fff >From: HHask@... >To: Mamemoms@... >Subject: NY Attorney General Sues Drug Maker Over Suppressed Paxil Test Data >Date: Thu, 3 Jun 2004 17:26:52 EDT > > >New York Times >June 3, 2004 > >New York State Official Sues Drug Maker Over Test Data > >By GARDINER HARRIS > >In a novel claim testing the way that the $400 billion worldwide >pharmaceutical industry is regulated, the New York State attorney general, Eliot Spitzer, >sued the British-based drug giant GlaxoSmithKline yesterday, accusing the >company of fraud in concealing negative information about its popular >antidepressant medicine Paxil. > >The civil lawsuit, filed in State Supreme Court in Manhattan, contends that >GlaxoSmithKline engaged in persistent fraud by failing to tell doctors that >some studies of Paxil showed that the drug did not work in adolescents and might >even lead to suicidal thoughts. Far from warning doctors, the suit contends, >the company encouraged them to prescribe the drug for youngsters. > >"The point of the lawsuit is to ensure that there is complete information to >doctors for making decisions in prescribing," Mr. Spitzer said in an >interview. "The record with Paxil, we believe, is a powerful one that shows that GSK >was making selective disclosures and was not giving doctors the entirety of the >evidence." > >GlaxoSmithKline officials issued a statement yesterday saying in part that >the company "has acted responsibly in conducting clinical studies in pediatric >patients and disseminating data from those studies." > >On Wall Street yesterday, the American depository receipts of GlaxoSmithKline >fell $1.38, or 3.2 percent, to $41.39. > >Mr. Spitzer filed his suit at a time that the tendency of many drug companies >to publicize only studies with positive results has come under increasing >criticism. > >As he has done in actions involving the financial services and mutual fund >industries, Mr. Spitzer is entering regulatory terrain that has been largely the >preserve of the federal government, in this case the Food and Drug >Administration. This time, though, he maintains that his suit is not a criticism of >federal drug regulators. > >"This isn't Harvey Pitt and the S.E.C.," he said, referring to the former >chief of the Securities and Exchange Commission, whom Mr. Spitzer criticized as >less than vigorous in enforcing federal securities laws. Instead, Mr. Spitzer >said that the F.D.A. had been hamstrung by court rulings that have used >free-speech arguments to limit the agency's power to regulate what drug companies can >say to doctors. Such rulings do not limit his powers, Mr. Spitzer said. > >"You cannot invoke free-speech arguments as a defense to fraud," he added. > >Similar suits against other drug companies are likely, Mr. Spitzer said. >"This is an area that we're interested in," he said, "and I think there are other >cases out there that are analogous." > >A spokeswoman for the F.D.A. would not comment on the lawsuit but noted that >the agency required companies to submit all data related to the safety of >their drugs. Because so much drug company data submitted is considered >proprietary, it is up to the F.D.A. to decide when to disclose possible public safety >concerns. > >That is what it did last year, when it warned doctors on the use of Paxil for >adolescents and children. Earlier this year, it required antidepressant >makers to strengthen suicide warnings on labels. > >British drug regulators have banned the use of all but Prozac for the >treatment of depression in adolescents and children. Prozac, made by Eli Lilly & >Company, received a major American endorsement this week when the widely >anticipated results of a study sponsored by the National Institute of Mental Health >indicated that Prozac was superior to talk therapy alone or a placebo in treating >depression among teenagers. The study did not address suicide risks. > >Civil suits have been filed against Glaxo and some other makers of >antidepressants by patients or surviving relatives, contending that the drugs caused >violent or suicidal behavior. Some criminal defendants have contended that >violent acts were a result of using the drugs. > >Mr. Spitzer's lawsuit is part of a broad assault by prosecutors on the drug >industry's marketing practices. Last month, for example, federal prosecutors in >Boston announced a settlement with the world's largest drug maker, Pfizer; >the company agreed to pay $430 million and to plead guilty to charges that its >Warner-Lambert unit promoted the drug Neurontin to doctors for the treatment of >conditions where no benefit had been proved. > >TAP Pharmaceuticals agreed to pay $800 million for inappropriate marketing >practices, and its former executives are facing federal criminal charges in >Boston. Schering-Plough has acknowledged in regulatory filings that it is likely >to be indicted for improper marketing practices. Other companies are being >investigated. > >At issue in most of these investigations, including Mr. Spitzer's Paxil suit, >is the marketing of approved drugs for off-label uses — those not >specifically approved by the F.D.A. While doctors are free to prescribe an approved drug >for any use, the manufacturers are supposed to limit their marketing to those >uses with F.D.A. clearance. > >The new wrinkle in Mr. Spitzer's suit is his argument that a drug maker is >committing fraud if it does not tell doctors about trials of a medication that >raise safety concerns. > >"I'm certainly not the person to determine whether Paxil is appropriate or >not for any given patient," Mr. Spitzer acknowledged. "But what I can do is >ensure the information to doctors is fair and complete so that those equipped to >make this determination can do so." > >Dr. Barry Perlman, president of the New York State Psychiatric Association, >said in an interview that his organization supported a crackdown on the failure >to disclose negative information on drugs. > >"Whenever we don't have the complete picture," he said, "we can't prescribe >ethically and appropriately, and that's an enormous obstacle to good care." > >Richard Merrill, a University of Virginia law professor and a former general >counsel at the F.D.A, compared Mr. Spitzer's suit to product-liability >lawsuits by individuals. He said the suit was the first by a public official against >the drug industry. > >Pharmaceutical companies sponsor most clinical trials of drugs and, in many >cases, they jealously guard the data that results. If a test suggests that a >drug is effective in treating a certain condition, the company will push to get >its results published in a prestigious journal. If the results reflect poorly >on the drug, they often never appear in public. > >Experts have long criticized the tendency in the industry to publish only >positive clinical trials, arguing that this distorts medical practice and >undermines the scientific process. Some have suggested that the results of all >clinical trials should be published in a federal registry. > >But some say that doctors are unlikely to consult such a registry and will >continue to be influenced by trial results published in leading journals. > >Mr. Spitzer's suit is the first to suggest a way of resolving such matters. >If a company's marketing message is at odds with the results of its own, >suppressed clinical trial, he argues, the company is liable for damages under >consumer fraud laws. > >In the case of Paxil, GlaxoSmithKline sponsored five trials of the drug in >adolescents suffering from major depression. The company undertook the trials to >qualify for a six-month extension of Paxil's patent granted under a federal >law that encourages the testing of drugs in children. But it published only one >of the trials, which showed mixed effect. The unpublished trials failed to >show any benefit for the drug and suggested that it might increase the risk of >suicide. > >An internal memo cited in the suit said the company should have "effectively >managed the dissemination of these data in order to minimize any potential >negative commercial impact." > >And, according to the suit, the company told its sales representatives that >"Paxil demonstrates remarkable efficacy and safety in the treatment of >adolescent depression." The suit contends that sales representatives passed this on to >doctors. > >The company's statement yesterday said the memo, written in 1998 — before the >merger of SmithKline Beecham and Glaxo Wellcome of Britain that created the >current company — "is inconsistent with the facts and does not reflect the >company position." >Copyright 2004 The New York Times Company > > >New York Times >June 3, 2004 > >Two Studies, Two Results, and a Debate Over a Drug > >By BARRY MEIER > >The two drug trials were known within SmithKline Beecham as Study 329 and >Study 377. > >Study 329 suggested that the company's popular drug Paxil might help >depressed adolescents. Study 377, completed not long afterward, indicated that Paxil >provided no more benefit than a sugar pill in treating depressed young people. > >But only the favorable study was widely publicized by Paxil's maker. The >company chose not to discuss publicly the trial with negative results, and those >findings came to light only when an outside researcher on the study team >decided to disclose them at a medical conference. > >"That particular study would have been buried," said that researcher, Dr. >Robert Milin of the Royal Ottawa Hospital in Canada. "It would have been buried >to the public." > >Federal regulators in this country are now scrambling to reassess the >effectiveness and safety of antidepressants like Paxil, after British regulators >touched off a controversy last year by asking drug companies for unpublished data >from antidepressant trials. That data suggested that several antidepressants, >including Paxil, might give rise to suicidal thoughts in some young users - a >potential problem not revealed in any published studies. > >Yesterday, the New York State attorney general, Eliot Spitzer, entered the >fray by taking the unusual step of suing Paxil's maker, which is now >GlaxoSmithKline. Mr. Spitzer's suit accuses the company of consumer fraud for not >disclosing all of its Paxil data. > >Officials of GlaxoSmithKline defend their record, saying they provided all >the results of their Paxil clinical trials to the Food and Drug Administration, >as required by law. But the stories of Study 329 and Study 377 provide a >window into a far broader issue - the fact that the results of many human clinical >trials of drugs are often never widely publicized and that, in some cases, >doctors may never learn that the trials were even conducted. > >These days, most drug trials are sponsored by pharmaceutical companies. And >for more than a decade, a growing number of medical experts have been urging >drug makers to release more trial data and to create uniform means of disclosing >results through central registries, so that policy makers and doctors can >easily learn the results. Those advocates argue that such central databases are >necessary because drug companies, as well as medical journals and researchers, >tend to spotlight only trials that show positive results. > >Last week, GlaxoSmithKline agreed to make two executives available for this >article to discuss its handling of Studies 329 and 377 and how information >about them was disseminated. But yesterday, a company spokeswoman, Mary Anne >Rhyne, said that in light of Mr. Spitzer's lawsuit the company had decided not to >allow those interviews. > >Under F.D.A. rules, a company seeking approval of a new drug must submit the >results of all the clinical trials it runs. But the agency holds that >information in confidence - on the ground that it is proprietary - until the drug is >approved for sale. At that point, summaries and descriptions of those trials, >but not the complete underlying data, are publicly released. > >Somewhat different rules apply to so-called postmarketing tests in which >approved drugs are investigated for new purposes - like prescribing >antidepressants for pediatric use. Safety information from such trials is supposed to be >promptly reported to the F.D.A. But postmarketing data involving the drug's >effectiveness need not be reported until the maker seeks agency approval for a new >claim or use, a process that could take years. > >"We fully understand the desire for access to information and we firmly >believe that consumers should be as well informed as possible," said an F.D.A. >official, who insisted on anonymity. "However, such a listing would not add the >information F.D.A. already receives under current regulations." For their part, >drug industry officials say that it is the editors of medical journals, not >corporate executives, who decide which trial reports to publish. With a few >exceptions, drug makers have resisted the idea of establishing trial registries. >And the industry's trade group, the Pharmaceutical Research and Manufacturers >of America, has never called for such an initiative. But Dr. Alan Goldhammer, >the group's associate vice president for regulatory affairs, said the group mi >ght revisit the issue in light of the antidepressant controversy. > >Currently, a few trial registries exist, like the National Institutes of >Health's database of current trials of drugs for life-threatening diseases. And in >two weeks, policy makers at the American Medical Association are expected to >vote on a proposal that would urge the government to create a public registry >of clinical drug trials. Only a few companies have responded to the calls by >some researchers for public registries. In 1996, the British unit of Schering, >the German drug maker, agreed to create such a listing. The British company >Glaxo Wellcome decided in 1998 to take a similar step. Two years later the >company merged with SmithKline Beecham, and officials of GlaxoSmithKline said in a >brief statement yesterday that they were now working on an improved version of >the registry. > >The drive to create databases of clinical trial results soon sputtered for >lack of industry support, according to people involved in the effort. But even >industry critics acknowledge that drug makers are not the only roadblocks to >the wider dissemination of trial results. Journals also favor research reports >that show strong findings, and researchers say they have little incentive to >push for the publication of a trial without a conclusive finding. > >Those who call for trial registries, however, argue that it is unethical not >to disseminate trial results widely. The participating patients, they say, >typically believe that the findings, whatever the outcome, will benefit medicine. >"We are telling people that they are participating in research," said Dr. >Kevin A. Schulman, a professor of medicine and business administration at Duke >University. "But most of the time what they are participating in is proprietary >marketing research by companies who have total discretion over whether to >publish the results." > >It is unclear how, or even if, a database of trial results would change the >practice of medicine. Some researchers say they can often retrieve unpublished >data by asking companies for it or by ferreting out abstracts of unpublicized >findings presented at meetings. > >Still, they point out that without a comprehensive trial registry they cannot >tell what they may be missing. Just as important, some experts say, a system >of disclosing trial results would help prevent the type of chaos now >surrounding the use of pediatric antidepressants because the debate over a drug's >efficacy and safety might have already taken place. > >The fates of Study 329 and Study 377 appear to underscore that point. Both >tests were conducted during the mid-1990's at various hospitals and medical >centers - Study 329 at facilities in the United States and Study 377 at test >centers outside of this country, including Canada, Mexico, Europe, South Africa and >the United Arab Emirates. > >Study 329, with its potentially positive findings for Paxil, was completed >first. Its results were presented beginning in 1998 at several meetings of >medical professionals. Meanwhile, a report of the trial, which was led by Dr. >Martin B. Keller, a department chairman at Brown University Medical School, was >submitted to a medical journal for publication, a process that subjects a study >to peer review by scientists not involved in the trial. > >Dr. Keller declined to be interviewed for this article. But Dr. Neil Ryan, a >professor at the University of Pittsburgh, who was also involved, said he >believed that the study was rejected by some journals before The Journal of the >Academy of Child and Adolescent Psychiatry accepted it for publication in 2001. > >In the case of Study 377, the one with negative findings, there were no press >releases or publications. And without the action of Dr. Milin and a Canadian >colleague, Dr. Jovan Simeon, the study's findings might have been seen only by >regulators and a few researchers. > >Dr. Milin was an unlikely rabble-rouser. In an interview, he said he was a >strong believer in the use of antidepressants like Paxil in adolescents. He >wanted to report the study's findings, he said, mainly because its negative >results might have reflected trial design flaws that he did not want to see repeated >in other studies. "I feel you need to present all the data even if it is >negative," he said. > >While drug trials in adults take place at a few sites, Dr. Milin and other >researchers said that one problem with the pediatric antidepressant tests was >that they were dispersed across a dozen or more clinical centers because each >unit often had only a few young patients who qualified. Dr. Milin said he was >spurred to take action after SmithKline officials told him in 1998 that they did >not intend to submit the study for publication. An internal 1998 SmithKline >memorandum, disclosed this year during the antidepressant controversy, also >said the company had "no plans to publish data from Study 377." > >Dr. Milin said that when he told SmithKline executives that he planned to >present the study's finding at a 1999 meeting of the American Academy of Child >and Adolescent Psychiatry, the company did not object. Dr. Milin said he last >heard from GlaxoSmithKline officials about six months ago, after the controversy >erupted over unpublished data from trials like Study 377. Company officials, >he said, wanted to make sure that the copy of the report they had in their >file was the same one he had presented five years earlier. > >As for Study 377, Dr. Milin said he assumed that SmithKline officials would >have publicized the trial, any design problems notwithstanding, had its results >been different. > >"If they had got a positive outcome," he said, "I would suspect that they >would have pushed to get it published." > >Copyright 2004 The New York Times Company | >