Demonstrating efficacy and effectiveness in clinical studies with recurrent event as primary end point: a chronic...

Pivotal clinical trials of persistent disorders such as chronic obstructive pulmonary disease and severe asthma often utilize recurrent event (e.g., exacerbations) as primary study end point. Such infrequent and correlated end points usually have skewed distributions, which can result in clinical efficacy criterion being met even while clinical effectiveness may be poor. Patients, prescribers and, increasingly, payers want evidence of both a medicine's clinical efficacy and its effectiveness. This duality in evidentiary requirements is causing a shift from the traditional one-size-fits-all blockbuster drug development paradigm to newer patient-centric models. Using a simulated study, we illustrate how clinical studies using enrichment designs can collect and present such patient-centric evidence that will simultaneously demonstrate clinical efficacy and effectiveness, while increasing probability of trial success and overall efficiency.