TY  - JOUR
T1  - The Prediction–Explanation Divide in Interpretable Structure–Activity Modelling and How Pharmaceutical Decisions Should Cross It
A1  - Sara Al-Fahd
A1  - Noura Al-Khalifa
A1  - Omar Al-Turki
JF  - International Journal of Pharmaceutical Research and Allied Sciences
JO  - Int J Pharm Res Allied Sci
SN  - 2277-3657
Y1  - 2025
VL  - 14
IS  - 1
DO  - 10.51847/0r77qJPUoT
SP  - 80
EP  - 89
N2  - Interpretable structure–activity modelling is increasingly expected to provide not only accurate predictions but also scientifically credible reasons for them. Yet prediction, interpretation, explanation, and molecular mechanism represent different epistemic achievements, and their conflation can produce persuasive but unsupported pharmaceutical narratives. This Original Interpretability Architecture Article defines the prediction–explanation divide and proposes a Decision-Adaptive Prediction–Explanation Crossing Architecture for determining when and how model outputs may support progressively consequential pharmaceutical decisions. The architecture separates predictive validity from attribution faithfulness, chemical coherence, perturbational concordance, and decision governance. It treats feature attribution, fragment highlighting, counterfactual generation, and concept-based explanations as complementary probes of model behaviour rather than independent demonstrations of molecular causation. Medicinal-chemistry validation is organized around chemically meaningful perturbations, including analogue series, matched molecular pairs, activity cliffs, prospective synthesis, orthogonal assays, and mechanistic interventions where appropriate. The architecture also identifies failure modes arising from dataset shift, inadequate applicability domains, unstable explanations, implausible counterfactuals, uncalibrated confidence, retrospective rationalization, and human confirmation bias. Governance requirements include explicit intended-use statements, evidence-proportional escalation, independent challenge, documented overrides, monitoring, and requalification after material changes. The principal contribution is an original conceptual framework that links explanatory claims to decision-specific evidence burdens and prevents direct movement from prediction to mechanism without external corroboration. The proposed gates and relationships remain hypotheses for prospective evaluation and do not establish clinical suitability, regulatory acceptance, universal applicability, or deployment readiness.
UR  - https://ijpras.com/article/the-predictionexplanation-divide-in-interpretable-structureactivity-modelling-and-how-pharmaceutic-hdmd9cx5u8azdf6
ER  -