A hierarchical Bayesian entry time realignment method to study the long-term natural history of diseases

A major question in clinical science is how to study the natural course of a chronic disease from inception to end, which is challenging because it is impractical to follow patients over decades. Here, we developed BETR (Bayesian entry time realignment), a hierarchical Bayesian method for investigating the long-term natural history of diseases using data from patients followed over short durations. A simulation study shows that BETR outperforms an existing method that ignores patient-level variation in progression rates. BETR, when combined with a common Bayesian model comparison tool, can identify the correct disease progression function nearly 100% of the time, with high accuracy in estimating the individual disease durations and progression rates. Application of BETR in patients with geographic atrophy, a disease with a known natural history model, shows that it can identify the correct disease progression model. Applying BETR in patients with Huntington’s disease demonstrates that the progression of motor symptoms follows a second order function over approximately 20 years.