Tracing Pharmacological Knowledge In Large Language Models

The morphological form of a word can often give cues to its meaning, but purely relying on these mappings can lead to overgeneralization in high-stakes domains. In the medical domain, for instance, LLMs can confidently reason about fictitious drugs from their affixes alone (e.g., wugcillin) and generate plausible-looking clinical content. We present a behavioral and mechanistic study of LLM "affix heuristics" in pharmacology. Using fictitious drug names built from real affixes, we show that affix signals alone elicit class-level pharmacological responses. We introduce a framework for identifying whether a model's drug semantics are driven mainly by the affix, the stem, or the drug name as a whole. Applied across 653 drugs, our framework reveals that models often induce drug meaning primarily through affix cues, yet rarely explicitly indicate this reliance, and sometimes incorrectly conflate properties among affix-sharing drugs. Activation patching across models further localizes this behavior to early-mid layers. These findings show that morphological shortcuts pose a subtle but measurable risk to safety.

Understanding whether large language models (LLMs) capture structured meaning requires examining how they represent concept relationships. In this work, we study three models of increasing scale: Pythia-70M, GPT-2, and Llama 3.1 8B, focusing on four semantic relations: synonymy, antonymy, hypernymy, and hyponymy. We combine linear probing with mechanistic interpretability techniques, including sparse autoencoders (SAE) and activation patching, to identify where these relations are encoded and how specific features contribute to their representation. Our results reveal a directional asymmetry in hierarchical relations: hypernymy is encoded redundantly and resists suppression, while hyponymy relies on compact features that are more easily disrupted by ablation. More broadly, relation signals are diffuse but exhibit stable profiles: they peak in the mid-layers and are stronger in post-residual/MLP pathways than in attention. Difficulty is consistent across models (antonymy easiest, synonymy hardest). Probe-level causality is capacity-dependent: on Llama 3.1, SAE-guided patching reliably shifts these signals, whereas on smaller models the shifts are weak or unstable. Our results clarify where and how reliably semantic relations are represented inside LLMs, and provide a reproducible framework for relating sparse features to probe-level causal evidence.

Background: The potential of large language models (LLMs) to automate and support pharmacoepidemiologic study design is an emerging area of interest, yet their reliability remains insufficiently characterized. General-purpose LLMs often display inaccuracies, while the comparative performance of specialized biomedical LLMs in this domain remains unknown. Methods: This study evaluated general-purpose LLMs (GPT-4o and DeepSeek-R1) versus biomedically fine-tuned LLMs (QuantFactory/Bio-Medical-Llama-3-8B-GGUF and Irathernotsay/qwen2-1.5B-medical_qa-Finetune) using 46 protocols (2018-2024) from the HMA-EMA Catalogue and Sentinel System. Performance was assessed across relevance, logic of justification, and ontology-code agreement across multiple coding systems using Least-to-Most (LTM) and Active Prompting strategies. Results: GPT-4o and DeepSeek-R1 paired with LTM prompting achieved the highest relevance and logic of justification scores, with GPT-4o-LTM reaching a median relevance score of 4 in 8 of 9 questions for HMA-EMA protocols. Biomedical LLMs showed lower relevance overall and frequently generated insufficient justification. All LLMs demonstrated limited proficiency in ontology-code mapping, although LTM provided the most consistent improvements in reasoning stability. Conclusion: Off-the-shelf general-purpose LLMs currently offer superior support for pharmacoepidemiologic design compared to biomedical LLMs. Prompt strategy strongly influenced LLM performance.