The integration of artificial intelligence (AI) into clinical decision support (CDS) holds promise for proactive, personalized, and precision care. However, current understanding of how to establish trustworthy human-AI partnerships is in its infancy, despite its critical importance for implementing AI in healthcare. We present the Asthma-Guidance and Prediction System (A-GPS) as a case study of a practice-integrated AI platform that demonstrates how trustworthy, generalizable and sustainable AI can be developed, evaluated, and implemented in real-world asthma care. We describe major challenges and solutions based on our real-world experience during the process and offer the practical framework, approaches, tools and workflow for implementing trustworthy, generalizable and sustainable AI in frontline practices. While A-GPS is an asthma-specific AI tool, it was built on top of a disease-agnostic electronic health record (EHR)-integrated clinical decision support (CDS) platform based on an Application Programming Interface (API)‑first backbone of reusable services. It was designed to reduce chart-review/processing burden and enable proactive, guideline-concordant asthma management by synthesizing fragmented longitudinal multimodal data into a clinical decision-relevant summary at the point of care. A-GPS platform integrates multiple natural language processing (NLP) algorithms to leverage free texts info in EHRs, machine learning model to offer risk stratification, and remote patient monitoring (RPM) approaches to capture real-time data from patients, enabling remote asthma (chronic disease) care. The platform has been deployed via Substitutable Medical Applications and Reusable Technologies-on-Fast Healthcare Interoperability Resources (SMART-on-FHIR) to ensure in-workflow delivery and maintainable governance making it flexible and interoperable across different EHRs systems and different chronic diseases. The translational maturity of A-GPS as an AI-powered CDS tool for pediatric asthma was demonstrated and sustained through engagement and co-design with diverse community and care team partners, including adult and pediatric Community Advisory Board, pediatric patients and their parents, clinicians (primary care providers and specialists), nurses, schedulers, as well as bioethicists and regulatory experts. Moreover, the tool was evaluated in two randomized clinical trial (RCT)s. The first trial showed a 67% reduction in clinicians' EHR review time, high clinician satisfaction, potential healthcare cost savings, fairness in model performance, and no adverse events. Trustworthiness was further assessed and supported through fairness evaluation by participant socioeconomic status (SES) using the HOUsing-based SocioEconomic Status (HOUSES) index, human-centered user interface/user experience (UI/UX) analysis, clinician workflow optimization, transparent governance practices, and best practices for regulatory science. The A-GPS experience operationalizes a reproducible, lifecycle-governed framework for generating decision-grade evidence on safety, effectiveness, usability, fairness, and workflow integration, directly addressing the translational gap between AI model development and trustworthy, sustainable deployment in real-world clinical environments. These efforts led to national recognitions, including invitation to the inaugural American Medical Informatics Association (AMIA) AI Showcase, and AI evaluation use case for a national health AI coalition. The second RCT evaluated the feasibility of integrating a remote patient monitoring (RPM) device (home spirometry) into the A-GPS platform, with a published RCT protocol that serves as a framework for RCT for evaluating AI models under the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines for RCTs that evaluate AI tools, offering the practical framework, approaches, tools, and workflow for trustworthy, generalizable and sustainable AI tools in asthma care. This work illustrates how team science, community engagement, implementation science, and learning health system principles can be operationalized to establish a human-AI partnership model to advance translational science and clinical care, with the goal of improving health for all.
Source
Wi, Chung-Il; Overgaard, Shauna; Malik, Momin; Watson, Dave; Sharma, Deepak; Le-Rademacher, Jennifer; Kelleher, Dan; Zheng, Lu; Ohde, Joshua; Lynch, Brian; Khurana, Ashwani; Sohn, Sunghwan; AlJuhani, Mahmoud M; Carpenter, Chris; Arteta, Manuel; Greenwood, Jason; Hartz, Martha; Foss, Randy; Polat, Elif; Absah, Imad; Davis, Carla; Gupta, Meera; Myers, Lynnea; Nordlund, Björn; Tao, Cui; Wieland, Mark L; Patten, Christi; Jones, Amie; Varkey, Prathibha; Loufek, Brenna T; Vidal, David E; Gopala, Nari; Klee, Eric; Shah, Vijay H; Halamka, John D; Callstrom, Matthew R; Rider, Nicholas L; Liu, Hongfang; Aliferis, Constantin; D Garovic, Vesna; J Juhn, Young. Journal of the National Medical Association, 2026. DOI: 10.1016/j.jnma.2026.04.001