel-Rahman, Gelareh Abulwerdi, Elimika Fletcher, Mohamed A Mohamoud, Apoorva Srinivasan, Nicholas Tatonetti, Rebecca Racz

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Clinical pharmacology and therapeutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Gilbert J BurckartOffice of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID https://orcid.org/0000-0003-2005-9301
Sherbet SamuelsOffice of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID https://orcid.org/0009-0001-1569-6157
Susan M Abdel-RahmanOffice of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID https://orcid.org/0000-0002-5815-2029
Gelareh AbulwerdiOffice of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID https://orcid.org/0000-0002-1036-6378
Elimika FletcherOffice of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID https://orcid.org/0000-0002-0345-4230
Mohamed A MohamoudOffice of Pediatric Therapeutics, Office of the Commissioner, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID https://orcid.org/0000-0002-5997-4876
Apoorva SrinivasanDepartment of Computational Biomedicine, Cedars-Sinai Medical Center, West Hollywood, California, USA.ORCID https://orcid.org/0009-0001-6036-7651
Nicholas TatonettiDepartment of Computational Biomedicine, Cedars-Sinai Medical Center, West Hollywood, California, USA.ORCID https://orcid.org/0000-0002-2700-2597
Rebecca RaczOffice of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA.ORCID https://orcid.org/0000-0002-5487-5692

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Drug safety in pediatric patients has always been a concern. Major tragedies with drugs in pediatric patients created an environment of caution, but the experience with pediatric legislation and drug development over the past 20 years has eased the cautionary approach to pediatric drug safety. The advent of new methods of safety testing, driven by the movement away from animal use in research, provides new opportunities to screen for and prevent adverse developmental effects of drugs on pediatric patients. One approach that can be explored for use in pediatric developmental safety testing is secondary pharmacology, or screening for off-target drug effects. Secondary pharmacology, which is an established screening mechanism described in ICH S7A, could provide the opportunity to answer important off-target questions. Examples of 12 specific secondary pharmacology targets related to adverse effects on pediatric development are provided. Clinical pharmacology plays a critical role in the interpretation of secondary pharmacology through quantitative studies necessary to validate positive findings and through the final assessment of the risk:benefit associated with these findings. In conclusion, secondary pharmacology screening has the potential to reduce animal testing while addressing two critical objectives: screening drugs for off-target effects and providing information on off-target effects relevant to pediatric developmental safety.

Indexed as

Child DevelopmentDrug DevelopmentDrug-Related Side Effects and Adverse ReactionsPediatricsPharmacology, ClinicalAnimalsChildDrug Evaluation, PreclinicalHumansRisk Assessment

Identifiers

PMID42693525
PMCPMC13541963

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.