Emerging Opportunities of Using Large Language Models for Translation Between Drug Molecules and Indications

A drug molecule is a substance that changes the organism's mental or physical state. Every approved drug has an indication, which refers to the therapeutic use of that drug for treating a particular medical condition. While the Large Language Model (LLM), a generative Artificial Intelligence (AI) technique, has recently demonstrated effectiveness in translating between molecules and their textual descriptions, there remains a gap in research regarding their application in facilitating the translation between drug molecules and indications, or vice versa, which could greatly benefit the drug discovery process. The capability of generating a drug from a given indication would allow for the discovery of drugs targeting specific diseases or targets and ultimately provide patients with better treatments. In this paper, we first propose a new task, which is the translation between drug molecules and corresponding indications, and then test existing LLMs on this new task. Specifically, we consider nine variations of the T5 LLM and evaluate them on two public datasets obtained from ChEMBL and DrugBank. Our experiments show the early results of using LLMs for this task and provide a perspective on the state-of-the-art. We also emphasize the current limitations and discuss future work that has the potential to improve the performance on this task. The creation of molecules from indications, or vice versa, will allow for more efficient targeting of diseases and significantly reduce the cost of drug discovery, with the potential to revolutionize the field of drug discovery in the era of generative AI.

Emerging Opportunities of Using Large Language Language Models for Translation Between Drug Molecules and Indications

A drug molecule is a substance that changes the organism's mental or physical state. Every approved drug has an indication, which refers to the therapeutic use of that drug for treating a particular medical condition. While the Large Language Model (LLM), a generative Artificial Intelligence (AI) technique, has recently demonstrated effectiveness in translating between molecules and their textual descriptions, there remains a gap in research regarding their application in facilitating the translation between drug molecules and indications, or vice versa, which could greatly benefit the drug discovery process. The capability of generating a drug from a given indication would allow for the discovery of drugs targeting specific diseases or targets and ultimately provide patients with better treatments. In this paper, we first propose a new task, which is the translation between drug molecules and corresponding indications, and then test existing LLMs on this new task. Specifically, we consider nine variations of the T5 LLM and evaluate them on two public datasets obtained from ChEMBL and DrugBank. Our experiments show the early results of using LLMs for this task and provide a perspective on the state-of-the-art. We also emphasize the current limitations and discuss future work that has the potential to improve the performance on this task. The creation of molecules from indications, or vice versa, will allow for more efficient targeting of diseases and significantly reduce the cost of drug discovery, with the potential to revolutionize the field of drug discovery in the era of generative AI.

Enhancing Large Language Models for Clinical Decision Support by Incorporating Clinical Practice Guidelines

Background Large Language Models (LLMs), enhanced with Clinical Practice Guidelines (CPGs), can significantly improve Clinical Decision Support (CDS). However, methods for incorporating CPGs into LLMs are not well studied. Methods We develop three distinct methods for incorporating CPGs into LLMs: Binary Decision Tree (BDT), Program-Aided Graph Construction (PAGC), and Chain-of-Thought-Few-Shot Prompting (CoT-FSP). To evaluate the effectiveness of the proposed methods, we create a set of synthetic patient descriptions and conduct both automatic and human evaluation of the responses generated by four LLMs: GPT-4, GPT-3.5 Turbo, LLaMA, and PaLM 2. Zero-Shot Prompting (ZSP) was used as the baseline method. We focus on CDS for COVID-19 outpatient treatment as the case study. Results All four LLMs exhibit improved performance when enhanced with CPGs compared to the baseline ZSP. BDT outperformed both CoT-FSP and PAGC in automatic evaluation. All of the proposed methods demonstrated high performance in human evaluation. Conclusion LLMs enhanced with CPGs demonstrate superior performance, as compared to plain LLMs with ZSP, in providing accurate recommendations for COVID-19 outpatient treatment, which also highlights the potential for broader applications beyond the case study.

In-Context Learning Functions with Varying Number of Minima

Large Language Models (LLMs) have proven effective at In-Context Learning (ICL), an ability that allows them to create predictors from labeled examples. Few studies have explored the interplay between ICL and specific properties of functions it attempts to approximate. In our study, we use a formal framework to explore ICL and propose a new task of approximating functions with varying number of minima. We implement a method that allows for producing functions with given inputs as minima. We find that increasing the number of minima degrades ICL performance. At the same time, our evaluation shows that ICL outperforms 2-layer Neural Network (2NN) model. Furthermore, ICL learns faster than 2NN in all settings. We validate the findings through a set of few-shot experiments across various hyperparameter configurations.

Foundation Metrics: Quantifying Effectiveness of Healthcare Conversations powered by Generative AI

Generative Artificial Intelligence is set to revolutionize healthcare delivery by transforming traditional patient care into a more personalized, efficient, and proactive process. Chatbots, serving as interactive conversational models, will probably drive this patient-centered transformation in healthcare. Through the provision of various services, including diagnosis, personalized lifestyle recommendations, and mental health support, the objective is to substantially augment patient health outcomes, all the while mitigating the workload burden on healthcare providers. The life-critical nature of healthcare applications necessitates establishing a unified and comprehensive set of evaluation metrics for conversational models. Existing evaluation metrics proposed for various generic large language models (LLMs) demonstrate a lack of comprehension regarding medical and health concepts and their significance in promoting patients' well-being. Moreover, these metrics neglect pivotal user-centered aspects, including trust-building, ethics, personalization, empathy, user comprehension, and emotional support. The purpose of this paper is to explore state-of-the-art LLM-based evaluation metrics that are specifically applicable to the assessment of interactive conversational models in healthcare. Subsequently, we present an comprehensive set of evaluation metrics designed to thoroughly assess the performance of healthcare chatbots from an end-user perspective. These metrics encompass an evaluation of language processing abilities, impact on real-world clinical tasks, and effectiveness in user-interactive conversations. Finally, we engage in a discussion concerning the challenges associated with defining and implementing these metrics, with particular emphasis on confounding factors such as the target audience, evaluation methods, and prompt techniques involved in the evaluation process.

Large Language Models Vote: Prompting for Rare Disease Identification

The emergence of generative Large Language Models (LLMs) emphasizes the need for accurate and efficient prompting approaches. LLMs are often applied in Few-Shot Learning (FSL) contexts, where tasks are executed with minimal training data. FSL has become popular in many Artificial Intelligence (AI) subdomains, including AI for health. Rare diseases affect a small fraction of the population. Rare disease identification from clinical notes inherently requires FSL techniques due to limited data availability. Manual data collection and annotation is both expensive and time-consuming. In this paper, we propose Models-Vote Prompting (MVP), a flexible prompting approach for improving the performance of LLM queries in FSL settings. MVP works by prompting numerous LLMs to perform the same tasks and then conducting a majority vote on the resulting outputs. This method achieves improved results to any one model in the ensemble on one-shot rare disease identification and classification tasks. We also release a novel rare disease dataset for FSL, available to those who signed the MIMIC-IV Data Use Agreement (DUA). Furthermore, in using MVP, each model is prompted multiple times, substantially increasing the time needed for manual annotation, and to address this, we assess the feasibility of using JSON for automating generative LLM evaluation.

From Military to Healthcare: Adopting and Expanding Ethical Principles for Generative Artificial Intelligence

In 2020, the U.S. Department of Defense officially disclosed a set of ethical principles to guide the use of Artificial Intelligence (AI) technologies on future battlefields. Despite stark differences, there are core similarities between the military and medical service. Warriors on battlefields often face life-altering circumstances that require quick decision-making. Medical providers experience similar challenges in a rapidly changing healthcare environment, such as in the emergency department or during surgery treating a life-threatening condition. Generative AI, an emerging technology designed to efficiently generate valuable information, holds great promise. As computing power becomes more accessible and the abundance of health data, such as electronic health records, electrocardiograms, and medical images, increases, it is inevitable that healthcare will be revolutionized by this technology. Recently, generative AI has captivated the research community, leading to debates about its application in healthcare, mainly due to concerns about transparency and related issues. Meanwhile, concerns about the potential exacerbation of health disparities due to modeling biases have raised notable ethical concerns regarding the use of this technology in healthcare. However, the ethical principles for generative AI in healthcare have been understudied, and decision-makers often fail to consider the significance of generative AI. In this paper, we propose GREAT PLEA ethical principles, encompassing governance, reliability, equity, accountability, traceability, privacy, lawfulness, empathy, and autonomy, for generative AI in healthcare. We aim to proactively address the ethical dilemmas and challenges posed by the integration of generative AI in healthcare.

ReDWINE: A Clinical Datamart with Text Analytical Capabilities to Facilitate Rehabilitation Research

Rehabilitation research focuses on determining the components of a treatment intervention, the mechanism of how these components lead to recovery and rehabilitation, and ultimately the optimal intervention strategies to maximize patients' physical, psychologic, and social functioning. Traditional randomized clinical trials that study and establish new interventions face several challenges, such as high cost and time commitment. Observational studies that use existing clinical data to observe the effect of an intervention have shown several advantages over RCTs. Electronic Health Records (EHRs) have become an increasingly important resource for conducting observational studies. To support these studies, we developed a clinical research datamart, called ReDWINE (Rehabilitation Datamart With Informatics iNfrastructure for rEsearch), that transforms the rehabilitation-related EHR data collected from the UPMC health care system to the Observational Health Data Sciences and Informatics (OHDSI) Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM) to facilitate rehabilitation research. The standardized EHR data stored in ReDWINE will further reduce the time and effort required by investigators to pool, harmonize, clean, and analyze data from multiple sources, leading to more robust and comprehensive research findings. ReDWINE also includes deployment of data visualization and data analytics tools to facilitate cohort definition and clinical data analysis. These include among others the Open Health Natural Language Processing (OHNLP) toolkit, a high-throughput NLP pipeline, to provide text analytical capabilities at scale in ReDWINE. Using this comprehensive representation of patient data in ReDWINE for rehabilitation research will facilitate real-world evidence for health interventions and outcomes.