Can a decision support system accelerate rare disease diagnosis? Evaluating the potential impact of Ada DX in a retrospective study

Abstract Background Rare disease diagnosis is often delayed by years. A primary factor for this delay is a lack of knowledge and awareness regarding rare diseases. Probabilistic diagnostic decision support systems (DDSSs) have the potential to accelerate rare disease diagnosis by suggesting differential diagnoses for physicians based on case input and incorporated medical knowledge. We examine the DDSS prototype Ada DX and assess its potential to provide accurate rare disease suggestions early in the course of rare disease cases. Results Ada DX suggested the correct disease earlier than the time of clinical diagnosis among the top five fit disease suggestions in 53.8% of cases (50 of 93), and as the top fit disease suggestion in 37.6% of cases (35 of 93). The median advantage of correct disease suggestions compared to the time of clinical diagnosis was 3 months or 50% for top five fit and 1 month or 21% for top fit. The correct diagnosis was suggested at the first documented patient visit in 33.3% (top 5 fit), and 16.1% of cases (top fit), respectively. Wilcoxon signed-rank test shows a significant difference between the time to clinical diagnosis and the time to correct disease suggestion for both top five fit and top fit (z-score -6.68, respective -5.71, α=0.05, p-value