Fwd: New Documents: Merck Used Doctors & Patients as Seeds to Boost Vioxx Sales

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ALLIANCE FOR HUMAN RESEARCH PROTECTION Promoting Openness, Full Disclosure, and Accountability http://www.ahrp.org and http://ahrp.blogspot.com FYIJust as Merck is finalizing a $4.85 billion settlement with thousands ofconsumers who suffered harm from the company's painkiller, Vioxx,  newrevelations about Merck's  corrupt marketing practices masquerading asscience, are laid out in a study whose authors examined roughly one millioninternal company memos and reports obtained from lawsuits against Merck.The 1999 study, known as ADVANTAGE, tested its since-withdrawn painkillerVioxx. The Associated Press reports (below) that Merck touted the study toparticipating doctors and patients as being designed to show whether Vioxxcaused fewer stomach problems than another drug. Instead, the researchersreport that the study was primarily a stealth marketing strategy whose truepurpose was to get hundreds of doctors and thousands of patients in thehabit of using Vioxx just in time for its launch. AP reports that the authors of the just released study reviewed the internalMerck memos discussing the strategy behind the study, called ADVANTAGE whileassisting plaintiffs' lawyers prepare for trials in Vioxx lawsuits.Dr. Daniel Carlat who interviewed the lead author, Dr. Kevin Hill, apsychiatrist at Harvard's McLean Hospital, describes how Merck used 600doctors and 5,557 patients as "Seeds" to boost Vioxx sales before it waseven approved!  The trial started in 1999.  There was absolutely noscientific goal or merit to this advance marketing prescribing strategy.See:http://carlatpsychiatry.blogspot.com/2008/08/new-documents-merck-used-doctors-and.html The ADVANTAGE study was published by the Annals of Internal Medicine in2003. The Annals editor, Harold Sox, told Bloomberg News that a subsequentanalysis found several patients suffered cardiovascular complications thatweren't reported in the original trial. That makes the new findings evenmore disturbing:  ``By publishing this article, we hope to shine a light on a practice thatappears to be widespread, that really involves an element of deceptionbecause patients aren't told the true purpose of the trial. `This is onepractice that appears to put patients at risk when there may be little or noscientific benefit to the research. Indeed, some patients were injured bythe drug.''*The fact that the study was approved by medical ethicsgatekeepers--institutional review boards--and by the arbiters ofscience--journal peer reviewers--confirms that the existing review processfails to filter out unethical drug trials and fails to detect marketingmasquerading as science.* Does anyone remember when Merck was presented as the paragon ofpharmaceutical corporate ethics?Its "stellar" reputation was achieved by the promotional hype ofinstitutions the company supported with cash: Among these, the Carter Center (the pharmaceutical subsidized playground ofJimmy and Rosalynn Carter) and Emory University. Indeed, in 2000, Merck's former CEO, Dr. P. Roy Vagelos, inaugurated theScience, Ethics & Society Initiative at Emory.See the promotional copy on Emory's Center for Ethics website:  "with President Carter, Dr. Vagelos went to Africa to begin the "free inperpetuity" distribution of Mectizan, a miracle drug that virtually curesRiver Blindness.""Merck's ability to undertake philanthropic ventures rested squarely on itssuccess in the drug development and marketing business. Further, as the CEOof a publicly traded corporation, Vagelos had a duty to steward Merck'sshareholders' resources carefully. But he managed to do so withoutcompromising Merck's commitment to social outreach. By cultivating a missionfirmly grounded in improving human life, Vagelos helped employees and stockholders to view Merck's ventures not as a giving away of profit, but as afulfilling of their responsibility to be good corporate citizens." http://www.ethics.emory.edu/content/view/198/114/Someone should look into the true story behind Merck's distribution ofMectizan.....Contact: Vera Hassner Sharavveracare212-595-8974ASSOCIATED PRESS Researchers: Merck Vioxx study was for marketingBy LINDA A. JOHNSON, AP Business WriterMon Aug 18, 5:16 PM ETA 1999 Merck & Co. study of its since-withdrawn painkiller Vioxx, touted toparticipating doctors and patients as meant to show whether Vioxx causedfewer stomach problems than another drug, was primarily a stealth marketingstrategy, researchers report.The true purpose was to get lots of doctors and patients in the habit ofusing Vioxx just in time for its launch, according to doctors who uncoveredinternal Merck memos discussing the strategy behind the study, calledADVANTAGE. They did so while reviewing roughly a million Merck documents forplaintiffs' lawyers preparing for trials in Vioxx lawsuits.Drug companies are widely suspected of doing many such "seeding," ormarketing studies, but there's been no "smoking gun" proving it before,according to the Annals of Internal Medicine, which published Merck'soriginal report on ADVANTAGE in 2003 and will publish the new reportTuesday.An accompanying editorial, co-authored by Annals editor Dr. Harold C. Sox,states the journal was not told the true purpose of ADVANTAGE, whichcompared Vioxx with an older, cheaper pain reliever, naproxen, when itpublished results indicating Vioxx was better tolerated.Dr. Jonathan Edelman, head of scientific affairs at Merck ResearchLaboratories, said Monday "the ADVANTAGE study was primarily a scientificstudy" designed and executed by the company's clinical research unit andthat any later use of data for marketing was a separate operation.But Dr. Kevin P. Hill said he and colleagues, while working as paidconsultants for lawyers representing plaintiffs who claimed Vioxx causedheart attacks or other harm, stumbled on documents indicating Merck'smarketing division designed ADVANTAGE and handled the data collection andanalysis.Using funding from the Robert Wood Johnson Foundation's clinical scholarsprogram, they searched further, uncovering items such as a memo from two topMerck executives nominating the study for an internal marketing award."The objectives were to provide product trial among a key physician group toaccelerate uptake of Vioxx as the second entrant in a highly competitive newclass," the memo states.ADVANTAGE used about 600 family doctors new to clinical research, with eachgetting a stipend plus fees for recruiting a handful of patients each. Mostclinical trials are run by a limited number of specialists at major teachinghospitals that each recruit hundreds of patients.Vioxx came on the market in June 1999, after rival Pfizer Inc.'s Celebrex.Both makers claimed their drug caused less cramping, diarrhea and dangerousgastrointestinal bleeding than other pain relievers. Merck battled hard formarket share, and Vioxx at its peak brought in about $2.5 billion a year.Hill, now a staff psychiatrist at McLean Hospital in Massachusetts, said heand his colleagues found documents indicating "ADVANTAGE was marketingframed as scientific research," with an emphasis on how much Vioxx doctorsin the study later prescribed."I don't think people would be willing to (risk side effects) if they knewthat the aim of a clinical trial was to boost profits for a pharmaceuticalcompany," Hill said.The study's name implied it had a scientific purpose: ADVANTAGE, orAssessment of Differences between Vioxx and Naproxen to AscertainGastrointestinal Tolerability and Effectiveness.But Hill said doctors participating in ADVANTAGE got a kit telling them howto talk to other doctors about Vioxx, and another Merck study running at thesame time, called VIGOR, also examined how safe Vioxx was for people withgastrointestinal problems, so ADVANTAGE wasn't needed. VIGOR's results werepublished in 2000.Merck spokesman Ron Rogers said Hill and his colleagues have been critics ofMerck and just cherrypicked "some documents to support their thesis."Dr. Bruce Psaty, a University of Washington epidemiologist, said Hill andhis colleagues had disclosed their conflict of interest in their report butthat the ADVANTAGE trial wasn't transparent about its purpose."I would think that at some level this is standard practice," he said ofseeding studies, but they don't come to light except during the discoveryphase of litigation.Dr. Ross McKinney, director of Duke University's bioethics center, saidseeding studies have been around for decades and usually are calledpostmarketing studies, meaning they're for drugs approved for sale. He saidmost never get published, but this one did because it addressed an importantscientific question, stomach tolerability, even though it was a seedingtrial. But McKinney said seeding studies make the public skeptical aboutenrolling in clinical studies."It's a serious violation of research ethics" and prevents patients fromfiguring out the risks and benefits of participating in the study, saidArthur Caplan, who heads University of Pennsylvania's medical ethicsdepartment.Whitehouse Station, N.J.-based Merck pulled Vioxx off the market on Sept.30, 2004, after its own research showed the then-blockbuster arthritistreatment doubled risk of heart attack and stroke. It has since reached a$4.85 billion settlement to end the bulk of personal injury suits overVioxx, and the first payment checks are slated to go out later this month.Sox, the Annals editor, and Dr. Drummond Rennie, the Journal of the AmericanMedical Association's deputy editor, wrote that the institutional reviewboards required to protect patients in clinical studies should ask whetheran experiment is a seeding study, particularly when there are obvious clues."Simply shining a bright light on their existence may have already sown theseeds of their destruction," they write.Copyright C 2008 The Associated Presshttp://www.bloomberg.com/apps/news?pid=20601087 & sid=a8ZT4hT0XK0Q & refer=homeBLOOMBERG NEWSMerck Vioxx Trial Was Strategy to Boost Drug's Sales (Update1)By Elizabeth Lopatto and Michelle Fay CortezAug. 19 (Bloomberg) -- A Merck & Co. study of Vioxx that the company saidshowed whether the painkiller was easier on the stomach than an older drugwas actually a marketing tool to boost sales, according to researchers.Their conclusions are based on 100 internal company memos and reports aboutthe study known as Advantage obtained from lawsuits against WhitehouseStation, New Jersey-based Merck over heart risks tied to Vioxx, nowwithdrawn. The trial of 5,557 patients started in 1999, just as Vioxx wascleared for sale, according to the Annals of Internal Medicine report.The study, which recruited 600 doctors, was crafted by Merck's marketingdepartment to get physicians to prescribe Vioxx, the researchers wrote. Thereport provides some of the first evidence of what is thought to be awidespread practice: enlisting doctors for a study to boost their confidencein a new drug and get them to promote it to colleagues, they said.The Advantage study ``was marketing masquerading as science,'' said leadauthor Kevin Hill, of Harvard Medical School in Boston, in an Aug. 15telephone interview. ``They went about this in a very analytic way, pickingdoctors who would be most influential, who will talk to other doctors andrecommend Vioxx to them, and thus increase prescriptions in the area,planting the seeds of additional Vioxx use.''The researchers had access to the data as part of their work as paidconsultants to lawyers suing Merck about the heart risks from Vioxx. Thedrug, which was introduced after Pfizer Inc.'s similar pain medicationCelebrex, generated $2.5 billion in annual sales before it was pulled fromthe market.Merck shares fell 26 cents to $35.45 at 10:25 a.m. in New York StockExchange composite trading. Merck's shares have fallen 39 percent this yearbefore today.Participating DoctorConrad Butwinick, an internal medicine physician in St. Paul, Minnesota, wasone of the 600 doctors recruited to participate in the study. He lamentedthe lack of information about the heart risks of the drug, which heconsidered one of the most effective treatments for arthritis.``If I had sensed that there was an ulterior motive, for physicians to havean amplified experience with the drug, I would have never done that,''according to Butwinick, who said he didn't remember participating in thestudy. ``I can't tell you that it didn't go on, but I would never go forthat.''Merck said the researchers from Harvard, Brown and Yale universities, andthe Mt. Sinai School of Medicine in New York, erred in their analysis andtook the memos out of context. They also didn't contact the company abouttheir work.Scientific AffairsThe study was conducted by the medical and scientific affairs unit, not themarketing unit, in its U.S. Human Health division, said Jonathan Edelman,executive director of Merck Research Laboratories' global center forscientific affairs. It compared Vioxx to naproxen, which hadn't beenpreviously studied, when given to patients already taking aspirin. Thosepatients were excluded from earlier trials, he said.``As with all Merck clinical research, there is a commercial interest,''Edelman said. ``The documents included in this article include an example ofthe marketing use for the data. The allegation by the authors that theprimary goal of the study was marketing is simply wrong.''The original study was published by the Annals of Internal Medicine in 2003.A subsequent analysis found several patients suffered cardiovascularcomplications that weren't reported in the original trial. That makes thenew findings even more disturbing, said editor Harold Sox in a telephoneinterview.`Patients at Risk'``By publishing this article, we hope to shine a light on a practice thatappears to be widespread, that really involves an element of deceptionbecause patients aren't told the true purpose of the trial,'' Sox said.``This is one practice that appears to put patients at risk when there maybe little or no scientific benefit to the research. Indeed, some patientswere injured by the drug.''Merck pulled Vioxx from the market in 2004 after a study linked it to heartdisease. The drugmaker has agreed to pay $4.85 billion to settle patientclaims that Vioxx, used by 84 million people worldwide, caused heart attacksor strokes.The Advantage study compared Vioxx to naproxen, an older medication, to seeif it was gentler on the stomach. About the same time, Merck started anothertrial, Vigor, at the request of the U.S. Food and Drug Administration todetermine if Vioxx was safer for the gastrointestinal tract. That madeAdvantage unnecessary, the researchers said.`Moral Offense'Such a trial is a ``moral offense,'' the authors wrote, because it'simpossible to know the intent for a pharmaceutical company's trial withoutaccess to internal documents. Further, ``seeding trials,'' may harm patientsfor marketing purposes. Findings from Advantage confirmed the increasedrisks for heart attack and stroke seen in Vigor.The study was called a seeding trial in many internal documents and themarketing officials in charge of it were nominated for the company's ``BestPhysician Program Award.'' The physicians who participated in the studyprescribed Vioxx significant more often than other doctors, the award memosaid.Jeffrey R. Lisse from the University of Arizona's Arthritis Center inTucson, the first author on the Advantage paper, has said he didn't have arole in data collection or analysis of the study results. He is on medicalleave and was unable to comment on the new study.The documents in the report were from two trials, Cona v. Merck & Co. andMcDarby v. Merck & Co., and were created between 1998 and 2006. All of theauthors worked as paid advisers to the plaintiffs.To contact the reporters on this story: Elizabeth Lopatto in New York atelopatto; Michelle Fay Cortez in Minneapolis atmcortez.Last Updated: August 19, 2008 10:30 EDT~~~~~~~~~~~~~~FAIR USE NOTICE: This may contain copyrighted (C ) material the use of whichhas not always been specifically authorized by the copyright owner. Suchmaterial is made available for educational purposes, to advanceunderstanding of human rights, democracy, scientific, moral, ethical, andsocial justice issues, etc. It is believed that this constitutes a 'fairuse' of any such copyrighted material as provided for in Title 17 U.S.C.section 107 of the US Copyright Law. This material is distributed withoutprofit.  =====In accordance with Title 17 U.S.C. Section 107, this material is distributed without profit to those who have expressed a prior interest in receiving the included information for research and educational purposes.