Optimizing Large Language Models for Causality Assessment in Pharmacovigilance: Developing a Performance Metric as Objective for Bayesian Hyperparameter Optimization
Mirrored from arXiv — NLP / Computation & Language for archival readability. Support the source by reading on the original site.
Computer Science > Computation and Language
arXiv:2607.03704 (cs)
[Submitted on 4 Jul 2026]
Title:Optimizing Large Language Models for Causality Assessment in Pharmacovigilance: Developing a Performance Metric as Objective for Bayesian Hyperparameter Optimization
Authors:Nicole Sonne Heckmann, Arnault-Quentin Vermillet, Søren Norlin Mølgaard, Manuela Del Castillo Suero, Lars Melskens, Gerard Ompad, Maurizio Sessa
View a PDF of the paper titled Optimizing Large Language Models for Causality Assessment in Pharmacovigilance: Developing a Performance Metric as Objective for Bayesian Hyperparameter Optimization, by Nicole Sonne Heckmann and Arnault-Quentin Vermillet and 4 other authors
View PDF
Abstract:Background: Growing individual case safety report (ICSR) volumes have intensified demand for scalable automated causality assessment. Large Language Models (LLMs) show promise, yet performance on clinically demanding tasks remains suboptimal and inference-time hyperparameter optimization has not been investigated. Objective: To develop a Gaussian Process (GP)-compatible optimization objective and investigate whether temperature optimization improves LLM-expert agreement on Naranjo causality assessment of FAERS ICSRs. Methods: Expert causality assessments were performed on 723 stratified FAERS cases. OpenAI's GPT-5.2 was evaluated using chain-of-thought (CoT) prompting. Four composite metrics were developed: Weighted Cosine Similarity (WCS), Information-Weighted Agreement Score (IWAS), Entropy-Weighted Agreement and Cosine Similarity Score (EWACS), and Consensus-Weighted Cosine Similarity (CWCS) and Bayesian optimization using a GP surrogate with Probability of Improvement (PoI) acquisition was applied across temperature [0, 2]. Results: GPT-5.2 outperformed prior biomedical LLMs at baseline (T = 0), achieving 74.1% agreement on question 5 and 65.4% on question 10 of Naranjo algorithm. Entropy analysis identified these as the sole informative optimization targets. Temperature showed no systematic population-level effect (\b{eta} = 0.002, p = 0.959). EWACS-guided Bayesian optimization improved causality classification agreement from 45.0% to 72.0% (+27 pp), with the largest gain in Doubtful cases (+42.9 pp). Conclusion: EWACS was identified as the optimal GP-compatible metric. The absence of a universal temperature optimum indicates LLM performance is driven primarily by ICSR content, yet case-specific temperature selection produced meaningful improvements, supporting temperature optimization for LLM-assisted pharmacovigilance.
| Subjects: | Computation and Language (cs.CL) |
| Cite as: | arXiv:2607.03704 [cs.CL] |
| (or arXiv:2607.03704v1 [cs.CL] for this version) | |
| https://doi.org/10.48550/arXiv.2607.03704
arXiv-issued DOI via DataCite (pending registration)
|
Submission history
From: Maurizio Sessa Dr. [view email][v1] Sat, 4 Jul 2026 04:49:14 UTC (7,705 KB)
Full-text links:
Access Paper:
- View PDF
View a PDF of the paper titled Optimizing Large Language Models for Causality Assessment in Pharmacovigilance: Developing a Performance Metric as Objective for Bayesian Hyperparameter Optimization, by Nicole Sonne Heckmann and Arnault-Quentin Vermillet and 4 other authors
References & Citations
Loading...
Bookmark
Bibliographic Tools
Code, Data, Media
Demos
Related Papers
About arXivLabs
Bibliographic and Citation Tools
Bibliographic Explorer Toggle
Bibliographic Explorer (What is the Explorer?)
Connected Papers Toggle
Connected Papers (What is Connected Papers?)
Litmaps Toggle
Litmaps (What is Litmaps?)
scite.ai Toggle
scite Smart Citations (What are Smart Citations?)
Code, Data and Media Associated with this Article
alphaXiv Toggle
alphaXiv (What is alphaXiv?)
Links to Code Toggle
CatalyzeX Code Finder for Papers (What is CatalyzeX?)
DagsHub Toggle
DagsHub (What is DagsHub?)
GotitPub Toggle
Gotit.pub (What is GotitPub?)
Huggingface Toggle
Hugging Face (What is Huggingface?)
ScienceCast Toggle
ScienceCast (What is ScienceCast?)
Demos
Replicate Toggle
Replicate (What is Replicate?)
Spaces Toggle
Hugging Face Spaces (What is Spaces?)
Spaces Toggle
TXYZ.AI (What is TXYZ.AI?)
Recommenders and Search Tools
Link to Influence Flower
Influence Flower (What are Influence Flowers?)
Core recommender toggle
CORE Recommender (What is CORE?)
arXivLabs: experimental projects with community collaborators
arXivLabs is a framework that allows collaborators to develop and share new arXiv features directly on our website.
Both individuals and organizations that work with arXivLabs have embraced and accepted our values of openness, community, excellence, and user data privacy. arXiv is committed to these values and only works with partners that adhere to them.
Have an idea for a project that will add value for arXiv's community? Learn more about arXivLabs.
More from arXiv — NLP / Computation & Language
-
Geometric and Behavioral Stratification in Transformer Residual Streams
Aug 14
-
Perturbation-based Regional Interpretability through Subtraction Mapping (PRISM): naming-error dissociations in language models and post-stroke aphasia
Aug 14
-
I-SDPO: Instance-Level Adaptive Self-Distillation Policy Optimization
Aug 14
-
Comment on "Modeling rapid language learning by distilling Bayesian priors into artificial neural networks"
Aug 14
Discussion (0)
Sign in to join the discussion. Free account, 30 seconds — email code or GitHub.
Sign in →No comments yet. Sign in and be the first to say something.