SynRL: Aligning Synthetic Clinical Trial Data with Human-preferred Clinical Endpoints Using Reinforcement Learning

Each year, hundreds of clinical trials are conducted to evaluate new medical interventions, but sharing patient records from these trials with other institutions can be challenging due to privacy concerns and federal regulations. To help mitigate privacy concerns, researchers have proposed methods for generating synthetic patient data. However, existing approaches for generating synthetic clinical trial data disregard the usage requirements of these data, including maintaining specific properties of clinical outcomes, and only use post hoc assessments that are not coupled with the data generation process. In this paper, we propose SynRL which leverages reinforcement learning to improve the performance of patient data generators by customizing the generated data to meet the user-specified requirements for synthetic data outcomes and endpoints. Our method includes a data value critic function to evaluate the quality of the generated data and uses reinforcement learning to align the data generator with the users' needs based on the critic's feedback. We performed experiments on four clinical trial datasets and demonstrated the advantages of SynRL in improving the quality of the generated synthetic data while keeping the privacy risks low. We also show that SynRL can be utilized as a general framework that can customize data generation of multiple types of synthetic data generators. Our code is available at https://anonymous.4open.science/r/SynRL-DB0F/.

A Perspective for Adapting Generalist AI to Specialized Medical AI Applications and Their Challenges

The integration of Large Language Models (LLMs) into medical applications has sparked widespread interest across the healthcare industry, from drug discovery and development to clinical decision support, assisting telemedicine, medical devices, and healthcare insurance applications. This perspective paper aims to discuss the inner workings of building LLM-powered medical AI applications and introduces a comprehensive framework for their development. We review existing literature and outline the unique challenges of applying LLMs in specialized medical contexts. Additionally, we introduce a three-step framework to organize medical LLM research activities: 1) Modeling: breaking down complex medical workflows into manageable steps for developing medical-specific models; 2) Optimization: optimizing the model performance with crafted prompts and integrating external knowledge and tools, and 3) System engineering: decomposing complex tasks into subtasks and leveraging human expertise for building medical AI applications. Furthermore, we offer a detailed use case playbook that describes various LLM-powered medical AI applications, such as optimizing clinical trial design, enhancing clinical decision support, and advancing medical imaging analysis. Finally, we discuss various challenges and considerations for building medical AI applications with LLMs, such as handling hallucination issues, data ownership and compliance, privacy, intellectual property considerations, compute cost, sustainability issues, and responsible AI requirements.

Can Large Language Models Replace Data Scientists in Clinical Research?

Data science plays a critical role in clinical research, but it requires professionals with expertise in coding and medical data analysis. Large language models (LLMs) have shown great potential in supporting medical tasks and performing well in general coding tests. However, these tests do not assess LLMs' ability to handle data science tasks in medicine, nor do they explore their practical utility in clinical research. To address this, we developed a dataset consisting of 293 real-world data science coding tasks, based on 39 published clinical studies, covering 128 tasks in Python and 165 tasks in R. This dataset simulates realistic clinical research scenarios using patient data. Our findings reveal that cutting-edge LLMs struggle to generate perfect solutions, frequently failing to follow input instructions, understand target data, and adhere to standard analysis practices. Consequently, LLMs are not yet ready to fully automate data science tasks. We benchmarked advanced adaptation methods and found two to be particularly effective: chain-of-thought prompting, which provides a step-by-step plan for data analysis, which led to a 60% improvement in code accuracy; and self-reflection, enabling LLMs to iteratively refine their code, yielding a 38% accuracy improvement. Building on these insights, we developed a platform that integrates LLMs into the data science workflow for medical professionals. In a user study with five medical doctors, we found that while LLMs cannot fully automate coding tasks, they significantly streamline the programming process. We found that 80% of their submitted code solutions were incorporated from LLM-generated code, with up to 96% reuse in some cases. Our analysis highlights the potential of LLMs, when integrated into expert workflows, to enhance data science efficiency in clinical research.

Demystifying Large Language Models for Medicine: A Primer

Large language models (LLMs) represent a transformative class of AI tools capable of revolutionizing various aspects of healthcare by generating human-like responses across diverse contexts and adapting to novel tasks following human instructions. Their potential application spans a broad range of medical tasks, such as clinical documentation, matching patients to clinical trials, and answering medical questions. In this primer paper, we propose an actionable guideline to help healthcare professionals more efficiently utilize LLMs in their work, along with a set of best practices. This approach consists of several main phases, including formulating the task, choosing LLMs, prompt engineering, fine-tuning, and deployment. We start with the discussion of critical considerations in identifying healthcare tasks that align with the core capabilities of LLMs and selecting models based on the selected task and data, performance requirements, and model interface. We then review the strategies, such as prompt engineering and fine-tuning, to adapt standard LLMs to specialized medical tasks. Deployment considerations, including regulatory compliance, ethical guidelines, and continuous monitoring for fairness and bias, are also discussed. By providing a structured step-by-step methodology, this tutorial aims to equip healthcare professionals with the tools necessary to effectively integrate LLMs into clinical practice, ensuring that these powerful technologies are applied in a safe, reliable, and impactful manner.

OmnixR: Evaluating Omni-modality Language Models on Reasoning across Modalities

We introduce OmnixR, an evaluation suite designed to benchmark SoTA Omni-modality Language Models, such as GPT-4o and Gemini. Evaluating OLMs, which integrate multiple modalities such as text, vision, and audio, presents unique challenges. Particularly, the user message might often consist of multiple modalities, such that OLMs have to establish holistic understanding and reasoning across modalities to accomplish the task. Existing benchmarks are limited to single modality or dual-modality tasks, overlooking comprehensive multi-modal assessments of model reasoning. To address this, OmnixR offers two evaluation variants: (1)synthetic subset: a synthetic dataset generated automatically by translating text into multiple modalities--audio, images, video, and hybrids (Omnify). (2)realistic subset: a real-world dataset, manually curated and annotated by experts, for evaluating cross-modal reasoning in natural settings. OmnixR presents a unique evaluation towards assessing OLMs over a diverse mix of modalities, such as a question that involves video, audio, and text, providing a rigorous cross-modal reasoning testbed unlike any existing benchmarks. Our experiments find that all state-of-the-art OLMs struggle with OmnixR questions that require integrating information from multiple modalities to answer. Further analysis highlights differences in reasoning behavior, underscoring the challenges of omni-modal AI alignment.

Model Swarms: Collaborative Search to Adapt LLM Experts via Swarm Intelligence

We propose Model Swarms, a collaborative search algorithm to adapt LLMs via swarm intelligence, the collective behavior guiding individual systems. Specifically, Model Swarms starts with a pool of LLM experts and a utility function. Guided by the best-found checkpoints across models, diverse LLM experts collaboratively move in the weight space and optimize a utility function representing model adaptation objectives. Compared to existing model composition approaches, Model Swarms offers tuning-free model adaptation, works in low-data regimes with as few as 200 examples, and does not require assumptions about specific experts in the swarm or how they should be composed. Extensive experiments demonstrate that Model Swarms could flexibly adapt LLM experts to a single task, multi-task domains, reward models, as well as diverse human interests, improving over 12 model composition baselines by up to 21.0% across tasks and contexts. Further analysis reveals that LLM experts discover previously unseen capabilities in initial checkpoints and that Model Swarms enable the weak-to-strong transition of experts through the collaborative search process.

Speculative Knowledge Distillation: Bridging the Teacher-Student Gap Through Interleaved Sampling

Recent advances in knowledge distillation (KD) have enabled smaller student models to approach the performance of larger teacher models. However, popular methods such as supervised KD and on-policy KD, are adversely impacted by the knowledge gaps between teacher-student in practical scenarios. Supervised KD suffers from a distribution mismatch between training with a static dataset and inference over final student-generated outputs. Conversely, on-policy KD, which uses student-generated samples for training, can suffer from low-quality training examples with which teacher models are not familiar, resulting in inaccurate teacher feedback. To address these limitations, we introduce Speculative Knowledge Distillation (SKD), a novel approach that leverages cooperation between student and teacher models to generate high-quality training data on-the-fly while aligning with the student's inference-time distribution. In SKD, the student proposes tokens, and the teacher replaces poorly ranked ones based on its own distribution, transferring high-quality knowledge adaptively. We evaluate SKD on various text generation tasks, including translation, summarization, math, and instruction following, and show that SKD consistently outperforms existing KD methods across different domains, data sizes, and model initialization strategies.

TableRAG: Million-Token Table Understanding with Language Models

Recent advancements in language models (LMs) have notably enhanced their ability to reason with tabular data, primarily through program-aided mechanisms that manipulate and analyze tables. However, these methods often require the entire table as input, leading to scalability challenges due to the positional bias or context length constraints. In response to these challenges, we introduce TableRAG, a Retrieval-Augmented Generation (RAG) framework specifically designed for LM-based table understanding. TableRAG leverages query expansion combined with schema and cell retrieval to pinpoint crucial information before providing it to the LMs. This enables more efficient data encoding and precise retrieval, significantly reducing prompt lengths and mitigating information loss. We have developed two new million-token benchmarks from the Arcade and BIRD-SQL datasets to thoroughly evaluate TableRAG's effectiveness at scale. Our results demonstrate that TableRAG's retrieval design achieves the highest retrieval quality, leading to the new state-of-the-art performance on large-scale table understanding.

Speculative RAG: Enhancing Retrieval Augmented Generation through Drafting

Retrieval augmented generation (RAG) combines the generative abilities of large language models (LLMs) with external knowledge sources to provide more accurate and up-to-date responses. Recent RAG advancements focus on improving retrieval outcomes through iterative LLM refinement or self-critique capabilities acquired through additional instruction tuning of LLMs. In this work, we introduce Speculative RAG - a framework that leverages a larger generalist LM to efficiently verify multiple RAG drafts produced in parallel by a smaller, distilled specialist LM. Each draft is generated from a distinct subset of retrieved documents, offering diverse perspectives on the evidence while reducing input token counts per draft. This approach enhances comprehension of each subset and mitigates potential position bias over long context. Our method accelerates RAG by delegating drafting to the smaller specialist LM, with the larger generalist LM performing a single verification pass over the drafts. Extensive experiments demonstrate that Speculative RAG achieves state-of-the-art performance with reduced latency on TriviaQA, MuSiQue, PubHealth, and ARC-Challenge benchmarks. It notably enhances accuracy by up to 12.97% while reducing latency by 51% compared to conventional RAG systems on PubHealth.

Accelerating Clinical Evidence Synthesis with Large Language Models

Automatic medical discovery by AI is a dream of many. One step toward that goal is to create an AI model to understand clinical studies and synthesize clinical evidence from the literature. Clinical evidence synthesis currently relies on systematic reviews of clinical trials and retrospective analyses from medical literature. However, the rapid expansion of publications presents challenges in efficiently identifying, summarizing, and updating evidence. We introduce TrialMind, a generative AI-based pipeline for conducting medical systematic reviews, encompassing study search, screening, and data extraction phases. We utilize large language models (LLMs) to drive each pipeline component while incorporating human expert oversight to minimize errors. To facilitate evaluation, we also create a benchmark dataset TrialReviewBench, a custom dataset with 870 annotated clinical studies from 25 meta-analysis papers across various medical treatments. Our results demonstrate that TrialMind significantly improves the literature review process, achieving high recall rates (0.897-1.000) in study searching from over 20 million PubMed studies and outperforming traditional language model embeddings-based methods in screening (Recall@20 of 0.227-0.246 vs. 0.000-0.102). Furthermore, our approach surpasses direct GPT-4 performance in result extraction, with accuracy ranging from 0.65 to 0.84. We also support clinical evidence synthesis in forest plots, as validated by eight human annotators who preferred TrialMind over the GPT-4 baseline with a winning rate of 62.5%-100% across the involved reviews. Our findings suggest that an LLM-based clinical evidence synthesis approach, such as TrialMind, can enable reliable and high-quality clinical evidence synthesis to improve clinical research efficiency.