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8 Professors demand independent investigation of death in clinical trial Monday, 27 December 2010 Why the tragic case of Dan Markingson and the culpability of the University of Minnesota won't go away...

The disturbing circumstances surrounding the enrollment and subsequent suicide of Dan Markingson (2004) after he was given an experimental antipsychotic drug, Seroquel, as a test subject in AstraZeneca's CAFE trial--having been enrolled while he was hospitalized under an involuntary commitment order--are continuing to generate outrage and dismay.

The case against AstraZeneca's corrupt practices is well documented in courts of law and in civil and criminal settlements with the Department of Justice: 

Kickbacks to physicians, rigged clinical trials in which company officials "cherry picked" the data to be disclosed while "burying" unfavorable study findings, the company's use of "smoke and mirrors" to obscure Seroquel's failed efficacy, AstraZeneca's failure to warn that Seroquel can cause diabetes and other health problems, and its illegal off-label marketing of Seroquel.  On April 27, 2010, AstraZeneca and the U.S. Dept. of Justice reached a $520 million settlement.  

But what of the case against the University of Minnesota and the psychiatrists who conducted the trial? Their actions and the significant financial stake they had in the trial, have never undergone independent scrutiny.

 Those familiar with the documented facts in the case, are convinced that the University of Minnesota and the psychiatrists who enrolled Markingson when he was mentally unstable--and who then refused to withdraw him despite his mother's frantic pleas--are culpable for the tragic results.

 This case encapsulates the corrupt practices that ensue when academia and the pharmaceutical industry become partners in joint financial ventures.

 Adding insult to fatal injury, the University of Minnesota treated Dan Markingson's mother, Mary Weiss, with callous disregard--an attitude comparable to that displayed by the Catholic Church toward victims of sexually abusive priests.

 Over the past several years, articles in the St. Paul Pioneer Press, Minneapolis Post, City Pages, and Mother Jones magazine have suggested an alarming string of ethical violations--including gross conflicts of interest by the psychiatrists and the University;  recruitment of mentally incompetent subjects;  and the integrity of the study itself--which, if true, suggest serious problems in the way that clinical research is conducted and overseen at the university.

 Dr. Charles Schulz, chief of psychiatry, and Stephen Olson, personally earned a combined $811,045 between 2002 and 2008 from pharmaceutical companies, including $261,364 from AstraZeneca, the sponsor of the CAFE Seroquel trial in which Dan Markingson was enrolled.

 The Minneapolis Post reported: “The University of Minnesota benefited financially from the study: More than $300,000 went to the Department of Psychiatry.”

In a searing article in Mother Jones, Dr. Carl Elliott reported that the U of Minnesota Department of Psychiatry had earned $15,648 for each person it enrolled in the AstraZeneca Seroquel study. And at the time that Markingson was enrolled in the study, Dr. Elliott wrote, the University was having a serious problem recruiting subjects--it risked being dropped by AstraZeneca as one of the study's trial sites.

 In 2000, Charles Schulz, chief of psychiatry at the University of Minnesota, gave a presentation at the American Psychiatric Association meeting in which he made misleading claims about the safety and efficacy of AstraZeneca's antipsychotic, Seroquel, calling the drug "significantly superior" to Haldol. In an AstraZeneca press release, he stated,  "I hope that our findings help physicians better understand the dramatic benefits of newer medications..."

His optimistic, but unsupportable statements belied the manufacturers' own assessment of the data: "The data don't look good," an AstraZeneca official, John Tumas, warned in an e-mail on March 23, 2000. That month, an internal company analysis of the raw data concluded: "It is clear that a claim of superiority for Seroquel over Haloperidol (Haldol) could not be generated using these data."

 In a 2009 interview with Pioneer Press, Schulz admitted that his prior statements were "exaggerated" and he acknowledged that his own study did not really show that Seroquel was more effective than the older drug. "That's a bit of a misunderstanding."

 But that message, by the chief of psychiatry at the University of Minnesota, carried weight. It served as a useful marketing pitch to boost the drug's  sales, which reached $4.5 billion annually.

http://www.examiner.com/mental-health-in-minneapolis/u-of-m-psychiatrist-s-charles-schulz-misleading-claims-about-seroquel

 Dr. Jerome Kassirer, the former editor of the New England Journal of Medicine, was prompted to express his disgust (September 15, 2010):

"The conflict of interest is disgusting, and it seems quite likely that the boy's death was an indirect consequence of the financial inducements of the study. At the very least, the university should have appointed an independent review board, dismissed all the hospital charges, and paid the boy's mother damages."

In November, 2010, eight University of Minnesota faculty members of the Department of Bioethics, sent a letter to the university's Board of Regents requesting the appointment of an outside panel of experts to investigate gross ethical issues raised by the 2004 suicide of Dan Markingson. (below) 

 Those ethical violations include:

"...recruiting a mentally ill, possibly incompetent subject into a research study while he was under an involuntary commitment order; large financial conflicts of interest on the part of the university researchers conducting the study; a payment structure for the study which included financial incentives to recruit and retain subjects rather than provide them with standard therapy; an allegedly biased study design aimed at generating positive results for AstraZeneca rather than investigating a genuine scientific question; the failure of university researchers to address the legitimate concerns of Mr. Markingson’s mother, Mary Weiss, who warned that her son was suicidal and who attempted for months to have him removed from the study as his mental condition deteriorated; the apparent development of a specialized unit in Fairview Hospital designed to identify severely mentally ill subjects for recruitment into research studies; and finally, a failure of the institutional oversight system for protecting human subjects of research.”

This case sheds light on how the commercialization of medicine devalues both the integrity of medical research and patients' rights reducing both to a means in the service of a financial end.

Additional background: University of Minnesota corrupt research legacy

In 1994, ten years before the tragic death of Dan Markingson, Dr. Bary Garfunkel, the Director of the University of Minnesota, Department of Child and Adolsescent Psychiatry, was sentenced to prison for falsifying documents related to clinical trials of Anafranil.

In 1995, Dr. John Najarian was indicted by a federal grand jury for theft and tax evasion related to the illegal sale of ALG, an experimental drug whose sales amounted to $80 million most of which went to the University of Minnesota. This resulted in NIH placing severe restrictions on the University's freedom to use research funds.

 

 Vera Hassner Sharav

 

http://www.medcitynews.com/2010/12/university-of-minnesota-profs-demand-investigation-of-drug-trial/

U. of Minnesota profs demand investigation of drug trial death

A group of University of Minnesota professors want the board of regents to investigate the suicide of a patient enrolled in a university-run drug study.

Led by Dr. Carl Elliott, the professors demand the regents appoint an independent outside panel of experts to examine the death of Dan Markingson, a mentally ill patient who killed himself after taking an experimental psychiatric drug developed by AstraZeneca. The professors accuse the school of several ethics violations, including financial conflict of interest and enrolling Markingson even though he may have been too sick to consent.

“Patients participating in research studies at the University of Minnesota need to be confident that the university is doing everything it can to protect them from harm,” stated a Nov. 29 letter to the regents board. “While it is understandable that some of our colleagues will have little interest in revisiting the case and the ethical questions it raises, we are persuaded that there is a disturbing and unjustifiable gap between how the University responded to this death and the careful, critical investigation it warrants.”

Markingson committed suicide in May 2004 after taking Seroquel, a psychiatric drug developed by AstraZeneca. Mary Weiss, Markingson’s mother, accused the university of of forcibly enrolling her son in the clinical trial even though Markingson was under an involuntary commitment order and may have been mentally incompetent to consent to the treatment.

A series of stories in the St. Paul Pioneer Press and Mother Jones magazine, the latter written by Elliott, suggested an improper financial relationship between university researchers and AstraZeneca, including incentive payments to recruit and retain patients for the study instead of providing standard therapy.

University officials deny the accusations, noting the Food and Drug Administration, Minnesota Attorney General’s Office and Board of Medical Practice all cleared the school.

“None found fault with the University, none found fault with the involved faculty, and none found any causal link between the … trial and the unfortunate death of Dan Markingson,” the university’s general counsel, Mark Rotenberg, wrote in response to the Mother Jones story.

In addition, a federal judge dismissed a lawsuit brought by Weiss.

“Faculty in our department of psychiatry have made great progress in pursuit of effective treatments for mental health disease,” Rotenberg wrote. “The department’s work — much through clinical trial efforts — has made a significant impact through its community clinical outreach and treatment programs. However, these conditions remain today among the most difficult to manage and treat. It is that challenge which our psychiatry faculty is seeking to address with its clinical research.”

In a separate interview, Elliott, who recently wrote a book critical of the drug industry, said the FDA investigation did not address key information.

“There is lots that the FDA report missed, and the FDA refuses to answer questions,” Elliott wrote in an e-mail. “The FDA did not mention the conflicts of interest, the financial incentives to enroll subjects and keep them in the study, the failure to exclude subjects at risk of homicide, the fact that Mary Weiss had tried for months to get her son out of the study, or the fact that Dan Markingson had been threatening murder when he was recruited into the study.”

“Bizarrely, it also concluded that ‘there is nothing different about this subject than others enrolled to suggest that he could not provide voluntary, informed consent,’ ” Elliott wrote. “This, despite the fact that only a few days earlier, the investigators had judged him incapable of consenting to antipsychotic drugs.”

Elliott also said new evidence suggests the company rigged the trial to show positive results.

Last year, the Star Tribune in Minneapolis reported that court documents showed AstraZeneca claimed its drug was superior to standard treatments for schizophrenia, even though the drug maker knew research did not back the claim.

Dr. Charles Schultz, chief of psychiatry at the university, presented research backing AstraZeneca’s claims to a medical conference. Schultz claims the company never shared its concerns with him.

http://motherjones.com/environment/2010/09/dan-markingson-drug-trial-astrazeneca

The Deadly Corruption of Clinical Trials

When you risk life and limb to help test a drug, are you helping science—or Big Pharma?

By Carl Elliott | September/October 2010 Issue

IT'S NOT EASY TO WORK UP a good feeling about the institution that destroyed your life, which may be why Mary Weiss initially seemed a little reluctant to meet me. "You can understand my hesitation to look other than with suspicion at anyone associated with the University of Minnesota," Mary wrote to me in an email. In 2003, Mary's 26-year-old son, Dan, was enrolled against her wishes in a psychiatric drug study at the University of Minnesota [1], where I teach medical ethics [2]. Less than six months later, Dan was dead. I'd learned about his death from a deeply unsettling newspaper series [3] by St. Paul Pioneer Press [4] reporters Jeremy Olson and Paul Tosto that suggested he was coerced into a pharmaceutical-industry study from which the university stood to profit, but which provided him with inadequate care. Over the next few months, I talked to several university colleagues and administrators, trying to learn what had happened. Many of them dismissed the story as slanted and incomplete. Yet the more I examined the medical and court records, the more I became convinced that the problem was worse than the Pioneer Press had reported. The danger lies not just in the particular circumstances that led to Dan's death, but in a system of clinical research that has been thoroughly co-opted by market forces, so that many studies have become little more than covert instruments for promoting drugs. The study in which Dan died starkly illustrates the hazards of market-driven research and the inadequacy of our current oversight system to detect them.

Mary Weiss is a slight, white-haired woman in her late sixties who smiles ruefully at any question, no matter how painful. She is the sort of Minnesota liberal who volunteers for political campaigns and signs her email with flowers. When we first met at a coffee shop in St. Paul, she was wearing an Obama pin on her sweater. Mary raised Dan alone, working a job at the postal service. Old photographs show Dan growing into his good looks; according to Mary, he was also a gifted student. In high school, Dan got a perfect score on the verbal portion of his SAT. He graduated from the University of Michigan in 2000 with an English degree, and that fall he moved to Los Angeles, hoping to become a screenwriter or an actor. To support himself, he got a job as a celebrity-tour bus driver.

When Mary went out to Los Angeles for a visit in the summer of 2003, it was clear Dan had changed. He'd adopted a new last name, Markingson. His behavior was bizarre. "He said, 'You haven't told me when the event is going to be,'" Mary said. She had no idea what he was talking about. The next day, he took her to his apartment. He'd encircled his bed with wooden posts, salt, candles, and money, which he said would protect him from evil spirits. He showed her a spot on the carpet that he said the aliens had burned.

I asked Mary how she'd reacted to all of this. "I panicked. I called 911," she replied. But when the police arrived, Dan was able to convince them she had overreacted. "He said, 'Oh, my mother just drove from Minnesota and she's very tired,'" she recalled. Worried that Dan was seriously ill, she tried to convince him to return to St. Paul. He visited her in August, returned briefly to California, and then came back to St. Paul in October.

Dan grew convinced that the Illuminati were orchestrating an event in Minnesota—a "storm" in which he would be called upon to murder his mother.

Dan grew convinced that the Illuminati were orchestrating an event in Duluth, Minnesota—a "storm" in which he would be called upon to murder people, including Mary. Some of his emails from late September 2003 suggest the extent of his delusions:

"I'm aware that people can cast spells that can hurt you at a distance. I'm aware that some people can read minds. I'm aware that some people might actually be 'hybrids' and not altogether human."

In another email, Dan wrote:

"I'm especially eager to attend this storm and SLAY those who deserve slaying. I will choose victims immediately... I HAVE NO EMOTIONAL ATTACHMENTS. I KILL FOR FUN!!"

On November 12, Dan said he would kill Mary if called upon to do so. She called the police. Dan was taken to Regions Hospital [5] in St. Paul. But the hospital had no psychiatric beds available, so after a few hours Dan was transferred to Fairview University Medical Center [6], a teaching hospital for the University of Minnesota Academic Health Center. He was treated by Dr. Stephen C. Olson [7], an associate professor in the university's psychiatry department, who prescribed Dan Risperdal [8] (risperidone), an antipsychotic drug often prescribed for patients with schizophrenia or bipolar disorder. (In Minnesota, doctors are allowed [9] to give antipsychotic drugs to mentally incompetent patients without their consent for up to 14 days, but only to prevent serious, immediate physical harm to the patient or others.) Olson believed Dan was psychotic and dangerous, and lacked the ability to make decisions regarding his treatment; on November 14 he signed a document that recommended Dan be committed involuntarily to a state mental institution, noting that he "lacks the capacity to make decisions regarding such treatment." Three days later, a clinical psychologist also recommended involuntary commitment, reiterating that Dan had threatened to slit his mother's throat.

In Minnesota, patients who have been involuntarily committed are given another option: a "stay of commitment." Patients can avoid being confined to a mental institution as long as they agree to comply with the treatment program laid out by their psychiatrist. On November 20, Olson asked for a stay of commitment. The court granted the stay for six months, stipulating that Dan had to follow the recommendations of his treatment team. Olson, however, did not simply recommend standard medical treatment. Instead, he proposed that Dan take part in an industry-funded study of antipsychotic drugs. The university's study coordinator, Jean Kenney, had Dan sign a consent form when Mary wasn't present, and on November 21, he was enrolled in the study.

On the surface, the study appeared benign. Its purpose was to compare the effectiveness of three "atypical" antipsychotic drugs, each of which had already been approved by the FDA: Seroquel (quetiapine), Zyprexa (olanzapine), and Risperdal (risperidone.) The study was designed and funded [10] by AstraZeneca, the manufacturer of Seroquel, and it called for 400 subjects experiencing their first psychotic episode to take one of the three drugs for a year. AstraZeneca called it the "CAFE" study [11], which stood for "Comparison of Atypicals in First Episode." The management of the CAFE study had been outsourced to Quintiles, a contract research organization, which was conducting it at 26 different sites, including the University of Minnesota. (For more on CROS, see "Trial by Hire [12].")

Yet the CAFE study was not without risks. It barred subjects from being taken off their assigned drug; it didn't allow them to be switched to another drug if their assigned drug was not working; and it restricted the number of additional drugs subjects could be given to manage side effects and symptoms such as depression, anxiety, or agitation. Like many clinical trials, the study was also randomized and double-blinded: Subjects were assigned a drug randomly by a computer, and neither the subjects nor the researchers knew which drug it was. These restrictions meant that subjects in the CAFE study had fewer therapeutic options than they would have had outside the study.

In fact, the CAFE study also contained a serious oversight that, if corrected, would have prevented patients like Dan from being enrolled. Like other patients with schizophrenia, patients experiencing their first psychotic episode are at higher risk of killing themselves or other people [13]. For this reason, most studies of antipsychotic drugs specifically bar researchers from recruiting patients at risk of violence or suicide, for fear that they might kill themselves or someone else during the study. Conveniently, however, the CAFE study only prohibited patients at risk of suicide, not homicide. This meant that Dan—who had threatened to slit his mother's throat, but had not threatened to harm himself—was a legitimate target for recruitment.

When Mary found out that Dan had been recruited into the CAFE study, she was stunned. "I do not want him in a clinical study," she told Olson. Just a few days earlier, Olson indicated in a petition to the court that Dan was both dangerous and mentally incapable of consenting to antipsychotic medication. How could he now be capable of consenting to a research study with the very same antipsychotics—especially when the alternative was commitment to a state mental institution?

After Dan was enrolled, he stayed at Fairview for about two more weeks. By that point, Olson thought Dan's symptoms were under control, but Mary was still very worried by his erratic behavior. She recalls meeting with the doctor: "Olson came in and sat down and opened his file and said, 'Oh, Dan is doing so well.' And I said, 'No, Dr. Olson, Dan is not doing well.' I think he was taken aback." Even so, on December 8, 2003, Dan was transferred to Theo House, a halfway house in St. Paul. He was required to sign an agreement confirming that he understood he could be involuntarily committed if he didn't continue taking his medication and keeping his CAFE study appointments.

At the halfway house, Dan often stayed in his room for days. On March 26, 2004 nearly four months after his discharge from Fairview, his thoughts were still "delusional and grandiose," according to a social worker's note. An occupational-therapy report from April 30 detailed Dan's condition: "Personal appearance disheveled. Isolated and withdrawn. Poor insight and self-awareness." Entries in a personal journal that Dan kept during this period don't show any obvious changes, suggesting that he was improving little, if at all. Mary felt he was becoming angrier. "He was so tense, with this ready-to-explode quality."

When the blind on the study was broken, researchers found that Dan was being treated with Seroquel, the drug manufactured by the study sponsor, AstraZeneca.

Olson saw things differently. "I disagree that he had significant deterioration," he testified in a 2007 deposition. However, it's unclear whether Olson actually saw Dan enough to make an informed judgment about his condition. Records suggest most of Dan's care was managed by social workers. In his deposition, Olson said he saw Dan approximately six times from the date he was admitted in November until he committed suicide in May. Whatever the doctor thought, his actions don't suggest that he felt Dan was improving. In late April 2004, as Dan's stay of commitment was about to expire, Olson recommended extending it for another six months—the duration of the CAFE study. He noted that Dan still had "little insight into his mental disorder" and might "place himself at risk of harm if he were to terminate his treatment."

Mary tried to get Dan out of the study or have his treatment changed. She called Olson and tried to see him. She wrote long, detailed letters expressing concerns about everything from Dan's diet and sleep habits to his medications. In total, she sent five letters to Olson and Dr. Charles Schulz—the chairman of the university's psychiatry department and a co-investigator on the CAFE study—communicating her alarm about Dan's condition, especially his inner rage. She received only one reply, dated April 28, from Schulz, who wrote that "it was not clear to me how you thought the treatment team should deal with this issue." Around that time, Mary left a voice message with Jean Kenney, the study coordinator, asking, "Do we have to wait until he kills himself or someone else before anyone does anything?"

Before dawn on the morning of May 8, a police officer and a Catholic priest knocked on Mary's door. Mike Howard, a family friend who lives at her house, answered. Later, in a deposition, Howard described what happened next: "Mary jumped out of her bed and went into the kitchen and stood there, and the priest extended his hand out and said, 'Mary, I'm here to tell you that Dan passed away.' And Mary just literally fell down to her knees and started to shriek and cry, and just started begging, 'Please, no, no, don't let this happen.'"

Dan had stabbed himself to death in the bathtub with a box cutter, ripping open his abdomen and nearly decapitating himself. His body was discovered in the early hours of the morning by a halfway-house worker, along with a note on the nightstand that said, "I left this experience smiling!" Later, when the blind on the study was broken, researchers found that Dan was being treated with Seroquel, the drug manufactured by the study sponsor, AstraZeneca.

 

For most of the past half-century, physicians have considered antipsychotic drugs to be among the most unpleasant chemicals in the medicine closet. Thorazine (chlorpromazine), the first antipsychotic, was developed in 1950, and while it could relieve some of the worst symptoms of schizophrenia, that relief came at a serious cost. Not only do antipsychotics often make patients feel sedated and sluggish (they used to be called "major tranquilizers [14]"), they can also cause irreversible "extrapyramidal [15]" symptoms, such as the shuffling gait, rigid muscles, and involuntary lip-smacking sometimes seen in patients who have been taking the drugs for years. The antipsychotics can also cause akathisia, a type of driven, agitated restlessness that ranges from unpleasant to excruciating. Until recently, psychiatrists reserved the drugs for patients with very severe mental illnesses.

By 2008, antipsychotics were the most lucrative class of drugs in America. Seroquel alone had nearly $4 billion in sales.

Over the past decade or so, however, antipsychotics have undergone an extraordinary rehabilitation. By 2008, they were the most lucrative class of drugs in America. Seroquel alone had nearly $4 billion in sales, making it the country's fifth most profitable drug. The transformation began in the mid-'90s, when pharmaceutical companies began pitching atypical antipsychotics such as Risperdal, Zyprexa, and Seroquel as more effective than older antipsychotics, but relatively free of their ugly side effects. The drugs were also very expensive—one study pegged the cost at 70 to 100 times that of an older drug—but if they didn't produce extrapyramidal symptoms, their enormous expense seemed justifiable. By the mid-2000s, atypicals were being prescribed [16] not just for schizophrenia but also for anxiety, agitation, insomnia, attention deficit hyperactivity disorder, and depression. The most remarkable upswing [17] came for patients diagnosed with bipolar disorder, which used to be seen as a rare illness. Once bipolar disorder could be treated with atypicals, rates of diagnoses rose dramatically, especially in children. According to a recent Columbia University study [18], the number of children and adolescents treated for bipolar disorder rose 40-fold between 1994 and 2003. Another study [19] found that nearly one in five children who visited a psychiatrist came away with a prescription for an antipsychotic drug, despite early reports of alarming side effects.

Recent years have seen a backlash. The most damaging blow to the atypicals was an authoritative 2005 study funded by the National Institute of Mental Health—the so-called CATIE study—which found that the atypical antipsychotics worked no better than a much older antipsychotic called Trilafon (perphenazine), which was developed in the 1950s. The CATIE study also found that, contrary to the way the drugs had been marketed, side-effect profiles of the atypicals were generally no better than the older drug. Other research showed that atypicals were associated with significant weight gain, increased risk of diabetes, and greater possibility of death in patients with dementia. After another large analysis in The Lancet found that most atypicals actually performed worse than older drugs, two senior British psychiatrists penned a damning editorial that ran in the same issue. Dr. Peter Tyrer [20], the editor of the British Journal of Psychiatry, and Dr. Tim Kendall of the Royal College of Psychiatrists wrote: "The spurious invention of the atypicals can now be regarded as invention only, cleverly manipulated by the drug industry for marketing purposes and only now being exposed."

The cleverest manipulation has been with the clinical trials themselves. For years, critics have charged that pharmaceutical companies massage trials to make their own drugs look better than they really are. One common tactic is to suppress unfavorable data. A notorious example [21] came in the 1990s, when a Wyeth safety officer overwrote the company's computer files, erasing evidence indicating that its diet drug, fen-phen, caused valvular heart disease. A less risky strategy is simply not to publish potentially damaging trials. In 2004, the Canadian Medical Association Journal described a leaked document indicating that GlaxoSmithKline had deliberately hidden two studies from regulators showing that its antidepressant, Paxil (paroxetine), could increase the risk of suicide in children. The company has paid [22] nearly a billion dollars in legal settlements over Paxil, including $390 million for suicides and attempted suicides related to the drug. Evidence of manipulation has also emerged in many of the high-profile pharmaceutical scandals of the past decade, from Merck's pain drug Vioxx [23] to the recent Senate investigation [24] into GlaxoSmithKline's diabetes drug Avandia.

"Thus far, we have buried trials 15, 31, 56. The larger issue is how do we face the outside world when they begin to criticize us for suppressing data."

Something similar has happened with the atypicals. A 2006 study in The American Journal of Psychiatry, which looked at 32 head-to-head trials of atypicals, found that 90 percent of them came out positively for whichever company had designed and financed the trial. This startling result was not a matter of selective publication. The companies had simply designed the studies in a way that virtually ensured their own drugs would come out ahead—for instance, by dosing the competing drugs too low to be effective, or so high that they would produce damaging side effects. Much of this manipulation came from biased statistical analyses and rigged trial designs of such complexity that outside reviewers were unable to spot them. As Dr. Richard Smith, the former editor of the British Medical Journal, has pointed out, "The companies seem to get the results they want not by fiddling the results, which would be far too crude and possibly detectable by peer review, but rather by asking the 'right' questions."

Initially, the controversy over atypical antipsychotics was focused largely on Eli Lilly [25] (PDF), the manufacturer of Zyprexa. In early 2009, it settled [26] litigation for a record-breaking $1.4 billion for illegal marketing and allegedly hiding the risks of the drug. More recently, however, the scandal [27] has spread to Seroquel. In April 2010, AstraZeneca agreed to pay $520 million to settle two federal investigations [28] and two whistleblower lawsuits alleging that it had marketed Seroquel illegally and concealed its health risks. The company faces more than 25,000 civil suits.

Documents unsealed in related civil suits suggest an alarming pattern of deception. Sales reps were instructed to tell doctors that Seroquel doesn't cause diabetes, even though the company knew about the link to diabetes [29] as early as 1997. Internal correspondence reveals company officials discussing how to hide or spin potentially damaging studies. "Thus far, we have buried trials 15, 31, 56," wrote a publications manager in 1999. "The larger issue is how do we face the outside world when they begin to criticize us for suppressing data."

One of those potentially damaging studies led back to the University of Minnesota. In the late 1990s, a clinical trial known as Study 15 unexpectedly failed to show that Seroquel was any better than Haldol [30], a generic antipsychotic that's been on the market since the 1960s. In fact, on the main measures, Seroquel performed worse than Haldol. The study also showed that Seroquel increased the risk of weight gain and diabetes. Internal correspondence repeatedly refers to Study 15 as a "failed study," and company officials discuss possible ways to spin or bury it. "I am not 100% comfortable with this data being made publicly available at the present time," wrote Richard Lawrence, a senior AstraZeneca official, in 1997. "However I understand that we have little choice...Lisa [Arvanitis, a company physician] has done a great 'smoke-and-mirrors' job." Lawrence referred approvingly to a strategy that he said would "put a positive spin (in terms of safety) on this cursed study." Later, apparently hoping to find a way to present Seroquel in a better light, the "commercial support team" performed an analysis of a number of other studies, but even that did not show Seroquel to be better than Haldol. Yet when a summary of the AstraZeneca data was presented at the American Psychiatric Association annual conference in 2000, the author claimed Seroquel was "significantly superior" to Haldol. That author was Dr. Charles Schulz, the University of Minnesota psychiatry department chair—and a well-compensated [31] consultant for AstraZeneca. In a press release claiming Seroquel's superiority over Haldol, Schulz praised it enthusiastically as a "first-choice antipsychotic."

Although the documents unsealed in the Seroquel litigation do not specifically mention the CAFE study in which Dan was enrolled, they do suggest that AstraZeneca planned to establish Seroquel as the "atypical of choice in first-episode schizophrenia," according to a 2000 "Seroquel Strategy Summary." A later document titled "Seroquel PR Plan 2001" discusses the agenda for an advisory panel meeting in Hawaii. Among the potential topics were the marketing of Seroquel to first-episode patients, adolescents, and the elderly. The document refers to these populations as "vulnerable patient groups."

"R&D is no longer responsible for Seroquel research—it is now the responsibility of Sales and Marketing." 

Even more alarming are internal documents suggesting that AstraZeneca was designing clinical trials as a covert method of marketing Seroquel. In 1997, when Dr. Andrew Goudie [32], a psychopharmacologist at the University of Liverpool, asked AstraZeneca to fund a research study he was planning, a company official replied that "R&D is no longer responsible for Seroquel research—it is now the responsibility of Sales and Marketing." The official also noted that funding decisions would depend on whether the study was likely to show a "competitive advantage for Seroquel."

Another set of documents from 2003 describes a glucose metabolism study apparently designed to fend off the charge that Seroquel causes patients to gain weight and become diabetic. One slide describes two purposes for the study: a "regulatory" purpose and a "commercial" purpose. The regulatory purpose was to "produce data that will help us defend the Seroquel label." The commercial purpose was to "produce data that will enable us to generate commercially attractive and competitive messages in relation to diabetes and weight." The document suggests several possible names for the study, including "Flexible Dose Approach Trial for Atypical Responses to Metabolism," which could be usefully shortened to the acronym FATFARM. (When I contacted AstraZeneca, a spokesperson would say only that Seroquel has been found "safe and effective" by the FDA and that it stands behind the CAFE study and the rest of its clinical research.)

Many clinical studies place human subjects at risk—at a minimum, the risk of mild discomfort, and at worst, the risk of serious pain and death. Bioethicists and regulators spend a lot of time and energy debating the degree of risk that ought to be permitted in a study, how those risks should be presented to subjects, and the way those risks should be balanced against the potential benefits a subject might receive. What is simply assumed, without much consideration at all, is that the research is being conducted to produce scientific knowledge. This assumption is codified in a number of foundational ethics documents, such as the Nuremberg Code [33], which was instituted following Nazi experiments on concentration camp victims. The Nuremberg Code stipulates that an "experiment should be such as to yield fruitful results for the good of society," and "the degree of risk to be taken should never exceed that determined by the humanitarian importance of the problem to be solved by the experiment."

But what if a research study is not really aimed at producing genuine scientific knowledge at all? The documents emerging in litigation suggest that pharmaceutical companies are designing, analyzing, and publishing trials primarily as a way of positioning their drugs in the marketplace. This raises a question unconsidered in any current code of research ethics. How much risk to human subjects is justified in a study whose principal aim is to "generate commercially attractive messages"?

 

In January 2005, the FDA began investigating the circumstances of Dan's suicide. In a report issued that July, before the larger pattern of Seroquel research had begun to emerge, Sharon L. Matson, the FDA investigator, exonerated the university. She wrote, "I did not find any evidence of misconduct, significant violation of the protocol, or regulations governing clinical investigators or IRBs"— the university institutional review board charged with reviewing studies to ensure that they measure up to recognized ethical standards. Matson specifically dismissed the suggestion that Dan was mentally incompetent to consent to the study, writing that "there was nothing different about this subject than others enrolled to indicate that he couldn't provide voluntary, informed consent." (The FDA refused my request to speak with Matson and would not answer questions about the case, citing privacy concerns.) Mary Weiss eventually sued the University of Minnesota, AstraZeneca, Olson, and Schulz, but her case did not even get to trial. District Court Judge John L. Holahan dismissed the suit in 2008 with a partial summary judgment. He ruled that in approving the CAFE study, the university IRB was performing the type of "discretionary function" that is protected from liability under the state's Tort Claims Act. The malpractice suit against Schulz was also dismissed, and the suit against Olson was eventually settled—for $75,000, which Mary says wasn't enough to cover the fees of the expert witnesses her attorneys hired. (Both Schulz and Olson declined to speak about the specifics of the clinical trial or the resulting suit. University spokesman Nick Hanson would say only, "To date, there has been no finding of wrongdoing from any of the investigations or reviews done by the university on this issue.")

The judge also dismissed the case against AstraZeneca. He blasted Mary's lawyers, saying that they had failed to establish that AstraZeneca had a duty to put the interests of research subjects over the interests of the company and the researchers. But he also lamented the lack of case law about clinical trials, saying on this particular point, "Try as it may, this Court's independent research has unearthed not a single case or statute to evidence or support such an alleged duty."

The judge further ruled that Mary's lawyers hadn't shown a causal link between Seroquel and Dan's suicide: An initial drug screening during autopsy had not found any Seroquel in his bloodstream, which suggested that Dan may not have been taking his medication. After the judgment, however, Mary discovered that Seroquel would not be detected in an ordinary drug screening; a special test is required. In the spring of 2008, she called the coroner's office in hopes of getting a special screening for Seroquel. To her surprise, she found that her lawyers and the defendants had already obtained one. The report was dated several days after the summary judgment was issued. It showed 73 nanograms per milliliter of Seroquel in his blood, suggesting that Dan was almost certainly taking the drug, although he may have missed the last scheduled dose before he died.

Although Mary's lawsuit was unsuccessful, it revealed some disturbing financial arrangements at the university. As a patient on public assistance, Dan's treatment would have normally generated little income for the university. Under its arrangement with AstraZeneca, however, the psychiatry department earned $15,648 for each subject who completed the CAFE study. In total, the study generated $327,000 for the department. In fact, during the months before Dan was enrolled, the department was apparently feeling pressure from Quintiles, the CRO that managed the study, to step up recruitment. According to emails written by Jean Kenney, the university's study coordinator, the site had been placed on probation for its recruitment problems, and they were still "struggling to get patients." In November 2002, Olson had managed to recruit only one subject in six months. That began to change in April 2003, when the psychiatry department established a specialized inpatient unit at Fairview hospital called Station 12, in which every patient could be evaluated for research. By December, Olson had recruited 12 more subjects, including Dan, and Olson had been featured in a CAFE study webcast for "turning an underperforming site into a well-performing site."(Quintiles refused to give comment on the case.)

Olson had another financial reason to maintain good relations with AstraZeneca. According to a disclosure statement for a 2006 conference, he was a member of the AstraZeneca "speaker's bureau," giving paid talks for the company. He had similar arrangements with Eli Lilly and Janssen, the makers of the other atypicals being tested in the CAFE study, as well as Bristol-Myers Squibb and Pfizer. In addition, Olson was working as a paid consultant for Lilly, Janssen, Bristol-Myers Squibb, and Pfizer. Although Olson is not required to disclose how much industry money he received, a public database maintained by the Minnesota pharmacy board indicates that Olson received a total of $240,045 from the pharmaceutical industry between 2002 and 2008, with $149,344 coming from AstraZeneca. Dr. Charles Schulz, his co-investigator and department chair, received an even greater sum: more than $571,000 from the industry, with $112,020 coming from AstraZeneca. The database does not reliably distinguish between payment by drug companies for consulting and speaking, which usually goes directly into a physician's pocket, and research grants, which go to the university and are used to help underwrite the salaries of the grant recipients. (Many academic physicians are required by their universities to generate a substantial portion of their salaries by obtaining research grants.)

In the US, the primary bodies charged with protecting research subjects are known as institutional review boards. (Read how IRBs are becoming privatized, next page.) According to the University of Minnesota, the purpose of its IRB is to "protect the rights and welfare of human research subjects." However, when the university's IRB officials were deposed under oath, they refused to admit that protecting subjects was their responsibility. "So it's not the institutional review board's purpose to protect clinical trial subjects, is that what you're saying?" asked Gale Pearson, one of the attorneys representing Mary Weiss. "That's true," replied Moira Keane, the director of the IRB. Astonished, Pearson kept returning to the question, to make sure that she understood it correctly. Keane refused to budge. Instead, she claimed that the role of the IRB was to make sure that Olson and the trial sponsor had a plan to protect subjects. (If this were true, it would render IRBs worthless: The sponsor and investigator are the ones that the IRB is supposed to protect subjects from.)

The University of Minnesota doesn't exactly have a stellar record of investigating internal misconduct. In 1994, the director of child and adolescent psychiatry, Dr. Barry Garfinkel, was sentenced to federal prison for five felonies related to research fraud involving the Ciba-Geigy drug Anafranil (clomipramine). The research assistant who blew the whistle in 1989 lost her job, and under the terms of a secret agreement struck with Garfinkel, the university kept the fraud secret for four years, until he was finally indicted. In 1995, the university was sanctioned by the National Institutes of Health after revelations that the head of transplant surgery, Dr. John Najarian, had generated millions of dollars for the university by illegally manufacturing and selling an immunosuppressant drug without FDA approval; an investigation by the Minneapolis Star Tribune revealed that the university had known of the illegal activity for years. Still more scandals have recently emerged, including a Senate investigation of the chairman of spinal surgery, Dr. David Polly, for failing to disclose $1.2 million he had been paid to consult for the device manufacturer Medtronic, and a series of investigative reports [34] in the New York Times about the industry ties of Minnesota physicians, including some connected to the university. When the scandals began to escalate several years ago, Dr. Deborah Powell, then the dean of the university's medical school, appointed a task force to devise a new conflict-of-interest policy. The policy was discarded after the Star Tribune revealed that the co-chair of the task force, Dr. Leo Furcht, had funneled $500,000 of university grant money into his own private company, which he later sold for $9.5 million. Furcht remains chairman of the laboratory medicine and pathology department at the university.

 

In 2007, the American Journal of Psychiatry published the results of the CAFE study. Among the 18 "serious adverse events" recorded for the 400 subjects in the study were an alleged homicide and five suicide attempts, including two successful suicides, both by patients taking Seroquel. (One of these patients, of course, was Dan Markingson.) According to the study authors—three AstraZeneca employees and seven academic physicians, many of whom also consulted for the company—the suicides occurred "despite the close attention provided in clinical research aftercare programs." The authors claimed that the CAFE study showed Seroquel to be of "comparable effectiveness" to Zyprexa and Risperdal for first-episode patients.

According to some experts, the study could hardly have shown otherwise, because it was designed to produce a good result for Seroquel. When I showed the published study to Dr. Peter Tyrer, the editor of the British Journal of Psychiatry, he said, "I would have major problems accepting a manuscript of that nature." According to Tyrer, the main problem is the small sample size. Of the 400 subjects enrolled, all but 119 stopped taking the drug before the yearlong study was finished. With so few subjects, the CAFE study was statistically underpowered and thus unlikely to detect any difference in effectiveness between the three drugs. The failure to detect a difference allowed AstraZeneca to claim that Seroquel was as good as the other drugs (or in the language of the study, "non-inferiority"). Tyrer told me, "In scientific terms this study is of very little value."

That's not the only problem. The CAFE study was supposedly designed to test the effectiveness of the three antipsychotics, but the way it did this was by measuring the rate of "all-cause treatment discontinuation," or the percentage of subjects who stopped taking their drug. That is, the CAFE study counted an antipsychotic as "effective" if a subject kept taking it until the end of the study. On the face of it, this type of measurement seems highly misleading; simply because a patient continues to take an antipsychotic does not mean that it is working. Many psychiatrists defend treatment discontinuation as a "pragmatic" way of measuring a drug's overall acceptability, but even by "pragmatic" standards the CAFE study presents a problem. More than 70 percent of subjects in the CAFE study stopped taking their assigned drug, and the most common reason was simply coded as "patient decision." According to Dr. John Davis, the Gillman Professor of psychiatry at the University of Illinois-Chicago, the authors of the CAFE study obscured their results by failing to say why patients decided to stop taking the drug—whether patients felt the side effects of the drug were too severe, for example, or if they felt the drug was not working. "It is the hiding of the critical outcomes that gives me pause," he says. "It does not make scientific sense to do a study and not measure one of the most important outcomes."

Yet another problem with the CAFE study is its failure to compare Seroquel to any older antipsychotics. "It's quite a marketing exercise to put all patients in the CAFE study on atypical antipsychotics," says Dr. Glen Spielmans, an associate professor of psychology at Minnesota's Metropolitan State University. "It removes the older drugs from the discussion." One reason AstraZeneca may have done this, he suggests, is that Study 15 had already shown Seroquel to be inferior to the older antipsychotic, Haldol.

The bluntest assessment of the study came from Dr. David Healy, a senior psychiatrist at Cardiff University in Wales. Healy is a former consultant to AstraZeneca, among other pharmaceutical companies, and a prominent critic of the industry. "This is a non-study of the worst kind," he said. "It is designed not to pick up a difference between the three drugs. It looks like an entirely marketing-driven exercise."

If these experts are right, then the study in which Dan Markingson committed suicide was not simply a matter of inadequate informed consent, or financial conflicts of interest, or even failure to monitor a subject's care. The ethical breach was built into the study from the start. It is one thing to ask people to take risks for science, or the common good, or to help other people. It is another thing entirely to ask them to risk their lives for the marketing goals of AstraZeneca.

 

Mary Weiss is a quiet woman, but her experience has left her angry and bitter. It's not hard to see why. In the years since she lost her son, she has written letters and filed complaints to one oversight body after the other, and so far she's gotten little but form letters, rejections, and dismissals. "Well, I don't think the loss can ever be replaced," her friend Mike Howard said in his deposition. "There is probably not a day in Mary's life that she hasn't thought about her son, and there is probably not a week goes by that she doesn't shed tears." Mary told me that until she and I had coffee last year in St. Paul, no one at the university had ever apologized or expressed regret for her son's death. In fact, after Dan died, Mary received a plant with a card from the CAFE study team. In words that echoed the bizarre, grisly message in Dan's suicide note, the card read, "We will miss his smile."

Of all the ways in which Mary Weiss has been damaged by the University of Minnesota, there is one episode that still brings a sting of shame to my face. When the lawsuit over Dan's death was dismissed, the university filed a legal action against Mary, demanding that she pay the university $57,000 to cover its legal expenses. Gale Pearson, one of Mary's attorneys, says that while such suits are technically permissible, she had never seen one filed in her previous 14 years of legal practice. The university agreed to drop the lawsuit against Mary only when she agreed not to appeal the judge's decision. "Maybe they want to chill anyone who might think of challenging the university, even if her child had died," Pearson said. "It gave me a sick feeling."

Source URL: http://motherjones.com/environment/2010/09/dan-markingson-drug-trial-astrazeneca Links: [1] http://www1.umn.edu/twincities/index.php [2] http://www.ahc.umn.edu/bioethics/facstaff/elliott_c/home.html [3] http://www.twincities.com/ci_9306735?nclick_check=1 [4] http://www.twincities.com/ [5] http://www.regionshospital.com/ [6] http://www.uofmmedicalcenter.org/ [7] http://www.psychiatry.umn.edu/faculty/olson/home.html [8] http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0000944 [9] http://www.ombudmhdd.state.mn.us/cctrc/medhearings.htm [10] http://www.astrazeneca.com/media/latest-press-releases/SEROQUEL-US-Marketing-Agreement?itemId=9289780 [11] http://clinicaltrials.gov/ct2/show/NCT00034892 [12] http://motherjones.com/environment/2010/09/clinical-trials-contact-research-organizations [13] http://www.ncbi.nlm.nih.gov/pubmed/18990713 [14] http://www.britannica.com/EBchecked/topic/28519/antipsychotic-drug [15] http://books.google.com/books?id=3WGdUgx4YuAC&pg=PA225&lpg=PA225&dq=thorazine+and+first+antipsychotic&source=bl&ots=2aEYZa9hty&sig=lee4AKPU9BSuFK45XvLFXoFNQT0&hl=en&ei=jXVHTNPUOMeCnQe2zui_BA&sa=X&oi=book_result&ct=result&resnum=7&ved=0CDYQ6AEwBg#v=onepage&q=thorazine%20and%20first%20antipsychotic&f=false [16] http://www.ncbi.nlm.nih.gov/pubmed/15278017 [17] http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0030185 [18] http://www.narsad.org/?q=node/390/latest-research [19] http://www.nytimes.com/2006/06/06/health/06psych.html?_r=1&th=&emc=th&pagewanted [20] http://bjp.rcpsych.org/misc/about.dtl [21] http://books.google.com/books?id=6jlpWE35fH0C&printsec=frontcover&dq=dispensing+with+the+truth&hl=en&ei=npdHTLWSHoOB8gbyxdSUBQ&sa=X&oi=book_result&ct=result&resnum=1&ved=0CCwQ6AEwAA#v=onepage&q=computer&f=false [22] http://www.bloomberg.com/apps/news?pid=20601103&sid=aEr_s70bGdYo [23] http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1481648/ [24] http://harkin.senate.gov/press/release.cfm?i=326378 [25] http://www.justice.gov/usao/pae/News/Pr/2009/jan/lilly_remarks.pdf [26] http://www.nytimes.com/2009/01/15/business/15drug.html?_r=1&ref=health [27] http://www.hhs.gov/news/press/2010pres/04/20100427a.html [28] http://www.justice.gov/ag/speeches/2010/ag-speech-100427.html [29] http://industry.bnet.com/pharma/10001228/e-mail-astrazeneca-knew-in-1997-that-seroquel-caused-weight-gain/ [30] http://www.medical-look.com/reviews/Haloperidol.html [31] http://www.twincities.com/ci_9316658 [32] http://www.liv.ac.uk/psychology/staff/agoudie.html [33] http://ohsr.od.nih.gov/guidelines/nuremberg.html [34] http://www.nytimes.com/2007/05/10/health/10psyche.html?pagewanted=all

                                                                                                 

FDA HEARING on reclassification of electroconvulsive therapy devices‏

  This hearing will be held at the Hilton Washington DC North/Gaithersburg, Ballroom, 620 Perry Pkwy., Gaithersburg, MD. on January 27 - 28, 2011  from 8 a.m. to 6 p.m.  Oral presentations from the public will be scheduled at approximately 10 a.m. on the 27th, immediately following the FDA’s presentation      Time is short.  If you plan to testify at this hearing, please contact the FDA's contact person for this hearing without delay. James M. Engles, M.S., M.B.A. Designated Federal Officer United States Food and Drug Administration Center for Devices and Radiological Health (CDRH) Medical Devices Advisory Committee Staff 10903 New Hampshire Avenue, Building 66, Room 1566 Silver Spring, MD 20993-0002 Phone: (301) 796-7543 Fax: (301) 847-8122

 

    If you cannot go, you can submit a written statement. As you know, ECT never went through the approval process now required for new devices by the FDA.  These devices were "grandfathered" into the system when the agency got jurisdiction in 1976.  Over the years, the shock industry has avoided any scrutiny of  their product for safety or efficacy.  All this changed in 2008 when the FDA sent letters to all manufacturers of devices in this category demanding clinical studies in this regard.  The industry responded by seeking a reclassification of their products to a lower category that does not require proof of efficacy on safety. This hearing is being held to determine the reclassification (from its highest Class III) to the lesser Class II (wheelchairs, etc) that do not require this regulatory procedure. Public safety and public responsibility demand that these devices get a full review by its regulatory agency. Vince http://www.fda.gov/AdvisoryCommittees/Calendar/ucm234979.htm

January 27-28, 2011, Neurological Devices Panel of the Medical Devices Advisory Committee Meeting Announcement

Food and Drug Administration [Docket No. FDA-2010-N-0585] Neurological Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting AGENCY: Food and Drug Administration, HHS. ACTION: Notice.             This notice announces a forthcoming meeting of a public advisory committee of the Food and Drug Administration (FDA). The meeting will be open to the public.                      Name of Committee: Neurological Devices Panel of the Medical Devices Advisory Committee.             General Function of the Committee: To provide advice and recommendations to the Agency on FDA's regulatory issues.             Date and Time: The meeting will be held on January 27 and 28, 2011, from 8 a.m. to 6 p.m.               FDA is opening a docket for public comment on this meeting. The docket number is FDA-2010-N-0585. The docket will open for public comment on November 26, 2010. The docket will close on January 25, 2011. Interested persons may submit electronic or written comments regarding this meeting. Submit electronic comments to http://www.regulations.gov. Submit written comments to the Division of Dockets Management, Food and Drug Administration, 5630 Fishers Lane, rm. 1061, Rockville, MD 20852. Submit a single copy of electronic comments or a paper copy of any mailed comments, except that individuals may submit one paper copy. Comments are to be identified with the docket number found in brackets in the heading of this meeting notice. Received comments may be seen in the Division of Dockets Management between 9 a.m. and 4 p.m., Monday through Friday. Location: Hilton Washington DC North/Gaithersburg, Ballroom, 620 Perry Pkwy., Gaithersburg, MD.                Contact Person: James Engles, Food and Drug Administration, Center for Devices and Radiological Health, 10903 New Hampshire Ave., Silver Spring, MD 20993, or FDA Advisory Committee Information Line, 1-800-741-8138 (301-443-0572 in the Washington, DC area), code 3014512513. Please call the Information Line for up-to-date information on this meeting. A notice in the Federal Register about last minute modifications that impact a previously announced advisory committee meeting cannot always be published quickly enough to provide timely notice. Therefore, you should always check the Agency’s Web site and call the appropriate advisory committee hot line/phone line to learn about possible modifications before coming to the meeting.               Agenda: On January 27 and 28, 2011, the committee will discuss and make recommendations regarding the possible reclassification of devices indicated for use in electroconvulsive therapy.               FDA intends to make background material available to the public no later than 2 business days before the meeting. If FDA is unable to post the background material on its Web site prior to the meeting, the background material will be made publicly available at the location of the advisory committee meeting, and the background material will be posted on FDA’s Web site after the meeting. Background material is available at http://www.fda.gov/AdvisoryCommittees/Calendar/default.htm. Scroll down to the appropriate advisory committee link.                        Procedure: Interested persons may present data, information, or views, orally or in writing, on issues pending before the committee. Written submissions may be made to the contact person on or before January 14, 2011. Oral presentations from the public will be scheduled at approximately 10 a.m., immediately following the FDA’s presentation, on January 27, 2011. Those individuals interested in making formal oral presentations should notify the contact person and submit a brief statement of the general nature of the evidence or arguments they wish to present, the names and addresses of proposed participants, and an indication of the approximate time requested to make their presentation on or before January 6, 2011. Time allotted for each presentation may be limited. If the number of registrants requesting to speak is greater than can be reasonably accommodated during the scheduled open public hearing session, FDA may conduct a lottery to determine the speakers for the scheduled open public hearing session. The contact person will notify interested persons regarding their request to speak by January 7, 2011.   Persons attending FDA's advisory committee meetings are advised that the Agency is not responsible for providing access to electrical outlets. FDA welcomes the attendance of the public at its advisory committee meetings and will make every effort to accommodate persons with physical disabilities or special needs. If you require special accommodations due to a disability, please contact AnnMarie Williams, Conference Management Staff, at 301-796-5966 at least 7 days in advance of the meeting. FDA is committed to the orderly conduct of its advisory committee meetings. Please visit our Web site at http://www.fda.gov/AdvisoryCommittees/AboutAdvisoryCommittees/ucm111462.htm for procedures on public conduct during advisory committee meetings. Notice of this meeting is given under the Federal Advisory Committee Act (5 U.S.C. app. 2).     Dated:   November 18, 2010.    Sign: Thinh Nguyen,         Acting Associate Commissioner for Special         Medical Programs.      ©2010 The Institute of Mind and Behavior, Inc. The Journal of Mind and Behavior Summer 2010, Volume 31, Number 3 Pages 265–270 ISSN 0271–0137 Doctors of Deception: What They Don’t Want You to Know about Shock Treatment. Linda Andre. New Brunswick, New Jersey: Rutgers University Press, 2009, 359 pages, $26.95 hardcover. Reviewed by David Cohen, Florida International University For a still undetermined number of people, entering the circle of psychiatric care begins a tragic process of disablement. Troubled or confused when they first contact officially accredited helpers for what are usually self-limiting and situational difficulties, their ensuing experiences with drugs or electroshock (electroconvulsive therapy, ECT) has a good chance of leaving them with diffuse stress syndromes and impaired cognition, sometimes for years. When this occurs, their injury is likely to be compounded because it is squarely denied or glossed over by those who have inflicted it and by nearly everyone else who should know better. Lacking a clear vocabulary to articulate their worsened predicament, and floundering in a previous or new subordinated social status, they watch helplessly as their discourse is dismissed as “mental illness.” A person thus diminished may be viewed as not believable, and if she persists in calling attention to her predicament, may be stigmatized as ungrateful or irresponsible. The dark side of the 60-year-old “biological revolution” in psychiatry is that when biological treatments “work,” treatments are praised, but when treatments harm, the responsibility is placed squarely upon their recipients or the intractability of their “disorders.” Nonetheless, to regain their integrity, to bear witness, or to fight injustice, some of these injured souls turn to advocacy and writing. Author and activist Linda Andre has written a marvelously lucid and ably documented book (over 500 references) that not only recounts her experiences and that of many others with electroshock, but mounts a systematic assault on the biomedical industrial complex and the willful distortions that many of its actors and servants — physicians, researchers, government regulators, journalists — engage in to maintain biomedical dominance and accrue benefits to themselves. In chapter after devastating chapter, Doctors of Deception describes, probes, analyzes, exposes, and deconstructs the entire electroshock industry. Andre focuses a steady gaze on the American Psychiatric Association’s (APA) successive reports on electroshock that have whitewashed the procedure. She details the Food and Drug Administration’s (FDA) tortuous evasions of its responsibility to evaluate objectively the risk of harm from shock devices by not requesting manufacturers to provide evidence of safety (unlike what it requires of manufacturers of any other medical device). She excoriates the small coterie of National Institute of Mental Health funded researchers whose careers are intertwined with shock machine manufacturers and the published sophism and casuistry that establish them as scientific experts on shock. She highlights the absence in the entire literature of a single well-controlled study testing the specific hypothesis that electroshock causes brain damage in humans, and she reviews study after study showing that shock impairs memory and other cognitive abilities. She portrays the confusion sowed by befuddled or manipulative journalists who announce, year after year for decades, that the “new” shock treatment is better and safer than the “old” and who cannot bring themselves to present injured shock survivors as anything but deluded or stubborn naysayers. Despite her elaborate portrayal of such a Kafkaesque system, one that has incarcerated and wounded her, Andre keeps an even, tranquil tone throughout the book, and at times compliments an obscurantist researcher for an occasional honest or forthright statement. The opening quote in Doctors of Deception is from iconic shock survivor and activist Marilyn Rice: “I don’t mean to say that these policies were ever written down or even necessarily known to the persons and organizations who have been actors in the drama, but they are detectable in the sweep of events and the rationalizations of the actors.” This quote expresses aptly the insight that complex systems can incarnate functions and finalities that escape the intentions of the actors themselves, but Andre does not spare the individual actors — far from it. She names names, exposes deeds, and attributes motives. That is perhaps why in the book’s dedication and in the acknowledgements, she describes it as a “dark” and a “sad” book. Andre appears simultaneously as revolted and resigned, angry and wise. Upon reading Doctors of Deception, even readers familiar with ECT’s history and literature — and familiar with the starkly opposite stances that characterize comments from both people who have received ECT and those who have studied or administered it — will discover that its author has many excellent reasons to take whatever stance she wishes. The book’s first chapter, “The Trouble with Time,” opens with Andre’s description of memory “loss” following the series of shocks she underwent as a 25-year-old woman after being forced into a psychiatric hospital where she was illegally detained (without formal commitment). The depressingly familiar story of her ignorance about coercive psychiatry compounds the tragedy. She states:The shock treatment erased five years of my life: four before, one after . . . . A period of time is wiped out as if it never happened . . . . Your life is essentially unlived. You never wrote that article, made that friend, took that trip, read that book, gave birth to that child. You didn’t just lose your suitcase; you can’t say where you got it, what it looks like, what you packed in it, what trips you’ve taken. You don’t know that you ever had it. (pp.3–4) The losses compound over time: Because I no longer knew who I was, I couldn’t build new relationships. Because I lost my knowledge and skills, I could no longer work. Because I couldn’t work, I became financially and socially marginal. Without work, friends, or identity, I lost my place in the world . . . . And so on, in a slow social death that can last a lifetime . . . . No one sees, no one knows; no one believes, unless they’ve had shock too. (p. 11) In two chapters, Andre discusses the eugenic conceptions that, she argues, set the stage for the acceptance of shock in America. She concludes that, “Without eugenic attitudes, no matter how it was brilliantly marketed, shock would have died off; countervailing forces would have been able to successfully unmask the marketing schemes” (p. 43). In “A Little Brain Pathology,” Andre reviews the numerous animal and human studies on the effects of electroshock that appeared in the 1940s and 1950s (ECT was invented in 1938), citing unambiguous excerpt after excerpt from investigators who typically concluded that significant brain damage was documented. She reminds readers that, “There was no sense in which the doctors at the time who admitted ECT was brain damaging felt they were saying anything unacceptable to the profession or the public” (p. 50). Nonetheless, a number of these psychiatrists did warn their profession and some, including Manfred Sakel, the inventor of convulsive treatment, asked pointedly whether ECT should continue to be applied. Andre cites extensively from Yale psychologist Irving Janis’ study in 1950 of amnesia following shock. According to Andre, the excerpts published by Janis “illustrate in a way no one else ever has how different ECT memory loss is from normal forgetting and how it has no parallel in ordinary human experience” (p. 60). She writes: “No one [since] the study was published has criticized Janis’s methodology. When his work is not ignored or dismissed, there are calls for its replication. These calls have been made for over fifty years, but to date no scientists have heeded them” (p. 63). The explanation is provided in the subsequent chapters, where Andre details how, despite increasing calls in the 1970s for studies that should use the latest techniques to establish the nature of organic and other defects that occur with ECT, the ECT industry strategy “was to grab ironfisted control over both the data and the terms of the debate, using tried and true public relations tactics, and to stay its course . . .” (p. 65). During the years that followed, a series of shock lawsuits established legal concerns over the intrusiveness of shock and its risks, and staked out a patient’s “right to refuse” it — if that patient was deemed “competent.” The shock industry woke up quickly. Andre argues that the key to shocking as freely as . . . before rights protection was in the legal definition of competency [which] includes the patient’s ability to understand the risks and adverse effects of the treatment. Organized psychiatry could define those risks as it pleased. If the APA said shock was harmless and could convince judges that it was, then any patient who disagreed with this assessment lacked an understanding of the risks of treatment . . . . (p. 83) Though the shock industry couldn’t make ECT safe, Andre argues that it didn’t need to. It needed rather to shape “what people, including the rank-and-file doctors and judges who would assess competency believed about shock, not what was actually true about it.” The problem was transformed by the ECT industry into a “public relations problem and not a medical, scientific, or moral problem” (p. 84). Within ten years, Andre demonstrates compellingly, the ECT industry had achieved a platform (with help of the APA’s power, numbers, money, and credibility, and an official, quasi-governmental report), control of the media (the ability to prevent, suppress or defuse negative portrayals of ECT through aggressive public relations campaigns), and control of the scientific journals (by controlling access to funding and publications). The parallels with the psychotropic drug industry, many of which have been revealed over the past few years, are obvious. Citing analysts’ views that a few well-respected opinion leaders with backing from the pharmaceutical industry were able to so thoroughly shape the views of thousands of practitioners about ineffective and harmful drugs, Andre notes that the comparatively smaller (“only” five-billion dollars) and incestuous shock industry was much more successful in this regard. How the media has jumped on the ECT public relations bandwagon is discussed and illustrated in a chapter entitled “The Lie That Won’t Die.” The lie is the fictional statement, never documented because no figures exist, that leads and frames nearly every mainstream story on shock that Andre has collected since the 1980s, that electroshock is making a comeback. The “near-identical comeback articles [have] titles like, ‘A New Image for Shock Therapy,’ ‘Taking the Shock out of Electroshock,’ and ‘Shock Therapy Loses Some of Its Shock Value.’ In a world in which media coverage feeds off itself, it now seems unthinkable that there could be any other way for covering shock in the mainstream media” (p. 214). In wrenching narratives of her meetings and interviews with the paragons of journalism at 20/20, 60 Minutes, the Phil Donahue Show, The Atlantic Monthly, and other media outlets, Andre describes what she calls “hit-and-run journalism”: . . . a total stranger asks you the most personal questions about yourself, requires you to answer every question he poses fully and truthfully (otherwise you will be suspected of hiding something), expects you to trust implicitly that he will not make any errors of fact or context when he publishes your name for thousands of people to see . . . . At the same time he will not tell you anything about his background, his motives, his opinions, whom else he has interviewed, or how he’s decided to frame the story . . . . This type of journalist makes himself inaccessible once the story is finished. He’s driven off and takes no responsibility for the damage he’s done to individuals or to the general level of public understanding of an issue. Why would he? He never intends to speak to the subject again . . . . Meanwhile, those who live with the issue every day, year after year, are left standing at the scene of the accident in disbelief, telling each other lamely, “If we hadn’t talked with them, it would have been even worse,” knowing that’s not true . . . . (pp. 222–223) Andre also shows that publicly trusted authorities, like the National Institute of Mental Health and the Surgeon General, have taken positions on ECT during the public relations era. In telling of her personal attempts to shape three major reports about ECT at federal or state levels, Andre reminds readers that “. . . whenever a government entity takes on ECT . . . these are hotly contested political statements, and the process by which they are developed is a political power struggle. Different constituencies fight for input, and the playing field is not level” (p. 231). We are shown over and over again that shock “survivors have always been excluded from a voice in research or policy, while industry spokesmen . . . made research and policy.” Though she finds this inequality to be true for all struggles for social change, “No two groups seem more unequal than psychiatrists and former ECT patients” (p. 233). The exclusion and dismissal of the negative views of shock recipients by actors representing professions, government, and industry, and the disparity between these actors’ power over resources is again illustrated by Andre’s foray into the workings of the FDA. This chapter, among others, is about the broader issue of citizens’ involvement in the process of science and health policy, and the struggle by patients and experts to castigate or elevate data as either “anecdotes” or “evidence.” In the case of the mostlyfemale ECT survivors trying to get their accounts into an FDA report of personal experiences with ECT, versus the mostly-male psychiatrists and shock-doctors trying to get their accounts in, the outcome again and again is depressingly familiar. Andre accepts fully that shock “works” in the short-term: A series of many electrically induced, closely spaced grand mal seizures, with the accompanying acute organic brain syndromes and the cumulative amnesia, is guaranteed to temporarily change mood and behavior . . . . It is a biological certainty that it is impossible to be depressed, or focus much on anything, while body and brain are struggling to recover from a grand mal seizure. (p. 96) She feels this is ECT’s biggest selling point, as patients come to ECT “experiencing extreme distress and/or are extremely distressing to others” (p. 96). But her review of the studies (or lack thereof ) leads her to state that “Rather than scientific evidence, the claim that ECT works is made by assertion and anecdote. There is no doubt that some patients are glad to have the short-term relief they obtain from ECT and . . . [d]esperate relatives are grateful for short-term respite . . . . But there is no evidence that ECT has any long-term benefit” (pp. 97–98). I find this to be an eminently reasonable summary of the accumulated evidence. This evidence, and how it has been skewed by the “moral choices” made by the industry, frame a later chapter of the book that asks, “Should ECT Be Banned?” Her reasoning here is cautious and inclusive, strengthened by evidence from so-called “informed consent forms” for ECT and by her recognition that some recipients claim benefits (as some recipients of any and all treatments have always claimed benefits). Nevertheless, Andre concludes as follows: Even knowing [all of the deceptions and the evidence on damage], some people would choose to have ECT, as some people choose to smoke. But people aren’t allowed to know. This is the strongest argument that ECT is immoral, and it makes a ban not only deeply consistent with the American values of freedom, choice, and autonomy, but the only way — at this point in history and given the choices the industry has made — to protect those values. (p. 286) Doctors of Deception is a compelling and comprehensive analysis and indictment of the modern psychiatric industrial complex. It is compelling because the motives, rationalizations, or lies of the actors in the system are presented in their own words. It is persuasive because the workings of the system to shape the very nature of public and scientific debate are taken apart, labeled one by one, and the relationships between the parts of this vast engine of deception are delineated. It is comprehensive because Andre frames each of her chapters within wider political and cultural issues surrounding the management of troubled people in society. Finally, it is unusual, because it weaves the author’s account of her struggle for survival and advocacy. Yet, even though the weight of the evidence paints a bleak picture and argues against an evolution of the system toward openness and practical changes making it easier for ordinary people and professionals to have access to less biased information about ECT, Andre notes in her concluding chapters and epilogue that some positive change does occur, like what has been occurring in the financially conflicted drug industry. These changes seem to illustrate the unpredictable dynamics of any vast social system. Andre believes that “a hundred unpredictable variables” will decide whether the great ECT deceptions will unravel. Still, she believes that for fundamental change to occur, “What’s needed, as always, are just a few individuals who care enough to put what’s right before everything else, who are willing to make personal sacrifices of time and resources, and who won’t give up” (p. 305 

 Electroshock does more harm than good.  Why is it not abolished?

http://apps.facebook.com/causes/sharings?context_id=195259&context_type=Cause&m=91d73f68&post_type=link

 Stop shocking our mothers and grandmothers.

http://www.psychiatry.freeuk.com/ECTreview.pdf

 

Love and Friendship

By

Emily Bronte

 Love is like the wild rose-briar; Friendship like the holly-tree. The holly is dark when the rose-briar blooms, But which will bloom most constantly? The wild rose-briar is sweet in spring, Its summer blossoms scent the air; Yet wait till winter comes again, And who will call the wild-briar fair? Then, scorn the silly rose-wreath now, And deck thee with the holly's sheen, That, when December blights thy brow, He still may leave thy garland green.

 

A song for Christmas

http://www.youtube.com/watch?v=ma3Nax8yyOE