Assessing heterogeneity in treatment initiation guidelines in longitudinal randomized controlled trials

Abstract

Treatment initiation guidelines are essential in healthcare, dictating when patients begin therapy. These guidelines are typically assessed through randomized controlled trials (RCTs) to measure their average effect on a population. However, this method may not fully account for patient heterogeneity. We introduce a refined analysis methodology that accounts for diverse times to treatment initiation (TTI) arising from these guidelines. We offer a more detailed perspective on the guidelines’ impact by analyzing homogeneous subpopulations based on their TTI. We develop a longitudinal regression model with smooth time functions to capture dynamic changes in average guideline effects on subpopulations (AGES). A unique weighting mechanism creates pseudo-subpopulations from RCT data, enabling consistent and precise estimation of smooth functions. The efficacy of our approach is validated through theoretical and numerical studies, underscoring its capacity to provide insightful statistical inferences. We exemplify the utility of our methodology by applying it to an RCT of the World Health Organization (WHO) guideline for adults with HIV. This analysis promises to enhance the evaluation of treatment initiation guidelines, leading to more personalized and efficient patient care.