Budget-Sensitive Discovery Scoring: A Formally Verified Framework for Evaluating AI-Guided Scientific Selection

arXiv:2603.12349v1 Announce Type: cross
Abstract: Scientific discovery increasingly relies on AI systems to select candidates for expensive experimental validation, yet no principled, budget-aware evaluation framework exists for comparing selection strategies — a gap intensified by large language models (LLMs), which generate plausible scientific proposals without reliable downstream evaluation. We introduce the Budget-Sensitive Discovery Score (BSDS), a formally verified metric — 20 theorems machine-checked by the Lean 4 proof assistant — that jointly penalizes false discoveries (lambda-weighted FDR) and excessive abstention (gamma-weighted coverage gap) at each budget level. Its budget-averaged form, the Discovery Quality Score (DQS), provides a single summary statistic that no proposer can inflate by performing well at a cherry-picked budget.
As a case study, we apply BSDS/DQS to: do LLMs add marginal value to an existing ML pipeline for drug discovery candidate selection? We evaluate 39 proposers — 11 mechanistic variants, 14 zero-shot LLM configurations, and 14 few-shot LLM configurations — using SMILES representations on MoleculeNet HIV (41,127 compounds, 3.5% active, 1,000 bootstrap replicates) under both random and scaffold splits. Three findings emerge. First, the simple RF-based Greedy-ML proposer achieves the best DQS (-0.046), outperforming all MLP variants and LLM configurations. Second, no LLM surpasses the Greedy-ML baseline under zero-shot or few-shot evaluation on HIV or Tox21, establishing that LLMs provide no marginal value over an existing trained classifier. Third, the proposer hierarchy generalizes across five MoleculeNet benchmarks spanning 0.18%-46.2% prevalence, a non-drug AV safety domain, and a 9×7 grid of penalty parameters (tau >= 0.636, mean tau = 0.863). The framework applies to any setting where candidates are selected under budget constraints and asymmetric error costs.