Merck ignored FDA warning on misleading Vioxx claims

In the ongoing trial in the case of Humeston versus Merck, one of the main points of contention is when Merck knew about the risks of Vioxx and what did it do about them. It is becoming quite clear now that Merck continued a well-organized campaign to massage the facts while it has data that showed that Vioxx was just too dangerous a drug to stay on the market.

Chris Seeger, the attorney for Frederick "Mike" Humeston pulled out a press release from May 2001 with the title "Merck Confirms Favorable Cardiovascular Safety Profile of Vioxx" (by the way, it is no longer possible to find this document on Merck's website nor the FDA's letter to Merck but thanks to Google's cache we were able to retrieve the latter document).

Thomas W. Abrams, Director, Division of Drug Marketing, Advertising, and Communications at the FDA wrote a waring letter to Merck President and CEO Raymond Gilmartin (who has since been fired for mishandling the recall of Vioxx). "Specifically, we refer to promotional audio conferences given on behalf of Merck by Peter Holt, MD, a press release, and oral representations made by Merck sales representatives to promote Vioxx. As part of its routine monitoring and surveillance program the Division of Drug Marketing, Advertising, and Communications (DDMAC) has reviewed your promotional activities and materials and has concluded that they are false, lacking in fair balance, or otherwise misleading in violation of the Federal Food, Drug, and Cosmetic Act (the Act) and applicable regulations."

The wording of the letter was very strong and accused the firm of minimizing the risks found in the VIGOR trial and misrepresenting the safety of the drug. The letter specifically mentioned that patients on Vioxx were observed to have a four to five fold increase in myocardial infarctions (MIs) compared to patients on the comparator non-steroidal anti-inflammatory drug (NSAID), Naprosyn (naproxen). Since the FDA is a government agency, it only did what the bureaucrats love to do - write memos. Most experts now believe that the right thing to do at that time was to ban Vioxx.

While the FDA criticized the fact that Merck was hypothesizing that Aleve may do a better job at protecting the heart but "that there is another reasonable explanation, that Vioxx may have pro-thrombotic properties." The FDA letter further continued, "You have also engaged in promotional activities that minimize the Vioxx/Coumadin (warfarin) drug interaction, omit important risk information, make unsubstantiated superiority claims against other NSAIDS, and promote Vioxx for unapproved uses and an unapproved dosing regimen. In addition, in misrepresenting the Vioxx/warfarin drug interaction you also misrepresent Vioxx’s safety profile by minimizing the potentially serious risk of significant bleeding that can result from using Vioxx and warfarin concomitantly."

The letter mentioned that by minimizing these potential risks and misrepresenting the safety profile for Vioxx raises significant public health and safety concerns. In a later study the FDA estimated that as many as 140,000 Americans have been injured by Vioxx and 60,000 may be dead.

Misleading audio conferences

It is also widely known that Merck hired several pseudo-experts who were getting paid by the company for speaking about the safety of Vioxx. One of them was Dr. Peter Holt who also attracted FDA's attention. The agency thought that "The promotional audio conferences identified above, arranged by, and presented on behalf of, Merck were false or misleading in that they minimized the MI results of the VIGOR study, minimized the Vioxx/Coumadin drug interaction, omitted important risk information, made unsubstantiated superiority claims, and promoted Vioxx for unapproved uses and an unapproved dosing regimen."

Regarding the press release that we could not find, as indicated above, the FDA says that "is also false or misleading for similar reasons stated above. Additionally, your claim in the press release that Vioxx has a "favorable cardiovascular safety profile," is simply incomprehensible, given the rate of MI and serious cardiovascular events compared to naproxen. The implication that Vioxx’s cardiovascular profile is superior to other NSAIDS is misleading; in fact, serious cardiovascular events were twice as frequent in the VIOXX treatment group (101 events, 2.5%) as in the naproxen treatment group in the VIGOR study."

Merck sales reps deceived doctors and FDA

Further the notorious sales reps of Merck who learned how to dodge safety questions from doctors by training through games like Dodgeball also were mentioned by FDA in the warning letter. "Merck sales representatives have engaged in false or misleading promotional activities that also minimize the potentially serious MI results observed in the VIGOR trial. Specifically, Merck sales representatives made false or misleading statements to DDMAC reviewers at two different professional meetings. At your exhibit booth during the 119th Annual Meeting of the Maryland Pharmacists Association (MPhA), in Ocean City, Maryland, June 9 – June 12, 2001, your representative stated that the increased MI rate seen in patients on Vioxx in the VIGOR study is due to the fact that naproxen works just like aspirin (i.e., inhibits clotting and platelet aggregation). In addition, during the Annual Meeting of the American Society of Health-Systems Pharmacists (ASHP), in Los Angeles, California, June 3 – June 6, 2001, your representative stated that Vioxx had a greater MI rate in the VIGOR trial because naproxen is cardioprotective, having platelet effects similar to aspirin. These statements made by your sales representatives are misleading for the reasons stated above," the FDA wrote.

Merck ignored FDA warnings

"Due to the seriousness of these violations, and the fact that your violative promotion of Vioxx has continued despite our prior written notification regarding similar violations," the FDA wanted Merck to act immediately. But as is well know now, Merck and FDA simply dragged the process for years due to bureaucratic delays. The drug was left on the market for another three years even as Merck and FDA fought over the language on the label of Vioxx.