1. What about VIOXX?

2. Adenomatous Polyp Prevention on Vioxx (APPROVe) Vioxx (rofecoxib) versus Placebo Basic Clinical Trial Objective: Assess whether Vioxx may prevent the recurrence of benign polyps in patients who have a history of such tumors. Study Outcome: Stopping rule invoked due to adverse safety finding: an increased risk of non-fatal cardiovascular events in those taking Vioxx in 25mg doses, which only became evident after 18 months.

3. VIOXX GI Outcomes Research (VIGOR) Vioxx versus Naproxen Comparative Clinical Trial Objective: Compare gastrointestinal (GI) outcomes in subjects using NSAIDs. Study Outcomes: New safety labeling for Vioxx. Patients taking Vioxx had fewer stomach ulcers and bleeding than patients taking naproxen, another non- steroidal anti-inflammatory drug (NSAID). However, the study also showed a greater number of heart attacks in patients taking Vioxx.

4. Notes Vioxx is a Cox-2 Inhibitor – the state of the art class anti-inflammatory medication. Other licensed drugs in this class include Celebrex and Bextra, which remain on the market.

5. Early Stopping Rules For phase III randomized trials, these issues are typically under the purview of an independent Data and Safety Monitoring Board (DSMB), composed of statisticians and clinical investigators not directly involved with the study. The DSMB is responsible for reviewing the data, performing interim analyses when the study reaches its specified number of events, and deciding whether or not to close the study on the basis of predetermined early stopping rules that relate to toxicity or outcome. If excess harm is observed, or if a statistically significant benefit is observed, the study is stopped early and the patient is informed of the results. If treatment is ongoing, the patient is typically offered the opportunity to receive the regimen that is perceived to be superior. Thus, the early stopping rule has the potential to minimize harm and to maximize benefit for those patients enrolled in a randomized trial.