Summary of Prepared Testimony
Raymond V. Gilmartin,
President, Chairman and Chief Executive Officer,
Merck and Co., Inc.
before the
United States Senate Committee on Finance
November 18, 2004
- The Food and Drug Administration approved Vioxx only after Merck had extensively studied the medicine.
- Merck continued to extensively study Vioxx after it was approved for marketing to gain more clinical information about the medicine.
- Merck has promptly disclosed the results of numerous Merck-sponsored studies to the FDA, physicians, the scientific community and the media and participated in a balanced, scientific discussion of its risks and benefits.
- Until data from the APPROVe clinical trial became available in September, the combined data from randomized controlled clinical trials showed no difference in confirmed cardiovascular event rates between Vioxx and placebo and Vioxx and NSAIDs other than naproxen.
- While epidemiological studies have an important role to play, given their inherent limitations, when both epidemiological studies and randomized controlled clinical studies are available, the randomized controlled clinical trials are the most persuasive evidence.
- As soon as the data from the APPROVe study became available, Merck acted quickly to withdraw the medicine from the market.
Prepared Testimony
Raymond V. Gilmartin,
President, Chairman and Chief Executive Officer,
Merck and Co., Inc.
before the
United States Senate Committee on Finance
November 18, 2004
Mr. Chairman, Senator Baucus, members of the Committee, my name is Ray Gilmartin and I am chairman, president and chief executive officer of Merck & Co. On behalf of the 60,000 men and women of Merck, I am pleased to have the chance to come before you to tell you more about who we are and what we stand for.
On the afternoon of September 24th, Dr. Peter Kim, President of Merck Research Laboratories, called to alert me to information he had received just that morning. The information was from an independent, external board of physicians and scientists monitoring the safety of patients in a major trial on Vioxx. He told me that in the trial we sponsored – known as APPROVe –there was an increased risk of confirmed cardiovascular events beginning after 18 months of continuous daily treatment in patients taking Vioxx compared to those taking placebo.
That call triggered a series of events that led, within four days of that call, to Merck contacting the FDA to tell them that we were going to withdraw Vioxx from the market.
The decision that we made to voluntarily withdraw Vioxx was difficult in several ways. Vioxx was the only nonsteroidal anti-inflammatory medicine or NSAID that was demonstrated to provide pain relief similar to high-dose NSAIDs and proven to reduce the risk of developing debilitating gastrointestinal side effects compared to those on NSAIDs. This was an important benefit for many who suffered from the pain of arthritis and other conditions. An estimated 15,000 Americans die each year from gastrointestinal bleeding associated with NSAID use.
Many patients counted on Vioxx to help them when no other medicine would. We believed that it would have been possible for Merck to continue to market Vioxx with labeling that would incorporate the new data.
On another level, however, the decision we made to withdraw Vioxx was easy. Given the availability of alternative therapies and the questions raised by the data, withdrawing Vioxx was consistent with an ethic that has driven Merck actions and decisions for more than one hundred years. Merck puts patients first.
I am pleased today to assist the Committee in better understanding this decision and the events that led to it. I would like to make three points clear at the outset.
First, the Food and Drug Administration approved Vioxx only after Merck had extensively studied the medicine and found it to be safe and effective. Merck continued to extensively study Vioxx after it was approved for marketing to gain more clinical information about the medicine.
Second, over the past six years, since the time Merck submitted a New Drug Application for Vioxx to the FDA, we have promptly disclosed the results of numerous Merck-sponsored studies to the FDA, physicians, the scientific community and the media and participated in a balanced, scientific discussion of its risks and benefits.
Third, until APPROVe, the combined data from randomized controlled clinical trials showed no difference in confirmed cardiovascular event rates between Vioxx and placebo and Vioxx and NSAIDs other than naproxen. When data from the APPROVe study became available, Merck acted quickly to withdraw the medicine from the market.
In my few minutes, I welcome the chance to review each of these points and welcome your questions.
Merck’s Actions in Response to Questions on Vioxx Safety
Mr. Chairman, as you know, no medicine is absolutely safe; all medicines have side effects. To determine both its risks and benefits, Merck extensively studied Vioxx before seeking regulatory approval to market it and we continued to conduct studies after the FDA approved Vioxx.
I have provided, with this statement, a timeline of our Vioxx research and development process to aid in the Committee’s understanding of the events.
Our original New Drug Application to the FDA for Vioxx included data on more than 5,000 patients with osteoarthritis. The clinical trials compared the effects of Vioxx to other non-naproxen NSAIDs and to placebo, and included data on patients who had been on Vioxx for longer than one year. In these studies, there was no difference in the rate of cardiovascular events between Vioxx and placebo, or between Vioxx and non-naproxen NSAIDs.
Prior to the FDA’s approval of Vioxx, we had initiated a study known as VIGOR. That study was designed to compare the gastrointestinal safety profile of Vioxx at twice its maximum recommended chronic dose with naproxen.
We chose naproxen for this study instead of placebo because we intended to test Vioxx in patients with rheumatoid arthritis. These are among the patients who we hoped would benefit from taking Vioxx. It would not have been ethical or practical to subject people suffering from arthritis pain to a placebo for a long time.
The preliminary results from the VIGOR trial became available to Merck in March, 2000. In the trial, there was a higher cardiovascular event rate in patients taking Vioxx than naproxen. These data were of concern to us.
It is important to note that, because the VIGOR study compared two drugs – Vioxx and naproxen – and not Vioxx and placebo, it was not possible to make a determination, based on the VIGOR study alone, whether naproxen was having a beneficial cardiovascular effect, or whether Vioxx was having a detrimental cardiovascular effect.
To help us evaluate the meaning of the VIGOR study, Merck took the step of looking into data from two trials we had already initiated in which patients with memory impairment or Alzheimer’s were given Vioxx or placebo. We found that there was no difference in cardiovascular event rates in these two trials.
These data, our earlier clinical data, and a pharmacological study that showed that naproxen had strong anti-platelet effects similar to aspirin, when it is taken regularly twice a day, as it was in VIGOR, led us to conclude that the best explanation for the difference in VIGOR was an effect of naproxen.
As Merck continued to monitor the safety of Vioxx, we recognized the value and interest in obtaining additional cardiovascular safety data on Vioxx and discussed how to obtain placebo-controlled data in the population of patients with pain in whom Vioxx was indicated. Among the issues we had to consider was the ethical difficulty in giving placebo, rather than a pain-relief medicine, to patients in pain over a longer period of time.
After deliberations with numerous outside advisers, Merck developed and discussed with the FDA a plan to prospectively analyze the cardiovascular event rates from three, large, placebo-controlled studies, two of which were already underway.
It was preliminary information from one of those long-term trials – the APPROVe study – that led to Merck’s decision to withdraw Vioxx.
Merck’s Disclosure of Safety-related Information on Vioxx
Merck has promptly disclosed the results of Merck-sponsored studies of Vioxx to the FDA, physicians, the scientific community and the media. By doing so, we fostered – both internally and externally – a robust scientific discussion of the risks and benefits of Vioxx.
In March 2000, when we received the results of the VIGOR study, we promptly issued a news release providing its conclusions and we submitted its results to the FDA. The cardiovascular results of VIGOR were widely reported and discussed at the time. Just two months later, we submitted the initial VIGOR results to the New England Journal of Medicine for publication and presented the data at a major scientific meeting.
We also worked diligently with the FDA to review the data and develop revised prescribing information. This revised prescribing information included the cardiovascular data from VIGOR and a cardiovascular precaution.
Since the time of our release of the VIGOR study data, there has been a healthy scientific discussion of the safety of Vioxx and other COX-2 inhibitors. This discussion has occurred within Merck’s laboratories and at external scientific forums.
Merck supported that discussion. However, when researchers published articles or gave speeches that presented misleading or inaccurate information about Vioxx, Merck sought to set the record straight about a medicine that provided significant benefits to patients.
We are confident that a careful and complete examination of Merck’s conduct shows that, at all times, we acted responsibly and in a manner consistent with Merck’s commitment to patient safety and our rigorous adherence to scientific investigation, openness and integrity.
Merck Acted Based on Data from a Placebo-Controlled Clinical Study
In light of the history of our detailed examination of the cardiovascular safety of Vioxx, Dr. Kim’s September 24th call to me was unexpected. Our clinical data – from our original application to the FDA seeking approval of Vioxx to that day – had shown no difference between Vioxx and placebo.
Mr. Chairman, Merck believed wholeheartedly in Vioxx. I believed wholeheartedly in Vioxx. In fact, my wife was a user of Vioxx until the day we withdrew it from the marketplace.
Much has been made of epidemiological studies conducted over the past few years about Vioxx.
Two points are worth noting about these studies.
First, because of the design limitations inherent in epidemiological studies, their results must be interpreted with caution. For example, years of epidemiological studies on hormone replacement therapy (HRT) appeared to indicate that HRT was heart and cancer protective. In fact, recent well-controlled clinical studies have proven the opposite.
Second, the epidemiological data were inconsistent. I have included with this statement a timeline of epidemiological studies involving Vioxx or other NSAIDs that illustrate this point.
While epidemiological studies have an important role to play, given their inherent limitations, when both epidemiological studies and randomized controlled clinical studies are available, the randomized controlled clinical trials are the most persuasive evidence.
Prior to APPROVe, there was no demonstrated increased risk of cardiovascular events for patients taking Vioxx compared to patients taking placebo or NSAIDs other than naproxen in randomized controlled clinical trials. And, we only found an increased risk of cardiovascular events because Merck continued to study Vioxx for such a long time period. In fact, Vioxx and aspirin are the only two NSAIDS for which there is significant, publicly available long-term safety data.
When Dr. Kim contacted me to describe the risk, Merck acted.
Conclusion
In conclusion, Mr. Chairman, throughout Merck’s history, it has been our rigorous adherence to scientific investigation, openness and integrity that has enabled us to bring new medicines to people who need them.
I am proud that we followed that same rigorous scientific process at every step of the way with Vioxx. Mr. Chairman, I would be pleased to answer the questions that you or the Committee might have.
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