From implicit prioritization to auditable decisions in natural product drug discovery

It proposes a prospective framework for formalizing how evidence is translated into experimental actions so that the process becomes auditable. Relative to prior practice that relies on largely tacit judgment, the framework explicitly requires the decision process to be documented and traceable. This is a framework article based on an synthesis of three recurring gaps in natural product discovery workflows; no experimental data or validation results are reported.

It designs a four-tier architecture linking source authentication, reproducible chemical fingerprinting, orthogonal prioritization and definitive characterization through documented decision gates. It organizes previously separate analytical steps into a tiered structure with explicit connecting conditions rather than independent analytical stages. This is a conceptual architecture; the text describes its linkage mechanism as 'documented decision gates' and provides no implementation cases or performance metrics.

It introduces an 'evidence ladder' that separates molecular-identification confidence from chemical novelty, biological novelty and translational relevance. In response to the gap of conflating analytical detection with molecular novelty, it explicitly separates different levels of evidence. This is a conceptual distinction, stated in the text as separating 'molecular-identification confidence from chemical novelty, biological novelty and translational relevance'; no specific quantitative thresholds for the tiers are given.

The framework aims to make an existing, largely tacit decision process more transparent, comparable and testable. It places the improvement focus on comparability and testability of decisions rather than solely on analytical throughput or detection capacity. This is the authors' stated intent for the framework; the text reports no cross-laboratory comparison or testability validation results.

The framework addresses the decision step from evidence to experimental action in natural product drug discovery, and is intended for laboratories and workflows seeking more transparent, comparable and testable prioritization and characterization decisions; its role is to prospectively formalize an existing decision process rather than to replace specific analytical techniques or chemical methods.

This is an abstract-level framework discussion; it does not provide specific operational criteria for the four-tier architecture and evidence ladder, concrete decision-gate conditions, or implementation cases and cross-laboratory validation results. Readers focused on how to put it into practice would still need more complete implementation details and validation evidence.