October 04,2004

Chairman Grassley questions FDA regarding Vioxx

September 30, 2004

Via facsimile and USPS mail: (202) 690-7380
Via facsimile and USPS mail: (301) 827-1960

The Honorable Tommy G. Thompson
Department of Health and Human Services
200 Independence Avenue, SW
Washington, D.C. 20201

Dr. Lester M. Crawford, D.V.M.
Acting Commissioner
U.S. Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857

Dear Secretary Thompson and Dr. Crawford:

Today, Merck & Co., Inc. (Merck) announced a voluntary world-wide withdrawalof its arthritis and acute pain medication, Vioxx; a highly unusual move by a major drugmanufacturer. According to media reports, the reason for this withdrawal stems fromdata of a three-year study intended to show that Vioxx prevents the reoccurrence ofpolyps in the colon and rectum. The data, recently reviewed by Merck, alsodemonstrated that there was an increased risk of heart attack and other cardiovascularcomplications beginning 18 months after patients started taking Vioxx.

The real news for me today is not so much why Merck pulled Vioxx off theshelves-we know that is because it causes heart attacks. The question in my mind is:Where has the Food and Drug Administration (FDA) been on Vioxx?

The FDA approved Vioxx in 1999. Since 1999,there have been many non-FDAconducted studies showing an increased risk in cardiovascular complications amongthose taking Vioxx. Specifically, in November 2000, Merck sponsored a study namedVIGOR. In that study, Merck determined that there were more serious cardiovascularevents occurring in patients taking Vioxx compared to patients taking naproxen, anotheranti-arthritic drug. This study was reviewed and discussed at the FDA's ArthritisAdvisory Committee Meeting (Advisory Committee) on February 8, 2001. An FDA TalkPaper, dated April 11, 2002, approved a new indication for Vioxx and new labelingchanges. The labeling changes advised patients and doctors of the potentialcardiovascular risks and benefits associated with using Vioxx. However, a carefulreading of that label appears to be at best non-committal and provides no guidance tophysicians and to the public.

In 2002, another study was published by Dr. Wayne Rayon Vioxx. This studyfound a two-fold increase in heart attack and sudden death associated with high doseVioxx. In May 2004, Dr. Solomon of Harvard found both low dose and high dose Vioxxincreased the risk of heart attack. Indeed, Dr. Solomon's study was startling because hefound a 21% increase for heart attacks with low dose Vioxx and a 70% increased risk ofheart attack with high doses of Vioxx as compared to a rival drug, Celebrex.

On or about August 25th, the FDA presented its own study on Vioxx. That studywas conducted by Dr. David Graham, an FDA epidemiologist. Dr. Graham's study forthe FDA study found that patients taking low dose Vioxx have a 50% greater chance ofsuffering a heart attack and sudden cardiac death than patients using Celebrex. Inaddition, Dr. Graham noted that the risk of heart attack and sudden cardiac death in thosepatients taking the highest recommended daily dose of Vioxx was three times that ofpatients taking standard painkillers.

Astonishingly, on or about September 8th, 2004, two weeks after Dr. Graham'sstudy, the FDA approved Vioxx for use in children with juvenile rheumatoid arthritis,despite the fact that Dr. Graham's study showed there was a very high risk of suddencardiac death and heart attacks in adults taking Vioxx. Why would the FDA approveVioxx for use among children with Dr. Graham's study in hand? Frankly, it seemscounter-intuitive. Why is the FDA approving new indications for Vioxx, especially forchildren, when shortly thereafter Merck is pulling the drug from the world-wide market?

Once again, the FDA has remained on the sidelines while life-threatening issuesthreatened the American public. Why has the FDA blindly dismissed a wealth of datashowing serious cardiovascular side effects occurring in patients using Vioxx since thedrug was approved in 1999? It appears that the FDA has yet again erred on the side ofproviding less information about the dangers associated with yet another drug, to thedetriment of the American public. Because of these new developments, and the fact thatthe FDA recently approved Vioxx for children, I request that the FDA respond to thefollowing questions and requests by October 25, 2004.

1. Describe in detail what action(s), if any, the FDA has takeri since VIGORto examine, address, or study the adverse affects of Vioxx. In preparingresponses to this question, please be sure to identify these actions by dateand please identify the FDA employee(s) by name and title who wereinvolved in these actions.

2. Describe in detail the results of all pre-marketing clinical studiesconducted on the use of Vioxx.

3. Provide copies of all FDA documents and materials relating to Vioxx andthe risk of cardiovascular complications including all papers, drafts, emails,agency evaluations, and any other documents relating to the use ofVioxx and the risk of cardiovascular complications.

4. Please make Dr. Graham available for an interview with my staff in theimmediate future to discuss his Vioxx study, among other related matters.

When preparing responses to the questions identified above, please re-state the questionand follow it with a detailed response. In the event that documents or other materials arerequested, please be sure to mark them accordingly. Please be on notice that this is anactive congressional inquiry. Accordingly, I request that you notify FDA employees,representatives and/or agents to preserve all documents and materials relating eitherdirectly or indirectly to this inquiry.

Thank you in advance for having your staff coordinate with my staff about thisletter by October 6, 2004. And please provide the requested information, explanationsand documents by October 25, 2004, unless it is available sooner. Should you have anyquestions regarding this letter, please do not hesitate to contact Emilia DiSanto orMichelle Anderson at (202) 224-4515. Allformal correspondence should be sent viafacsimile to (202) 228-2131 and original by Us. mail. Please do not hesitate to contactme if you have any concerns.


Charles E. Grassley