From Scores to Safe Sets: Exact Safety--Constrained Decoding for Medication Recommendation

Animesh Agarwal, Meysam Ghaffari, Nina Fatehi, Anushka Swarup, Carlos Morato

Recent generative medication recommendation systems ultimately produce sets of drugs, but drug--drug interaction (DDI) constraints depend on the set as a whole. A natural post-hoc approach is to first predict medications and then locally repair interacting pairs by removing one drug at a time. We ask whether this local repair step itself introduces avoidable error. Using fixed medication scores from FLAME's frozen classifier on MIMIC-III, we compare increasingly strong local repair strategies with an exact global decoder while holding the scores, output size, and DDI constraint fixed. The global decoder jointly selects the highest-scoring feasible medication set using mixed-integer linear programming. Across validation and test splits, global decoding consistently achieves higher Jaccard similarity than greedy repair, degree-aware repair, and degree-aware repair strengthened with exhaustive 1-swap local search. Its advantage is small under loose DDI constraints and becomes larger as the constraint tightens; on the test split it reaches +0.0064 Jaccard over the strongest local baseline at the strict DDI operating point. The finding also holds across a fine accuracy--DDI sweep at…