On Friday, Merck (MRK) - Get Report lost its first Vioxx trial and promptly said it would appeal the Texas state court jury verdict. The company is facing at least 4,100 individual personal injury suits, a host of class-action lawsuits and litigation claiming Merck's handling of Vioxx violated securities laws as well as laws governing retirement plans. And that's only the U.S. cases. Here's a look at how Merck and Vioxx wound up in court.

November 1998

: Merck submits an application to the Food and Drug Administration seeking approval for the Cox-2 inhibitor drug Vioxx as a treatment for osteoarthritis, on the basis of clinical trials involving 5,400 patients. Merck says rates of cardiovascular risk were "similar" among patients taking Vioxx, placebo or other pain relievers.

January 1999

: Merck begins the Vigor trial designed to test gastrointestinal impact of Vioxx. A month later, Merck begins the first of two tests to determine if Vioxx has a beneficial effect on Alzheimer's disease patients.

May 1999

: The FDA approves Vioxx.

February 2000

: Merck starts the Approve trial designed to ascertain if Vioxx reduces certain colon polyps.

March 2000

: Merck receives preliminary results of Vigor trial, suggesting higher risk of cardiovascular problems among patients taking Vioxx vs. patients taking the pain reliever naproxen. Merck later speculates that the difference is caused by the heart-protective effect of naproxen rather than the heart-risk effect of Vioxx.

March 2000

: Merck announces preliminary results of Vigor trial and submits data to the FDA. Later in the year, Vigor trial results are published in the

New England Journal of Medicine

.

February 2001

: FDA advisory committee holds a hearing on Vigor trials.

April 2002

: After lengthy discussions with the FDA, Merck revises the Vioxx label to include precautions about cardiovascular risk cited in the Vigor trial. Critics would later allege that Merck showed a lack of urgency in changing the label, arguing that this was an example of Merck having known the drug could cause heart problems.

Aug. 25, 2004

: Preliminary data from an FDA-financed study show patients who took Vioxx had a higher cardiovascular risk than patients who took

Pfizer's

(PFE) - Get Report

Celebrex. Merck disputes the study's methodology. The FDA posts a more detailed version of the study on its Web site in November 2004, but says the article hasn't been subject to standard peer review. In early 2005, a version of the article is printed in the medical journal

The Lancet

.

Sept. 23, 2004

: The independent safety monitoring board for the Approve trial recommends that Merck end the trial because of results showing that long-term use of Vioxx -- more than 18 months -- increases risk of heart attacks and strokes compared with patients who took a placebo. There is no difference in risk among patients taking Vioxx or placebo for less than 18 months.

Sept. 30, 2004

: Merck says it is withdrawing Vioxx from the U.S. and worldwide markets.

Oct. 29, 2004

: Merck receives conditional approval from the FDA for Arcoxia, a cousin of Vioxx. However, this approval is contingent upon Merck completing more long-term safety and efficacy tests. At the time, Arcoxia is sold in 48 countries. Merck says it will work with regulators "to assess whether changes to the prescribing information for this class of drugs, including Arcoxia, are warranted." Merck continues to test and develop Arcoxia for the U.S. market.

Nov. 8, 2004

: Merck reveals that its handling of Vioxx is being investigated by the Justice Department and by the

Securities and Exchange Commission

.

Nov. 18, 2004

: The Senate Finance Committee holds a hearing on Merck and the FDA. Dr. David J. Graham, a veteran FDA researcher, accuses the agency of "a profound regulatory failure" in evaluating Vioxx that could easily be repeated with other drugs." Graham is the lead author of the FDA study that criticized Vioxx.

Dec. 23, 2004

: The FDA issues a

public health advisory urging doctors to weigh carefully the risks in prescribing medications for arthritis and pain, adding that they limit the use of medications known as Cox-2 inhibitors, which includes Vioxx and Pfizer's Celebrex and Bextra. The FDA urges patients to pay closer attention to the labels of certain over-the-counter medications for pain relief.

Feb. 7, 2005

: In advance of three days of FDA advisory committee hearings on Cox-2 drugs and other painkillers, FDA staff members issue a report

raising questions about two experimental Cox-2 drugs, Arcoxia from Merck and Prexige from

Novartis

(NVS) - Get Report

. The two companies continue to test and develop their drugs for the U.S. market.

Feb. 18, 2005

: An FDA advisory panel votes 17-15 that Vioxx

could be returned to the U.S. market under certain circumstances and restrictions. The panel also recommends, via a 17-13 vote with two abstentions, that Bextra remain on the market. The panel supports Celebrex by a 31-1 vote. Merck says it hasn't decided if it will return Vioxx to the U.S. market, a remark that it has repeated often. Last month, an advisory panel to Canada's health department

recommended 12-1 that Vioxx be reinstated. Again, Merck says it hasn't made a decision, adding that it will discuss the matter with health regulators.

April 7, 2005

: At the urging of the FDA, Pfizer suspends sales of Bextra. Pfizer disagrees with the FDA's recommendation, and it continues talking to the agency about how the drug can be returned to the market. The FDA also requires tougher labels on Celebrex, all other prescription pain relievers and all over-the-counter pain relievers to warn against cardiovascular risk.

May 5, 2005

: Richard T. Clark, a longtime Merck executive, replaces Raymond V. Gilmartin as chief executive. Gilmartin would have reached mandatory retirement age by March 2006.

Aug. 19, 2005

: A Texas state court jury votes

against Merck in the first Vioxx product liability trial, assessing $253.4 million in economic and punitive damages.

Merck says it will appeal.