*Nov. 1998 - Merck files an application with the FDA seeking U.S. approval of Vioxx.
December 1998 - Food and Drug Administration approves Pfizer Inc.'s Celebrex, the first Cox-2 inhibitor, to treat arthritis. Cox-2 drugs, part of the nonsteroidal anti-inflammatory (NSAID) drug class, inhibit the Cox-2 enzyme, which promotes inflammation, but protect users against stomach bleeds and ulcers, unlike other NSAIDS.
Jan. 1999 - Vioxx Gastrointestinal Outcomes Research (VIGOR) trial begins, aiming to show whether Vioxx causes fewer ulcers and other gastrointestinal problems than the standard arthritis treatment naproxen.
*Feb. 1999 - Merck begins first clinical trial of Vioxx to see whether it can treat Alzheimer's disease. A second trial begins in April 2000.
May 20, 1999 - FDA approves Vioxx for the relief of osteoarthritis symptoms, management of acute pain and primary dysmenorrhea, or painful menstruation.
March 2000 - Merck unveils data from Alzheimer's trials, which it said showed no difference in heart problems between patients on Vioxx and others taking a placebo.
June 2000 - Merck gives FDA results of VIGOR study, which shows Vioxx users suffered five times as many heart attacks as users of the older painkiller naproxen, sold under the brand name Aleve. Merck attributes the disparity to naproxen's cardioprotective qualities rather than a defect in Vioxx, garnering a rebuke from the FDA for making that assertion without scientific proof
Feb. 2001 - FDA Arthritis Advisory Committee meets to discuss the gastrointestinal VIGOR study.
Sept. 2001 - Merck receives a warning letter from the FDA about the company's post-VIGOR Vioxx promotional campaign "that minimizes the potentially serious cardiovascular findings" and "misrepresents the safety profile of Vioxx."
Nov. 2001 - Pfizer's Bextra, also a Cox-2 inhibitor, approved by FDA.
April 11, 2002 - FDA approves changes to Vioxx label which include cardiovascular risks, gastrointestinal benefits and a new use to treat rheumatoid arthritis.
Sept. 2004 - Merck stops long-term APPROVe study, saying it showed Vioxx could double risk of heart attack or stroke if taken for 18 months or longer. APPROVe had focused on whether Vioxx could prevent reoccurrence of colon polyps, and on cardiovascular effects
Sept. 27, 2004 - Merck tells the FDA a study to see if Vioxx could prevent colon polyps showed twice the risk of heart attacks among patients taking Vioxx for 18 months as those who took placebos.
Sept. 28, 2004 - FDA officials meet with Merck, which tells the agency it will voluntarily withdraw Vioxx. Two days later Merck announces the withdrawal.
Nov. 18, 2004 - Congress holds hearing on Merck and the FDA's handling of the drug's safety issues.
Feb. 2005 - FDA panel concludes Vioxx, Celebrex and Bextra all pose heart risks, but should be available to consumers.
April 7, 2005 - Pfizer withdraws Bextra from the market at request of the FDA, which said it carries additional risks of serious, sometimes fatal skin reactions. The FDA also says not just Cox-2 inihibitors, but all prescription NSAID drugs, should carry a black-box warning label about cardiovascular risks.
July 13, 2005 - A jury of seven men and five women is seated to hear the Ernst Vioxx lawsuit in semi-rural Brazoria County, south of Houston.
July 19, 2005 - U.S. District Judge Eldon Fallon schedules the first federal Vioxx trial for Nov. 28.
Aug. 19, 2005: - Texas jury finds Merck liable or the death of Robert Ernst, awarding his widow $229 million in punitive damages and $24 million for mental anguish and loss of companionship to the widow of a Texas man. That will be reduced to about $26 million under Texas caps on punitive damages; Merck plans to appeal.
Sept. 14, 2005 - The second Vioxx trial begins with opening arguments in New Jersey Superior Court in Atlantic City, as lawyers for Boise, Idaho postal worker Frederick "Mike" Humeston argue his Sept. 18, 2001, heart attack was caused by Vioxx, which he had been taking for about two months.
Oct. 24, 2005 - In its quarterly earnings report, Merck says that as of Sept. 30, it has been named as a defendant in about 6,400 lawsuits over Vioxx _ about 160 of them potential class-action suits _ and has signed agreements with about 3,000 other claimants temporarily suspending the clock on their state's time limit to file suit. At least several hundred at additional lawsuits are filed in October.
Nov. 3, 2005 - Merck is exonerated in a New Jersey lawsuit involving a man who suffered a heart attack after taking Vioxx but survived. The case was the first tried of thousands of cases filed against Merck in the state.
Dec. 8, 2005 - The New England Journal of Medicine says Merck deleted dangers linked to Vioxx, including three heart attack deaths among users, in its analysis of the VIGOR study.
Dec. 12, 2005 - A U.S. judge declares a mistrial in the first federal lawsuit after a jury fails to reach a unanimous verdict in a case brought by the widow of a Florida man. The case will be retried in New Orleans commencing February 6, 2006.
* = Source: Merck