Introduction
nonfatal stroke, T2D, death, CVOTs, nonfatal myocardial infarction, heart failure, diabetes
EVENT, RECRUITMENT, UNSTABLE ANGINA, SECONDARY, EVENTS, HEART FAILURE, TYPE 2 DIABETES, DIABETES
Large randomized cardiovascular outcome trials (CVOTs) in type 2 diabetes (T2D) have changed the landscape of diabetes care, providing more complete evidence about the risk–benefit profile of glucose-lowering medications. Critical to trial design, planning, and conduct is having a well-considered power calculation and sample size estimate, which inform trial size and duration. In an event-driven trial, understanding true event accrual rates and the efficiency of the trial processes to collect and verify events is also critical during design and participant follow-up to appropriately set the budget, distribute trial site and monitoring resources, monitor predicted versus actual event rates, and plan end-of-trial activities.Typically, data from previously completed trials conducted in similar populations are used to model predicted event rates, using assumptions of static event rates over time. However, scarce objective evidence exists to support those modelling assumptions. An alternate hypothesis might suggest increasing event rates over time if clinical trial participants are assumed to be healthier than the population they represent as a result of the inclusion criteria or self-selection for trial participation. Such selection could produce initial within-trial event rates lower than anticipated but increasing as the trial progresses, driven by aging and accumulation of comorbidities. Alternatively, in a time-to-first-event paradigm, apparent event rates could decrease over time if a competing risk for death exists. Understanding event accrual rates during trial follow-up is further complicated by continuous recruitment, which produces non-linear accumulation of patient-years and events, and by fluctuation in the efficiency of the processes by which events are identified and confirmed, usually through adjudication.Here, we examine both the true event rates and the within-trial event accrual pattern over time for confirmed first events of 4-point major adverse cardiovascular (CV) events (MACE-4; defined as CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina), and key secondary endpoints including the individual MACE-4 components, hospitalization for heart failure (hHF), and all-cause mortality (ACM) in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS).