Yu Akagi

Yu Akagi, Tomohisa Seki, Toru Takiguchi et al.

Counterfactual simulation - exploring hypothetical consequences under alternative clinical scenarios - holds promise for transformative applications such as personalized medicine and in silico trials. However, it remains challenging due to methodological limitations. Here, we show that an autoregressive generative model trained on real-world data from over 300,000 patients and 400 million patient timeline entries can generate clinically plausible counterfactual trajectories. As a validation task, we applied the model to patients hospitalized with COVID-19 in 2023, modifying age, serum C-reactive protein (CRP), and serum creatinine to simulate 7-day outcomes. Increased in-hospital mortality was observed in counterfactual simulations with older age, elevated CRP, and elevated serum creatinine. Remdesivir prescriptions increased in simulations with higher CRP values and decreased in those with impaired kidney function. These counterfactual trajectories reproduced known clinical patterns. These findings suggest that autoregressive generative models trained on real-world data in a self-supervised manner can establish a foundation for counterfactual clinical simulation.

Kazuma Kobayashi, Yasuyuki Takamizawa, Mototaka Miyake et al.

Explainability is key to enhancing artificial intelligence's trustworthiness in medicine. However, several issues remain concerning the actual benefit of explainable models for clinical decision-making. Firstly, there is a lack of consensus on an evaluation framework for quantitatively assessing the practical benefits that effective explainability should provide to practitioners. Secondly, physician-centered evaluations of explainability are limited. Thirdly, the utility of built-in attention mechanisms in transformer-based models as an explainability technique is unclear. We hypothesize that superior attention maps should align with the information that physicians focus on, potentially reducing prediction uncertainty and increasing model reliability. We employed a multimodal transformer to predict lymph node metastasis in rectal cancer using clinical data and magnetic resonance imaging, exploring how well attention maps, visualized through a state-of-the-art technique, can achieve agreement with physician understanding. We estimated the model's uncertainty using meta-level information like prediction probability variance and quantified agreement. Our assessment of whether this agreement reduces uncertainty found no significant effect. In conclusion, this case study did not confirm the anticipated benefit of attention maps in enhancing model reliability. Superficial explanations could do more harm than good by misleading physicians into relying on uncertain predictions, suggesting that the current state of attention mechanisms in explainability should not be overestimated. Identifying explainability mechanisms truly beneficial for clinical decision-making remains essential.