Domain-Specific LLMs Improve Clinical Trial Outcome Prediction, Probing Matches Fine-Tuning

arXiv:2610.41710v1 Announce Type: new Abstract: Clinical trial failures are a major barrier to efficient drug development, incurring substantial costs and delaying patient access to effective therapies. Structured approaches such as the Hierarchical Interaction Network (HINT) predict trial outcomes by explicitly modelling interactions between drugs, diseases and protocols, but make limited use of the free text in trial registrations. We evaluate two domain-specific language models, BioBERT (108M parameters) and BioMistral (7B parameters), for phase-level outcome prediction on the TOP benchmark (12,477 trials), representing each trial as text built from ten ClinicalTrials.gov fields. We compare fine-tuning (full fine-tuning for BioBERT, low-rank adaptation for BioMistral) with probing, in which the pretrained model is frozen and only a lightweight classifier is trained on its embeddings. On the held-out test set of each phase, all four language-model variants achieved higher ROC-AUC (0.613--0.772) and PR-AUC (0.649--0.901) than the published HINT results, corresponding to relative PR-AUC gains of 10--20\%. F1 differences were small and mixed, and no model, including HINT, clearly exceeded the F1 of a trivial classifier that predicts success for every trial. Under the configurations tested, probing performed comparably to fine-tuning: fine-tuned models scored highest on ROC-AUC and PR-AUC in Phases I and II, and frozen BioMistral embeddings in Phase III (ROC-AUC 0.772; PR-AUC 0.901), although most differences between variants were below 0.03 and were not tested for significance. These results suggest that pretrained biomedical representations already encode signal relevant to trial outcome, and that probing is a computationally cheaper alternative to fine-tuning for this task.