An Application of the Cure Model to a Cardiovascular Clinical Trial
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An Application of the Cure Model to a Cardiovascular Clinical Trial Varadan Sevilimedu1 · Shuangge Ma3 · Pamela Hartigan2 · Tassos C. Kyriakides2 Received: 15 October 2019 / Revised: 9 October 2020 / Accepted: 12 October 2020 © International Chinese Statistical Association 2020
Abstract Intermediate events play an important role in determining the risk of a medical condition over time and should thus be accounted for in survival analysis. Myocardial infarction (MI) is one such condition whose hazard also depends upon the possible occurrence of an intermediate event—acute coronary syndrome (ACS). Accounting for the role that a possible ACS event plays in altering the hazard of MI becomes complicated when there is a cured fraction in the population. Data from the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial presents the scenario where the existence of a cured fraction is highly likely. In this article, we model the risk of developing an MI, while properly accounting for the effect/impact of a probable intermediate ACS event on that risk in the presence of a cured fraction. We adapt a maximum likelihood estimation approach to estimate the regression coefficients of this multi-part cure model. Simulation demonstrates satisfactory performance of the proposed estimator. We also utilize this dataset to explore the use of a proportionality constraint to help reduce the dimensionality of this multi-part model. The analysis yields novel findings that can be useful in guiding clinical practice. Keywords Intermediate event · Cure model · Proportionality
* Varadan Sevilimedu [email protected] 1
Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
2
Department of Veteran Affairs, Coordinative Studies Program, West Haven, CT, USA
3
Yale University School of Public Health, New Haven, CT, USA
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Vol.:(0123456789)
Statistics in Biosciences
1 Introduction This study is motivated by the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, which assessed the effect of percutaneous coronary intervention (PCI) on the incidence of myocardial infarction [6]. The primary objective of this study is to compare the efficacy of PCI plus optimal therapy to optimal therapy alone in the prevention of MI. The primary end point of the study is the time to MI. Myocardial infarction is characterized by irreversible damage to heart tissue due to the lack of blood supply to the heart. With an annual incidence of approximately 0.8 million, MI is one of the leading causes of morbidity and mortality in the United States. Therefore, understanding its risk factors and the role of intermediate events in altering this risk may assist the prevention of MI [4]. The COURAGE trial data contains records of 2287 patients with objective evidence of MI and significant coronary artery disease who were randomly assigned to either PCI with optimal drug therapy or optimal drug therapy alone. Patients were randomiz
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