From: "VERACARE" Newsgroups: misc.activism.progressive Subject: Psychiatry's Opinion Leaders Financial Ties to Industry Followup-To: alt.activism.d Organization: ? Lines: 452 Message-ID: Date: 11 Jul 2006 21:13:59 -0500 ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP) Promoting Openness, Full Disclosure, and Accountability http://www.ahrp.org FYI Two probing first rate investigative reports document how psychiatry's treatments are shaped by "opinion leaders" whose professional recommendations are compromised by their substantial, largely undisclosed, financial ties to drug companies. Whether their faculty positions are at Harvard or Stanford, one cannot discern a modicum of science to back up their treatment recommendations. 1. David Armstrong of the Wall Street Journal documents violations of medicine's foremost ethical principle, "first, do no harm," by influential academic psychiatrists who promote psychotropic drugs for pregnant women that will cause harm to their developing infants. Specifically, thirteen leading industry-financed psychiatrists from Harvard, UCLA and Emory, published a report in JAMA (2006) whose aggressive promotion in the local and national media was designed to frighten pregnant women and to dissuade them from stopping antidepressants during pregnancy. The authors emphasized a (previously unreported) risk of relapse, disregarding a body of evidence (documented since 1993) demonstrating that exposure to serotonin (SSRI antidepressants) in utero has caused birth defects, cardiac malformation, respiratory distress, and severe withdrawal syndrome in infants. The authors even disregarded manufacturers' disclosure on SSRI-SSNRI drug labels which acknowledge that the drugs pose risks of harm to neonates who "have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding." (June 2004) http://www.fda.gov/medwatch/SAFETY/2004/safety04.htm#effexor http://www.ahrp.org/infomail/04/06/29.php Indeed, documented evidence of drug-induced harm in infants is mounting-most likely reflecting the widespread misuse of these drugs by pregnant women. A study of 1,213 women by Dr. Christina Chambers, published in the NEJM (2006) warned about an alarming six-fold increase in a dangerous respiratory condition--persistent pulmonary hypertension (PPHN)--among babies born to mothers who used SSRI's late in their pregnancy. PPHN is a condition marked by severe respiratory failure, normally occurring in about one or two infants per 1,000 births. However, for babies exposed to antidepressants late in pregnancy, the rate rose to six to 12 births per 1,000. And of babies born with the condition 10% to 20% do not survive. Demonstrating their disdain for scientific evidence, Industry-paid psychiatrists at Harvard disparage Dr. Chambers' study, arguing its findings didn't "jibe" with their experience. Psychiatrists who recommend antidepressants for pregnant women may be more intent on reversing declining SSRI sales than protecting infants. SSRI sales have plummeted since 2004. The percentage change between 2004 and 2005: Zoloft ($3.1 billion) down 2%; Paroxetine (generic, $0.5 billion) down 27%; Paxil (GSK, $0.3 billion) down 61%; Prozac ($0.2 billion) down 7%. Lexapro alone showed increased sales: ($2.1 billion) up 19%. The WSJ reveals that the lead author of the JAMA report-Dr. Lee S. Cohen, a Harvard Medical School professor and director of the perinatal and reproductive psychiatry research program at Massachusetts General Hospital - "is a longtime consultant to three antidepressant makers, a paid speaker for seven of them and has his research work funded by four drug makers. None of his financial ties were reported in the study. In total, the authors failed to disclose more than 60 different financial relationships with drug companies." JAMA's failure to enforce its conflict of interest disclosure policy raises serious questions about the journal's role as a promoter of industry's marketing agenda rather than a gatekeeper protecting the integrity of scientific and ethical standards in research. Dr. Cohen and his co-authors would have us believe that they are not of the same human species as the rest of us when claiming "their financial links have no bearing on their research work or what they say about antidepressant use during pregnancy in interviews or lectures." However, "he declined to specify what he does in his consulting role for the companies or how much he is paid, other than to say "we are not talking about megabucks." Dr. Cohen said "it didn't seem relevant" for him and several of his co-authors to disclose their industry relationships in the JAMA paper in part because the study was funded by the government, not drug makers. The WSJ reveals that Harvard Medical School Symposia for doctors, billed as "CME--continuing medical education--you can trust," are rigged as they are almost exclusively comprised of psychiatrists with financial ties to drug makers who promote the expansive use of psychotropic drugs. Indeed, the Mass General psychiatry academy "itself is funded by six drug makers, including two antidepressant makers." "The work of these academic researchers highlights the role of "opinion" or "thought" leaders coveted by drug companies because of their ability to influence not only the practice of doctors, but popular opinion as well. In the case of antidepressant use during pregnancies, the industry-paid opinion leaders have become dominant authorities in the field. They help establish clinical guidelines, sit on editorial boards of medical journals, advise government agencies evaluating antidepressants and teach courses on the subject to other doctors. In some cases, the financial ties between industry and these leading researchers are not disclosed." See: http://online.wsj.com/article/SB115257995935002947.html 2. The second report in a series by Paul Jacobs of the Mercury News (California Bay area) documenting conflicts of interest at Stanford University focuses on the substantial financial interests of its chairman of psychiatry, Dr. Alan Schatzberg who "announced with considerable fanfare" that he may have found a better way to treat depression in "a repackaged version of RU-486, the controversial abortion pill," which he claimed, "may be the equivalent of shock treatments in a pill'' without the side effects." Mercury News notes, "Schatzberg has more than a purely scientific interest in this particular pill. He has a financial conflict of interest." Dr. Schatzberg "administers a $600,000-a-year federal grant, part of which pays for ongoing research at the medical school on mifepristone, the key ingredient in RU-486, in depression. He is also co-founder of Corcept Therapeutics in Menlo Park, a publicly traded company that hopes to turn mifepristone into an approved treatment for depression and other psychiatric ills. He sits on the company's board of directors, chairs its scientific advisory board and is one of its largest shareholders. And because the company has an exclusive license from Stanford for Schatzberg's discovery, the university also stands to profit from Corcept's work. "The stakes for Schatzberg, his company, the university and severely depressed patients are huge. Corcept estimates that 3 million patients could benefit from the drug. Schatzberg, whose family has paper profits of nearly $12 million from Corcept stock, could reap millions more if the company's treatment is approved." Dr. Schatzberg's extensive financial ties to pharmaceutical companies are listed at: http://www.mercurynews.com/mld/mercurynews/living/education/15004544.htm?tem plate=contentModules/printstory.jsp "Such conflicts are surprisingly common in the high-stakes world of academic medical research. But what makes Schatzberg's case unusual is that two other top research psychiatrists have publicly attacked his work and accused him of shoddy science. Schatzberg's conflict is a lesson in how hard it can be for a leading scientist at a major medical school to disentangle his outside financial interests from his academic role." An unusual development (in psychiatry) is that Dr. Schatzberg's published and public claims were challenged by two prominent psychiatrists. Mercury News outlines the details of a poster critique by Drs. Bernard J. Carroll and Robert T. Rubin who "systematically picked apart the conclusions in three published studies of RU-486 in depression, two by Schatzberg and his colleagues, one by an independent group..The poster, presented at the annual meeting of the ACNP juxtaposed positive public statements about the drug by Schatzberg and other researchers and juxtaposed those statements against the individual's financial interest in Corcept. There, for example, was Schatzberg saying RU-486 may be "the equivalent of shock treatments in a pill" and a statement pointing out that he owned 3 million shares of Corcept stock. The point was hard to miss: Researchers with a financial interest were expressing "considerable enthusiasm" for a treatment of questionable effectiveness. See: http://www.mercurynews.com/multimedia/mercurynews/archive/posteranddebate.pd f Contact: Vera Hassner Sharav 212-595-8974 verac...@ahrp.org http://online.wsj.com/article/SB115257995935002947.html THE WALL STREET JOURNAL Drug Interactions: Financial Ties to Industry Cloud Major Depression Study At Issue: Whether It's Safe For Pregnant Women To Stay on Medication JAMA Asks Authors to Explain By DAVID ARMSTRONG July 11, 2006; Page A1 EXCERPT For pregnant women considering whether to continue taking antidepressant drugs, a study in a February issue of the Journal of the American Medical Association, or JAMA, contained a sobering warning: Stopping the medication greatly increases the risk of relapsing into depression. The study authors -- most of them leading psychiatrists at Massachusetts General Hospital, the University of California Los Angeles and Emory University -- said their results challenged a common assumption that hormonal changes during pregnancy protected expectant mothers against depression. In their article, they predicted the findings would prompt some women to stay on their depression medication through pregnancy. That was good news for the makers of big-selling antidepressants, who have recently faced growing questions about the safety of their medications when used during pregnancy. But the study, and resulting television and newspaper reports of the research, failed to note that most of the 13 authors are paid as consultants or lecturers by the makers of antidepressants. The lead author --Lee S. Cohen, a Harvard Medical School professor and director of the perinatal and reproductive psychiatry research program at Massachusetts General Hospital -- is a longtime consultant to three antidepressant makers, a paid speaker for seven of them and has his research work funded by four drug makers. None of his financial ties were reported in the study. In total, the authors failed to disclose more than 60 different financial relationships with drug companies. Dr. Cohen and some of his coauthors subsequently hit the lecture circuit, telling physicians about their findings while also spotlighting flaws in other recent studies that have found increased risks to babies born to mothers who use antidepressants. The work of these academic researchers highlights the role of "opinion" or "thought" leaders coveted by drug companies because of their ability to influence not only the practice of doctors, but popular opinion as well. In the case of antidepressant use during pregnancies, the industry-paid opinion leaders have become dominant authorities in the field. They help establish clinical guidelines, sit on editorial boards of medical journals, advise government agencies evaluating antidepressants and teach courses on the subject to other doctors. In some cases, the financial ties between industry and these leading researchers are not disclosed. The researchers, including Dr. Cohen, maintain that their financial links have no bearing on their research work or what they say about antidepressant use during pregnancy in interviews or lectures. The pharmaceutical companies say the academic researchers they work with provide important expertise that benefits patients. "It is important to remember that this is a partnership with the mutual goal of advancing science and enhancing patient care," says a Pfizer spokeswoman. But such ties are prompting a growing debate in the medical community. Some physicians say they worry that it's hard to get unbiased information about treatment options for depressed pregnant women and that safety concerns about the use of antidepressants during pregnancy are being wrongly discounted. "Whether or not to keep taking an antidepressant during pregnancy is a critical question for pregnant women suffering from depression," says Adam Urato, a Bradenton, Fla., obstetrician and perinatologist who publicly questioned Dr. Cohen and colleagues about their industry relationships during a recent online training session. "What these pregnant women and the providers who care for them need is expert advice that is free from pharmaceutical industry influence or the suggestion of bias that results when these experts are being paid by so many antidepressant manufacturers." JAMA says its policies require that authors of studies disclose financial ties to the medical industry. JAMA's editor-in-chief, Catherine D. DeAngelis, says the journal wasn't aware of the relationships Dr. Cohen and some co-authors of the February article had to drug companies. "As soon as JAMA found out that they didn't disclose, we contacted the corresponding author, Dr. Cohen, and asked for his explanation," she says. "We have one and it will be published very soon in an upcoming issue of JAMA." Dr. Cohen said his industry relationships have no influence on his research work or public comments on the issue. He added that the drug companies "tend to pick people who are expert in this area." He declined to specify what he does in his consulting role for the companies or how much he is paid, other than to say "we are not talking about megabucks." Dr. Cohen said "it didn't seem relevant" for him and several of his co-authors to disclose their industry relationships in the JAMA paper in part because the study was funded by the government, not drug makers. Big Ramifications Whether or not pregnant women continue or stop the use of antidepressants has big ramifications for makers of those drugs. Women are twice as likely to suffer from depression as men and have a 25% risk of developing depression during their lifetime, according to U.S. government estimates, with that risk peaking during childbearing years. The American Medical Association estimates that over 1% of pregnant women in the U.S., or more than 40,000, are taking antidepressants. Sales of antidepressant drugs in the U.S. last year exceeded $12.5 billion, according to IMS Health, which tracks prescription drug sales. Recently, new concerns have been raised about the safety of antidepressants during pregnancy, mostly among the large class of drugs known as selective serotonin re-uptake inhibitors, or SSRI's. Eli Lilly & Co.'s Prozac, Pfizer Inc.'s Zoloft and Glaxo SmithKline PLC's Paxil are all SSRI's. Some studies have found an increased risk of a potentially fatal breathing disorder and an increased risk of seizures and fetal death among infants born to mothers using a broad spectrum of SSRI's, including these drugs. And two studies have found an increased risk in cardiac malformations in babies born to Paxil users. Drug makers say patients need to decide with their physician if taking an antidepressant during pregnancy is the right thing to do. "It is obviously a weighing of benefits and risks between the patient and their physician," says GlaxoSmithKline spokeswoman Mary Anne Rhyne. "We try to be as transparent as possible in providing information to factor into that analysis." Most antidepressants carry warning labels that explain the potential risks to the unborn baby. Xxxx cut xxxx Write to David Armstrong at david.armstr...@wsj.com1 Copyright 2006 Dow Jones & Company, Inc. All Rights Reserved http://www.mercurynews.com/mld/mercurynews/living/education/15004512.htm?tem plate=contentModules/printstory.jsp Mercury News Science critics make issue of financial ties Mon, Jul. 10, 2006 By Paul Jacobs EXCERPT For more than 20 years, Stanford University psychiatrist Alan F. Schatzberg has been hunting for a better way to treat the most severely depressed patients. A few years ago, he announced with considerable fanfare that he may have found it in an unlikely place -- a repackaged version of RU-486, the controversial abortion pill. It ``may be the equivalent of shock treatments in a pill'' without the side effects, he said in a Stanford news release. Yet Schatzberg has more than a purely scientific interest in this particular pill. He has a financial conflict of interest. The 61-year-old chairman of Stanford's psychiatry department administers a $600,000-a-year federal grant, part of which pays for ongoing research at the medical school on mifepristone, the key ingredient in RU-486, in depression. He is also co-founder of Corcept Therapeutics in Menlo Park, a publicly traded company that hopes to turn mifepristone into an approved treatment for depression and other psychiatric ills. He sits on the company's board of directors, chairs its scientific advisory board and is one of its largest shareholders. And because the company has an exclusive license from Stanford for Schatzberg's discovery, the university also stands to profit from Corcept's work. Such conflicts are surprisingly common in the high-stakes world of academic medical research. But what makes Schatzberg's case unusual is that two other top research psychiatrists have publicly attacked his work and accused him of shoddy science. Schatzberg's conflict is a lesson in how hard it can be for a leading scientist at a major medical school to disentangle his outside financial interests from his academic role. The Stanford professor says he has done everything required under the rules: He's disclosed his corporate ties to the university and the government. He has identified them in published papers and lectures. And he's kept a distance from RU-486 depression research on campus even while administering federal grants that pick up the costs. ``The reality is when people invent something at a university and they may in fact get a royalty, they've created some conflict,'' Schatzberg said. ``But conflicts only materialize with success, when there might be a benefit.'' But two independent experts on medical statistics, asked by the Mercury News to review key papers co-written by Schatzberg about the effects of RU-486 on depression, agree with his critics: The studies published to date, they say, are not properly analyzed. Schatzberg defends his studies as solid preliminary research and says the criticisms fail to grasp the importance of publishing promising early findings in drug development.``We're trying to do something to help very badly ill patients and if it's successful the field will be advanced,'' he said. ``I didn't come into this because of business. What motivates me is to help people.'' The stakes for Schatzberg, his company, the university and severely depressed patients are huge. Corcept estimates that 3 million patients could benefit from the drug. Schatzberg, whose family has paper profits of nearly $12 million from Corcept stock, could reap millions more if the company's treatment is approved. Unusual dispute As its tongue-twisting name implies, the American College of Neuropsychopharmacology is dedicated to research that probes the workings of the brain. Schatzberg is a past president. Members try not to miss its annual meeting, typically held in December in a warm climate. It was at the 2004 meeting in San Juan, Puerto Rico, that Schatzberg's critics publicly unveiled their critique of his work in the form of a poster -- really a scientific paper in outline form, pinned to a board in an exhibit hall. The contents were explosive. The poster, by Drs. Bernard J. Carroll and Robert T. Rubin, systematically picked apart the conclusions in three published studies of RU-486 in depression, two by Schatzberg and his colleagues, one by an independent group. But in a departure from the usual give and take of scientific debate, the poster quoted positive public statements about the drug by Schatzberg and other researchers and juxtaposed those statements against the individual's financial interest in Corcept. There, for example, was Schatzberg saying RU-486 may be ``the equivalent of shock treatments in a pill'' and a statement pointing out that he owned 3 million shares of Corcept stock. The point was hard to miss: Researchers with a financial interest were expressing ``considerable enthusiasm'' for a treatment of questionable effectiveness.The poster was seen by many of the top brain scientists in the country, people whose opinions matter deeply to Schatzberg as well as his critics. Carroll, former head of psychiatry at Duke University and now semi-retired in Carmel, recalls that people came up to him during the session, slapped him on the back and said, ``It's about time somebody said this.'' But he and Rubin soon learned that other members, Schatzberg among them, were furious. A lawyer for Corcept says the ACNP admonished Carroll and Rubin for their conduct. Both Carroll and Rubin say they were faulted for making their criticisms public, not for the content of the presentation. Even now, Schatzberg can hardly contain his anger. ``Those that are critical,'' he said, ``ought to be careful about impugning others.'' In his genes Medicine and psychiatry seem to be in Alan Schatzberg's genes. His father was a general practitioner in New York. His sister, brother-in-law and niece are all psychiatrists. ``When I got out of medical school in 1968,'' he said, ``biological psychiatry was just starting and I found it fascinating.'' The talk therapy pioneered by Sigmund Freud was making room for chemistry. Patients who might have spent the rest of their lives in psychiatric wards were being sent home with prescriptions, and a new generation of drugs would become billion-dollar-a-year blockbusters. After completing his training and a stint in the U.S. Air Force, Schatzberg joined Harvard's renowned McLean Hospital, famous for its treatment of celebrity poets like Robert Lowell, Anne Sexton and Sylvia Plath. By the 1980s, Schatzberg and a junior faculty member, Dr. Anthony J. Rothschild, had worked out a theory to explain the underlying cause of what they believed to be a distinct disease, ``psychotic major depression.'' These were patients who not only were profoundly depressed, but who also might believe they were being tailed by the police, that their co-workers were out to get them or that the devil was taking control of their thoughts. The standard treatment is electroshock or a combination of drugs. But electroshock requires general anesthesia, causes memory loss and is expensive. And the drugs can cause weight gain, diabetes and uncontrolled movements. Schatzberg and Rothschild came to believe that high levels of the stress hormone cortisol might explain what was happening to their gravely depressed patients. They speculated that a drug to block cortisol could be an effective treatment. Ironically, this idea was partly based on earlier work by Carroll and Rubin, now Schatzberg's outspoken critics. The main ingredient in RU-486 is mifepristone, a chemical known to block cortisol. But because of the controversy surrounding abortion, RU-486 was then impossible to obtain, said Rothschild. In 1991, Schatzberg became chairman of the psychiatry department at Stanford, where he continued his work on depression. When RU-486 became available for research a few years later under President Clinton, Schatzberg and Dr. Joseph K. Belanoff, a young psychiatrist on a fellowship in the department, began testing the pill in a handful of severely depressed patients. They were encouraged by the results of their pilot study, funded by a National Institutes of Health grant. So was the university. In 1997, Stanford applied for a patent covering mifepristone and related compounds when used to treat depression. Schatzberg and Belanoff would each be entitled to a 14 percent cut of any licensing fees and royalties paid to the university. Xxx cut xxx Enter the gadflies: Bernard Carroll recalls first reading the Biological Psychiatry study in his home-office in Carmel, where he runs his non-profit institute, the Pacific Behavioral Research Foundation. ``The `spin' was unmistakable,'' Carroll said. His reaction, he said, was ``sadness and dismay at the low standards evident in the report and in the editorial commentary.'' That commentary, written by the journal's editors, described the work as a possible ``paradigm shift in the treatment of depression.'' Later that afternoon, he got a call from his friend Robert Rubin, then a professor of psychiatry at Drexel University and Allegheny General Hospital in Pittsburgh. The two had become self-appointed guardians of scientific rigor in psychiatric research -- gadflies who periodically fire off salvos to journals to complain about papers that don't measure up to their standards. They sent such a letter to Biological Psychiatry. They criticized Schatzberg for claiming the drug ``may be the equivalent of shock treatments in a pill.'' They accused the authors of ``obfuscation'' and the editors of ignoring the study's ``fatal flaws.'' Schatzberg and Belanoff responded, saying the letter was an ``ad hominem attack,'' and that Carroll and Rubin had ``cut and pasted snips of quotes . . . and mis-characterized what we said.'' Weighing what to do with this unusually heated exchange, the journal's editors sent the correspondence to four outside, anonymous reviewers, who split, two and two, on whether the letter and response should be published. In the end, the editors decided not to print the exchange, setting the stage for Carroll and Rubin to go public in Puerto Rico.``It was the suppression of our considered critique that caused us to pay increasing attention to Corcept's claims,'' Carroll said. Xxx cut xxx Contact Paul Jacobs at pjac...@mercurynews.com or (530)756-0236. FAIR USE NOTICE: This may contain copyrighted (C ) material the use of which has not always been specifically authorized by the copyright owner. Such material is made available for educational purposes, to advance understanding of human rights, democracy, scientific, moral, ethical, and social justice issues, etc. It is believed that this constitutes a 'fair use' 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 without profit.