February 15

Rolling Stone – Marketing a Phony “Miracle” Drug


The article is long, it covers a sizable territory: early enthusiasm for the promise the new antipsychotic drugs held, against the (by then) acknowledged intolerable effects of existing neuroleptic / antipsychotic drugs; the failure of science to this day, to answer basic questions about schizophrenia; Eli Lilly’s frantic effort to replace Prozac (which was going off patent); the aggressive sales pitch of Lilly’s reps; growing disillusion about the drugs among prominent psychiatrists at Yale and Harvard; the TMAP algorithm scam and Allen Jones, the whistleblower whose testimony led two public officials to lose their jobs—Steven Fiorello, Pennsylvania pharmacist who was convicted of a felony, and Dr. Steven Shon, medical director of the Texas Mental Health department who was forced to resign; Lilly’s aggressive off-label marketing campaign; the erosion of FDA power under the Bush administration, and Eli Lilly’s ties to the Bush family; the lawsuits which are absorbed as the cost of doing business; finally, the inescapable contrast between how much better people with schizophrenia fare in the developing world—with minimal access to drugs—compared with patients in the West whose treatment is centered on the drugs.

For almost a decade only “a few figures on the fringe of the medical profession” noted the dichotomy between the claimed efficacy of Zyprexa, and the demonstrable harm produced in patients.

Now mainstream professors at Yale and Harvard are acknowledging the marketing success of antipsychotics are not justified by the evidence. None of the drugs used to treat schizophrenia work very well—and they all produce debilitating irreversible physical and neurological damage. The drugs’ failure is related to the lack of understanding about schizophrenia. Scientists acknowledge, “We actually have a profound ignorance of the specific molecular mechanism of schizophrenia.”

“We tend to think of drugs as solving discrete problems — penicillin to eliminate bacteria, insulin to modify diabetes — but the antipsychotics are shooting at an invisible target. With schizophrenia,” says Dr. William Eaton, chairman of Johns Hopkins, Department of Mental Health, "we don't know what the hell is going on."

It is well to remember that effective drugs, such as antibiotics, don’t need multi-million marketing campaigns.

Wells sought to understand how, Zyprexa, a drug created to treat schizophrenia—in a very tiny population mostly inhabiting county jails and state prisons—wound up being used on depressed moms and misbehaving kids—and how Eli Lilly turned a flawed and dangerous drug into a $16 billion a year bonanza.

The development of Zyprexa and the other antipsychotics in its class (‘atypical’) affords a window into the interaction of key institutions–academic psychiatry, professional organizations, consumer advocates, the FDA, and the media—which came under the influence of the pharmaceutical industry.

Wells writes:
“The most vivid models we have of corporate deception come from the tobacco industry, where scientists working in company labs, behind sealed walls, conducted misleading experiments out of public view and then told the wider world they had found things they hadn't. But the pharmaceutical industry is immune to this kind of conspiracy. The size of clinical trials and the federal regulations that govern them mean that a company can never develop and study a molecule in-house; it relies on a platoon of contracted researchers, specialists at academic institutions, who test the molecules and then publish their findings in academic journals.”

But when those who conduct the trials sell their professional integrity, signing secret confidentiality agreements which prevent them from publishing the actual research findings; and when influential academics pen their name to industry-sponsored ghostwritten reports in those journals; and when prominent physicians are recruited to promote the drugs as “safe and effective” for unapproved uses–thereby broadening the number of patients exposed to the drugs’ harmful effects; the result is even worse than the deception by the tobacco industry. After all, smokers were not urged to “ask your doctor” if smoking is right for you… Prominent doctors with impressive academic credentials did not serve as paid consultants helping tobacco companies to promote smoking.

To accomplish the extraordinary marketing feat and generating “irrational exuberance” among clinicians, drug manufacturers took control of the drug testing process—including data analysis, authorship (penned by prominent academic psychiatrists), publication placement in key journals—and key academic psychiatrists were recruited for their professional influence to persuade clinicians and public policy officials that a class of drugs—the new ‘atypical’ antipsychotics—were better and safer than the old drugs, despite evidence contradicting such claims. FDA’s impotence vis-à-vis this powerful industry was accomplished after the Reagan administration made it a policy to gut the FDA: “Simply put, the FDA was no longer in a position to independently evaluate the effectiveness — and risks — of a drug like Zyprexa.”

It is understandable that well-meaning psychiatrists who treated patients with schizophrenia, sought better treatment without the debilitating side effects of the older drugs which they by then recognized as so painful that patients simply stopped taking them, were excited by the promise of an alternative. However, the marketing hype did not make sense from the very beginning: a top Lilly executive announced that its new schizophrenia drug, Zyprexa, has "the potential to be a billion-dollar-a-year drug." Dr. William Wirshing, a psychiatrist at UCLA, is quoted saying: "I almost pulled off the road and crashed into the side rail." At the time, the entire market for atypical antipsychotics was only $170 million. "How the hell do you make $1 billion? I mean, who are we gonna give it to? It's not like we're making any more schizophrenic brains."

And then there were the early red flags about dangerous adverse effects: “Wirshing saw very quickly, however, that Lilly had a problem: Many of his patients taking Zyprexa were gaining a startling amount of weight. The pattern was as sudden as it was consistent. For the first few days they were on the drug, you weren't aware of any palpable difference. But by the end of the week, you could see the weight gain, almost in real time. Bellies and thighs started spreading, faces started puffing out. By the end of a year, the results were stunning. Some of his patients had gained more than 125 pounds.”

When Dr. Wirshing brought his concerns about Zyprexa to executives at the company, they tried to dismiss the evidence. “First they told him that it was just the skinny schizophrenics who were getting fat. Wirshing re-examined his data; it wasn't true. Then they told him that it was the schizophrenia itself that was causing the weight gain, rather than the drug. Wirshing was apoplectic: "If schizophrenia causes that much weight gain, how come I've been working with schizophrenics for 20 years and didn't know that?"

But how did the FDA fail to notice the obvious dangers? “In 1995, as the company was preparing to submit Zyprexa for approval to the Food and Drug Administration, Lilly convened a panel of experts to review the results of its largest study. The specialists concluded that Zyprexa produced an average weight gain of 24 pounds in a single year. One in six patients, clinical trials later revealed, gained more than 66 pounds. Such a staggering side effect, doctors knew, could elevate a patient's blood-sugar levels — an indication that the drug could cause diabetes.”

“the data Lilly submitted in its application to the FDA that same year led the agency to draw a far less alarming picture of the drug. Relying on a database of 51 separate and conflicting studies provided by the company, the FDA concluded that patients taking Zyprexa for one year would have an average weight gain of only 11 pounds. "It's akin to the guys from the cigarette companies going, 'Well, it doesn't cause cancer,'” Wirshing says. "It's just plain not true."

It would be nine years before a comprehensive government study (CATIE) would reverse many of the claims that surrounded Zyprexa and other atypical antipsychotics, and raise disturbing questions about their risks. And nine years, in the pharmaceutical industry, is a lifetime.

The pharmaceutical industry and the federal government have always had an unusually intimate relationship — the government is industry's biggest customer and ostensibly its watchdog. The FDA regulates the development of a drug and, at least in theory, the marketing that follows its release. However, the FDA, the National Institute of Health, and the IRS receive hundreds of millions of dollars in user fees, grants, and taxes. Because Medicaid and Medicare buy such a large portion of drugs — particularly in the case of the antipsychotics, since virtually no schizophrenics can afford private insurance — the companies lobby those agencies, and their state subsidiaries, to try to win preferences for their own medications.”

To ensure that their more expensive antipsychotics and antidepressants were the recommended treatment of choice for which the government will pay for, drug companies initiated and paid-for the TMAP Algorithm formulary, signed off by a “consensus” panel of “expert” academic psychiatrists. TMAP is the most lucrative scam in medicine.

An influential player missing from the Rolling Stones article, is Steven Hyman MD PhD, the Director of the National Institutes of Mental Health, a leading neuroscientist, and a Harvard Professor whose enthusiastic endorsement of both the SSRI antidepressants and atypical antipsychotics, was expressed in widely publicized 1998 letter to the Director of the Center for Medicaid State Operations at HCFA, in which he expressed concern that the high cost of the atypical antipsychotics might constrain their use:

‘In some parts of the country, we understand that health care systems will not routinely allow new patients to be started on atypical antipsychotic medications until they have failed a course of the standard (less expensive generic) antipsychotic medications. We see no scientific justification for such a practice and consider it particularly ill advised. . . This is a situation in which HCFA and the NIH institutes working in concert can have a substantial beneficial effect on the health care of the American people.” (http://www.medaccessonline.com/articles/index.php?articleID=5 and artcategoryID1=1)

But in 2002, Allen Jones, an investigator in the Pennsylvania inspector general's office, became convinced that government officials had been enrolled in marketing the drugs. Jones uncovered evidence showing that TMAP promoters included not only prominent psychiatrists, but government officials who set state mental health policies. These officials served as paid “experts” declaring the new antipsychotics “superior.” Though contradicted by the scientific evidence, their opinions had the mantle of government authority, thus ensuring a market and a continuing flow of sales.

TMAP is an epic fraudulent scheme not unlike Bernard Madoff’s $50 billion Ponzi scheme, which SEC investigators failed to detect for over a decade. Harry Markopolos, a financial expert recognized that Maddoff’s claimed investment return rates were implausible in 1999. They were, therefore, fraudulent. He recently testified at a Congressional hearing how Maddoff relied on 14 “feeder” funds that funneled investor funds to Madoff for a commission. http://online.wsj.com/article/SB123376121943648081.html

Allen Jones recognized “a big red flag” when he observed that TMAP promoters claimed Zyprexa and the other new antipsychotics were better than the old drugs. But they relied on biased research by industry-paid doctors, “a practice so commonplace that for most medical professionals, it barely registers — it's just part of the background noise.” However, “independent science, minus the drug-industry money, had come to a different conclusion." Underscoring the scope and magnitude of the TMAP fraud, 18 states adopted TMAP or TMAP versions. What's amazing is how well and for how long both of these fraudulent schemes worked.

Those involved in crafting and promoting TMAP, and those who helped Eli Lilly promote the expansive marketing of Zyprexa were not only collaborators in fraud—they were instrumental in causing severe harm to tens (if not hundreds) of thousands of people—including children and the elderly—some of whom have been killed by the drug.

“Indeed, internal documents show that Lilly's own experts were criticizing the company for covering up the link between Zyprexa and diabetes: "I do believe they made a very strong point that unless we come clean on this, it could get much more serious than we might anticipate," one Lilly executive warned in an internal e-mail in October 2000. But in hospitals and doctor's offices, the company's sales force continued to push Zyprexa as a wonder drug. In a common industry practice, Lilly persuaded leading psychiatric experts to endorse the drug and then paid them to tout it to doctors, who had little expertise when it came to antipsychotics.” Former Lilly Zyprexa sales rep, Ahari was struck by how perfectly the strategy worked: Most doctors, pressed for time, did not "approach the education they were getting from the industry with any skepticism at all."

The visible physical harm produced by Zyprexa, confirmed by internal company documents, could not have gone unnoticed by treating clinicians: “The weight gain was visible and striking. "You'd see it from one visit to the next," says Dr. John Abramson, a clinical instructor at Harvard Medical School who has studied the atypicals. "They'd come back, and they'd look like a different person. It looked like someone stuck an inflation needle in them and pumped them full of air." There were other effects, too. Patients got dizzy; they got tired; some saw their blood-sugar and cholesterol levels spike.”

“Between 2000 and 2004, the deaths of 45 children were linked to the atypicals. Some were strikingly young. An eight-year-old boy died of cardiac arrest. A four-year-old boy died of complications from diabetes. Perhaps most vivid of all was the case of a 15-year-old boy in South Florida referred to by social workers as a "runner," a kid who kept fleeing his exasperated foster parents to return to his birth mother. Admitted to a psychiatric hospital by a judge, the boy was tethered to a chair and pumped full of atypical antipsychotics, presumably to calm him. When his lawyer came to visit him, she found the boy not only sedated, but suffering from another acknowledged side effect of the atypicals: His breasts had become engorged and started to leak milk. The boy was lactating.”

“Visiting the most celebrated mental-health centers in the United States, it is hard to conclude that, even after the innovation of the atypicals, the drugs make a decisive difference in care.” It is difficult, therefore, to brush off the profession’s failure to recognize the disparity between clinical evidence and marketing hype as “overbright enthusiasm” or “irrational exuberance” or to accept the excuse offered by prominent psychiatrists such as, Dr. Peter Tyrer, Imperial College in London: “Almost the whole scientific community was conned into thinking — as a consequence of good marketing — that this was a different and better set of drugs. The evidence, as it's all added up, has shown this to be untrue."

If the whole scientific community was “conned,” they should hand in their license as they do not merit the status of “learned intermediaries.” Furthermore, leading psychiatrists who concealed their significant conflicts of interest, serving as industry’s consultants and promoters, who conducted rigged clinical trials and penned their name to fraudulent reports—reports that have polluted the scientific literature—continue to hold sway as prominent leaders within the profession. Shame on the psychiatric establishment for its failure to say, enough of the lies, enough corruption!

The devastating consequences of deregulation–which gave free rein to predatory profit seekers—is demonstrated in both, the economic meltdown and the transformation of medicine from its therapeutic mission into an accomplice for Big Pharma. The dire consequences of predatory market manipulation are borne by American consumers and taxpayers.

TIME Magazine has named 25 People to Blame for the Financial Crisis (24 men and one woman). Who will name the names in the medical community who are to blame for the drug-induced mental health crisis?

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