Teratogenic Risk Impact and Mitigation (TRIM): Study Protocol for the Development of a Decision Support Tool to Prioritize Medications for Risk Mitigation

Almut G Winterstein; Celeste L Y Ewig; Yanning Wang; Nicole E Smolinski; Gita A Toyserkani; Cynthia LaCivita; Leila Lackey; Sara Eggers; Esther H Zhou; Vakaramoko Diaby; Amir Sarayani; Thuy Thai; Judith C Maro; Sonja A Rasmussen

doi:10.1007/s40264-024-01488-4

Teratogenic Risk Impact and Mitigation (TRIM): Study Protocol for the Development of a Decision Support Tool to Prioritize Medications for Risk Mitigation

Drug Saf. 2024 Nov 5. doi: 10.1007/s40264-024-01488-4. Online ahead of print.

Authors

Almut G Winterstein^{1

2

3}, Celeste L Y Ewig⁴, Yanning Wang^{4

5}, Nicole E Smolinski⁴, Gita A Toyserkani⁶, Cynthia LaCivita⁶, Leila Lackey⁶, Sara Eggers⁶, Esther H Zhou⁶, Vakaramoko Diaby⁷, Amir Sarayani⁸, Thuy Thai⁹, Judith C Maro⁹, Sonja A Rasmussen¹⁰

Affiliations

¹ Department of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, FL, USA. almut@ufl.edu.
² Center for Drug Evaluation and Safety, University of Florida, Gainesville, FL, USA. almut@ufl.edu.
³ Department of Epidemiology, University of Florida, Gainesville, FL, USA. almut@ufl.edu.
⁴ Department of Pharmaceutical Outcomes and Policy, University of Florida, Gainesville, FL, USA.
⁵ Department of Health Outcomes and Biomedical Informatics, College of Medicine, University of Florida, Gainesville, FL, USA.
⁶ Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
⁷ Health Economics and Value Evidence Partnership, Otsuka Pharmaceutical Development Corporation Inc, Princeton, NJ, USA.
⁸ Janssen Research and Development, Johnson & Johnson, Brisbane, CA, USA.
⁹ Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
¹⁰ Department of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.

PMID: 39499480
DOI: 10.1007/s40264-024-01488-4

Abstract

Introduction: Preventing prenatal exposure to teratogenic medications is an important goal of regulatory risk mitigation efforts. In the USA, as of March 2024, 11 teratogenic medications have a required Risk Evaluation and Mitigation Strategy (REMS) program. It is unclear whether these programs target those medications with the most significant impact on public health and adverse pregnancy outcomes.

Objectives: This study aims to develop an innovative decision support tool that uses explicit, quantifiable criteria to facilitate prioritization of teratogenic medications for risk mitigation strategies.

Methods: The Teratogenic Risk Impact and Mitigation (TRIM) decision support tool will be developed by a national panel via a modified Delphi approach to define measurable criteria, and a multi-criteria decision analysis to estimate criteria weights within a discrete choice experiment. The TRIM scores will then be calculated for 12 teratogenic drugs with active or eliminated REMS programs and for 12 teratogenic drugs without REMS. These drugs will be identified based on highest prenatal exposure prevalence in claims data of privately and publicly insured individuals. Data for the TRIM criteria levels for these 24 drugs will be identified from evidence searches and ad hoc analyses of the same claims data.

Conclusions: Teratogenic Risk Impact and Mitigation is intended to inform regulatory decision making about the need for risk mitigation programs for teratogenic medications by providing explicit, quantifiable, evidence-based criteria. The TRIM scores of 24 teratogenic drugs may provide benchmarks for considering REMS for marketed and new teratogenic medications.

Grants and funding

HHS75F40121C00188/U.S. Food and Drug Administration