Turgay Ayer

Rachael Fleurence, Xiaoyan Wang, Jiang Bian et al.

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.

Rachael L. Fleurence, Dalia Dawoud, Jiang Bian et al.

Introduction: Generative artificial intelligence (AI), particularly large language models (LLMs), holds significant promise for Health Economics and Outcomes Research (HEOR). However, standardized reporting guidance for LLM-assisted research is lacking. This article introduces the ELEVATE GenAI framework and checklist - reporting guidelines specifically designed for HEOR studies involving LLMs. Methods: The framework was developed through a targeted literature review of existing reporting guidelines, AI evaluation frameworks, and expert input from the ISPOR Working Group on Generative AI. It comprises ten domains, including model characteristics, accuracy, reproducibility, and fairness and bias. The accompanying checklist translates the framework into actionable reporting items. To illustrate its use, the framework was applied to two published HEOR studies: one focused on systematic literature review tasks and the other on economic modeling. Results: The ELEVATE GenAI framework offers a comprehensive structure for reporting LLM-assisted HEOR research, while the checklist facilitates practical implementation. Its application to the two case studies demonstrates its relevance and usability across different HEOR contexts. Limitations: Although the framework provides robust reporting guidance, further empirical testing is needed to assess its validity, completeness, usability, as well as its generalizability across diverse HEOR use cases. Conclusion: The ELEVATE GenAI framework and checklist address a critical gap by offering structured guidance for transparent, accurate, and reproducible reporting of LLM-assisted HEOR research. Future work will focus on extensive testing and validation to support broader adoption and refinement.

Zilong Wang, Ali Abdeen, Turgay Ayer

Randomized controlled trials often do not represent the populations where decisions are made, and covariate shift across studies can invalidate standard IPD meta-analysis and transport estimators. We propose a placebo-anchored transport framework that treats source-trial outcomes as abundant proxy signals and target-trial placebo outcomes as scarce, high-fidelity gold labels to calibrate baseline risk. A low-complexity (sparse) correction anchors proxy outcome models to the target population, and the anchored models are embedded in a cross-fitted doubly robust learner, yielding a Neyman-orthogonal, target-site doubly robust estimator for patient-level heterogeneous treatment effects when target treated outcomes are available. We distinguish two regimes: in connected targets (with a treated arm), the method yields target-identified effect estimates; in disconnected targets (placebo-only), it reduces to a principled screen--then--transport procedure under explicit working-model transport assumptions. Experiments on synthetic data and a semi-synthetic IHDP benchmark evaluate pointwise CATE accuracy, ATE error, ranking quality for targeting, decision-theoretic policy regret, and calibration. Across connected settings, the proposed method is best or near-best and improves substantially over proxy-only, target-only, and transport baselines at small target sample sizes; in disconnected settings, it retains strong ranking performance for targeting while pointwise accuracy depends on the strength of the working transport condition.

Zilong Wang, Turgay Ayer, Shihao Yang

Estimating heterogeneous treatment effects is critical in domains such as personalized medicine, resource allocation, and policy evaluation. A central challenge lies in identifying subpopulations that respond differently to interventions, thereby enabling more targeted and effective decision-making. While clustering methods are well-studied in unsupervised learning, their integration with causal inference remains limited. We propose a novel framework that clusters individuals based on estimated treatment effects using a learned kernel derived from causal forests, revealing latent subgroup structures. Our approach consists of two main steps. First, we estimate debiased Conditional Average Treatment Effects (CATEs) using orthogonalized learners via the Robinson decomposition, yielding a kernel matrix that encodes sample-level similarities in treatment responsiveness. Second, we apply kernelized clustering to this matrix to uncover distinct, treatment-sensitive subpopulations and compute cluster-level average CATEs. We present this kernelized clustering step as a form of regularization within the residual-on-residual regression framework. Through extensive experiments on semi-synthetic and real-world datasets, supported by ablation studies and exploratory analyses, we demonstrate the effectiveness of our method in capturing meaningful treatment effect heterogeneity.

Zhaowei She, Zilong Wang, Jagpreet Chhatwal et al.

The COVID-19 pandemic has exerted a profound impact on the global economy and continues to exact a significant toll on human lives. The COVID-19 case growth rate stands as a key epidemiological parameter to estimate and monitor for effective detection and containment of the resurgence of outbreaks. A fundamental challenge in growth rate estimation and hence outbreak detection is balancing the accuracy-speed tradeoff, where accuracy typically degrades with shorter fitting windows. In this paper, we develop a machine learning (ML) algorithm, which we call Transfer Learning Generalized Random Forest (TLGRF), that balances this accuracy-speed tradeoff. Specifically, we estimate the instantaneous COVID-19 exponential growth rate for each U.S. county by using TLGRF that chooses an adaptive fitting window size based on relevant day-level and county-level features affecting the disease spread. Through transfer learning, TLGRF can accurately estimate case growth rates for counties with small sample sizes. Out-of-sample prediction analysis shows that TLGRF outperforms established growth rate estimation methods. Furthermore, we conducted a case study based on outbreak case data from the state of Colorado and showed that the timely detection of outbreaks could have been improved by up to 224% using TLGRF when compared to the decisions made by Colorado's Department of Health and Environment (CDPHE). To facilitate implementation, we have developed a publicly available outbreak detection tool for timely detection of COVID-19 outbreaks in each U.S. county, which received substantial attention from policymakers.

Zhaowei She, Zilong Wang, Turgay Ayer et al.

Rapid and accurate detection of community outbreaks is critical to address the threat of resurgent waves of COVID-19. A practical challenge in outbreak detection is balancing accuracy vs. speed. In particular, while estimation accuracy improves with longer fitting windows, speed degrades. This paper presents a machine learning framework to balance this tradeoff using generalized random forests (GRF), and applies it to detect county level COVID-19 outbreaks. This algorithm chooses an adaptive fitting window size for each county based on relevant features affecting the disease spread, such as changes in social distancing policies. Experiment results show that our method outperforms any non-adaptive window size choices in 7-day ahead COVID-19 outbreak case number predictions.