Documents Suggest Merck Tried to Censor Vioxx Critics

Part 1: Documents Suggest Merck Tried to Censor Vioxx Critics by Snigdha Prakash

All Things Considered, June 9, 2005 · Because of intense interest in this report, NPR has decided to present a full transcript.

Introduction: NPR's story about Merck and its efforts to suppress safety concerns about the painkiller Vioxx continues with a look at how Merck exerted its influence in the world of top medical institutions. NPR's Snighda Prakash presents part two of her report.

Transcript: Introduction: At least 38,000 Americans are believed to have died from taking the pain pill Vioxx before it was withdrawn last year. Drug maker Merck is now facing thousands of lawsuits.

Over the past few months, it has emerged that the company was aware for years that Vioxx might be dangerous. Now, new documents obtained by NPR suggest that even as Merck was making Vioxx into a bestseller, the company was putting pressure on independent doctors. The company's apparent aim: to keep them from discussing evidence of Vioxx's potential safety problems. The documents show that Merck exerted pressure not only on individual doctors, but also on several of the nation's top medical schools.

Merck tells NPR it did nothing wrong. NPR's Snigdha Prakash has the first story in a two-part report.

Transcript: When a drug company wants to sell a pill to a doctor, its best salesperson is usually another doctor.

Of course, drug companies don't call that selling. They call it "medical education." Or even medical research.

Well before Merck launched Vioxx, the company was targeting influential doctors who could help it build Vioxx's sales.

When they located a prospect, they entered the details about that doctor into a spreadsheet at headquarters. Spreadsheet entries included items such as:

"...treats all of the major sports teams, including the Lakers basketball team and the Dodgers baseball team, as well as the high-profile members of our society."

"... 2,4OO prescriptions per year... also known nationally... Writes for a lot of rheumatology textbooks."

Merck's vast army of sales representatives gathered intelligence on what it would take to win over individual doctors. Their notes included the following strategic observations:

"Use in many speaking engagements... At least $20,000 for speaking engagements for the remainder of the year."

One of the physicians whom Merck recruited to promote Vioxx was Gurkirpal Singh of Stanford University.

Merck wanted Singh on board because he was a senior researcher on a seminal study of arthritis patients. The study showed that older painkillers, such as Naproxen, commonly caused gastrointestinal bleeding. It established the need for new painkillers, such as Vioxx and its rival, Celebrex, that were gentler on the stomach.

NPR has examined Merck documents provided by sources working with individuals and families who allege Vioxx harmed them. They're now suing Merck.

Among those documents is a memo that shows Merck started to focus on Singh in April or May of 1998 -- almost two years before Vioxx was ready for market. The overture was successful. A year later, Merck was launching Vioxx, and Singh was an important spokesman.

One document reads: "March-May 1999. Aggressively scheduled Dr. Singh for talk in preparation for launch... Reviews and feedback of Dr. Singh's presentations were generally positive." And it notes that "Dr. Singh commanded relatively large honoraria."

Merck paid Singh fees of up to $2,500 for each talk. He gave 40 talks over seven months.

"One setting which is where I was speaking predominantly was in the grand round situation in hospitals, or in medical schools, or in the universities, where like you're giving a formal lecture to the physicians," Singh said. "It's always lectures to physicians. And then the other set is usually these evening programs that drug companies arrange, where you also present your research, and then there's often a dinner with it."

Merck was pushing hard to catch up with rival drug maker Pfizer. Pfizer's new painkiller, Celebrex, had beaten Vioxx to market by a few months. It was gobbling up market share.

Then in early 2000, Merck got news of a potential problem. A large study commissioned by the company showed that patients on Vioxx suffered more heart attacks, strokes and deaths than those on the older pain pill Naproxen.

For some researchers, the results were a red flag that Vioxx might be dangerous. But according to the company, the new evidence was outweighed by many previous studies that showed the drug was safe.

Merck scientists interpreted the study in a postive way. In a series of press releases, Merck said the study showed that the older drug protected against heart attacks -- not that Vioxx caused them. The company confirmed that Vioxx was safe for the heart.

Merck gave the study data to the Food and Drug Administration, and the two began a protracted debate over what the study meant, and what to tell doctors and patients about it.

Meanwhile, despite the positive spin of Merck's press releases, Singh was uneasy about the new study.

"I was worried, because obviously this was something new," Singh said. "This was something we had never seen before."

As an independent scientific expert, Gurkirpal Singh wanted to evaluate the study for himself.

Singh asked Merck repeatedly for the data. "I wanted to know how many heart attacks, how many strokes, how many deaths were occurring in each one of the groups, and what were these actual number of patients at risk, and how many ended up having an event," he said.

Singh says for months, Merck's scientific education department assured him that the results would be available soon -- at one scientific meeting, then another. They never were.

Singh got tired of waiting. He shared his concerns with at least one prominent European scientist, and he began to allude to his concerns in talks.

"June 19, 2000: 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."

The Merck sales machine, which included the departments of marketing, scientific education and physician outreach, had begun to show its other face. It had paid Singh fat speaking fees. Now it was canceling many of his educational lectures.

The documents obtained by NPR show that for much of June 2000, Merck executives conferred on how to rein in their skeptical consultant. At least 23 local, regional and national executives took part in the discussions. They feared that just as Singh's credibility had opened doors for Merck, it could close them.

Singh was widely respected at the FDA. He also had connections with large institutional buyers that were vital to Vioxx's sales.

Terry Strombom, who was senior business director for the San Francisco region, sent an e-mail on June 5, 2000, that shows Merck was walking a tight rope -- it wanted to censor Singh, but was afraid of alienating him. The e-mail read:

"The one thing I am pretty sure of is that Dr. Singh could impact us negatively if he chose to do so... 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."

The e-mails show that at the same time that Merck was trying to censor Singh, at least one Merck official acknowledged that Singh's concerns about Vioxx were legitimate.

Heather Robertson, the coordinator of health education liaisons for the San Francisco region, reported on a conversation with Singh's main scientific contact at Merck, who has since left the company. Her e-mail of June 5, 2000, read:

"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."

Later, Merck would advise its sales representatives not to discuss Vioxx's risks to the heart, and to have doctors send their questions to headquarters.

We showed the Merck documents to David Rothman, director of the Center on Medicine as a Profession at the Columbia University College of Physicians and Surgeons. He says the Merck documents consistently show a disregard for the substance of the scientific arguments about Vioxx.

"The drug companies will use the language of objective neutral science," Rothman says. "But what speaks much louder is 'You're for us, or you're again' us. And if you're again' us, we're going to try to get you.'"

Merck's surveillance system had many ways to pick up who was for them or against them. Physicians, including advocates with financial ties to Merck, contacted the company when they heard criticism.

A document from July 21, 2000, reads: "Communication from advocate regarding a program given by Dr. Singh... It was hyper-inflammatory."

Singh's allegiance was shifting. He was now promoting Vioxx's rival, Celebrex. He was being paid by Pfizer, and he was telling his audiences that Merck had refused to answer his questions about Vioxx's safety. A July 2000 document notes: "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."

Merck's sales force was also keeping tabs on the buzz in doctors' offices. As sales representatives gave out free Vioxx samples, they asked doctors if they'd heard anything new about Vioxx. The sales reps would transmit this intelligence via voicemail to the company's National Service Center. Another Merck document, from July 26, 2000, notes:

"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."

A week later, Singh would convey his concerns to one of the country's largest and most influential drug purchasers, the Department of Veterans Affairs. The VA started asking Merck if Vioxx was safe for the heart. The company's most senior scientists were brought in to answer the VA's questions. It was clearer than ever that Singh had become a major liability for the company.

Dealing with Singh was now a job for Merck's senior vice president for medical and scientific affairs -- Dr. Louis Sherwood. Sherwood was a former academic and had been chief of medicine at a top medical school.

Merck documents obtained by NPR show that a detailed account of Singh's activities was now prepared for Sherwood. Almost a dozen Merck executives were involved. A senior regional executive who had supervised Singh's scientific handlers sent this Oct. 4, 2000, e-mail:

"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."

The profile of Dr. Singh is remarkably complete," says Columbia's David Rothman, who reviewed the final document for NPR. "One can't help but almost frame it in terms of an FBI dossier, except here Dr. Singh is not cavorting with possible communists, or possible gangsters. Here the dossier is filled with Dr. Singh's take on Vioxx, who is Dr. Singh talking to. It's scrupulously watched and very, very carefully recorded."

The profile was dispatched to Sherwood and six other executives. Around the same time, Singh heard from a friend inside Merck: "I was told that Dr. Lou Sherwood, who was then vice president at Merck, had become 'very interested,' in quotes, in what I was doing, and that Dr. Sherwood is "very powerful, and he's going to crush you and he's going to fix you.'"

Dr. Louis Sherwood's campaign to "fix" Vioxx critic Gurkirpal Singh began with a series of phone calls to Singh's bosses at Stanford University.

"I don't usually receive phone calls on a Saturday at home from representatives of drug companies," says James Fries, a professor of medicine at Stanford. "So it was definitely unusual."

The call came on Oct. 28, 2000. " I received a call from a medical director at Merck, stating that someone on my staff had been making wild and irresponsible public statements about the cardiovascular side effects of Vioxx," Fries says. He says Sherwood hinted there would be repercussions for Fries and Stanford if Singh's statements didn't stop. He was left with the sense that Merck's financial support to Stanford was at risk.

Fries started making calls of his own and learned that researchers at seven other institutions, including the University of Minnesota, the University of Texas Southwestern and a Harvard teaching hospital, had also raised doubts about Vioxx's safety. Sherwood had placed calls to those institutions as well.

"A number of investigators who had spoken publicly had been called or the chairs of their departments had been called, "Fries says. "The deans of their medical schools, and a variety of veiled and not so veiled threats had been made -- that they were saying bad things about the drug company, and that the people to whom they reported should take steps to see that this stopped."

At Merck, Medical Director Sherwood wrote an e-mail to bring the marketing department up to speed. NPR has obtained that e-mail. It suggests that part of Merck's strategy to suppress criticism was intimidation. The e-mail, dated Nov. 7, 2000, reads:

"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."

Sherwood advises one of the marketing executives how to pressure Singh himself. He says: "Tell Singh that we've told his boss about his Merck-bashing." And tell him, " should it continue, further actions will be necessary (don't define it.) "

Lisa Bero is a professor of clinical pharmacy and health policy at the University of California, San Francisco. She's done extensive research showing how funding from drug companies influences academic science. She reviewed Sherwood's email at NPR's request.

"I didn't realize how powerful the drug companies thought they were," Bero said. "For example, having enough influence over a department to say 'change what your faculty member is saying.' I haven't ever seen that documented before."

Another document written by Sherwood shows Merck tried to use that influence on several occasions. After Stanford Professor James Fries learned about Sherwood's calls to other medical institutions, he sent a strongly worded letter to Merck's CEO. The letter questioned the propriety of Sherwood's calls. Sherwood wrote an internal memo in response. NPR has obtained that memo.

In it, Sherwood writes there was no "orchestrated campaign or specific program" to deal with what he calls '"problem individuals." Yet, he lists groups of Merck executives who managed those critics. The memo, dated Jan. 23, 2001, reads in part:

"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."

And Sherwood implies that when that happened, he did lean on Vioxx critics -- and on their institutions: "Without trying to appear immodest, I believe I am the most respected physician in the pharmaceutical industry among academic chairs and deans... Therefore, 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."

UCSF's Bero says, "Well, the first thing I thought is, 'What kind of leverage are we talking about?' And the first thing I thought of was money, in all the various ways that it can come to departments."

In 2004, Stanford's medical school got 9 percent of its research budget -- $29 million -- from drug companies. NPR surveyed several medical schools and found that's not unusual.

"Look, medical research is expensive," says David Rothman of the Columbia University College of Physicians and Surgeons. "No one can take a call from a drug company high official, critical of an investigator, and not realize that behind that call is the implicit reminder, implicit threat -- 'If you can't control your folks, how do you expect us to continue to do business with you?''"

Merck and Sherwood deny the allegations in this story. Ted Mayer, a lawyer representing Merck, says, "Merck was not trying to silence critics. The scientific or the safety profile of this product was very well known in data that was available to the public, and it was vigorously debated in the public, and it's perfectly appropriate to have that vigorous debate."

Mayer says Merck was concerned about Dr. Singh because many of his talks went far beyond that vigorous debate: "The number of people who heard those talks and who were physicians and understood the data well believed that those talks contained unbalanced and inaccurate information, and that the views weren't supported by the data and were kind of at the extreme end among hundreds of scientists who were making these kinds of presentations."

In an interview with NPR, Dr. Louis Sherwood says it was rare for him to complain to department heads. He says he firmly believes in academic freedom. He says he only made calls when faculty members were being unfair to Merck and acting unprofessionally.

"I never, never made any threats to withdraw funding or hamper anyone's faculty appointment," Sherwood said. "Under no circumstances did I ever do that."

"No one likes to be criticized," Sherwood said. "Now sometimes, when an academic physician is criticized for his or her actions, they may interpret that as a threat. But under no circumstances did I threaten Stanford or Dr. Fries or anyone with funding issues or anything else. That would've been inappropriate."

FDA whistleblower Doctor David Graham estimates that at least 38,000 people died from taking Vioxx. Drummond Rennie, deputy editor of the Journal of the American Medical Association, notes that "each one of those is somebody, is a real person, with a real family, real people who grieve for them."

"I think it's the job of a physician, physicians who're doing research, physicians who work in drug companies -- all physicians -- to care about that," Rennie said.

Merck says its physicians strongly believed in the safety and benefits of Vioxx. The company says the risks of Vioxx weren't clear until just last fall, when, it says, Merck acted promptly and voluntarily withdrew Vioxx.

An informal survey of medical schools by NPR found that some schools rely on funding from pharmaceutical and other health-industry sources.

The issue is taking on increasing importance. Government funding for medical research is not expected to increase in coming years and could decline. Medical schools will be more reliant on private, for-profit industry for funding. That raises concerns about academic freedom and restrictions on what researchers can and cannot say in print and in public

"Some poor guy discovered that most ulcers are caused by a bacteria. Proved it, was screaming it from the rooftops, and was completely ignored."

Great point!!!!

The same was true of scurvvy two hundred years ago. It was thought scurvvy was an std (sailors mainly got it and we all know about sailors). A doctor proved it was the lack of Vit C but was laughed at.

The scurvvy/std myth lasted until as late as 1920 (there are medical magazine articles arguing the issue from that date).

Myth have a life of their own.

Vioxx - best medicine ever invented. Cured my arthritis nearly instantaneously. A miracle drug.

Thank you for saying that. My mother was put on Vioxx July 6, 1999. It went on the market July 1, 1999. My mom was 85 years old. Within a day or two she was pain free for the first time in years. Her death over three years later had nothing to do with Vioxx. It was certainly a miracle drug for her and made her final years more comfortable.

Most drugs work for some people for some time but one cannot say because only a percentage of people die of their side effects that they are wonderful.

Thalidomide and even mercury did have benifits for thousands of people but were all the horrific, deformed babies worth it?

Many people die before the long term 'side effects' kick-in while ofhers seem immune from them.

It is those who are not so lucky that determine the drugs safety.

Thalidomide

In Europe and Canada during the early 1960s, thalidomide was prescribed to treat morning sickness in pregnant women. At that time, it was not approved in the United States because Dr. Frances Kelsey from the Food and Drug Administration (FDA) stated there was insufficient proof of the drug’s safety in humans.

Thalidomide was soon banned worldwide when it was discovered that it caused tragic birth defects. According to the March of Dimes (MOD, November 1998), "More than 10,000 children around the world were born with major malformations, many missing arms and legs, because their mothers had taken the drug during early pregnancy.

Mothers who had taken the drug when arms and legs were beginning to form had babies with a widely varying but recognizable pattern of limb deformities.

The most well-known pattern, absence of most of the arm with the hands extending flipper-like from the shoulders, is called phocomelia. Another frequent arm malformation called radial aplasia was absence of the thumb and the adjoining bone in the lower arm. Similar limb malformations occurred in the lower extremities.

The affected babies almost always had both sides affected and often had both the arms and the legs malformed. In addition to the limbs, the drug caused malformations of the eyes and ears, heart, genitals, kidneys, digestive tract (including the lips and mouth), and nervous system.

Thalidomide was recognized as a powerful human teratogen (a drug or other agent that causes abnormal development in the embryo or fetus). Taking even a single dose of thalidomide during early pregnancy may cause major birth defects."

Overall people, I think the drug industry and modern medicine has yielded a significantly more positive than negative impact on our population's health. Sure, drug companies are profit takers too. But the alternative, means no more progress. (what was the last great drug advance offered from France?) And how can you people sit there and knock these HIV drugs? gimme a break. I remember just 10 years ago when entire hospital wings were devoted to dying AIDS patients. Its like bitching that offered water isnt cold enough when you're dying of thirst in the desert.

This article needs to be taken with a grain of salt.

No kidding. Who does NPR expect drug makers to market drugs to if not doctors? If anyone wonders why doctors are leaving, hospitals are closing and health care is outrageously expensive you can start with idiots like those at NPR, ambulance chasing lawyers, and the high cost of insurance to guard against things like this.

Yes, all medication has side-effects and works differently on people. There is not a guaranteed outcome. I would rather trust the drug companies, the doctors, the hospitals, and the pharmacists than a bunch of lunatics at NPR and ambulance chasing whores.

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