Introduction. Generative Artificial Intelligence, particularly large language models (LLMs), offers transformative potential for Health Economics and Outcomes Research (HEOR). However, evaluating the quality, transparency, and rigor of LLM-assisted research lacks standardized guidance. This article introduces the ELEVATE AI LLMs framework and checklist, designed to support researchers and reviewers in assessing LLM use in HEOR. Methods. The ELEVATE AI LLMs framework was developed through a targeted review of existing guidelines and evaluation frameworks. The framework comprises ten evaluation domains, including model characteristics, accuracy, comprehensiveness, and fairness. The accompanying checklist operationalizes the framework. To validate the framework, we applied it to two published studies, demonstrating its usability across different HEOR tasks. Results. The ELEVATE AI LLMs framework provides a comprehensive structure for evaluating LLM-assisted research, while the checklist facilitates practical application. Validation of the framework and checklist on studies of systematic literature reviews and health economic modeling highlighted their ability to identify strengths and gaps in reporting. Limitations. While the ELEVATE AI LLMs framework provides robust guidance, its broader generalizability and applicability to diverse HEOR tasks require further empirical testing. Additionally, several metrics adapted from computer science need further validation in HEOR contexts. Conclusion. The ELEVATE AI LLMs framework and checklist fill a critical gap in HEOR by offering structured guidance for evaluating LLM-assisted research. By promoting transparency, accuracy, and reproducibility, they aim to standardize and improve the integration of LLMs into HEOR, ensuring their outputs meet the field's rigorous standards.

Objective: This article offers a taxonomy of generative artificial intelligence (AI) for health economics and outcomes research (HEOR), explores its emerging applications, and outlines methods to enhance the accuracy and reliability of AI-generated outputs. Methods: The review defines foundational generative AI concepts and highlights current HEOR applications, including systematic literature reviews, health economic modeling, real-world evidence generation, and dossier development. Approaches such as prompt engineering (zero-shot, few-shot, chain-of-thought, persona pattern prompting), retrieval-augmented generation, model fine-tuning, and the use of domain-specific models are introduced to improve AI accuracy and reliability. Results: Generative AI shows significant potential in HEOR, enhancing efficiency, productivity, and offering novel solutions to complex challenges. Foundation models are promising in automating complex tasks, though challenges remain in scientific reliability, bias, interpretability, and workflow integration. The article discusses strategies to improve the accuracy of these AI tools. Conclusion: Generative AI could transform HEOR by increasing efficiency and accuracy across various applications. However, its full potential can only be realized by building HEOR expertise and addressing the limitations of current AI technologies. As AI evolves, ongoing research and innovation will shape its future role in the field.

This paper introduces Llettuce, an open-source tool designed to address the complexities of converting medical terms into OMOP standard concepts. Unlike existing solutions such as the Athena database search and Usagi, which struggle with semantic nuances and require substantial manual input, Llettuce leverages advanced natural language processing, including large language models and fuzzy matching, to automate and enhance the mapping process. Developed with a focus on GDPR compliance, Llettuce can be deployed locally, ensuring data protection while maintaining high performance in converting informal medical terms to standardised concepts.

This review introduces the transformative potential of generative Artificial Intelligence (AI) and foundation models, including large language models (LLMs), for health technology assessment (HTA). We explore their applications in four critical areas, evidence synthesis, evidence generation, clinical trials and economic modeling: (1) Evidence synthesis: Generative AI has the potential to assist in automating literature reviews and meta-analyses by proposing search terms, screening abstracts, and extracting data with notable accuracy; (2) Evidence generation: These models can potentially facilitate automating the process and analyze the increasingly available large collections of real-world data (RWD), including unstructured clinical notes and imaging, enhancing the speed and quality of real-world evidence (RWE) generation; (3) Clinical trials: Generative AI can be used to optimize trial design, improve patient matching, and manage trial data more efficiently; and (4) Economic modeling: Generative AI can also aid in the development of health economic models, from conceptualization to validation, thus streamlining the overall HTA process. Despite their promise, these technologies, while rapidly improving, are still nascent and continued careful evaluation in their applications to HTA is required. To ensure their responsible use and implementation, both developers and users of research incorporating these tools, should familiarize themselves with their current limitations, including the issues related to scientific validity, risk of bias, and consider equity and ethical implications. We also surveyed the current policy landscape and provide suggestions for HTA agencies on responsibly integrating generative AI into their workflows, emphasizing the importance of human oversight and the fast-evolving nature of these tools.

Compared to the wide array of advanced Monte Carlo methods supported by modern probabilistic programming languages (PPLs), PPL support for variational inference (VI) is less developed: users are typically limited to a predefined selection of variational objectives and gradient estimators, which are implemented monolithically (and without formal correctness arguments) in PPL backends. In this paper, we propose a more modular approach to supporting variational inference in PPLs, based on compositional program transformation. In our approach, variational objectives are expressed as programs, that may employ first-class constructs for computing densities of and expected values under user-defined models and variational families. We then transform these programs systematically into unbiased gradient estimators for optimizing the objectives they define. Our design enables modular reasoning about many interacting concerns, including automatic differentiation, density accumulation, tracing, and the application of unbiased gradient estimation strategies. Additionally, relative to existing support for VI in PPLs, our design increases expressiveness along three axes: (1) it supports an open-ended set of user-defined variational objectives, rather than a fixed menu of options; (2) it supports a combinatorial space of gradient estimation strategies, many not automated by today's PPLs; and (3) it supports a broader class of models and variational families, because it supports constructs for approximate marginalization and normalization (previously introduced only for Monte Carlo inference). We implement our approach in an extension to the Gen probabilistic programming system (genjax.vi, implemented in JAX), and evaluate on several deep generative modeling tasks, showing minimal performance overhead vs. hand-coded implementations and performance competitive with well-established open-source PPLs.

We propose a framework for constructing and analyzing multiclass and multioutput classification metrics, i.e., involving multiple, possibly correlated multiclass labels. Our analysis reveals novel insights on the geometry of feasible confusion tensors -- including necessary and sufficient conditions for the equivalence between optimizing an arbitrary non-decomposable metric and learning a weighted classifier. Further, we analyze averaging methodologies commonly used to compute multioutput metrics and characterize the corresponding Bayes optimal classifiers. We show that the plug-in estimator based on this characterization is consistent and is easily implemented as a post-processing rule. Empirical results on synthetic and benchmark datasets support the theoretical findings.

Natural Language Inference (NLI) is fundamental to many Natural Language Processing (NLP) applications including semantic search and question answering. The NLI problem has gained significant attention thanks to the release of large scale, challenging datasets. Present approaches to the problem largely focus on learning-based methods that use only textual information in order to classify whether a given premise entails, contradicts, or is neutral with respect to a given hypothesis. Surprisingly, the use of methods based on structured knowledge -- a central topic in artificial intelligence -- has not received much attention vis-a-vis the NLI problem. While there are many open knowledge bases that contain various types of reasoning information, their use for NLI has not been well explored. To address this, we present a combination of techniques that harness knowledge graphs to improve performance on the NLI problem in the science questions domain. We present the results of applying our techniques on text, graph, and text-to-graph based models, and discuss implications for the use of external knowledge in solving the NLI problem. Our model achieves the new state-of-the-art performance on the NLI problem over the SciTail science questions dataset.

Open-domain question answering (QA) is an important problem in AI and NLP that is emerging as a bellwether for progress on the generalizability of AI methods and techniques. Much of the progress in open-domain QA systems has been realized through advances in information retrieval methods and corpus construction. In this paper, we focus on the recently introduced ARC Challenge dataset, which contains 2,590 multiple choice questions authored for grade-school science exams. These questions are selected to be the most challenging for current QA systems, and current state of the art performance is only slightly better than random chance. We present a system that rewrites a given question into queries that are used to retrieve supporting text from a large corpus of science-related text. Our rewriter is able to incorporate background knowledge from ConceptNet and -- in tandem with a generic textual entailment system trained on SciTail that identifies support in the retrieved results -- outperforms several strong baselines on the end-to-end QA task despite only being trained to identify essential terms in the original source question. We use a generalizable decision methodology over the retrieved evidence and answer candidates to select the best answer. By combining query rewriting, background knowledge, and textual entailment our system is able to outperform several strong baselines on the ARC dataset.