Babajide Owoyele

Stefan Konigorski, Sarah Wernicke, Tamara Slosarek et al.

N-of-1 trials are the gold standard study design to evaluate individual treatment effects and derive personalized treatment strategies. Digital tools have the potential to initiate a new era of N-of-1 trials in terms of scale and scope, but fully-functional platforms are not yet available. Here, we present the open source StudyU platform which includes the StudyU designer and StudyU app. With the StudyU designer, scientists are given a collaborative web application to digitally specify, publish, and conduct N-of-1 trials. The StudyU app is a smartphone application with innovative user-centric elements for participants to partake in the published trials and assess the effects of different interventions on their health. Thereby, the StudyU platform allows clinicians and researchers worldwide to easily design and conduct digital N-of-1 trials in a safe manner. We envision that StudyU can change the landscape of personalized treatments both for patients and healthy individuals, democratize and personalize evidence generation for self-optimization and medicine, and can be integrated in clinical practice.

Stefan Konigorski, Johannes E. Vedder, Babajide Alamu Owoyele et al.

Large foundation models (LFMs) transform healthcare AI in prevention, diagnostics, and treatment. However, whether LFMs can provide truly personalized treatment recommendations remains an open question. Recent research has revealed multiple challenges for personalization, including the fundamental generalizability paradox: models achieving high accuracy in one clinical study perform at chance level in others, demonstrating that personalization and external validity exist in tension. This exemplifies broader contradictions in AI-driven healthcare: the privacy-performance paradox, scale-specificity paradox, and the automation-empathy paradox. As another challenge, the degree of causal understanding required for personalized recommendations, as opposed to mere predictive capacities of LFMs, remains an open question. N-of-1 trials -- crossover self-experiments and the gold standard for individual causal inference in personalized medicine -- resolve these tensions by providing within-person causal evidence while preserving privacy through local experimentation. Despite their impressive capabilities, this paper argues that LFMs cannot replace N-of-1 trials. We argue that LFMs and N-of-1 trials are complementary: LFMs excel at rapid hypothesis generation from population patterns using multimodal data, while N-of-1 trials excel at causal validation for a given individual. We propose a hybrid framework that combines the strengths of both to enable personalization and navigate the identified paradoxes: LFMs generate ranked intervention candidates with uncertainty estimates, which trigger subsequent N-of-1 trials. Clarifying the boundary between prediction and causation and explicitly addressing the paradoxical tensions are essential for responsible AI integration in personalized medicine.