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Human Rights Defenders

“All human beings are born free and equal in dignity and rights. They are endowed with reason and conscience and should act towards one another in a spirit of brotherhood.”

 Universal Declaration of Human Rights

Article 1

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Senator Grassley Drug Companies Pay Drs

Mental Health and Human Rights Law in Europe

 

When they first confront the mental health system, many do not realize what their rights are under US civil law or under international human right law. There are routine human rights abuses by those entrusted with the care, treatment, and social support to those with mental health disabilities. Persons who are experiencing mental health challenges or who have a mental health disability have difficulty expressing their needs and to bring forth allegations of neglect or abuse. There are several concepts within human rights mental health law that human rights advocates and those who advocate for the disabled should know.



Consent to medical treatment:

There is a general right for all human persons to be free of inhuman treatment and individuals also have the legal right to privacy under international human rights law. International human rights case law supports the concept that individuals do have the legal right to decide whether a proposed medical treatment will be performed on them. The human right to decide one's own treatment does not disappear just because it is more convenient or financially more beneficial for the caregivers or for the family members of the individual to force treatment. This right to decide to refuse treatment is a human right we all enjoy. Mental health treatment under human rights law should be the same as other treatments in regards to consent to treatment.

But it is a sad fact that this right has not necessarily been consistently protected and thus through our mental health systems extended to people with mental disabilities. But because those with mental health disabilities are often detained, this then often automatically leads to forced treatment. This does not necessarily need to happen. It is not theoretically inconsistent with confining someone in a psychiatric facility, but still leaving them with the authority to decide treatment decisions.

For the last 20 years in Canada it has been the practice to allow patients with mental health disabilities who have mental capacity to make treatment decisions, to have the right to make those decisions regardless of whether they are hospitalized or subject to legal confinement.

In regards to the prevention of torture, it has been the opinion of the international courts in Europe, North America and Australia that patients who understand the relevant information be allowed to make treatment decisions. The Committee for the Prevention of Torture (CPT) has stated:

"Patients should, as a matter of principle, be placed in a position to give their free and informed consent to treatment. The admission of a person to a psychiatric establishment on an involuntary basis should not be construed as authorising treatment without his consent. It follows that every competent patient, whether voluntary or involuntary, should be given the opportunity to refuse treatment or any other medical intervention. Any derogation from this fundamental principle should be based upon law and only relate to clearly and strictly defined exceptional circumstances."[i]

 

Detainment:

The guarantee of liberty is perhaps the most important human right in relation to the detention of mentally disordered people. [ii] In a United Kingdom legal case a patient detained under a restriction order at Rampton Hospital suffered a four year delay between his initial conditional discharge and his absolute discharge. The delay was due to lack of appropriate hostel placement. [iii] This kind of lengthy delay brings up human rights issues. In Belgium case a mentally disordered patient was kept in prison because no hospital bed was available for him. He succeeded in pressing charges of false imprisonment. [iv]Thus according to international human rights case law, in order for the detention of a person of unsound mind to be lawful the following minimum criteria must be met:

* Except in emergency cases, no one can be deprived of liberty unless he or she can be reliably shown to be of unsound mind on the basis of objective medical expertise

* The mental disorder must be of a kind or degree warranting compulsory confinement

* The validity of continued confinement depends on the persistence of the disorder.

 

Right to speedy review of detention:

When detained, a patient have a legal entitlement to a "speedy" review of detention and release if the detention is not lawful.[v] When the detention is being reviewed by the tribunal, the patient is entitled to the same information provided to other members of the tribunal panel which is reviewing the detention. This means that the patient would have the right to call witnesses and have them cross examined on his or her behalf.

 

Effects of psychiatric medication:

 

Although for some patients psychiatric medication has desirable effects, it is also true that these medications have some highly invasive adverse effects, including nerve damage, sexual dysfunction, drooling, nausea, sleep disorder, depression, and others, depending on the medication. Patients can have coherent and valid reasons for refusing medication. Some persons voluntarily take medication and feel that it helps them and restores them to the person they once were. But for others they experience medications as removing the person they think of themselves and often giving a duller and less free person a feeling that the drug is controlling them. Forcing medication on such patients raises serious human rights issues of individual freedom.

 

Capacity to make treatment decisions:

Patients need to have the intellectual capacity to understand basic information about their   diagnosis and proposed treatment. Correspondingly doctor's have a responsibility to communicate the information in terms the patient can understand and to make efforts to be available to answer questions the patient may have. Scepticism by the patient in such circumstances does not mean that the person does not have capacity to make treatment decisions. Even if the patient, due to their disability, cannot believe the doctor's diagnosis that doesn't mean that the patient does not have capacity to make treatment decisions. Essentially, people have the right to make treatment decisions. Principle 19 of the UN's "Principles for the Protection of Persons with Mental Illness" (which are reproduced as Appendix 2 below) mandates that:

Informed consent is consent obtained freely, without threats or improper inducements, after appropriate disclosure to the patient of adequate and understandable information in a form and language understood by the patient on:

(a) The diagnostic assessment;

(b) The purpose, method, likely duration and expected benefit of the proposed treatment;

(c) Alternative modes of treatment, including those less intrusive;

(d) Possible pain or discomfort, risks and side-effects of the proposed treatment.

 

Paragraph 41 of the standards of the European Committee for the Prevention of Torture state that "consent to treatment can only be qualified as free and informed if it is based on full, accurate and comprehensible information about the patient's condition and the treatment proposed; to describe ECT as "sleep therapy" is an example of less than full and accurate information about the treatment concerned. Consequently, all patients should be provided systematically with relevant information about their condition and the treatment which it is proposed to prescribe for them. Relevant information (results, etc.) should also be provided following treatment."

Judicial hearing for treatment decisions:

No treatment should be provided except in emergency situations until a determination of capacity has been made through a judicial hearing for treatment decisions. The hearing must be by an independent arbiter, and be judicial in character. In addition there must be a right of the patient to return for re-consideration of the situation at regular intervals. A hearing to determine incapacity is required. Persons, who are lacking capacity, are often institutionalized and overmedicated. These psychiatric medications may adversely affect the individual's quality of life and even shorten the person's life expectancy. Thus it is important that overmedication minimized, the views of the patient are considered and the quality of life issues explored. So an effective means of reviewing the treatment plans is important.

These are just some of the basic principles of human rights of persons with a mental health disability.


[i] CPT Standards, 2002, CPT/inf/E (2002) 1, para 41

[ii] Winterwerp v Netherlands (1979) 2 EHRR 387

[iii] Stanley Johnson v United Kingdom [1997] EHRLR 105-8

[iv] Aerts v Belgium, ECHR Reports of Judgments and Decisions 1998

[v] E v Norway [1994] 17 EHRR 30

Thomas Szasz on Psychiatry

Gwen Olsen Former Pharmaceutical Sales Representative Speaks Out

Pharmaceutical Companies spend more marketing than in Research & Development

According to PublicIntegrity.org, more than a third of pharmaceutical companies' resources go into promotion and marketing.


Company Marketing costs vs costs of Research and Development

Pfizer $16.90 billion in marketing and only $7.68 billion in research & development
Glaxo Smith Kline $12.93 billion marketing and only $5.20 billion research & dev.
Sanofi-Aventis $5.59 billion in marketing $9.26 billion in research & development
Johnson & Johnson $15.86 billion in marketing $5.20 billion in research & development
Merck $7.35 billion in marketing $4.01 billion in research & development
Novartis $8.87 billion in marketing $4.21 billion in research & development
AstraZeneca $7.84 billion in marketing $3.80 billion in research & development
Hoffman La Roche $7.24 billion in marketing $4.01 billion in research & development
Bristol-Myers Squibb $6.43 billion in marketing $2.50 billion in research & development
Wyeth $5.80 billion $2.46 billion in marketing in research & development
Abbott Labs $4.92 billion in marketing $1.70 billion in research & development

Annually, the industry spends nearly twice as much on marketing as it spends on research and development, although drug companies report neither total precisely. Various news reports estimate that the industry spent anywhere between $30 billion to $60 billion on marketing in 2004. The trade group PhRMA estimates its members spent $39 billion on R&D that year. As this information shows, the same year, 11 major companies reported spending close to $100 billion on marketing, along with administrative expenses not categorized separately. Those companies reported spending $50 billion on R&D. In 2004, Pfizer spent almost $120 million for media ads for Lipitor, the world's number-one selling prescription drug, while companies promoting erectile dysfunction treatments Viagra, Levitra and Cialis spent $425 million. Direct to consumer advertisement has also grown significantly: from $791 million in 1996 to $3.8 billion in 2004.

Eli Lilly Executive Dr. John Virapen

Medical Whistleblower inteviewed Former Eli Lilly executive, Dr. John Virapen Ph.D. on Monday July 27, 2009 at 9 AM Central Time on BlogTalk radio. What he can reveal to us is especially important in the wake of the recent $1.4 billion settlement from drug maker, Eli Lilly.John Virapen used to be the executive director of the Swedish branch of Eli Lilly & Company, one of the biggest internationally active pharmaceutical companies. Dr. John Virapen has been working for more than 35 years for the pharmaceutical industry, as manager for several companies such as Eli-Lilly and Novo Nordisk. He lives now in Germany and has written a book,   Side Effects: Death, about his experiences which is available in English, Swedish and German.It is available as a e-book at this link 


http://www.side-effects-death.com/tag/john-virapen

While working for Eli Lilly, John Virapen engaged in the development of aggressive marketing strategies, which included to massive corruption in more than one occasion. He participated in the resolute distribution of drugs, which cause massive and dangerous side effects like the death of the patient. Pharmaceutical companies invest the considerable amount of 35,000 Euro per year and physician to get the physicians to prescribe their products. John Virapen says that more than 75 percent of leading scientists in the field of medicine are paid for by the pharmaceutical industry. In some cases corruption prevailed in the approval and marketing of drugs. John Virapen writes that illnesses are made up by the pharmaceutical industry and specifically marketed to enhance sales and market shares for the companies in question. Pharmaceutical companies increasingly target children.

The drug giant, Eli Lilly, recently pleaded guilty to promoting its drug Zyprexa for uses not approved by the Food and Drug Administration (FDA). Eli Lilly was found guilty of pushing Zyprexa for extra label uses, withholding research to the public and false advertising. The criminal fine of $515 million is the largest ever in a health care case, and the largest criminal fine for an individual corporation ever imposed in a United States criminal prosecution of any kind. Eli Lilly will also pay up to $800 million in a civil settlement with the federal government and the states.

There have been years of withheld information regarding the adverse side effects of pharmaceuticals promoted by Eli Lilly, including the possible role of Prozac in inducing suicide and homicide. The signs of drug induced violence and suicidality were there since Prozac was first tested in pre-marketing trials. There were suppressed clinical reports of Prozac's adverse side effects including psychotic episodes, completed suicides and attempted suicides. Long term effects of the use of SSRI's like Zyprexa have not been fully independently studied but these drugs are routinely prescribed for long term use. Preliminary studies of some of Eli Lilly's drugs pointed to serious potential adverse side effects of chronic use including: debilitating movement disorders, seizures, cardiac problems, diabetes and Parkinson's disease.

Hear Dr. John Rengen Virapen live on www.BlogTalkRadio.com/medicalwhistleblower at 9 AM Central Time 7/27/09 interviewed by Dr. Janet Parker DVM, Executive Director of Medical Whistleblower.

Read about his story on the web at: http://1phil4everyill.wordpress.com/2009/07/09/14-dr-john-rengen-virapen-blows-the-whistle-on-his-former-big-pharma-employer/

Listen to internet radio with MedicalWhistleblower on Blog Talk Radio

Pfizer too big to Nail - Federal Crimes but who pays

By Drew Griffin and Andy Segal, CNN Special Investigations Unit

(CNN) -- Imagine being charged with a crime, but an imaginary friend takes the rap for you.

What happened when Pfizer, the world's largest pharmaceutical company, was caught illegally marketing Bextra, a painkiller that was taken off the market in 2005 because of safety concerns.

When the criminal case was announced last fall, federal officials touted their prosecution as a model for tough, effective enforcement. "It sends a clear message" to the pharmaceutical industry, said Kevin Perkins, assistant director of the FBI's Criminal Investigative Division.

Internal company documents show that Pfizer and Pharmacia (which Pfizer later bought) used a multimillion-dollar medical education budget to pay hundreds of doctors as speakers and consultants to tout Bextra.

But in November 2001, the U.S. Food and Drug Administration said Bextra was not safe for patients at high risk of heart attacks and strokes.

The FDA approved Bextra only for arthritis and menstrual cramps. It rejected the drug in higher doses for acute, surgical pain.

Promoting drugs for unapproved uses can put patients at risk by circumventing the FDA's judgment over which products are safe and effective. For that reason, "off-label" promotion is against the law.

So Pfizer and the feds cut a deal. Instead of charging Pfizer with a crime, prosecutors would charge a Pfizer subsidiary, Pharmacia & Upjohn Co. Inc.

The CNN Special Investigation found that the subsidiary is nothing more than a shell company whose only function is to plead guilty. 

Pfizer  paid nearly $1.2 billion in a criminal fine for Bextra, the largest fine the federal government has ever collected.

It paid a billion dollars more to settle a batch of civil suits -- although it denied wrongdoing -- on allegations that it illegally promoted 12 other drugs.

 

See the entire article at:

http://www.cnn.com/2010/HEALTH/04/02/pfizer.bextra

Listen to internet radio with MedicalWhistleblower on Blog Talk Radio

Clinical trials have become marketing exercises for Big Pharma

Mother Jones * September/October 2010

Clinical trials have become marketing exercises for Big Pharma -- and cash-strapped universities are helping make the sale. Too bad for Dan Markingson.

Making a Killing 

by Carl Elliott



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, where I teach medical ethics. Less than six months later, Dan was dead. I'd learned about his death from a deeply unsettling newspaper series by St. Paul Pioneer Press 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 over- sight 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 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 in St. Paul. But the hospital had no psychiatric beds available, so after a few hours Dan was transferred to Fairview University Medical Center, a teaching hospital for the University of Minnesota Academic Health Center. He was treated by Dr. Stephen C. Olson, an associate professor in the university's psychiatry department, who prescribed Dan Risperdal (risperidone), an antipsychotic drug often prescribed for patients with schizophrenia or bipolar disorder. (In Minnesota, doctors are allowed 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 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, 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," page 60.) 

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. 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." 

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"), they can also cause irreversible "extrapyramidal" 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. 

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 not just for schizophrenia but also for anxiety, agitation, insomnia, attention deficit hyperactivity disorder, and depression. The most remarkable upswing 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, the number of children and adolescents treated for bipolar disorder rose 40-fold between 1994 and 2003. Another study 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, 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 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 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 to the recent Senate investigation into GlaxoSmithKline's diabetes drug Avandia. 

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, the manufacturer of Zyprexa. In early 2009, it settled litigation for a record-breaking $1.4 billion for illegal marketing and allegedly hiding the risks of the drug. More recently, however, the scandal has spread to Seroquel. In April 2010, AstraZeneca agreed to pay $520 million to settle two federal investigations 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 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, 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 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." 

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, 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, 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 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." 

 



Those interested in an investigation by a journalist of psychiatric drug company research fraud are encouraged to obtain the Sept./Oct 2010 issue of Mother Jones and read the "Making a Killing" article here. Carl Elliott reveals how clinical trials and even whole universities are manipulated by the pharmaceutical industry.  

 

    A DECADE AGO, when the inspector general of the department of Health and Human Services (HHS) investigated the recruitment practices of pharmaceutical trials, researchers complained that research sponsors were demanding unrealistically tight deadlines to enroll subjects. Asked by the IG what sponsors were looking for in trial sites, one researcher replied, "Number one-rapid enrollment. Number two-rapid enrollment. Number three-rapid enrollment." Many researchers attributed the unrelenting pressure to the fact that trials were being managed by business people, not clinicians.

 

    Over the past 20 years, medical research has become a largely privatized, and thoroughly Taylorized, business. Two-thirds of clinical trials are now privately run. Many trials are advertised by patient recruitment specialists, carried out by "contract researchers," approved by for-profit ethics boards, and written up for publication by commercial medical education agencies. The largest of the new private industries are contract research organizations (CROS), which range from small niche agencies to multinational corporations that manage all aspects of clinical trials, from ethics approval and subject recruitment to the submission of clinical data to the FDA. Quintiles, the company that managed the study in which dan Markingson was enrolled, is the largest, with 14 percent of the $11.4 billion global market.

 

    CROS save money for pharmaceutical companies by deploying the principles of industrial management: breaking trials down into narrow, discrete steps, which can be carried out with maximum efficiency by specialized workers who can be paid relatively low wages. According to Vanderbilt University social scientist Jill Fisher, author of Medical Research for Hire, very little experience is required to be a CRO "monitor" -- a middle manager, often a nurse, who coordinates the various sites involved in a study. Monitors usually make less than their counterparts at universities or pharmaceutical companies, and job turnover is very rapid. Fisher says, "The goal of many monitors is to be hired by the pharmaceutical industry."

 

    In contrast, the private physicians paid to supervise clinical trials are often very well- compensated. A part-time contract researcher conducting four or five clinical trials a year can expect to earn an average of $300,000 in extra income. Yet they generally have little if any research training. They do not generate original scientific ideas, design studies, or analyze the results. Their main role is to help recruit subjects and oversee their trial participation.

 

    Research subjects are the most highly prized commodities in the clinical trials industry. Four out of five clinical trials are delayed because of difficulties recruiting subjects. These delays can be costly, as the patent clock on new drugs starts ticking as soon as the patent is filed.

 

    As CROS have discovered, many research subjects can be persuaded to enroll because they have no health insurance or because they are too poor to afford medication. (According to Fisher, a common CRO term for these patients is "ready-to-recruit.") In the CAFE study, for instance, a Quintiles study monitor suggested that each of the CAFE study site coordinators try recruiting subjects at homeless shelters. Nevertheless, early on the University of Minnesota trial site was apparently struggling to keep subjects in the study.

 

    "Having trouble with Subject 002," Jean Kenney, the university's CAFE study coordinator, wrote in a January 2003 email to Quintiles. "His sister just died, his father has terminal cancer and now the grandmother is sick. He missed a visit and now just missed the next one." Another issue was slow recruitment. "Have had another person show interest from inpatient and then the parent put pressure on and said 'No' (third time this has happened)," Kenney wrote. The Quintiles study monitor was consistently upbeat and encouraging. "Try not to get too frustrated!" she advised. "Hopefully your hard work will start to pay off soon!"

 

    Many CROS market their ability to locate subject populations that are "treatment- naïve," meaning patients who have not yet been treated for their illness or who are not taking any other medications. often treatment-naïve subjects are easier to find in poorer countries, where trials can also be conducted with less oversight from the FDA. In 2008, according to HHS, 78 percent of subjects enrolled in clinical trials lived outside the United States, including 13,000 subjects in Peru, where the FDA conducted no inspections.

 

    CROS have been involved in some notable clinical trial scandals. In the 1990s, Pharmaceutical Product development, or PPD, one of the largest, was implicated in a notorious fraud scheme carried out by Dr. Robert Fiddes, who used his Southern california Research Institute to falsify records and invent patients while conducting trials for nearly every major pharmaceutical company. In 2006, at a trial site at a hospital near London, six healthy subjects nearly died after the CRO Parexel paid them 2,000 pounds each to become the first humans to test an experimental compound. In 2005, Bloomberg News reporters discovered that SFBC International Inc. was paying undocumented immigrants to serve as drug guinea pigs in a converted Holiday Inn. The Miami motel was subsequently demolished for fire and safety violations, and the company changed its name to PharmaNet. In 2009, PharmaNet was acquired by JLL Partners, a New York hedge fund.

 

    Today, if cash-strapped academic centers want to compete for the revenue generated by industry-sponsored trials, they must play by new rules. Academic institutional review boards must approve trials quickly to compete with for-profit IRBs (see page 63), and academic study coordinators must recruit subjects quickly to compete with private trial sites. The competition is even stiffer for academic physicians, many of whom must generate part of their own university salaries by obtaining grants and contracts from external funding sources. If academic physicians want to do clinical trials for the pharmaceutical industry, they must compete with contract researchers, who offer little to the body of science but carry out industry-tailored trials efficiently. Such arrangements often reduce academic physicians to little more than industry helpers, collecting data according to a company protocol. All these factors, it seems, were at play in the study that Dan Markingson was enrolled in when he died. -- C.E.

 

Profit pressures gut guinea pigs' only safeguard: institutional review boards.

 

    ESTABLISHED IN the 1970s in response to scandals such as the Tuskegee syphilis experiment, institutional review boards are the primary means of protecting research subjects in the United States. Until recently, most IRBs were volunteer committees of clinicians and researchers in the teaching hospitals and medical schools where the research in question was being conducted. But as clinical research began to enter the private sector, a new type of IRB emerged: independent boards that review studies in exchange for a fee, promising a faster review. There are about 40 for-profit IRBs operating in the US, generating more than $100 million in annual revenue. Some for-profit IRBs are professional and serious-minded, while others present a more entrepreneurial face. Take Liberty IRB, a for-profit IRB in Florida that boasts on its website that it is the winner of the 2008 "Make Mine a Million $ Business" competition, a contest described as "a cross between The Apprentice and American Idol."

 

    Paid by the companies whose protocols they review, for-profit IRBs have a direct interest in keeping their clients happy. If one for-profit IRB rejects a study as too dangerous, the sponsor can simply send it to another one. defenders argue that companies have an interest in getting a strict ethical review, if only to ward off potential litigation. But recent events suggest otherwise. In March 2009, the government Accountability office revealed the results of a sting operation it conducted on coast IRB, a colorado outfit with more than $9 million in revenue in 2008. The GAO set up a phony company testing an obviously dangerous "bogus medical device" in a research protocol so "excessively vague" no reputable IRB should approve it: The protocol lacked results from animal studies and didn't reveal where the study would take place, or what institution would carry it out. The principal investigator listed had an expired medical license; the only contact information was a post office box and a cell phone number. Yet coast IRB approved the product unanimously and deemed it "probably very safe." According to the GAO, coast IRB had reviewed 356 research studies in five years and rejected only one.

 

    So are the old academic IRBs any better? Located within academic health centers that now compete with contract research organizations for clinical trials, they also face pressure to approve trials quickly. As trials have become more complex, academic IRBs have become expensive, costing an average of nearly $750,000 per year -- with some costing more than $4 million. As a result, some universities are outsourcing reviews to for-profit IRBs. others have decided to shift the cost back to the pharma companies, like the University of Minnesota, which charges $2,500 to review industry-sponsored studies. -- Carol Elliot

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NACDA Guidelines for Administration of Drugs to Human Subjects

  1. Preamble


The National Advisory Council on Drug Abuse (NACDA) recognizes the importance of research involving the administration of drugs with abuse potential, and dependence or addiction liability, to human subjects. These drugs may include caffeine, nicotine, alcohol, opiates, cocaine, amphetamine, barbiturates, benzodiazepines and other compounds with known or suspected abuse/dependence liability. This research can produce scientific knowledge that is essential to understanding and addressing problems of drug abuse and addiction, and is particularly important in the development of effective, scientifically based treatment and prevention strategies.

Research involving the administration of drugs must be designed, reviewed, and conducted within the fundamental and broader ethical principles governing all biomedical and behavioral research with human subjects. These principles have been articulated in the Belmont Report, which provides a broad framework for establishing and evaluating specific aspects of ethics in research with human subjects. While a complete reading of the Belmont Report (http://www.hhs.gov/ohrp/humansubjects/guidance/belmont.html) is required for a full understanding of these principles and their application in complex ethical issues involved in research on human subjects, the principles can be summarized as follows:

Respect for Persons - Individuals must be given the opportunity to choose what shall or shall not happen to them and their decisions must be informed and protected. Persons with diminished autonomy or capacity are entitled to protection.

Beneficence - Researchers must go beyond the obligation to avoid inflicting harm and maximize the potential benefits of the research to individuals and society.

Justice - Fairness and equality must guide the distribution of the benefits and burdens of research involving human subjects.

The general principles of ethics in human investigation are also addressed in such documents as: 

    1. the Nuremberg Code of 1947,
    2. the Helsinki Declaration of 1964 (most recently revised in 1989),
    3. guidelines from professional organizations, such as the American Psychological Association,
    4. a number of relevant books including "Ethics and Regulation of Clinical Research," authored by Robert J. Levine (Urban and Schwarzenberg, Baltimore-Munich, Second Edition 1986); and
    5. the Code of Federal Regulations (CFR), 45 CFR Part 46, "Protection of Human Subjects".


Investigators conducting NIDA sponsored research outside of the United States and its territories are encouraged to also seek guidance from guidelines/codes/regulations that pertain to that specific research setting.

The Council notes that responsibility for development and implementation of ethical research protocols falls upon more than one individual or group. It rests first with the principal investigator and next with the Institutional Review Board (IRB), as required by the Code of Federal Regulations (CFR), 45 CFR Part 46, "Protection of Human Subjects." IRBs must review and approve all Department of Health and Human Services (HHS) conducted or funded research protocols involving human subjects. The levels of review for projects supported by the Institutes and Centers of the National Institutes of Health are the Scientific Review Groups (SRGs), the National Advisory Councils and Institute staff. Human subject concerns raised by either an SRG or a Council are conveyed to the principal investigator as well as to the applicant's institution. The program staff of the Institute, in consultation with the Office for Extramural Programs (OEP) have the responsibility for resolving human subject concerns before any study involving human subjects can be undertaken. Program staff are responsible for requesting and the OHRP is responsible for negotiating assurances of compliance with institutions that will be engaged in the research and for which no assurances covering the research are in place at the institutions.

However, while these important regulations, principles, and guidelines form an important context for research involving administration of drugs, the NACDA believes there are additional, specific ethical and safety points that must be considered by investigators and IRBs. Thus, these NACDA guidelines focus on the issues that arise in research involving administration of drugs with abuse/dependence liability, and are intended to identify issues to be considered in the development and review of research protocols involving drug administration to human subjects.  

Purpose of These Guidelines


The guidelines are not intended to supplant the functions of either the IRB or OHRP. They are advisory to applicants, IRBs, IRGs, and others. They are not codified and do not constitute Federal regulation. Rather, the guidelines are intended to encourage a sensitive, ethical approach that is also consistent with the best current practices and experience in the field of drug abuse research.

The NACDA also notes that the principal responsibility for approval of a research project involving human subjects rests with the local IRB. Though the SRG, NACDA, and Institute staff have a responsibility to consider human subject issues, it is the local institution and its IRB, which are most aware of the many complex factors affecting the acceptability of proposed procedures. However, it is clear that IRBs have varied in their reviews of drug abuse research, thus, there is a need for uniform guidelines.

Research involving drug administration can raise issues that go beyond protection of human subjects per se, including the legal or moral concerns often raised by the sensitive behaviors being studied. It is important not to allow these issues to deflect from a proper focus on the dual values of promoting needed scientific research on a critical health problem and on the protection of human subjects. For that reason, specific training and proper expertise of individuals involved in ethical review of projects in this area are especially needed. Thus, the NACDA suggests that local IRBs should obtain outside advice when they do not have sufficient familiarity with drug abuse research issues. Such procedures are consistent with 45 CFR 46.107(f).  

 

General Issues


The NACDA recommends consideration of a number of general issues applicable to drug administration research involving human subjects, regardless of the specific population. These issues are:  

A.    Risk/Benefit


Research with volunteer participants begins with a careful appraisal of all risks and benefits. Considerations include importance and validity of the scientific information to be gained, degree of risk to research participants, and availability of alternative research approaches and information sources. Ultimately, there must be a favorable balance of potential benefit against risk; without this favorable balance, a research protocol cannot be justified.

In assessing the risks and benefits, the IRB should take into account the qualifications and experience of the research team, the appropriateness and adequacy of the research design, and the suitability of any site where the administration of drugs and other interventions occur. Depending on the level of expertise of the research team, a project may not be judged to have an acceptable risk/benefit ratio even if the project has a sound scientific hypothesis and research design. Similarly, the site of the research may influence risk/benefit decisions. The NACDA also notes that the local IRB ultimately is responsible for considering the many complex factors involving the research team's qualifications and experience in conducting similar studies, the suitability of the research site, and local policies affecting the acceptability of proposed procedures.  

B. Data Safety Monitoring Board


The NACDA recognizes the importance of a Data Safety Monitoring Board, which is responsible for collecting and analyzing safety-sensitive data during the course of a study to monitor for adverse effects and other trends. Such trends might include a clear indication that one treatment is significantly better than another, particularly when one arm of the trial involves a placebo control. Such data monitoring findings would warrant modification or termination of the trial, or notification of subjects about new information that might affect their willingness to continue in the trial. Information on data safety monitoring is available in the Institutional Review Board Guidebook (1993, Office for Protection from Research Risks), on NIDA's web site at http://www.nida.nih.gov/Funding/DSMBSOP.html and in the NIH policy statement at http://grants.nih.gov/grants/guide/notice-files/not98-084.html.  

 

C.  Informed Consent


The NACDA reiterates the basic principle that the investigator has the primary responsibility for assuring that the informed consent process gives potential participants all the information they need to make a voluntary and informed decision. IRBs, as well, should assure that the informed consent documents convey all relevant information in language readily understandable by the research participants and/or guardians. Also, the NACDA recommends that the investigator give adequate consideration to the mental and physical conditions and motives of the individuals in terms of their ability to fully understand the context of the informed consent. If there is a question about a potential subject's ability to give informed consent, an independent clinician, ethical consultant, or uninvolved third party with appropriate qualifications should be asked to evaluate this ability if the subject is to be entered or continued in the study. Finally, as discussed in Section B, above, the IRB is responsible that the information in the informed consent is updated with any new findings regarding safety and efficacy of the procedure under investigation.  

D.   Subject Selection


The NACDA emphasizes the need for care in subject selection so that appropriate participants are recruited to address the research question and to ensure that adequate safeguards are followed to prevent unnecessary risk. The issues relating to subject selection are addressed in more detail in the Section IV.  

E.  Confidentiality


Investigators should be aware that once drug abuse histories are placed in patient records, such records must be handled with extreme confidentiality. These confidentiality requirements sometimes go beyond those for many other medical or research records. Further, investigators and IRBs should be aware that special Federal requirements might apply to certain drug abuse records used in research. Information about this may be found in the Code of Federal Regulations (CFR) under 42 CFR Part 2, "Confidentiality of Alcohol and Drug Abuse Patient Records."

Investigators also should be aware that the Secretary, HHS, may authorize persons engaged in biomedical, behavioral, clinical, or other research to protect the privacy of individuals who are the subject of such research by withholding from all persons not connected with the conduct of such research the names or other identifying characteristics of research subjects. Persons so authorized to protect the privacy of such individuals may not be compelled in any Federal, State, or local civil, criminal, administrative, legislative, or other proceedings to identify such individuals (42 CFR Part 2a). However, investigators, research participants, and IRBs should be aware that there are no absolute guarantees of confidentiality.  

 

Specific Issues


The NACDA recommends that these important issues be considered in the development and review of research involving the administration of to human subjects. 

 Medical and Psychological Screening and Services


Care should be taken to ensure that study personnel who are administering the drug(s) and who are responsible for the associated care of the subjects have the proper training and experience in administering drugs to humans. Investigators should specify the level of training and experience study personnel will have prior to their direct involvement in drug administration.

Medical and psychological screening procedures must be carried out to ensure that participants chosen for the study will not be harmed by drug administration. To further assure this, appropriate monitoring and medical support services must be available during the study. The amount of medical support necessary will depend on the study protocol (e.g., drug(s) under study, route and rate of drug administration). At a minimum, a nurse or physician available "on call" may be appropriate. This may be amplified to require a nurse to be present with a physician available, or to require a physician to be present, if the demands of the study require it.

Medical and psychological screening procedures may be of particular significance in elderly subjects. Such subjects may be undergoing gradual changes in anatomy and physiology that may alter the effects of drugs.  

 

A.  Administration of Drugs to Individuals Who Have Never Used Drugs


It is expected that research involving the administration of drugs of abuse to individuals who have never used drugs prior to study participation would occur only in the rarest of circumstances and with the strongest justification. Such research must be justified very strongly within the requirement that (1) the question under study cannot be reasonably or validly answered without their participation and (2) there exists a strongly favorable risk/benefit assessment. It should be remembered that a wide range of potentially abusable drugs might be the focus of drug administration research--from caffeine and nicotine to cocaine and opiates. Depending on the drug, limited investigator-controlled exposure to these drugs may have very different levels of risk for potential participants. Casual drug users may be appropriate research subjects, given that the benefits outweigh the risks of participation.  

B.   Involvement of Individuals Currently Addicted to Drugs and/or Are Frequent Drug Abusers


Research which requires individuals who are addicted to drugs and/or are frequent drug abusers to be administered drugs warrants special attention. As stated above, investigators should take into consideration current, recent, and past drug use and thoroughly assess the participant's ability to provide informed consent. There are a number of extremely important principles that need to be addressed by anyone considering or evaluating requests to undertake such research. These include the following: a) a serious and concerted effort be made to link these individuals to drug abuse treatment; b) inclusion of medical examination and screening to assure the absence of any medical or mental condition for which further drug exposure would be contraindicated; and c) a thorough assessment of the risks entailed if participants are to be exposed to higher doses, rate of administration, and/or new route of administration than they would normally encounter by their own choice in their usual circumstance.

If the subject has participated in prior drug intervention trials, a list of previous dosing regimens, (i.e. drug, dosage, frequency, duration), should be included in the evaluation record. Prior drug failures should be indicated. If the patient currently is taking (or has been prescribed) medications to prevent or reduce addiction, similar information should be evaluated. Extreme care must be exercised when admitting any patient in a trial when the subject is taking any concomitant medication. Possible drug interactions should be evaluated thoroughly before admitting the patient in the trial. Concern regarding drug interactions between the test drug and concomitant medications (prescribed for the subject for preexisting conditions) is sufficient in some cases to exclude subjects from a study.  

C.   Administration of Drugs to Incarcerated Individuals


In accordance with the Code of Federal Regulations (CFR) 45 CFR Part 46 Subpart C, additional protections must be given to research involving prisoners as subjects. Such consideration is given because prisoners may be under constraints to full voluntary participation in a research project because of their incarceration and/or the conditions of their legal supervision.  

D.   Administration of Drugs to Individuals with Mental Disorders


In addition to the basic protections offered in the Code of Federal Regulations, additional protection must be given to research involving persons with mental disorders that may affect decision making capacity. Persons with such disorders may have impaired capacity to give voluntary consent that must be considered. Investigators are encouraged to review the recommendations of the National Bioethics Advisory Commission, "Research Involving Persons with Mental Disorders That May Affect Decision Making Capacity" (December 1998). Administration of drugs that might exacerbate existing mental conditions either acutely or chronically must have a compelling rationale.  

E.  Drug Doses and Routes of Administration


To minimize the risk, participants should be exposed to the least amount of drug necessary to achieve the purpose of the study. Sometimes it may be necessary for participants to be administered new drugs and/or doses of drugs greater than that they would normally consume by their own choice in their usual circumstance, or to be exposed to a new route of administration. Under those circumstances, the rationale for exposure to new drugs, to higher doses, or to new routes of administration should be clear and compelling.

F.  Prior and Current Drug Treatment Status


Another factor that must be taken into consideration in any decision regarding administration of drugs of abuse to human subjects is the subject's current and prior drug treatment experience. With regard to subjects currently in treatment, administration of drugs of abuse as part of an experimental study rarely is appropriate and should only be done under the most structured circumstances. This is because there is great risk of impeding a subject's efforts at rehabilitation.

In general, in-treatment or treatment-seeking individuals should not be given drugs of abuse. However, there can be circumstances in which such research is appropriate. In-treatment or treatment-seeking individuals who have an addiction history may be uniquely appropriate for some types of research. In these cases investigators have a special burden to establish a compelling rationale for the inclusion of these participants. Priority always must be given to what is in the best interest of the participant/patient. Participants should not be recruited simply for the convenience of the investigator. Any situation where drug administration could potentially interfere with the treatment process or motivation of the patients almost certainly will be contraindicated.

Investigators also have an additional burden for ensuring proper participation in the informed consent process. Among current and past drug users, special issues arise regarding their interest in, and level of commitment to, abstinence. Treatment providers should be consulted with consent of the subjects prior to use of such subjects.

G.  Prior and Current Treatment Experience


If the subject has participated in prior drug intervention trials, a list of previous dosing regimens, (i.e. drug, dosage, frequency, duration), should be prepared. Prior drug failures should be indicated. If the patient is on current therapy for possible efficacy against a substance of abuse, similar information should be obtained. Care must be exercised when admitting any patient in a trial when the subject is taking any concomitant medication. Possible drug interactions should be evaluated thoroughly before admitting the patient in the trial.

H.   Women With Childbearing Potential


Women of childbearing potential should not be automatically excluded from participation in clinical research. The NIH policy is that women must be included in all NIH-supported biomedical and behavioral research projects involving human subjects, unless a clear and compelling reason shows that inclusion is inappropriate.

I.  Pregnant Women


Risk/benefit considerations virtually always would preclude administration of drugs to pregnant women as this may endanger the fetus. One notable exception would be in the treatment of pregnant, substance dependent subjects. Therefore, it is the responsibility of the investigator to have a very compelling rationale for such a study; and to take adequate precautions, throughout the study, to prevent inappropriate administration of drugs to women who are, or may be, pregnant. Pregnancy always must be assessed using an acceptable pregnancy test. While menstrual and contraceptive history may be useful, the assessment of pregnancy status should not be made solely by self-reported information. As with all research, investigators and IRBs must adhere to the additional requirements pertaining to research involving fetuses, pregnant women, and human in vitro fertilization as contained in HHS Regulations for the Protection of Human Subjects, 45 CFR Part 46, Subpart B.

J.   Special Considerations Across the Lifespan


If the hypothesis being tested requires the involvement of individuals under age 18 and the risk/benefit assessment is favorable, the investigator must: (1) obtain the individual's consent and/or assent to participate in the study; (2) obtain permission from the parent(s) or guardian for the individual to participate in the study, as appropriate; and (3) comply with any applicable local laws governing such research. As with all research, investigators and IRBs must adhere to the additional requirements for the protection of children involved as subjects in research, as contained in HHS Regulations for Protection of Human Subjects, 45 CFR Part 46, Subpart D.

As stated in Section IV, Part A, elderly subjects also constitute a vulnerable population. Such subjects must be given special considerations because they may be undergoing gradual changes in anatomy and physiology that may alter or be altered by the metabolism and short and long-term effects of drugs.

K.   Study Personnel Training and Experience


Care should be taken to ensure that study personnel who are administering the drug(s) and who are responsible for the associated care of the subjects have the proper training and experience in administering drugs to humans. Investigators should specify the level of training and experience study personnel must have prior to their direct involvement in drug administration.

L.   Infection Risk Reduction Counseling and Testing


Persons that use drugs are often at special risk for contracting and transmitting HIV, tuberculosis (TB), hepatitis, syphilis and other infectious diseases. Infection risk reduction interventions have been demonstrated to effectively reduce these behaviors. NIDA has established a policy (NIH Guide for Grants and Contracts, June 9, 1995) that strongly encourages NIDA-funded researchers to offer HIV education and counseling and infection testing available to research subjects.

M.  Safety of Research Participants Outside of the Research Site


A concern is the possibility that individuals who have been administered drugs in a study may still be under the effects of those drugs and, upon leaving the laboratory, drive or engage in behavior that may be harmful to themselves or others. The consent form and research protocol should address the estimated period of time that the research participant likely will have to stay at the research facility. Participants must be kept under observation for that period and when dismissed from the laboratory, participants should be informed of the potential performance impairments to be expected during this period. Investigators also should determine, depending on the nature of the study and the subject, the likelihood of any delayed reaction from participation in the study. Discharge personnel should have the necessary training and experience to determine whether the subject is impaired. If it is determined that the subject is impaired, provisions should be made to provide the appropriate intervention. Another concern arises in studies that manipulate "cue reactivity," which may mimic a drug effect, to ensure that the research participant is not discharged in a heightened state of desire for drug that would put the individual at risk of drug use or relapse. Discharge personnel should have the necessary training and experience to determine that the subject is not at such risk, and assessments to make this determination should be specified. If it is determined that the subject is at risk, provisions should be made to provide the appropriate intervention.

N. Referral to Treatment


Investigators should be knowledgeable about available drug abuse treatment options and, where medically indicated, offer research participants referral to treatment before, during, and at the conclusion of study participation. Investigators who identify co-morbid or coincident diseases in study participants should provide or refer them to appropriate medical care.

O.   Incomplete Disclosure


On relatively rare occasions, an element of deception or incomplete disclosure of information about the research methods or goals may be justified in drug abuse as well as other research; for example, when researching expectancy and placebo effects. Any such withholding which results in the exclusion or alteration of some or all of the elements of informed consent in 45 CFR Section 46.116 must be approved by the IRB in accordance with the waiver requirements of 45 CFR Section 46.116(c). At the conclusion of participation in the research protocol, research participants should have a general and study specific debriefing. In addition, participants should have the opportunity to be informed of study results and their significance upon completion of the study analysis.

The consent form should clearly indicate that they might receive drugs, the types of drugs, and information on the amount they may receive. Information about risks must never be withheld for the purpose of eliciting the cooperation of volunteer participants. Truthful answers must always be given to direct questions about research. (See also page 6 of the Belmont Report.) 

P.   Participation in Research


Payment to research participants for their time and inconvenience is an acceptable practice in drug abuse as well as other biomedical research. The payment should not be exploitive or coercive in the sense of unduly tempting individuals to participate. In this regard, alternatives to cash payments should be considered (e.g., vouchers for food, movies, clothing, etc.). When cash payments are considered important and appropriate, the payment could be made in installments or to a third party.


Conclusion

These principles represent a brief summary of basic issues relating to research involving the administration of drugs to human subjects. It should be recognized that there are benefits in addition to risks to individuals who participate in research. Such benefits may include medical and psychological evaluation, HIV counseling and testing, and referral to drug abuse treatment.

Further information on human subject research may be obtained from the Office for Human Research Protection and from the National Institute on Drug Abuse at the following locations.

Office for Human Research Protection
6100 Executive Boulevard, Suite 3B01
Rockville, MD 20892-7507
(301) 496-7005

National Institutes of Health
Office of Human Subjects Research
Office of Intramural Research
9000 Rockville Pike
Building 10, Room 1C116 (MSC 1154)
Bethesda, MD 20892-1154
(301) 402-3444

National Institute on Drug Abuse
Office of Science Policy and Communications
National Institute on Drug Abuse
6001 Executive Boulevard,
Bethesda, MD 20892-9591
(301) 442-6071

These Guidelines were revised and approved by the National Advisory Council on Drug Abuse on September 13, 2000

Mark Taylor's testimony before the FDA 9/13/2004


I am Mark Allen Taylor and I am a victim of the SSRI antidepressant era. I took six to thirteen bullets in the heart area in the Columbine High School shooting when Eric Harris on Luvox opened fire that now infamous day.


They almost had to amputate my leg and my arm. My heart missed by only one millimeter. I had three surgeries. Five years later I am still recuperating.


I went through all this to realize that SSRI antidepressants are dangerous for those who take them and for all those who associate with those who take them.


I hope that my testimony today shows you that you need to take action immediately before more innocent people like me, and you, do not get hurt or die horrible deaths as a result.


As Americans we should have the right to feel safe and if you were doing your job we would be safe. Why are we worrying about terrorists in other countries when the pharmaceutical companies have proven to be our biggest terrorists by releasing these drugs on an unsuspecting public?


How are we suppose to feel safe at school, at home, on the street, at church or anywhere else if we cannot trust the FDA to do what we are paying you to do? Where were you when I and all of my classmates got shot at Columbine?


You say that antidepressants are effective. So why did they not help Eric Harris before he shot me?


According to Eric they "helped" him to feel homicidal and suicidal after only six weeks on Zoloft. And then he said that dropping off Luvox cold turkey would help him "fuel the rage" he needed to shoot everyone. But he continued on Luvox and shot us all anyway.


So, why did these so called antidepressants not make him better? I will tell you why. It is because they do not work.


We should consider antidepressants to be accomplices to murder.

See Mark's book "I Asked, God Answered ... a Columbine Miracle."


Silencing the Truth about the Drug Luvox and Homicidal Thoughts

Mark Taylor was only a high school student when he had sustained terrible injuries during the violent shooting spree at the Columbine school.  Mark had suffered incredible blood loss resulting from 7 - 13 bullets as he laid on the ground at Columbine for almost 2 hours  help could arrive.  That traumatic memory will always remain with Mark Taylor, the memories of the  shooting and lying there helpless for two hours with bullets whizzing around him while bleeding from nearly a dozen bullet wounds.  Some bullets still even now remain embedded in his spine and near his aorta.  Because of the way the bullets ravaged Mark’s body, it was even impossible for the surgeons to count the wounds.  The estimated bullet count ranges from 8 to 13.  

Miraculously, Mark showed courage, strength and resiliency and  eventually went on to a full medical recovery.  Mark even wrote a book about his experience and  went on a book tour, and even was brave enough to testify before the FDA.  Because of the notoriety of the case,  Mark Taylor  was interviewed on numerous television broadcasts and his story in public eye .  

Because of his horrendous experience, Mark Taylor became a truth teller regarding the dangers of antidepressants and SSRI medications and how those medications cause patients to have violent thoughts,  homicidal ideations and thoughts of suicide.   These drugs have long been known to have these severe side effects and there is a black box warning about this required by the FDA to be put on these medications.  But doctors ignore these warnings and give these medications to patients anyway.  One of these patients receiving this kind of medication was Eric Harris, the student who decided that fateful day to shoot and kill his fellow students at Columbine.

This  antidepressant, Luvox is still on the market and now has "homicidal ideation" listed as a side effect.   Homicidal ideation is not just one thought of homicide, but constant ruminating thoughts of killing and how to accomplish that. This warning about tendencies to violence, based on pre-marketing research data - before the drug ever hit the market or was approved by the FDA, was kept from an unsuspecting  public and the drug marketed to patients for years.

Eric Harris, one of the Columbine shooters,  was taking the anti-depressant Luvox when he decided to kill his fellow students. The first antidepressant Eric Harris was given was Zoloft. Within six weeks of taking the drug Eric reported he was having homicidal and suicidal thoughts.   Clearly doctors suspected the antidepressant because they took him off the drug immediately.   Eric Harris was taken off that drug but then was put on Luvox.   The Luvox caused him to also have violent thoughts and with homicidal intent Eric Harris killed students at Columbine.  The Columbine families filed a legal law suit against Solvay, the maker of the antidepressant Luvox.

The drug companies threatened to counter sue to Columbine victims so as a result all the victims retracted their law suits except Mark Allen Taylor. Mark stood up to the pressure and intimidation by the big drug company which had much to loose by the publicity brought by Mark's tragic victims story.   Solvay already had bad press about their drug hitting the news because a patient, Matthew Beck, who was also on Luvox, went on a shooting spree at the Connecticut Lottery killing four co-workers before taking his own life.  In another Luvox case, a decorated police officer from New Jersey was prescribed Luvox and while on this medication he shot six persons – killing them.  This police officer, Edward L. Lutes along with Mark Allen Taylor filed a lawsuit against Luvox.  This lawsuit caused the drug manufacturer to pull the drug off the market in the U.S.A.  Mark Taylor had survived more gunshot wounds during the shooting rampage than anyone else.  Mark's courage and that of a decorated police officer in NJ, Edward L. Lutes, stopped the sale of this dangerous drug, Luvox.

But this stop on the marketing and  sale of this dangerous drug, Luvox,  which had already caused these violent deaths was short lived.  Mark Taylor was subsequently  legally ill advised by an attorney who encouraged him to sign a settlement agreement anyway even though he was clearly emotionally suffering PTSD as a result of the shooting trauma.  Mark was that day in negotiations with the opposing attorneys for hours and was lead to believe that he was himself in legal trouble.  Mark Taylor was deceived and coerced into signing a settlement with the drug maker Solvay.  This attorney, it was later determined,  had formerly worked for the drug giant GlaxoSmithKline and was on friendly terms with the pharmaceutical industry and was urging Mark Taylor to sign settlement papers so as to rapidly close the case. Then after the settlement was signed the judge decided to seal the evidence on the case.  This made the evidence of the homicidal effects of this drug Luvox unavailable to public scrutiny.  Then Solvay sold the market rights to Luvox in the USA to Jazz Pharmaceuticals.

The pharmaceutical industry has great political and financial power over what happens in mental health care. Now years later, to silence Mark Taylor's efforts to expose the dangers of antidepressants and how they cause patients to have homicidal thoughts,  Mark Taylor is now being treated with the very class of drugs that he warned the public about and he is also threatened with permanent imprisonment by mental health authorities.

After many public appearances about the dangers of psychiatric medications like Luvox, Mark and his mother, Donna Taylor were traveling in Arizona when suddenly he seemed to be having seizures.  Going immediately to the emergency hospital,  Mark and his mother were ill prepared for the actions of the mental health professionals who then unexpectedly decided to keep him hospitalized on a long term basis.  Mark then ended up  in a hospital  while his family was prevented from communicating with him and he was ultimately held without his family's consent for over a year, while being force drugged.

While hospitalized the Arizona Mental Health Officials, choose to put Mark on a psychiatric drug that is considered a “last resort” medication:

Clozapine (sold as Clozaril, Azaleptin, Leponex, Fazaclo, Froidir; Denzapine, Zaponex in the UK; Klozapol in Poland, Clopine in NZ/Aus) is an antipsychotic medication used in the treatment of schizophrenia, and is also used off-label in the treatment of bipolar disorder.  There are three pharmaceutical companies that market this drug at present: Novartis Pharmaceuticals (manufacturer), Mylan Laboratories and Ivax Pharmaceuticals (market generic clozapine).

Clozapine was the first of the atypical antipsychotics to be developed, It was first introduced in Europe in 1971, but was voluntarily withdrawn by the manufacturer in 1975 after it was shown to cause agranulocytosis, a condition involving a dangerous decrease in the number of white blood cells, that led to death in some patients.

In 1989, after studies demonstrated that it was more effective than any other antipsychotic for treating schizophrenia, theU.S. Food and Drug Administration (FDA) approved clozapine’s use but only for treatment-resistant schizophrenia. The FDA requires blood testing for patients taking clozapine.

The FDA also requires clozapine to carry five black box warnings for

    agranulocytosis,
    seizures,
    myocarditis,
    for “other adverse cardiovascular and respiratory effects”, and for
    “increased mortality in elderly patients with dementia-related psychosis.”

In 2002 the FDA approved clozapine for reducing the risk of suicidal behavior for patients with schizophrenia.Clozapine is usually used as a last resort in patients that have not responded to other anti-psychotic treatments due to its danger of causing agranulocytosis as well as the costs of having to have blood tests continually during treatment. The withdrawal effects Clozapine are severe and life-threatening.

Mark, the courageous Columbine miracle boy, who survived what many did not, and who lived to be an advocate for others,  is now hospitalized long term with doctors forcing on him the very type of drug that he advocated should be removed off the market.  This drugging regime has left Mark unable to communicate and to care for himself.  His mother, Donna Taylor, has been appointed as his legal guardian.  Now, under the best of circumstances, Mark Taylor faces one to two years of recovery.   Mark has been victimized again by the pharmaceutical industry and the medical professionals who support this forced drugging with anti-depressants and SSRI's and he may never fully recover from this continued misuse and abuse of psychiatric medications.

 

Secret Deals in Court Cases Hide the Truth about SSRI's

When SSRI antidepressants such as Prozac, Paxil and Zoloft were first introduced in the late 1980's and early 1990's there were reports of increasing violent behavior including suicide and homicide. There were in 2003 reports by British authorities and the U.S. Food and Drug Administration about unpublished studies showing an increased risk of suicide in children and teenagers taking Paxil. Prior reports of suicidal and homicidal acts in adults taking SSRIs have been minimized by the pharmaceutical company defenders and mainstream doctors, who claim that suicide is common in depression anyway.

 

The recent violence Nov. 5, 2009 at Fort Hood in Texas in which a military psychiatrist shot and killed 13 people and wounded 30 others gives us good reason to reconsider these psychiatric drug treatments for military personnel and veterans. This incident reminded me of the Northern Illinois University mass shootings where former grad student Stephen Kazmierczak killed 5 students and wounding dozens of others before committing suicide himself.  This gunman had been taking the drug Paxil prior to his mass killings. The drug manufacturer had been deliberately withholding information about violent behavior as an adverse effect of the medication.   Now the drug Paxil carries a black box warning about homicide and suicide. (See the insightful article by Drs. Healy, Herxhiemer and Menkes on Antidepressants and Violence: Problems at the interface with medicine and law.)

 

On Sept 14, 2004, an FDA panel voted 18 to 5 to require manufacturers of all antidepressants to add black box warnings to their product labeling.  A month later, the FDA adopted the panel's recommendations. The warning reads in part: "Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with Major Depressive Disorder (MDD) and other psychiatric disorders. Anyone considering the use of [Drug Name] or any other antidepressant in a child or adolescent must balance this risk with the clinical need.  Patients who are started on therapy should be observed closely for clinical worsening, suicidality, or unusual changes in behavior."  The warning specifically links antidepressant use to suicidal behavior in four percent of kids on these drugs compared to two percent for kids on placebos.

 

No type of antidepressant is helpful in every clinical case or even indicated.  As a class of drugs SSRIs can create a unique combination of side effects that may severely impair judgment and impulse control in individual patients. Excessive doses of antidepressants can cause brain dysfunctions including disorientation, confusion, and cognitive disturbances.  In combat veterans suffering PTSD, impulsive behavior, especially if coupled with impaired cognitive functioning, can be dangerous. Antidepressants can also trigger similar, manic-like symptoms in people whose depression is part of a manic-depressive syndrome, which often gets overlooked when people are given SSRIs.

Is public safety enhanced when “patients” are given SSRI’s and are persons on SSRI’s less likel y to do gun violence?  The pharmaceutical corporations would lead you to believe that a person taking these drugs is less likely to commit suicide and  less likely to do gun violence to others.  But is that really true?

 

The use of secret settlements to withhold information about a known harm of a pharmaceutical drug was very evident in the Fentress case, in which the Kentucky Supreme Court found that lawyers who engaged in an ongoing trial after a secret settlement had already been reached. Judge Potter said their conduct showed "a serious lack of candor with the trial court, and there may have been deception, bad faith conduct, abuse of the judicial process or perhaps even fraud." [Potter v. Eli Lilly & Co., 926 S.W.2d 449, 454 (Ky. 1996).]

 

In summary the Fentress case was about a violent incident in September 1989.  Joseph Wesbecker armed himself with an AK-47, walked into the Louisville printing plant where he had worked, and started shooting his former co-workers.  After killing eight people, wounded twelve more, and the man finished matters by committing suicide with his gun. Only one month before, Wesbecker had begun taking Prozac.  The known problems of violent behavior of patients on this medication had been withheld from the public, governmental regulators and even medical professionals.  The lawyers for the shooting victims soon focused on the drug Prozac, manufactured by Eli Lilly, as the cause for Wesbecker's unexpected violence.  With the sales of the drug Prozac at $1.7 billion in 1994 there was a lot at stake in this legal case. The Plaintiff's counsel had information about the withholding of research findings regarding another Eli Lilly drug Oraflex. In 1985, Lilly had pled guilty to twenty-five criminal counts of failing to report adverse reactions to Oraflex, including four deaths, to the Food & Drug Administration. But then suddenly during the trial the Oraflex evidence was no longer going to be presented to the court.

 

There was an experienced and astute Judge on the case, John Potter, who suspected something was afoul despite the lawyers' denials and their references to a damages phase,  Judge Potter suspected that a deal had been made before closing argument.  When the plaintiffs didn't file a notice of appeal, Potter became suspicious and thus called in the lawyers from both sides for consultation.  But the lawyers continued to deny that a settlement had been reached.  When the appeals court ruled against Judge Potter saying he no longer had jurisdiction, Potter was not satisfied and appealed the case to the Kentucky Supreme Court.  Finally in a Supreme Court hearing, lawyers for both sides finally acknowledged that they had indeed settled all money issues and had agreed to go through only the liability phase of the trial no matter what the result.  Judge John Potter took the "high road," acting consistently with the judiciary's responsibility, and protecting the public interest.  Thus the role of the judiciary in deciding matters of privacy and sealed records is an important balancing act of sometimes competing interests but which must also take into account the public's right to know especially when there is a compelling public interest.

"He who learns but does not think, is lost. He who thinks but does not learn is in great danger."

Confucius

Ways Psychiatric Survivors Resist Institutionalization

 

Institutionalization 

1.  Certification (medical arrest)

2.  Commitment (medical incarceration) 

3.  Treatment (chemical incarceration)

4.  Restraint, isolation (physical control) 

5.  Illness education (indoctrinization)

 

Resistance 

1. Question, challenge, second opinion

2. Reticence, feign, appeal

3.  Non-compliance, self-medication

4.  Defacement, violence, dissociation, self-injury 

5. Parrot, challenge, research, publish

“Too often we underestimate the power of a touch, a smile, a kind word, a listening ear, an honest compliment, or the smallest act of caring, all of which have the potential to turn a life around.”

― Leo Buscaglia

Medical Whistleblower Advocacy Network

MEDICAL WHISTLEBLOWER ADVOCACY NETWORK

P.O. 42700 

Washington, DC 20015

MedicalWhistleblowers (at) gmail.com

CONTACT


"Never impose on others what you would not choose for yourself."  Confucius

"It is not the critic who counts; not the man who points out how the strong man stumbles, or where the doer of deeds could have done them better. The credit belongs to the man who is actually in the arena, whose face is marred by dust and sweat and blood; who strives valiantly; who errs, who comes short again and again, because there is no effort without error and shortcoming; but who does actually strive to do the deeds; who knows great enthusiasms, the great devotions; who spends himself in a worthy cause; who at the best knows in the end the triumph of high achievement, and who at the worst, if he fails, at least fails while daring greatly, so that his place shall never be with those cold and timid souls who neither know victory nor defeat."

Theodore Roosevelt- Excerpt from the speech "Citizenship In A Republic", delivered at the Sorbonne, in Paris, France on 23 April, 1910