title: Using missing data techniques to explore the lack of survival effect: illustration with the CABG patch trial.
abstract: The Multicenter Automatic Defibrillator Implantation Trial (MADIT) showed a conclusive 54 per cent reduction in mortality in patients with inducible sustained monomorphic ventricular tachycardia (VT) and impaired left ventricular function who received an implantable defibrillator compared with those who did not. The Coronary Artery Bypass Graft (CABG) Patch Trial, which studied a patient population with a similar extent of left ventricular dysfunction and overall cardiovascular risk, demonstrated no mortality benefit from placement of an implantable defibrillator. All patients in the MADIT trial were 'VT inducible', while this criterion was neither required nor evaluated for entry into the CABG Patch Trial. A statistical approach to estimating with good accuracy the fraction of CABG Patch patients who were inducible at the time of their randomization from the prevalence of VT inducibility in the surviving CABG Patch Trial control population during follow-up is presented. This more generally applicable approach estimates the mixing percentage using missing data techniques. We present the mathematical and physiological basis of the assumptions underpinning the mixture model and its estimation procedure. The mixture model forms the basis for the electrophysiological substudy to the CABG Patch Trial, which directly tests the hypothesis that the difference in the frequency of inducible VT between the MADIT and CABG Patch patients populations is sufficient to account for the difference in effect on mortality.
authors.affiliation: Departments of Medicine (Cardiology) and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. jeff.rottman@mcmail.vanderbilt.edu
authors.forename: J N
authors.initials: JN
authors.lastname: Rottman
authors.forename: B
authors.initials: B
authors.lastname: Levin
authors.forename: M C
authors.initials: MC
authors.lastname: Paik
authors.forename: W Y
authors.initials: WY
authors.lastname: Tsai
authors.forename: J T
authors.initials: JT
authors.lastname: Bigger
mesh_terms: D000465:Algorithms; D002986:Clinical Trials as Topic / Q000706:statistics & numerical data*; D015331:Cohort Studies; D003198:Computer Simulation; D001026:Coronary Artery Bypass / Q000401:mortality; D017147:Defibrillators, Implantable; D004594:Electrophysiology; D005500:Follow-Up Studies; D006801:Humans; D016013:Likelihood Functions; D008954:Models, Biological; D015233:Models, Statistical; D016016:Proportional Hazards Models; D019919:Prosthesis Implantation / Q000401:mortality; D016019:Survival Analysis; D017180:Tachycardia, Ventricular / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy; D018487:Ventricular Dysfunction, Left / Q000401:mortality / Q000503:physiopathology* / Q000628:therapy