The REMS Sensitivity Index
Below is a qualitative index of the likelihood that FDA may require a REMS for a specific development compound as part of the NDA submission.
The presence of any attribute increases the probability of a REMS requirement; some items may be more highly weighted than others:
- New mechanism of action
- Theoretical risk based on new MOA
- Small clinical study population
- High stakeholder interest in off-label, especially if off-label population is large
- Biologic product
- Serious adverse event(s) identified in clinical trials, especially if they are related to liver enzyme elevation, QTc prolongation, drug-drug interactions, or teratogenicity
- Identified risk emerged in clinical trials and a protocol was implemented that was shown to effectively mitigate that risk
- Sponsor is a small company with limited prior regulatory experience
- Product is reformulated in a new delivery system (i.e., 505.b.2 product)
- Other products in the therapeutic class have REMS
- Risk requires high compliance with obtaining lab test values by physicians or patients in order to mitigate the adverse event
