fifth most frequently prescribed NSAIDs but first and second in cost, respectively; for primary-care physicians they were ninth and twelfth most frequently prescribed NSAIDs and first and fourth in cost. Sales and marketing efforts were supported by two large trials, the Celecoxib Long-term Arthritis Safety Study (CLASS) in JAMA, and the Vioxx Gastrointestinal Outcomes Research (VIGOR). The VIGOR trial was later proven to have been based on faulty data, and Vioxx was eventually withdrawn from the market. VIGOR study and publishing controversy The VIGOR (Vioxx Gastrointestinal Outcomes Research) trial, "which was the making of Merck's drug rofecoxib (Vioxx)," was at the center of a dispute about the ethics of medical journals. In the VIGOR trial, over 8,000 patients were randomized to receive either naproxen or rofecoxib (Vioxx). Both studies concluded that COX-2 specific NSAIDs were associated with significantly fewer adverse gastrointestinal effects. In the CLASS trial which compared Celebrex 800 mg/day to ibuprofen 2400 mg/day and diclofenac 150 mg/day for osteoarthritis or rheumatoid arthritis for six months, Celebrex was associated with significantly fewer upper gastrointestinal complications (0.44% vs. 1.27%, p = 0.04), with no significant difference in incidence of cardiovascular events in patients not taking aspirin for cardiovascular prophylaxis. The VIGOR trial results were published in 2000 in the New England Journal of Medicine Bombardier and his research team claimed that there was "an increase in myocardial infarction in the patients given rofecoxib (0.4%) compared with those given naproxen (0.1%)" and "patients given naproxen experienced 121 side effects compared with 56 in the patients taking rofecoxib," a "marvellous result for Merck" which "contributed to huge sales of rofecoxib." Merck's scientists incorrectly interpreted the finding as a protective effect of naproxen, telling the FDA that the difference in heart attacks "is primarily due to" this protective effect. In September 2001, the United States Food and Drug Administration (FDA) sent a warning letter to the CEO of Merck, stating, "Your promotional campaign discounts the fact that in the VIGOR study, patients on Vioxx were observed to have a four to five fold increase in myocardial infarctions (MIs) compared to patients on the comparator nonsteroidal anti-inflammatory drug (NSAID), Naprosyn (naproxen)." This led to the introduction, in April 2002, of warnings on Vioxx labeling concerning the increased risk of cardiovascular events (heart attack and stroke). By 2005 The New England Journal of Medicine published an editorial accusing the Bombardier et al. of deliberately withholding