$\texttt{AMEND++}$: Benchmarking Eligibility Criteria Amendments in Clinical Trials

Clinical trial amendments frequently introduce delays, increased costs, and administrative burden, with eligibility criteria being the most commonly amended component. We introduce \textit{eligibility criteria amendment prediction}, a novel NLP task that aims to forecast whether the eligibility criteria of an initial trial protocol will undergo future amendments. To support this task, we release $\texttt{AMEND++}$, a benchmark suite comprising two datasets: $\texttt{AMEND}$, which captures eligibility-criteria version histories and amendment labels from public clinical trials, and $\verb|AMEND_LLM|$, a refined subset curated using an LLM-based denoising pipeline to isolate substantive changes. We further propose $\textit{Change-Aware Masked Language Modeling}$ (CAMLM), a revision-aware pretraining strategy that leverages historical edits to learn amendment-sensitive representations. Experiments across diverse baselines show that CAMLM consistently improves amendment prediction, enabling more robust and cost-effective clinical trial design.

SECRET: Semi-supervised Clinical Trial Document Similarity Search

Clinical trials are vital for evaluation of safety and efficacy of new treatments. However, clinical trials are resource-intensive, time-consuming and expensive to conduct, where errors in trial design, reduced efficacy, and safety events can result in significant delays, financial losses, and damage to reputation. These risks underline the importance of informed and strategic decisions in trial design to mitigate these risks and improve the chances of a successful trial. Identifying similar historical trials is critical as these trials can provide an important reference for potential pitfalls and challenges including serious adverse events, dosage inaccuracies, recruitment difficulties, patient adherence issues, etc. Addressing these challenges in trial design can lead to development of more effective study protocols with optimized patient safety and trial efficiency. In this paper, we present a novel method to identify similar historical trials by summarizing clinical trial protocols and searching for similar trials based on a query trial's protocol. Our approach significantly outperforms all baselines, achieving up to a 78% improvement in recall@1 and a 53% improvement in precision@1 over the best baseline. We also show that our method outperforms all other baselines in partial trial similarity search and zero-shot patient-trial matching, highlighting its superior utility in these tasks.

TrialSynth: Generation of Synthetic Sequential Clinical Trial Data

Analyzing data from past clinical trials is part of the ongoing effort to optimize the design, implementation, and execution of new clinical trials and more efficiently bring life-saving interventions to market. While there have been recent advances in the generation of static context synthetic clinical trial data, due to both limited patient availability and constraints imposed by patient privacy needs, the generation of fine-grained synthetic time-sequential clinical trial data has been challenging. Given that patient trajectories over an entire clinical trial are of high importance for optimizing trial design and efforts to prevent harmful adverse events, there is a significant need for the generation of high-fidelity time-sequence clinical trial data. Here we introduce TrialSynth, a Variational Autoencoder (VAE) designed to address the specific challenges of generating synthetic time-sequence clinical trial data. Distinct from related clinical data VAE methods, the core of our method leverages Hawkes Processes (HP), which are particularly well-suited for modeling event-type and time gap prediction needed to capture the structure of sequential clinical trial data. Our experiments demonstrate that TrialSynth surpasses the performance of other comparable methods that can generate sequential clinical trial data, in terms of both fidelity and in enabling the generation of highly accurate event sequences across multiple real-world sequential event datasets with small patient source populations when using minimal external information. Notably, our empirical findings highlight that TrialSynth not only outperforms existing clinical sequence-generating methods but also produces data with superior utility while empirically preserving patient privacy.