Methods for safety and endpoint ascertainment: identification of adverse events through scrutiny of negatively adjudicated events.

Background: The primary goal of phase 2 and 3 clinical trials is to evaluate the safety and effectiveness of therapeutic interventions, and efficient and reproducible ascertainment of important clinical events, either as clinical outcome events (COEs) or adverse events (AEs), is critical. Clinical outcomes require consistency and clinical judgment, so these events are often adjudicated centrally by clinical events classification (CEC) physician reviewers using standardized definitions. In contrast, AEs are reported by sites to the trial coordinating center based on common reporting criteria set by regulatory authorities and trial sponsors.

Reporting Clinical End Points and Safety Events in an Acute Coronary Syndrome Trial: Results With Integrated Collection.

Background: End points and adverse events (AEs) are collected separately in clinical trials, yet regulatory requirements for serious AE reporting vary across regions, so classifying end points according to seriousness criteria can be useful in global trials.

Methods And Results: In the Apixaban for Prevention of Acute Ischemic Events 2 (APPRAISE-2) trial, patients with a recent acute coronary syndrome were randomized to apixaban or placebo for the prevention of recurrent ischemic events. Suspected end points (myocardial infarction, stroke, or bleeding) were adjudicated by an independent clinical events classification committee.

Pooled analysis of adverse event collection from 4 acute coronary syndrome trials.

Background: Adverse event collection in randomized clinical trials establishes drug safety. Although costly and regulated, it is rarely studied.

Methods: Adverse event data from 4 clinical trials (APPRAISE-2, PLATO, TRACER, TRILOGY ACS) comprising 48,118 participants with acute coronary syndromes were pooled to compare patterns and determinants of reporting.

Clinical effectiveness of coronary stents in elderly persons: results from 262,700 Medicare patients in the American College of Cardiology-National Cardiovascular Data Registry.

Objectives: The aim of this study was to compare outcomes in older individuals receiving drug-eluting stents (DES) and bare-metal stents (BMS).

Background: Comparative effectiveness of DES relative to BMS remains unclear.

Methods: Outcomes were evaluated in 262,700 patients from 650 National Cardiovascular Data Registry sites during 2004 to 2006 with procedural registry data linked to Medicare claims for follow-up.

Comparing classifications of death in the Mode Selection Trial: agreement and disagreement among site investigators and a clinical events committee.

Clinical events committees (CECs) are the current standard for endpoint adjudication in clinical trials. However, little data exist with which to compare CEC and site investigator determinations or to evaluate internal agreement among CEC members. Using data from the Mode Selection Trial in Sinus Node Dysfunction (MOST), we analyzed classifications of death in order to compare internal agreement among CEC physician reviewers and agreement between the CEC and site investigators.