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Evaluation Video

Oral Presentation

Session: EmBRACEing Collaborations for Benefit-Risk Decision Making

The Teratogenic Risk Impact and Mitigation (TRIM) Tool: Development of explicit criteria for teratogenicity risk mitigation programs

Monday, August 26, 2024
1:45 PM – 2:00 PM CEST
Location: Room III
Background: Decisions about the implementation of risk mitigation programs involve a broad range of considerations. An evidence-based decision tool could facilitate prioritizing teratogenic medications for risk mitigation programs.

Objectives: To develop explicit, measurable criteria for inclusion in the Teratogenic Risk Impact and Mitigation (TRIM) tool, which may inform decisions about need for risk mitigation beyond labelling of teratogenic medications

Methods: We recruited a national panel of experts familiar with clinical aspects of drug use during pregnancy, prevention of prenatal exposure, and risk mitigation decisions. Within a modified Delphi approach, experts were convened in focus groups to identify criteria to be considered when evaluating teratogenic medications for need for risk mitigation. Proposed items were consolidated into specific criteria via multiple rounds of surveys. Feedback received from each Delphi round was used to inform subsequent revisions until consensus (>80% agreement) was achieved. For each criterion, we then developed metrics using the same Delphi consensus approach; metrics were derived from supporting literature and targeted analyses in Merative™ MarketScan and Medicaid claims data to quantify background use and prenatal exposure risk of 140 medications with known teratogenic risk.

Results: Our panel included 33 experts, including 14 (42.4%) involved in the care of pregnant individuals, 12 (36.4%) with prior experience with risk mitigation programs and one consumer representative. 36 proposed criteria were consolidated into 6 with explicit metrics over 6 Delphi rounds. The final TRIM criteria include: 1) background use among persons of childbearing potential (high [>15]/moderate/low [ < 0.5] prevalence of medication use per 100,000 persons) based on tertiles from claims data analyses; 2) overall medication benefit among persons of child-bearing potential (high/moderate/low considering seriousness of the condition and availability of alternatives); 3) seriousness of teratogenic outcome (very serious [e.g., infant death] / moderately serious [e.g., spontaneous abortion]), 4) excess risk of teratogenic outcome (high [>5%] /moderate/low [ < 0.5%] attributable risk), 5) certainty regarding teratogenicity (high/moderate/low) and 6) risk of exposure during pregnancy (high [>15] /moderate/low [ < 5] incidence of prenatal exposure per 1000 user-years based on tertiles from claims data analyses).

Conclusions: The TRIM criteria provide an expert-informed, explicit decision framework. Criteria will be weighted and summarized in a total score that could facilitate prioritization of teratogenic medications for risk mitigation programs.