Evaluating Treatment Effect with Mixed Endpoints in a Phase IV Cancer Trial – Frequentist Approach

Music City Center 

Advancements in cancer therapies have significantly improved long-term survival. However, survivors face higher risks of long-term morbidities and mortality. Those treated with cardiotoxic therapy (anthracyclines or chest radiation) are at greater risk of cardiovascular diseases that include Afterload (AF) as a continuous variable and Fractional Shortening (FS) as a binary variable. FS is classified as abnormal (FS < 0.28) or normal (FS ≥ 0.28). Hudson et al. (2007) evaluated risk factors for these outcomes independently. This manuscript presents a likelihood-based approach for jointly analyzing these mixed endpoints. We illustrate this by assessing the effect of risk group (AR vs. NAR) on the cardiovascular outcomes of AF and FS using Hudson et al.'s (2007) data. First, we analyze AF and FS separately using a linear regression model and a probit model. Then, we apply joint modeling to account for FS-AF correlation and compare results with the independent approach of analysis. Additionally, we conduct simulations to assess the performance of the joint modeling approach under different sample sizes and correlation values to evaluate the operating characteristics.

Frequentist Approach

Mixed Endpoint

Probit Model

Linear Regression

Hotelling’s T-Squared Test

Simulation 

Survey Research Methods Section