May 22, 2006
Former Vioxx users could be at risk of developing strokes for years, a prominent scientist said this week after evaluating new data from a 107-page report on patients who were followed for a year after they stopped the drug
“It may be that Vioxx is causing permanent damage to the cardiovascular system, accelerating atherosclerosis or a sustained increase in blood pressure,” said Dr Curt Furberg, a professor of public health at Wake Forest University, and a member of the FDA Safety and Risk Management Advisory Committee, according to a report by Reuter’s news on May 18, 2006.
During his examination of the report, Dr Furberg determined that within the one-year follow-up of the APPROVE study, 7 Vioxx users had strokes, and 2 others had mini-strokes, compared with no strokes in patients taking a placebo.
“These data raise some very important questions because for a while we assumed Vioxx caused temporary problems, and here it is more than that,” Dr Furberg told Reuters. “It could be causing permanent damage.”
“In the past we weren’t quite sure of the stroke risk,” he added, “so stroke is now back on the agenda in a bigger way.”
Also this week the Wall Street Journal reported that heart attack risks for Vioxx users increase long before the 18 month period claimed by Merck. The new report is the 1-year follow-up to the APPROVE trial and includes a graph tracking “confirmed thrombotic cardiovascular events,” that shows that at four months of use, the number of CV events among Vioxx users began to outnumber those in patients who were given a placebo.
On May 18, 2006, CNN’s Moneyline reported that: “Merck is denying news reports that suggest new data from the drug maker indicates Vioxx increased heart attack risks earlier than previously reported and that the risk for stroke persisted long after the patient stopped taking the drug.”
But then when has it ever done anything but deny its wrongdoings?
This appears to be a month of reckoning for Merck because another study published earlier this month in the online edition of the Canadian Medical Journal, Queen’s University researcher Linda L’vesque, along with James Brophy and Bin Zhangat at McGill University in Montreal Canada, found that 25% of Vioxx users who suffered a heart attack did so within 14 days of taking the first dose.
What this all means to Merck’s legal team is that the stakes are getting higher and the company’s SEC filings indicate the drug giant knows it.
Last year, Merck had listed a reserve of $675 million for legal defense expenses related to Vioxx; but in January 2006, the company announced that it had increased the fund by $295 million to cover legal costs through 2007.
According to Merck’s SEC filings, in 2005, the company had worldwide sales of $22 billion, compared to $22.9 billion for 2004. Total sales decreased 4% for the year, which Merck says, reflects a decrease of 7% related to the VIOXX withdrawal, offset by revenue growth in all other products of 3%.
Included in marketing and administrative expenses, the company noted reserves solely for future legal defense costs for Vioxx litigation recorded in the 4th quarter of 2005 and 2004, of $295 million and $604 million, respectively, as well as $141 million associated with the withdrawal of Vioxx recorded in 2004.
According to a January 31, 2006 Merck press release, there are “9,650 lawsuits, which include approximately 19,100 plaintiff groups alleging personal injuries resulting from the use of VIOXX.”
In addition, another 3800 plaintiffs have signed tolling agreements, meaning they have cut a deal with Merck to forego suing in the short term; but should Merck start losing Vioxx lawsuits in marginal cases, attorneys say, those thousands are likely to multiply.
There are also numerous lawsuits filed against Merck for claims other than personal injuries. For instance, the Attorney General of Texas, Greg Abbott, has filed a lawsuit seeking $250 million, accusing Merck of defrauding Texas citizens by representing Vioxx as safe when applying for the drug’s approval to be included on the state’s list of drugs approved to be covered for patients on Medicaid.
According to the lawsuit’s complaint, Merck’s failure to disclose the harmful effects of Vioxx, while offering it to the state’s Medicaid program as a safe painkiller, violates the Texas Medicaid Fraud Prevention Act and the Texas Medicaid program reimbursed pharmacists $56 million for Vioxx prescriptions over a five-year period.
In another case, on March 31, 2006, a New Jersey court of appeals upheld a class action lawsuit against Merck filed by private insurers and HMOs, as third-party payors, under the New Jersey Consumer Fraud Act, to recover losses incurred in purchasing Vioxx for their health plans.
The appellate court ruled that Judge Carol Higbee of New Jersey Supreme Court properly exercised her discretion in certifying a nationwide class. “New Jersey’s contacts with this dispute are both extensive and weighty,” the appeals court said, noting the fact that Merck was a New Jersey corporation and that most of Vioxx-related research and marketing efforts took place in the state.
“Given the confluence of New Jersey contacts and interest,” the court stated, “choosing New Jersey as the site for this nationwide class action is not unconstitutionally ‘arbitrary or unfair’”.
On July 29, 2005, Judge Higbee had granted a motion by the International Union of Operating Engineers Local #68 Welfare Fund, a labor union health plan, to allow the lawsuit to proceed as a nationwide class action, based on allegations that Merck engaged in widespread and systematic concealment of data concerning the safety and health risks of Vioxx.
“This Court,” the judge wrote, “sees no reason why the duty to be honest about the safety and usefulness of a drug when marketing it as a product for sale should not extend to the third party payors who actually pay for the purchase of drugs for members.”
Chris Seeger, the lead attorney for the union health plan, states that “the decision applies to all non-governmental third-party payors in the country, including health insurers, unions, and large employers, who paid for Vioxx prescriptions for their plan members.”
“The decision,” he says, “also allows for all such third-party payors in the country to prosecute their allegations of being misled by Merck’s misrepresentations and concealments concerning Vioxx in one class action, rather than in a multitude of individual actions.”
The plaintiffs contend that had they been properly informed of the facts, they would not have included Vioxx on their lists of approved drugs or reimbursed their members for its high cost. In this type of case, the plaintiffs do not have to prove Vioxx caused any injuries or deaths. All they have to prove is that Merck continued to push the sale of the drug after it knew of the increased risks it posed.
Besides recouping costs of purchasing Vioxx for their plan members, if successful, the third-party payors would be entitled to triple damages under the New Jersey Consumer Fraud Act.
That said, Merck must have a lot confidence in its legal team because it reportedly has not reserved any money for liability. Which means it probably plans on using the same trial strategy that has proven somewhat effective so far.
Search out and destroy the credibility of the expert witnesses who might testify for the plaintiffs.
Several of the most feared witnesses provided a preview of their testimony at a November 18, 2004, hearing before the Senate Finance Committee, where the topic was focused on whether the FDA and Merck had failed to protect the public against Vioxx.
In his opening statement, the chairman of the committee, Senator Charles Grassley (R-Iowa), set the parameters for what he called the biggest drug disaster in US history.
“Merck acknowledged that Vioxx carried with it serious cardiovascular risk,” he told the audience, “when it withdrew the drug from the market.”
However, he explained, during “today’s hearing we will hear about the red flags that were raised about those risks in the years before and the years after Vioxx was approved by the Food & Drug Administration.”
The star of the hearing was FDA whistleblower, Dr David Graham, who told the panel that his superiors at the FDA tried to suppress the results of a recent study that determined that Vioxx at low doses was associated with a 50% increase in the risk; and doses of greater than 25 mg a day showed a 370% increase in the risk of heart attacks.
In reviewing the documents on the Vioxx-related studies, a strange coincidence appeared. As it turns out, the report for the above study, authored by Dr Graham, has the exact same date, September 30, 2004, that Merck supposedly “voluntarily” took Vioxx off the market and it says it was sent to Paul Seligman, MD, then acting director of the FDA’s Office of Drug Safety.
“Disturbingly,” Dr Graham wrote in the report, “while evidence of increased cardiovascular risk with rofecoxib continued to accrue following VIGOR in 2000, the only study to examine the gastrointestinal benefits of rofecoxib compared to celecoxib found that the risk of hospitalization for gastrointestinal bleeding was significantly increased in patients treated with rofecoxib.”
“Additionally,” he continued, “this reviewer was unable to identify articles demonstrating a substantial benefit with the high-dose strength of rofecoxib that would counter-balance the level of cardiovascular risk shown in VIGOR or any subsequent observational study, including this one,” he wrote.
Dr Graham’s report and testimony at the hearing led many doctors and scientists, at home and abroad, to conclude that the FDA was in large part responsible for the deaths of tens of thousands of Americans, because it allowed Vioxx to remain on the market for years while Merck made billions of dollars off the sale of the drug.
Critics liken the rise and fall of Vioxx to a masterful public relations coup of aggressive marketing and ineffective regulation. In the months following the hearing, Merck and the FDA, came under attack from experts all over the world. Two months after Vioxx was pulled off the market, Dr Richard Horton, editor in chief of the British medical journal Lancet, wrote: “With Vioxx, Merck and the F.D.A. acted out of ruthless, short-sighted, and irresponsible self-interest.”
Other experts demanded an explanation. A team of scientists from the University of Berne, Switzerland, expressed distain in the December 2004 Lancet saying: “Our findings indicate that Vioxx should have been withdrawn several years earlier.”
“The reasons why manufacturer and drug licensing authorities did not continuously monitor and summarize the accumulating evidence need to be clarified,” they said.
In the weeks following the hearing, Dr Graham was interviewed on a series of TV news programs and was also featured in articles in USA Today, Newsweek, the Wall Street Journal, and the Washington Post, leaving a trail of ammunition for attorneys to use in court as far as Dr Graham’s opinions.
However, federal judge Eldon Fallon dealt Merck a major blow in April 2006, when he ordered Dr Graham to testify in a deposition for the Vioxx multidistrict litigation proceedings in response to subpoena issued by attorneys for the plaintiffs.
In addition to Dr Graham, the equally forthright expert witness, Dr Gurkirpal Singh, MD, Adjunct Clinical Professor of Medicine at Stanford University School of Medicine also testified at the November 18, 2004, hearing through a video conference due to health problems.
Dr Singh is a rheumatologist by training with research expertise in drug safety and epidemiology. For the hearing, Dr Singh was asked to review internal company documents and emails between Merck scientists and executives that had been subpoenaed by Congress.
Dr Singh began his testimony by pointing out that as far back as 1996, Merck was already considering the possibility that a clinical trial of Vioxx versus a non-selective NSAID, would find that patients treated with Vioxx would have an increased risk of cardiovascular complications.
“We now know that by November of 1996,” Dr Singh told the panel, “Merck scientists were seriously discussing a potential risk of Vioxx – association with heart attacks.”
At that time, he said, it was not known that Vioxx could cause heart attacks, but the discussion focused on the issue that by inhibiting platelets, other painkillers may protect against heart attacks. Vioxx has no effect on platelets, and thus may seem to increase the risk of heart attacks in studies comparing it to other painkillers, he said.
“This was a serious concern because the entire reason for the development of Vioxx was safety,” he explained. “If the improved stomach safety of the drug was negated by a risk of heart attacks,” Dr Singh said, “patients may not be willing to make this trade-off.”
“Merck scientists,” he told the committee, “were among the first to recognize this.”
“At this point in time,” he said, “scientists should have started a public discussion about this potential trade-off, and designed studies that would more carefully evaluate the risk-benefit ratio of the drug.”
“It appears from the internal Merck e-mails provided to me,” he advised, “that in early 1997, Merck scientists were exploring study designs that would exclude people who may have a weak heart so that the heart attack problem would not be evident.”
“Clinical trials should be designed to test a drug under “real world” circumstances – on patients who are most likely to use the drug,” Dr Singh told the panel.
“Clinical trials should not be designed,” he said, “to selectively favor one outcome over another by excluding people similar to those who would take the drug after its approval.”
“Certainly,” he continued, “clinical trials should not be designed to put marketing needs in front of patient safety – we need to know how a drug behaves in people who are going to take it, even if it “kills the drug”.
Referring to documents provided to him by the Committee, Dr Singh said, “there were many other internal discussions within Merck on these concerns of heart attack-stomach bleed trade-offs, although the practicing physician did not learn of any of this till many years later,” he added.
For instance, one document in 1998 authored by Merck scientist, Dr Doug Watson, presented an analysis of serious heart problems with Vioxx compared to patients enrolled in studies of other Merck drugs and concluded that in women, the risk of heart problems was more than double compared to people not taking any drug in other studies.
“To the best of my knowledge,” Dr Singh said, “these data were never made public.”
“This is when a public scientific discussion of the pros and cons of the medication should have started,” he told the committee.
By 1999, he said, more serious problems were emerging. “By the time Merck had filed for the approval of Vioxx,” he informed the panel, “there were several small studies evaluating the efficacy and safety of Vioxx in patients with pain and arthritis.”
“None of these studies were large enough to study the risk-benefit trade offs of stomach bleeds versus heart attacks,” he explained.
But in a careful review of Merck’s FDA drug application for Vioxx, he told the panel, “Dr. Villalba noticed that “thomboembolic events are more frequent in patients receiving VIOXX than placebo…”.
The review showed that among 412 patients taking a placebo, only one had a cardiovascular event; but among the 1631 patients receiving 12.5 mg or more of Vioxx, 12 had a cardiovascular event.
This meant that not only did Vioxx not inhibit the platelets, Dr Singh said, but for some reason, it was likely to promote heart attacks. “Many scientists would consider this three-fold difference as an early warning sign,” he explained.
“It is my opinion,” he told the panel, “that at this point in time, larger and more definitive studies should have been done before the drug was approved.”
Dr Singh noted that Vioxx was no more effective than any other available pain-killer and at the time, there were nearly 30 such drugs on the market in the US. Celebrex, he said, had no such risk and had been available for 6 months prior to Vioxx.
“There was certainly no emergent need to approve Vioxx without further studies if there were lingering safety concerns,” he said. “The trade-off of heart attacks for the rare instances of stomach bleeds,” he advised, “is not a reasonable one.”
But instead, he reminded the panel, “the drug was approved by the FDA in a priority review within 6 months – with no discussion on the heart attack trade-off.”
“The prescribing physicians,” he noted, “remained unaware of any of these data or discussions, till much later – with the new label change in April, 2002.”
Dr Singh explained, that the VIGOR study was the first public release of information about the heart attack-stomach bleed trade-off. The 500% increase in the risk of heart attacks found in VIGOR stunned him, he said.
At the time that the results were announced, Dr Singh said he was involved in teaching and some of his educational lectures were sponsored by Merck. “I was strongly in favor of this new class of drugs,” he explained, “and before the VIGOR trial, was unaware of any significant heart attack issues.”
Merck’s press release on the study, with a brief mention of the heart attack risk was not enough for him to continue to educate doctors in his lectures Dr Singh said, so he asked Merck for more detailed data, and when he was unable to obtain the information after multiple requests, he added a slide to his presentation that showed a man – representing the missing data – hiding under a blanket.
Up until this time, Dr Singh said, Merck had responded to all of his requests promptly. But when he persisted in his enquiries, he told the committee, “I was warned that if I continued in this fashion, there would be serious consequences for me.”
“I was told that Dr. Louis Sherwood, a Merck senior vice-president, and a former Chief of Medicine at a medical school, had extensive contacts within the academia and could make life “very difficult” for me at Stanford and outside,” he testified.
And as it turns out, Dr Sherwood did call Dr Singh’s superiors at Stanford University to complain.
However, documents that have surfaced in litigation over the past couple of years, reveal that Dr Singh had no idea how important he had become in the minds of Merck officials.
The documents show that for most of June 2000, Merck officials had their heads together trying to come up with a plan to rein in Dr Singh. He presented a major problem because he was widely respected at the FDA and also had connections with large institutional buyers that were vital to Merck sales.
On June 5, 2000, Merck senior business director, Terry Strombom, sent an email that shows Merck found itself caught between a rock and a hard place. “The one thing I am pretty sure of is that Dr. Singh could impact us negatively if he chose to do so,” he wrote. “I would recommend we handle this very carefully… I just don’t think canceling all the programs and walking away completely will serve us well in the long term,” he said.
Another email shows one official acknowledging that Dr Singh’s criticisms about Vioxx were valid. On June 5, 2000, Heather Robertson, a coordinator of health education projects, reported a conversation with Dr Singh’s contact at Merck, (who had since left the company) in an email that said:
“I spoke to Kirsten directly for the first time this past week to learn that Dr. Singh makes a balanced presentation (he must since he is an FDA advisor) but reports product information that is not favorable to Merck… Kirsten feels that no amount of work would change Dr. Singh’s position, and although we may not like to hear about it, his information is scientifically accurate.”
On June 19, 2000, a marketing manager, Susan Baumgartner, wrote an email saying: “Dr. Singh continues to play up the cardiovascular adverse events associated with Vioxx… I think there are many other speakers who deliver good messages, and we should not risk supporting the negative messages that he continues to deliver.”
Merck also had a high-tech surveillance system in place in the medical community where doctors, many with financial ties to Merck, would contact the company whenever they heard criticism. A July 21, 2000, memo reads: “Communication from advocate regarding a program given by Dr. Singh… It was hyper-inflammatory.”
A July 2000 document shows that Merck even knew about the cartoon he used in his lectures and reads: “Received reports that Dr. Singh showed a cartoon of a character hiding under a blanket and asked the audience to speculate about what it is that Merck is trying to hide.”
Other documents show sales reps were gathering information as they made their rounds to doctors’ offices and would use voicemail to relay the data to Merck’s National Service Center. A July 26, 2000 memo reads: “NSC report that at nine meetings in the L.A. area over the last three days, Singh presented sessions that were very unfavorable to Vioxx.”
Around this same time, Dr Singh made his concerns about Vioxx known to one of Merck’s largest Vioxx buyers, the Department of Veterans Affairs. Reportedly it was at this point that Dr Sherwood elevated himself to the director of damage control and a detailed report began to be compiled on Dr Singh’s activities, with nearly a dozen Merck executives involved.
An October 4, 2000 memo, by a senior regional executive states: “I have in excess of 80 e-mails pertaining to interactions with Dr. Singh from March 1999 to present. The following is my best recollection of what has happened. Because of the sensitive nature of the following, I strongly encourage you not to share with anyone unless they clearly have a need to know.”
Less than a month later, Dr Sherwood called Dr Singh’s boss at Stanford University, Dr James Fries.
“I don’t usually receive phone calls on a Saturday at home from representatives of drug companies,” Dr Fries said during an interview with National Public Radio, of a call he received from Dr Sherwood on October 28, 2000. “So it was definitely unusual,” he said.
Dr Fries told NPR he received a call “stating that someone on my staff had been making wild and irresponsible public statements about the cardiovascular side effects of Vioxx.”
According to Dr Fries, Dr Sherwood hinted there would be repercussions for Stanford if Dr Singh did not stop making negative statements about Vioxx and he was left with the impression that Merck’s financial support to Stanford University was at risk.
Back at Merck, on November 17, 2000, apparently believing his efforts were successful, Dr Sherwood wrote an email to the marketing department that said: “Fries and I discussed getting Singh to stop making the outrageous comments he has in the past few months… I will keep the pressure on and get others at Stanford to help.”
In another email, he specifically directed one Merck executive to pressure Dr Singh himself. “Tell Singh that we’ve told his boss about his Merck-bashing,” he wrote. And tell him, “should it continue, further actions will be necessary (don’t define it.),” he said.
However, after speaking to Dr Sherwood, Dr Fries told NPR he started making calls of his own and learned that Dr Sherwood had called 7 other institutions, including the University of Minnesota, the University of Texas Southwestern and a Harvard teaching hospital, where researchers had raised concerns about the safety of Vioxx.
After Dr Fries learned about those calls, he wrote a letter to Merck CEO, Raymond Gilmartin, and questioned the propriety of Dr Sherwood’s calls in what Dr Fries referred to as, “a consistent pattern of intimidation of investigators by Merck.”
The letter included the warning: “There is a line that you can’t go across. … It had gone over that line.”
In response to questions from his boss, on January 23, 2001, Dr Sherwood wrote a memo saying there was no “orchestrated campaign or specific program” to deal with “problem individuals.”
But then he went on to discuss how he only gets involved if other Merck department heads are unsuccessful in their attempts to “balance” critics. “I will only get involved when our representatives… regional medical directors, Merck research lab physicians… or key individuals in the therapeutic business group have felt frustrated by their inability to reach out or to ‘balance’ selected individuals,” he wrote.
And he boasted about his own importance in dealing with officials at Universities. “Without trying to appear immodest,” Dr Sherwood wrote, “I believe I am the most respected physician in the pharmaceutical industry among academic chairs and deans…”
“Therefore,” he continued, “when I call them on a matter of urgent concern, they generally take it seriously… This has been a source of strength… as I have been able to exert balanced leverage in some difficult situations.”
This slew of internal documents have become a real problem for Merck’s legal team. In fact, in the first Vioxx jury trial decided on August 19, 2005, where a Texas jury awarded the widow of a Vioxx user $253.5 million, the plaintiff’s attorney, Mark Lanier, used many of them to show jurors how hard Merck worked to silence doctors like Dr Singh and the back and forth letters between Merck’s CEO and Dr Fries were very effective in accomplishing that task.
Prior to the trial, in June 2005, Merck’s legal team filed a motion with the court in a feeble attempt to suppress the leaked documents claiming a story in the “national media” had revealed a privileged attorney-client communication that could prejudice a jury against Merck after the Associated Press reported that Merck scientists had contacted company lawyers in 2000 about reformulating Vioxx over concerns it could cause cardiovascular problems.
So anyways, on November 18, 2004, when Dr Singh told the Senate committee, “I learnt that this was a persistent pattern of intimidation by Dr. Sherwood,” he obviously did not yet know the half of it.
But he did say that the harassment stopped after Dr Fries wrote to Merck’s CEO.
Dr Singh told the committee that he had objected to the way Merck published the results of the VIGOR study in the New England Journal of Medicine, because it minimized the significance of heart attacks, but prominently discussed the reduction of stomach bleeds in patients taking Vioxx.
He pointed out how Merck did not mention that patients on Vioxx had more serious adverse events, and more hospitalizations than patients on Naproxen.
But Merck’s misdeeds included more than omissions. Company documents obtained during the congressional investigation, show that in April 2000 Merck developed a “Cardiovascular Card,” and Merck’s sales reps were instructed to refer doctors who raised questions about cardiovascular risks to the card, which claimed that Vioxx was eight to 11 times safer than other similar painkillers.
The card made no reference to the VIGOR study and even though an FDA advisory committee had voted that doctors should be informed of the finding of the VIGOR study in 2001, Merck subsequently sent a memo to sales reps that stated, “Do not initiate discussions of the FDA arthritis committee… or the results of the… VIGOR study.”
In addition, sales reps were told to respond to doctors’ questions about the study by saying, “I cannot discuss the study with you”
In closing his testimony, Dr Singh said, he was especially annoyed when a few weeks before the November 18, hearing, “Merck announced that the published VIGOR data was “preliminary” and that the “final” data was presented to the FDA.”
“To the best of my knowledge,” he said, “the VIGOR paper did not indicate anywhere that the data were preliminary or incomplete.”
“Nor, did I ever see a correction or erratum indicating this fact,” he advised the panel, “up until a few weeks ago, almost 4 years later.”
He also criticized the fact that it took the FDA 2 years to add the heart attack risks to the Vioxx label, and noted that even then, the change supported mostly Merck’s position, not the one advanced by FDA’s own reviewers in public hearings.
“The FDA should regulate the drug companies,” he advised the panel, “not collaborate or negotiate with them if there is any question of public safety.”
Dr Singh also told the committee that it was important to recognize that the APPROVE study that led to the Vioxx withdrawal from the market, was not a safety study, it was an efficacy study, designed to add another indication for Vioxx treatment.
It was not a large enough study to detect a heart attack risk, he explained, “that it did find a risk was a lucky break for patients,” he said, “but this is not what it was designed to do.”
In addition, he told the panel that the FDA approval process needs to be open and subject to public scrutiny and that once a drug is approved, all the data supporting its approval should be put in the public domain.
And since an FDA reviewer had concerns about heart attacks before its approval, Dr Singh said, the FDA could have provided a conditional approval that would have required Merck to complete large safety studies within a certain time frame.
“The failure to conduct large long-term safety studies,” he told the committee, “subjected millions of patients over 4 years to a drug whose safety had been questioned by the FDA even before its approval.”
“This is not the proudest chapter in drug approval in the US,” he concluded.
A group of 12 attorneys, who were appointed by Federal District Judge Eldon Fallon to manage pretrial discovery for all federal lawsuits, has developed a Vioxx trial package that includes a guide for pursing a lawsuit against Merck and contains all the damaging documents and evidence available against the drug giant.
The package also includes parts of video statements made by top Merck officials, and courtroom slides with text and visuals.
It also includes the videotaped deposition testimony of expert cardiologist Dr Eric Topol, one of the first experts to raise questions about the safety of Vioxx and the first expert witness to experience the power of Merck’s wrath.
Shortly after learning that Vioxx had been recalled, in October 2004, Dr Topol, wrote an oped for the New York Times, and posted a column on the New England Journal of Medicine’s web site, and called for a congressional review of what he called the Vioxx “catastrophe.”
“The senior executives at Merck and the leadership at the FDA,” he wrote, “share responsibility for not having taken appropriate action and not recognizing that they are accountable for the public health.”
A little over a year later, Dr Topol, testified in a videotaped deposition, first played at a Houston jury trial on December 3, 2005, and said that Vioxx posed an “extraordinary risk,” and that he had urged Merck to conduct more trials.
Dr Topol said that after the 2000 VIGOR study showed patients using Vioxx faced an increased risk of a heart attack, he began his own evaluations after finding “discrepancies” between Merck’s studies and the data submitted to the FDA.
After analyzing 3 Vioxx studies, Dr Topol said he found patients began experiencing higher rates of heart problems “four to six weeks after the start of taking Vioxx.”
“There was not any question about” the link between Vioxx and heart ailments, he told the jury.
Dr Topol, testified that 3 years before the drug was pulled off the market, he and two colleagues published a paper in the Journal of the American Medical Association that raised the issue of whether Vioxx caused heart problems.
Dr Topol pointed out that although they published clear warnings about the cardiovascular risk in 2001, the FDA never ordered a trial to determine the extent of the problem and said Merck countered the JAMA article with a “relentless series of publications” and numerous papers in peer-reviewed medical literature written by Merck employees and consultants.
During his testimony, Dr Topol told the jury how a colleague at the Cleveland Clinic, Richard Rudick, had informed him that Raymond Gilmartin, the former CEO of Merck, had called the Cleveland Clinic board of trustees and complained about Dr Topol in mid-October 2004, after he criticized Merck’s handling of the Vioxx situation in the New York Times and New England Journal of Medicine.
He described how Mr Gilmartin called the chairman of the board, and said “what has Merck ever done to the Cleveland Clinic to warrant this?’
Dr Topol told the jury that Mr Gilmartin’s approach “appalled” him.
Two days after his deposition was played in court, Dr Topol found himself removed as provost and chief academic officer at the Cleveland Clinic medical school.
According to Dr Topol, he was told early in the morning not to attend a meeting of the clinic’s board of governors, because the position of chief academic officer had been abolished.
Dr Tope was somewhat vindicated later in December 2005, with the publication of an “Expression of Concern” by the editors of the New England Journal of Medicine, that charged that the VIGOR, published in the journal in 2000, was submitted to the journal after data on 3 heart attacks and other cardiovascular events among trial participants was deleted by Merck.
According to an article by Amanda Gardner in Health Day Reporter, right after Vioxx was removed from the market, the editors opened a computer diskette that had been submitted with the study and found a blank table with no data – lines had been drawn but not filled in.
“They did not know what should have been in there,” Sandra Jacobs, a spokeswoman for the NEJM said. “It raised some concern, but we didn’t know enough to act on it,” Jacobs added.
On November 21, 2005, Ms Garner says, NEJM’s executive editor, Dr Gregory Curfman, was deposed for a Vioxx trial and during the process, a July 5, 2000 memorandum came to light that indicated that at least 2 of the VIGOR authors knew of the problems 2 weeks before submitting the first of two revisions, and four-and-a-half months before the study was actually published.
Dr Curfman told HealthDay that electronic records showed “a pre-submission version of the study from which data, including the number of heart attacks and deaths, were deleted by a Merck editor two days before submission.”
As a dedicated scientist and health practitioner with nothing to gain, in hindsight, it appears that Dr Topol certainly paid a high price for committing the simple act of truth-telling to protect the public from a dangerous drug and its pusher.
As a small law firm practitioner turned legal reform activist, Attorney Zena Crenshaw is highly critical of Merk’s debilitating cross examinations of experts who essentially claim the company recognized Vioxx’s potential cardiac risks before it went on the market.
Ms Crenshaw is the Executive Director for National Judicial Conduct and Disability Law Project, Inc, a legal reform organization combating abuses of the American legal system that are facilitated by judicial misconduct.
She explains that such is a signature tactic of “mega-corporations” that it seems only “mega-lawfirms” and governmental agencies can neutralize.
Ms Crenshaw says, “the grueling questions help liken American courts to the playgrounds of bullies.”
“Some prescription drug manufacturers,” she says, “clearly bully scientists who challenge their products and ethics.”
“To survive the ordeal emotionally and with credibility intact,” Ms Crenshaw advises, “witnesses for alleged victims need to become smooth courtroom actors, as well as experts in their fields.”
“If the process is not appropriately bridled by judges,” she notes, “the “search for truth” will have much less to do with American jurisprudence than the “quest to win”.”
Merck’s SEC filings on April 27, 2006, list the following upcoming Vioxx trial dates:
Doherty New Jersey Superior Court, Atlantic County June 5, 2006
CA Coordinated California Superior Court, Los Angeles County June 21, 2006
Barnett Eastern District of Louisiana (MDL) July 24, 2006
Kozic Florida Circuit Court, Hillsborough County July 31 – August 25, 2006
Anderson Tribal Court of the Mississippi Band of Choctaw Indians August 7, 2006
Hatch / McFarland New Jersey Superior Court, Atlantic County September 11, 2006
Smith Eastern District of Louisiana (MDL) September 11, 2006
Crook Alabama Circuit Court, Jefferson County, October 26, 2006
Mason Eastern District of Louisiana (MDL) October 30, 2006
Miller or Rigby Texas District Court, Harris County, November 8, 2006
Dedrick Eastern District of Louisiana, (MDL) November 27, 2006
Filed under: 2006, FDA, FDA hearing, Graham, MEDICAID, Merck, NSAIDs, stroke, Vioxx, whistleblower