Mitigation of outcome conflation in predicting patient outcomes using electronic health records

Artificial intelligence (AI) models utilizing electronic health record data for disease prediction can enhance risk stratification but may lack specificity, which is crucial for reducing the economic and psychological burdens associated with false positives. This study aims to evaluate the impact of confounders on the specificity of single-outcome prediction models and assess the effectiveness of a multi-class architecture in mitigating outcome conflation.

We evaluated a state-of-the-art model predicting pancreatic cancer from disease code sequences in an independent cohort of 2.3 million patients and compared this single-outcome model with a multi-class model designed to predict multiple cancer types simultaneously. Additionally, we conducted a clinical simulation experiment to investigate the impact of confounders on the specificity of single-outcome prediction models.

While we were able to independently validate the pancreatic cancer prediction model, we found that its prediction scores were also correlated with ovarian cancer, suggesting conflation of outcomes due to underlying confounders. Building on this observation, we demonstrate that the specificity of single-outcome prediction models is impaired by confounders using a clinical simulation experiment. Introducing a multi-class architecture improves specificity in predicting cancer types compared to the single-outcome model while preserving performance, mitigating the conflation of outcomes in both the real-world and simulated contexts.

Our results highlight the risk of outcome conflation in single-outcome AI prediction models and demonstrate the effectiveness of a multi-class approach in mitigating this issue.

The number of predicted outcomes needs to be carefully considered when employing AI disease risk prediction models.