Timeline of the Vioxx Recall



Posted: Wednesday, October 13, 2004

by
http://www.yourlawyer.com

Jerrold Parker, Esq. is a founding partner of Parker & Waichman Attorneys at Law. Parker & Waichman ( www.yourlawyer.com) is a personal injury law firm that specializes in pharmaceutical side effects litigation. Parker & Waichman has represented victims of Vioxx side effects for over three years. Below is the Timeline of the Vioxx Recall

1. On November 23, 1998 , Merck submitted its New Drug Application (NDA) to the U.S. Food and Drug Administration.

2. On April 20, 1999, the Advisory Committee on Arthritis Drugs (FDA) met to review Vioxx.

3. The FDA approved Vioxx on May 20, 1999 for the use for the management of acute pain in adults and for relief of the signs and symptoms of osteoarthritis. (The original safety database included approximately 5,000 patients on Vioxx and did not, according to Merck, show an increased risk of heart attack or stroke). For more information visit www.vioxx-side-effects.com .

4. On October 8, 1999 , less than five months after Vioxx was approved by the FDA, Merck updated the package insert, ( I NEED THE NATURE OF THE CHANGES).

5. On November 18, 1999, a meeting of the Data and Safety Monitoring Board (DSMB) concerning the Vioxx/VIGOR study (in which all voting members of the committee were to be independent from Merck), took place where they discussed their concerns of the, “excess deaths and cardiovascular adverse experiences," that was observed in the group using Vioxx as compared to the patients who were taking Naproxen.

  • In June of 2000, there was information presented at the European United League against Rheumatism, (Merck is a member and a corporate sponsor of this organization) that demonstrated a statistically significant increase in hypertension and myocardial infarction.
  • The VIGOR study, submitted to the FDA in June 2000, (VIGOR - Vioxx® Gastrointestinal Outcomes Research which is the same study that gave rise to the memo of Dr. Targum, referred to in #8, below), sponsored by Merck, was primarily designed to look at the effects of Vioxx on side effects such as stomach ulcers and bleeding. This study showed that patients taking Vioxx had fewer stomach ulcers and bleeding than patients taking another drug, Naproxen. However, this study revealed a statistically significant increase in the number of cardiovascular events, (over 100% increase), myocardial infarctions/heart attacks, (approx. 400% increase), and strokes in patients taking who have taken Rofecoxib as compared to those receiving Naproxen.
    • a. On February 8, 2001, at an FDA Arthritis Advisory Committee Meeting, the VIGOR study ( sponsored by Merck) was discussed. The FDA Arthritis Advisory Committee met to discuss concerns with the unexpected findings of cardiovascular risks and myocardial infarctions associated with the use of Vioxx disclosed in the VIGOR study. (Not on the side effects such as stomach ulcers and bleeding that the VIGOR study was intended to study). It is important to note that the purpose of the VIGOR study was an attempt by Merck to do away with usual NSAID gastrointestinal warnings on Vioxx. There were no cardiac endpoints assessed in the VIGOR study. Despite Merck’s claim that Vioxx would have the same GI problems as general NSAID’s, the Food & Drug Administration, when faced with a lack of data in this regard, required Merck to carry the same GI warnings as general NSAID’s. It had been a major marketing tool that Vioxx does not cause the same GI problems as do other NSAIDs.

    8. On February 1, 2001, a memo was prepared by Dr. Shari L. Targum, an employee at the FDA, a Medical Officer, Division of Cardio-Renal Drug Products (and a graduate from Bronx High School of Science and NYU School of Medicine), had, as one of her responsibilities, the review of the data concerning Vioxx. The memo documented the serious cardiac events and myocardial infarctions and related deaths for participants in the study who was using Vioxx. These ADE’s were being found in the early stages of the VIGOR study. In her memo, she indicates that as early as November 18, 1999, at a meeting of the Data and Safety Monitoring Board (DSMB) concerning the Vioxx/VIGOR study (in which all voting members of the committee were to be independent from Merck), a discussion took place concerning the “excess deaths and cardiovascular adverse experiences" in the group using Vioxx as compared to the patients taking Naproxen. (see # 5, above)

    9. In 2001, the concerns arising out of the VIGOR study were crystallized by Debabrata Mukherjee, Steven Nissen, and Eric Topol in JAMA in their review paper specifically highlighting the cardiovascular side-effect profile of COX-2 inhibitors.

    10. On May 22, 2001, despite the mounting evidence of the association of Vioxx to strokes and heart attacks, Merck issued a press release entitled “Merck Confirms Favorable Cardiovascular Safety Profile of Vioxx", also claiming Vioxx has a “… favorable cardiovascular safety profile"

    11. On June 16, 2001 Merck issued another press release (released in Europe), entitled “Vioxx Similar to Placebo and Three (3) Widely Prescribed NSAID's Regarding Cardiovascular Events".

    12. On July 11, 2001, Merck modified the package insert for Vioxx. ( I NEED THE NATURE OF THE CHANGES).

    13. On August 22, 2001, a study published in Journal of the American Medical Association by Drs. Mukherjee, Nissen, and Topol, researchers from the Cleveland Clinic, indicated that Vioxx was linked to a 200% increase in blood clots, heart attacks and strokes based on their review of previous clinical trials.

    14. In September 2001, the American Heart Association, the National Stroke Association and the Arthritis Foundation asked Merck to test whether Vioxx increased the risk of heart attack and stroke.

    a. After it reviewed all of its Vioxx studies, Merck claimed there was no evidence that, in comparison with other NSAIDs, the drug increased the risk of heart problems. Merck attributed the difference to a heart-protective effect it said the other drug had.

    15. The FDA, obviously upset that Merck was minimizing the potential safety risks of Vioxx and promoting it for unapproved uses, sent Merck a "Warning Letter" on September 17, 2001. The letter demanding that Merck discontinue promoting Vioxx to doctors for unofficial uses, found after a review of several of Merck's promotional conference calls and sales pitches, that the promotions by Merck "are false, lacking in fair balance, or otherwise in misleading in violation of the Federal Food, Drug, and Cosmetic Act (the Act) and applicable regulations," wrote Thomas W. Abrams, the director of the FDA's division of Drug Marketing, Advertising and Communications. It also required Merck to send letters about the deception to the medical community.

    16. On April 11, 2002 the FDA instructed Merck to include in the package insert certain precautions based on results of the VIGOR studies.

    17. On April 11, 2002 Merck announced that it had added rheumatoid arthritis to the list of approved uses for Vioxx.

    18. In August of 2002, Dr. Topol and Dr. Falk, a Cleveland Clinic gastroenterologist, published an editorial in The Lancet, encouraging further warnings and labeling regarding the cardiovascular effects of Cox-2 drugs.

    However, even following these warnings, and in the face of mounting evidence for the cardiovascular side-effects of rofecoxib, aggressive direct-to-consumer marketing of this questionable drug continued unabated.

    19. In April, 2004, a study published in the journal, Circulation, observed an elevated risk of hospitalization for AMI among elderly Medicare enrollees treated with rofecoxib. This risk was higher in persons taking > 25 mg of rofecoxib than in patients taking the most common dosages used of 25 mg. The risk was elevated during the first 90 days of exposure but not thereafter.

    20. In late 8/2004, at a presention in Bordeaux, France, at the annual meeting of The International Society for Pharmacoepidemiology, new data from a trial sponsored by the Food and Drug Administration indicate patients administered Vioxx (rofecoxib) 25 mg or more per day have a risk of experiencing an acute myocardial infarction (AMI) or sudden cardiac death that is more than three times that of remote non-steroidal anti-inflammatory drug users. Researchers analyzed data from a subset of Kaiser Permanente patients, aged 18 to 84 years, who were treated with a COX-2-selective or non-selective NSAID between Jan. 1, 1999, and Dec. 31, 2001. Patients were enrolled in the study beginning with their first prescription and followed until the end of the study period, disenrollment, AMI or death. In the trial, approximately 1.4 million patients contributed 2.3 million person-years of observation time. The study population included 40,405 patients administered Celebrex and 26,748 Vioxx recipients. Overall, there were 8,199 acute cardiac events, including 6,675 AMI cases and 1,524 cases of sudden cardiac death observed during the trial. Results showed that treatment with Vioxx 25 mg/day or more conferred a 3.15-fold greater risk of AMI or sudden cardiac death compared with “remote use of any NSAID." Such a risk was also observed with lower doses of Vioxx (less than 25 mg/d), but did not achieve statistical significance.

    21. What then finally tipped the balance in the risk-benefit equation leading to the September 30th, 2004 dramatic global withdrawal of rofecoxib was the APPROVe study (Adenomatous Polyp Prevention Vioxx®) which was a multi-centre, randomized, placebo-controlled, double-blind study investigating the effects of rofecoxib on the recurrence of neoplastic large bowel polyps in 2600 patients with a previous history of colorectal adenoma. It was stopped prematurely on the instruction of the data and safety monitoring board after the investigators found that after 18 months treatment, patients taking rofecoxib had twice the risk of a myocardial infarction compared with those receiving placebo.

  • On September 30, 2004, Merck & Co., Inc., the manufacturer of Vioxx, announced a voluntary withdrawal of the arthritis and pain relief drug from the worldwide drug market, after results from a clinical trial indicated that Vioxx users may have an increased risk of suffering a heart attack, stroke, or other cardiovascular event. Merck's action was not ordered by the U.S. Food and Drug Administration (FDA), but was initiated by Merck based on its own findings from the clinical trial.
    • NOTE: It also turns out that Vioxx, despite the slick TV and magazine ads, has not been shown to be significantly more effective than the much cheaper nonprescription anti-inflammatories such as Tylenol and Advil.

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    Top-level comments on this article: (1 total)
    » left by rochelle
    from grahamstown, south africa     5 years 225 days ago.
    i would find it most helpful if the before and after package insert of vioxx could be made available please
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