Sample size requirement in trials that use the composite endpoint major adverse cardiovascular events (MACE): new insights

Abstract

Background The real impact of the degree of association (DoA) between endpoint components of a composite endpoint (CE) on sample size requirement (SSR) has not been explored. We estimate the impact of the DoA between death and acute myocardial infarction (AMI) on SSR of trials using use the CE of major adverse cardiac events (MACE). Methods A systematic review and quantitative synthesis of trials that include MACE as the primary outcome through search strategies in MEDLINE and EMBASE electronic databases. We limited to articles published in journals indexed in the first quartile of the Cardiac & Cardiovascular Systems category (Journal Citation Reports, 2015–2020). The authors were contacted to estimate the DoA between death and AMI using joint probability and correlation. We analyzed the SSR variation using the DoA estimated from RCTs. Results Sixty-three of 134 publications that reported event rates and the therapy effect in all component endpoints were included in the quantitative synthesis. The most frequent combination was death, AMI, and revascularization (n = 20; 31.8%). The correlation between death and AMI, estimated from 5 trials¸ oscillated between − 0.02 and 0.31. SSR varied from 14,602 in the scenario with the strongest correlation to 12,259 in the scenario with the weakest correlation; the relative impact was 16%. Conclusions The DoA between death and AMI is highly variable and may lead to a considerable SSR variation in a trial including MACE.

Cardiovascular Adverse Events and Immune-related Adverse Events Associated with PD-1/PD-L1 Inhibitors for Head and Neck Squamous Cell Carcinoma (HNSCC): A Real-world study (RWS) by Bayesian Disproportional Analysis Based on the FDA Adverse Event Reporting System (FAERS)

“…We grouped PT according to the characteristics of adverse events (Supplementary Table 1). Using the International Classi cation of Diseases, clinical revision, the tenth edition (ICD-10-CM) diagnostic code de nes MACE, including cardiovascular death, non-fatal heart attack, non-fatal stroke, heart failure, malignant arrhythmia, myocarditis, pericardial disorders [33][34][35][36]. Other cardiovascular events mainly include general heart disease, bleeding, and thrombosis.…”