AIMS: The selection of optimal endpoints for cardiovascular clinical trials continues to be challenging. We examined an alternative interpretation of a series of trials when the individual event severity is considered. METHODS AND RESULTS: We analysed three contemporary myocardial infarction (MI) trials of early percutaneous coronary intervention after fibrinolysis, using a weighted composite method. This method allows the examination of the heterogeneity in the direction and magnitude of component endpoints, and multiple events (vs. first event). We incorporated a physician-assessed severity of each component endpoint in all patients for the five-item composite in the largest study, Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI), which enrolled 1059 ST-elevation MI patients. The traditional approach yielded event-free survival probabilities of 0.89 [95% confidence interval (CI) 0.86-0.91] for the early invasive arm and 0.83 (95% CI 0.79-0.86) for the standard care arm (P = 0.004). After accounting for the clinician-investigator-determined weights, the effective survival probabilities were 0.93 (95% CI 0.91-0.95) for the early invasive arm and 0.93 (95% CI 0.90-0.95) with no significant difference (P = 0.54). The same pattern was observed in the three-trial cohort using a four-item composite with an observed improvement in event-free survival outcomes (P = 0.01), which was no longer apparent after the severity weights were considered (P = 0.44). CONCLUSION: This analysis highlights the importance of considering the relative severity and multiple events in the evaluation of a clinical trial.
AIMS: The selection of optimal endpoints for cardiovascular clinical trials continues to be challenging. We examined an alternative interpretation of a series of trials when the individual event severity is considered. METHODS AND RESULTS: We analysed three contemporary myocardial infarction (MI) trials of early percutaneous coronary intervention after fibrinolysis, using a weighted composite method. This method allows the examination of the heterogeneity in the direction and magnitude of component endpoints, and multiple events (vs. first event). We incorporated a physician-assessed severity of each component endpoint in all patients for the five-item composite in the largest study, Trial of Routine Angioplasty and Stenting after Fibrinolysis to Enhance Reperfusion in Acute Myocardial Infarction (TRANSFER-AMI), which enrolled 1059 ST-elevation MI patients. The traditional approach yielded event-free survival probabilities of 0.89 [95% confidence interval (CI) 0.86-0.91] for the early invasive arm and 0.83 (95% CI 0.79-0.86) for the standard care arm (P = 0.004). After accounting for the clinician-investigator-determined weights, the effective survival probabilities were 0.93 (95% CI 0.91-0.95) for the early invasive arm and 0.93 (95% CI 0.90-0.95) with no significant difference (P = 0.54). The same pattern was observed in the three-trial cohort using a four-item composite with an observed improvement in event-free survival outcomes (P = 0.01), which was no longer apparent after the severity weights were considered (P = 0.44). CONCLUSION: This analysis highlights the importance of considering the relative severity and multiple events in the evaluation of a clinical trial.
Authors: Alexander C Fanaroff; Derek Cyr; Megan L Neely; Jeffery Bakal; Harvey D White; Keith A A Fox; Paul W Armstrong; Renato D Lopes; E Magnus Ohman; Matthew T Roe Journal: Circ Cardiovasc Qual Outcomes Date: 2018-12
Authors: Ugochukwu N Udogwu; Andrea Howe; Katherine Frey; Marckenley Isaac; Daniel Connelly; Dimitrius Marinos; Mitchell Baker; Renan C Castillo; Gerard P Slobogean; Robert V O'Toole; Nathan N O'Hara Journal: BMC Med Res Methodol Date: 2019-12-26 Impact factor: 4.615