The New York Times Business
February 11, 2005
By BARRY MEIER and STEPHANIE SAUL
At times, it is necessary to "neutralize" the opposition, or at least Merck & Company executives seemed to think so.
In 1999, the company's new pain drug, Vioxx, was beaten to pharmacy shelves by a competing drug, Celebrex. Merck apparently hoped that nationally known rheumatologists like Dr. Roy Altman could help it catch up.
At a dinner that year in Miami, a Merck executive asked Dr. Altman what it would take to win his support, the doctor recalled. Dr. Altman said he told the executive that he wanted to run a clinical trial involving Vioxx, and, later, Merck put up $25,000 for it.
"Show me the money," appeared on an internal Merck document near Dr. Altman's name. He said those were neither his words nor his intent. He also said his involvement in the trial did not affect his prescribing.
Merck's dinner with Dr. Altman, internal company documents show, was a brief stop in a long-running campaign by Merck to enlist the support of doctors for Vioxx or, at the least, to defuse their support for Celebrex - to "neutralize" them as the documents put it.
"We were all aware that there was a great deal of marketing" at the time, said one doctor who was named in the Merck "neutralize" documents, Dr. Robert Ettlinger, a rheumatologist in Tacoma, Wash. "Like a Coke-Pepsi war."
The company's campaign was one part of a broader marketing effort that helped propel Vioxx to annual sales of $2.5 billion, until it was with-drawn from the market last September after a clinical trial found that it increased the risk of heart attacks and strokes. And next week, an advisory panel to the Food and Drug Administration will review whether the agency should add warnings or restrictions on the use of Celebrex and other drugs known as COX-2 inhibitors, a category that also includes Vioxx.
In a statement, Merck said that it stood behind its marketing programs and added that all were intended to provide accurate information about its products.
With respect to references to a program to "neutralize" physicians, Merck said that when doctors had "misinformation" or a "lack of information" about a drug, it "provided information to bring them back to a balanced or neutral position."
Drug companies routinely try to woo doctors to prescribe or promote their drugs, taking them out to fancy meals, hiring them as speakers, or contributing to medical schools. But the internal Merck documents offer a rare, behind-the-scenes look into the extremes of this process - one that may have blurred the line between legitimate promotion and offering inducements to doctors to prescribe a drug.
In recent months, federal investigators, state officials, Congressional committees and lawyers for plaintiffs have obtained thousands of internal Merck documents while pursuing investigations and lawsuits related to Vioxx.
The New York Times obtained the documents cited in this article - records that include e-mail messages, memorandums and spreadsheets - through a public official. Some of those records involved physicians Merck sought to "neutralize," while others described promotional activities aimed at doctors not on that list.
In the "neutralize" documents written by a Merck marketing executive, company officials identified dozens of influential but "problem" physicians whom the company believed had either a negative view of Merck or Vioxx or were active boosters of Celebrex.
To win them over, the documents show, Merck officials planned to offer them carrots like clinical trials, posts as consultants or give them grants.
"Attached is the complete list of 36 physicians to neutralize with background information and recommended tactics," the marketing official wrote in an e-mail message.
Merck officials insisted that all the activities they financed were "educational." But one part of a standardized form requesting payments to doctors had a somewhat less erudite tone. It read "Expected Outcome/Return on Investment."
To be sure, some claims made in the Merck internal documents and other company memos might have reflected idle boasts by company sales officials seeking to impress their superiors. In addition, the Merck documents indicated that some of tactics were meant to counter moves by Celebrex.
As part of the COX-2 marketing war, Merck monitored its competitors' activities, regularly compiling digests of instances in which physicians speaking on behalf of Celebrex made statements that it viewed as misleading or false. Many of those internal complaints involved claims that some academic researchers were inflating Celebrex's benefits while exaggerating Vioxx's side effects.
In a statement, Pfizer, which now makes and markets Celebrex, said that it always strived to provide a balanced picture of Celebrex's risks and benefits and that it could not comment on specific incidents that might have involved other companies that were once part of Celebrex's promotion. Over the years, Merck and Pfizer or its marketing partners all received warning letters admonishing them for misleading claims.
Both Celebrex and Vioxx were marketed as a safer alternative to traditional pain relievers like Advil and Aleve, which can cause ulcers and stomach bleeding.
The "neutralize" list reflected the battle for the hearts and minds of doctors in the COX-2 wars. One physician on the list - Dr. Ettlinger from Tacoma - was described in Merck documents as an adviser to the formulary board of a regional insurer who was being "heavily courted by Searle and Pfizer."
At the time, Searle was the manufacturer of Celebrex, and Pfizer helped market it.
A Merck document recommended that Dr. Ettlinger be giving more paid speeches, be invited to more meetings and be asked to do more drug trials. "He is participating in a number of clinical trials," the Merck memo noted. "Keep him busy." In bold letters beneath Dr. Ettlinger's name was the term "neutralized."
The physician said in an interview that he was "absolutely shocked" that he had been singled out for attention, saying he regularly gave speeches for many drug companies. Such work never affected the drugs he prescribed, including Vioxx or Celebrex, he said.
But in some cases, Merck sales officials apparently hoped that showering physicians with favors would bring some returns, the records indicate. For example, one Merck representative requested in 1999 that the company make a $25,000 donation to the West Coast Sports Medicine Foundation, a nonprofit organization founded by Dr. Keith Feder, a Los Angeles-area orthopedic surgeon. The foundation helps pay medical insurance for low-income students in California so they can have the coverage required by the state to participate in team sports.
A Merck sales representative said in the document that the $25,000 payment to the foundation was needed to "be competitive with Searle," which, had also made such a grant. In a form requesting the payment, the Merck representative listed the "Expected Outcome/Return on Investment" as "51 percent share of COX-2 market in 2000."
In an interview, Dr. Feder confirmed that the foundation had received money from both Searle and Merck, but said that the grants helped support a continuing medical education program and were not intended to influence his prescribing habits and did not do so.
"It had nothing to do with their product in any way, shape or form," he said.
Concerns about the sales of Celebrex and Vioxx also came up in connection with Dr. Max Hamburger, a rheumatologist in Melville, N.Y. Dr. Hamburger, who was also on Merck's "neutralize" list, headed a large consortium of physicians in the New York metropolitan area who, by the time Vioxx went on the market, were "high-volume prescribers and huge adopters of Celebrex."
At the time, Dr. Hamburger was approaching drug companies to subsidize retreats for his group during which the physicians would put together guidelines on what drugs to prescribe.
"Companies that provide funding will receive preferred status with its members and those that do not will have trouble accessing" the group, the Merck memo stated. "Price tag is $25,000."
Merck officials stated in the internal document that Pfizer and Searle had already agreed to pay. And Merck did so, too, the document shows. On the "neutralize" list, Dr. Hamburger was described as having been "turned around" and the word "advocate" appears.
In an interview, Dr. Hamburger said that his group solicited funds from a large number of pharmaceutical companies to support its educational meetings and that payments from those drug makers did not influence the medications prescribed.
As for his description as an advocate, Dr. Hamburger said he was a strong believer in the value of COX-2 drugs but not a champion of any company's medication.
James Sheehan, a federal prosecutor in Philadelphia who specializes in health care fraud, did not review the documents. But, speaking generally, he said that while drug companies can give money to doctors for educational or scientific purposes, payments intended to influence whether a physician prescribes a drug might qualify as an illegal kickback.
Asked about the propriety of the company's marketing program, Merck said in a statement that it stood behind its marketing and would defend it.
"Merck believes that the provision of educational grants to support the exchange of information in a medical or scientific form is not only proper but is a valuable contribution," the company said.
Merck also said that the documents reviewed by The Times reflected only a selection of the company's marketing materials and so might misrepresent its activities.
In the end, Merck's efforts might not have been needed in some cases and failed to work in others. Several doctors on the company's list of "problem" physicians said they had no problem with Merck or Vioxx, while others said they felt that the drug, while frequently killing pain better than Celebrex, did have its own problematic side effects like increasing blood pressure and fluid retention.
As for Dr. Altman, who is now a professor of medicine at the University of California, Los Angeles, he never spoke for Merck or said he felt any more pressure from the company after the dinner in Miami. As for the $25,000 study Merck financed to look for the drug's value in the treatment of gout, he said he never completed it. He could not recruit enough patients for it.
Copyright 2005 The New York Times Company