Risk Minimization Programs for Teratogenic Drugs: How to Move from Art to Science

Background: Teratogenicity is a major drug safety risk of concern to patients, regulators, and sponsors. To date, there are over 130 drugs with known teratogenicity risk, of which about 10% have had additional risk minimization measures beyond drug labeling. These programs, known as pregnancy prevention programs (PPP) in the EU or Risk Evaluation and Mitigation Strategy in the US are implemented to mitigate prenatal exposure. Regulators in the EU and US have recently issued draft guidance on when such programs may be deemed necessary to ensure a favorable benefit-risk balance. Yet, such decisions lack fully conclusive data, and criteria may be challenging to apply in a reproducible manner. Moreover, the determination of which safe-use elements are necessary (e.g., educational materials) is driven by expert opinion and lacks evidence of (comparative) effectiveness and burden of each approach. Novel methods could provide a holistic evaluation of such programs to elucidate intended and unintended consequences and generate the necessary knowledge for evidence-based regulatory decision-making.

Objectives: This symposium will discuss new regulatory perspectives in the EU and US and novel pharmacoepidemiologic approaches to inform decision-making regarding when to require, how to design and implement, and how to measure the impact of pregnancy prevention programs.

Description: The symposium will include five presentations and a panel discussion:
1. New Regulatory perspectives to advance best practices (EMA and FDA - PB and GT)
2. Pharmacoepidemiology meets decision science: the Teratogenic Risk Impact and Mitigation (TRIM tool) (Academia - AGW)
3. Implementation science for optimal program design (CRO - MS)
4. Pharmacoepidemiology for program evaluation (Industry - AS)
5. What is to come: AI, patient preference, qualitative research (Panel)

The participants will enjoy an overview of the importance of risk mitigation, program effectiveness, and challenges to implementing such programs in the EU and US. Recent EMA and FDA guidance documents regarding additional risk minimization programs will be discussed with a special focus on pregnancy prevention programs. Advances in regulatory science to inform PPP requirements will be illustrated based on the FDA-funded TRIM project that incorporates pharmacoepidemiology and decision science approaches. The session will continue with a discussion on implementation science principles to improve program design and conduct, followed by a presentation on traditional and novel pharmacoepidemiologic research for PPP evaluation. A panel discussion will conclude this session to provide a futuristic view of how one could incorporate novel approaches in research and drug development projects.