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WSJ.com - Merck Documents Shed Light on Vioxx Legal Battles:
When Merck & Co. pulled its painkiller Vioxx from the market in September, it said it was acting because a clinical trial had shown that users were at increased risk of heart attacks or strokes after 18 months.
That conclusion, and how it was reached, are the central issues for Merck in defending itself against a wave of lawsuits -- 575 as of the company's latest count, representing about 1,400 Vioxx users -- accusing the company of negligence. The suits could start being heard in courtrooms as soon as May. Previously undisclosed company records, which were reviewed by The Wall Street Journal, are casting light on the coming legal battles.
The records, which plaintiffs' attorneys have, show that the external committee charged with monitoring the drug's safety in the clinical trial had early data suggesting that users could be at increased risk of certain heart problems after as little as four months. Notes from committee meetings show that members were watching the “concerning nature of the trends” about Vioxx's possible effects on heart attacks and strokes from their first meeting. The records also show that the committee of five included one Merck employee and two doctors who had done consulting work for the company. One of the consultants was the lead author on a paper written with Merck scientists that defended Vioxx's safety and criticized a study raising safety concerns about the drug. All those issues are expected to be probed by plaintiffs' attorneys.
The records also show that the committee kept the trial going despite its concerns because it hoped to find whether Vioxx might prove effective in reducing colon polyps, a potential precursor to cancer. The records indicate that members did see some evidence of beneficial effects, while keeping an eye on numbers suggesting a possible increased risk of heart attacks, strokes and other cardiovascular problems among the Vioxx users in the trial, compared with those taking a placebo (see related article).
It was when those numbers met the test of statistical significance that the trial was halted, prompting Merck to yank the drug. Merck said that during the trial, 45 of the 1,287 patients who took Vioxx experienced heart attacks or strokes, compared with 25 patients out of 1,299 taking placebos.
Early on, the committee requested data looking at the combined rates of heart attacks, strokes, congestive heart failure, pulmonary edema and cardiac failure. That data showed that some Vioxx patients began to experience one or more of the problems much earlier than the 18-month mark.Congestive heart failure is the inability of the heart to pump blood efficiently, causing someone with the condition to become short of breath and tired with minimal exertion. The heart's inability to pump efficiently as a result of congestive heart failure can lead to fluid buildup, particularly in the lungs, which is called pulmonary edema. Hypertension, or high blood pressure, can lead to congestive heart failure.
A chart tracking the rate of those combined problems showed a clear separation between the side effects reported by some Vioxx users and those taking placebos beginning at 120 days, or about four months.
In her statement, Ms. Wainwright writes that hypertension and fluid retention are “known side effects” of Vioxx, and “this was clearly stated in Vioxx's label. So it would be expected to see a higher rate relative to placebo of these and related side effects, including potentially congestive heart failure” among Vioxx takers. She writes, “These events are very different from heart attacks and strokes.”
Noting the clinical trial's purpose of studying Vioxx's effects on polyps, Ms. Wainwright also writes that “the consistent trend” indicated a “rather dramatic beneficial effect.” That meant the committee had to balance the drug's risk profile “so as not to prematurely (or inappropriately) end a trial that might show significant benefits,” she writes.
Notes from committee meetings make it clear that members were studying a growing trend of heart attacks and strokes. At its last meeting, last Sept. 17, at which the committee decided to halt the trial, the notes show that “the trend for excess risk” for heart attacks and strokes “has continued to grow at each meeting over the last 1-2 years.” The minutes note that in May 2003, committee data showed a 20% higher chance of heart attack or stroke in Vioxx patients than in those taking placebos. The risk grew steadily to a 40% higher rate in November 2003, 80% higher in February 2004 and finally 120% in September 2004.
