Abstract:
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Regulatory agencies including the United States Food and Drug Administration (FDA), the European Medicines Agency (EMA), and Health Canada have recommended that, prior to filing for marketing approval, new antihyperglycemic agents (AHA) developed to treat Type 2 Diabetes Mellitus (T2DM) undergo a cardiovascular (CV) risk assessment in 2 stages. In order for a new AHA to be approved for marketing, Stage 1 must rule out an increase in CV risk of 80% based on a composite endpoint of major cardiovascular adverse events. Post-approval, Stage 2 must rule out an increase in CV risk of 30%. Methods for the 2-stage approach including group sequential designs, alpha spending allocation, monitoring and estimating CV event and dropout rates, censoring CV events after treatment discontinuation, primary and sensitivity analyses for executing this strategy will be discussed.
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