 |
|
|
|
|
MEDICINE MEN HUSTLE HAPPINESS: New Cures Demand New Diseases
by Robert P. Helms
June 2004
FOR THE BETTER PART of its 70,000-year existence, the human race has had nothing to treat its frequent feelings of helplessness, anxiety, and inadequacy, and likely believed it was experiencing these unpleasant and even debilitating emotions through some fault of its own. By the 1950s, modern psychiatry determined that if these problems were intense enough and recurred often enough, they were in fact a disease called clinical depression, which, they estimated, afflicted fifty people per million. Today, that rate has grown by a factor of 2,000. About 18.8 million American adults over the age of 18 will experience a depression-related illness this year, according to the National Institute of Mental Health, and as many as 25 million of all ages are taking antidepressants.
To prescription drug manufacturers like Eli Lilly & Co., these millions of depressed Americans represent a large and extremely lucrative market. Prozac, the company's blockbuster antidepressant, has generated $21 billion in sales for Lilly since being approved by the Food and Drug Administration (FDA) in 1987. (Prozac is a selective serotonin reuptake inhibitor or SSRI antidepressant, which acts by increasing the amount of the neurotransmitter serotonin present in the brain.) But in 2001, Lilly lost its exclusive patent to produce and sell the drug and its monopoly on U.S. sales. The company soon began testing another drug, duloxetine, which it hopes to bring to market by the end of this year under the name Cymbalta. While Prozac acts on only one brain chemical, serotonin, duloxetine also affects levels of a second chemical, norepinephrine, which the body releases during periods of stress. Analysts have predicted the drug could make the company as much money as Prozac once had.
Lilly had already tested duloxetine extensively in paid, volunteer human subjects, but in 2003 the FDA asked for one more test, examining the effects of high doses of duloxetine on the heart. Lilly recruited one hundred women for the test, one of whom was 19-year-old Traci Johnson, a Bible student from Bensalem, Pa. who volunteered to earn money to pay her tuition. The trial was conducted at a Lilly facility in Indianapolis, where a Lilly doctor interviewed Johnson and determined that she was a healthy subject with no history of depression. For four weeks, Lilly gave her larger and larger doses of duloxetine, culminating on January 28, when she was given 400 milligrams—five times the regular dose. During the next four days, she was rapidly weaned off the drug and, on February 3, switched to a placebo. Then, on February 7, Johnson tied her scarf to a shower curtain rod in a bathroom at the Lilly research unit and hung herself. She left no note.
Her pastor in Philadelphia, Rev. Joel Barnaby, was at home watching the film O Brother, Where Art Thou? with his two sons when he got the call from the Rev. Paul Mooney, who heads the college Johnson had been attending. Barnaby drove his Jeep Wrangler up Interstate 95 to the family's home and waited with Traci's sister for her parents, who were out to dinner, to return.
“This is one of the saddest things I have to tell you in my role as a pastor,” Barnaby, who has since acted as the family's spokesman, remembers telling Traci's parents, Mike and Peggy. “'Your daughter Traci has been found dead in her room in the control facility of the Eli Lilly company.' Their faces turned pale. I remember her mother Peggy saying, ‘Oh my lord help me …' She was weeping in my arms, it was such a shock. The parents had been assured there was no risk. They thought that because this was a big pharmaceutical company, they can't hurt you. Their trust was the foundation of her going into it.”
Rev. Barnaby remembers Johnson as an energetic and cheerful girl, active in the Greater Church of Philadelphia, a Pentecostal church in Kensington. She'd ministered to the homeless, sung in the choir, taught Sunday school and tutored children from the neighborhood. She had gone to Indianapolis to become a professional preacher. Why would she suddenly kill herself?
“It is my conviction that the drug had everything to do with this. I believe that it is a direct cause of her death,” Barnaby said.
In an interview conducted over email, Eli Lilly spokesman Philip Belt disagreed, but declined to offer an alternative explanation: “Suicide is always difficult to understand, and we may never know why this young woman took her life. Based on everything we have learned so far … we do not believe her death was related to her participation in our study.”
But this was not the same story that other test subjects got immediately following Johnson's suicide. According to reports in the Indianapolis Star, Dr. Mark Leibowitz lied to four other women in the study, telling them that Johnson had a history of depression and shouldn't have made it through the screening process. Leibowitz was the lead physician of the company conducting a simultaneous duloxetine trial for Lilly at a second site in California. He was aware that if news of the Johnson suicide caused his subjects to walk out, the trial would have to be conducted all over again, potentially delaying Cymbalta's approval.
The questions surrounding the drug companies' credibility being asked in Bensalem and Kensington are also happening all over the world. As I write, committees in both houses of the U.S. Congress are investigating alleged conflicts of interest between the drug industry, the National Institutes of Health (NIH), and the FDA. Late last month, University of Cincinnati law professor and historian of the FDA James O'Reilly told the Denver Post, “The FDA is now in the business of helping lawsuit defendants, specifically the pharmaceutical companies.” In a May hearing, U.S. Rep. James Greenwood (R-Pa.) said scientists with NIH, the government agency responsible for regulating drug tests, “are either very close to the line or have crossed the line,” in their outside dealings with biotechnology and pharmaceutical companies. “If we are serious about upholding the highest ethical standards at the NIH, then NIH scientists should not even be close to the line.”
Overseas, officials have gone even further. Last month, an Australian judge found a woman who had tried to kill herself and her children not guilty because she was taking two SSRI-type antidepressants, which “substantially contributed” to her offenses. In the United Kingdom, Member of Parliament Paul Flynn called the drug companies “disease mongers” who encourage and profit from their customers' dependency. He noted that while the use of antidepressants increased more than fivefold between 1994 and 2003, there was no comparable decrease in the number of suicides.
A GUINEA PIG'S VIEW
Since 1995, I have volunteered to be a human guinea pig for about seventy medical experiments, testing the safety of experimental drugs and observing how the drugs acted with different diets or when other drugs were in my body. Although I have not been to the Lilly unit where Johnson died, I know others who have and there is little about the place that sets it apart from my old haunts, where pharmaceutical companies have paid me between $150 and $450 per day to put all kinds of experimental substances into my perfectly healthy body. I've taken antiretrovirals designed to fight HIV, immunosupressants that beat back the body's attempts to reject a transplanted organ, blood thinning agents, and anti-inflammatories. Previously, these drugs had only been tasted on animals and human tissue in test tubes. As a participant in a Phase I test, I was often one of the very first humans to take them.
Sometimes the work amounts to showing up on time, not being afraid of needles, and not eating anything that will disrupt the study. Such was the case when I was paid to take low doses of three drugs that were already on the market, in combination with grapefruit juice or water (a rather obvious placebo). On other occasions, being a human guinea pig was more demanding, like the time I had dozens of electrical leads taped to my chest and three catheters fastened into the veins of my arm to measure my response to a new formulation of amiodarone, a drug used to correct irregular heartbeats. One of my fellow guinea pigs told me he could feel the drug follow along his arm, cross over to his heart, and then rise to his head, which as through he'd been hit with a bat. Fortunately, I got the placebo that time.
I was saddened by the news of Johnson's death and the company's behavior afterwards, but I was not surprised. I have hired out only my body for drug experiments, never my mind. I consider clinical trials for psychiatric drugs to be too risky and the companies that make them too dishonest. I've known many people who've made their money testing antidepressants, most of which have been SSRIs. SSRIs act on serotonin, a brain chemical that regulates mood, sleep and appetite. In 1996, one of my close friends emerged from an SSRI trial $3,250 richer, but unwilling to eat or bathe, hardly ever sleeping, and so delusional as to believe that his life was the basis for the film Twelve Monkeys. After his condition improved a few weeks later, he refused to acknowledge or discuss what had happened. Later, when I reported the story in my zine, Guinea Pig Zero, and Harper's magazine reprinted the report, the company that made and tested the drug threatened Harper's and I with a libel suit.
THE PRICE OF SILENCE
Drug companies spend millions of dollars researching and testing their drugs, getting them approved by the FDA and marketing them to the public, so they have every reason to be concerned with what's being said about their products. This is particularly the case with antidepressants, whose very legitimacy as a treatment is often called into question. Earlier this year, Dr. Andrew Mosholder of the FDA's Office of Drug Safety wrote a long memorandum concluding that children given antidepressants were more likely to become suicidal. He was supposed to publicly present these findings to an FDA advisory committee on February 1, but his superiors at the agency pulled him off the agenda. In an interview with the New York Times, Dr. Robert Temple, associate FDA director of medical policy said “it would have been entirely inappropriate to present as a conclusion an analysis of data that were not ripe.” This raises the question of just what would count as ripe data, as the FDA had specially assigned Mosholder the task of analyzing twenty-two clinical trials of seven different drugs given to 4,250 children and reporting back with his conclusions.
There is also the question of whether the risk may be even greater than Mosholder found. Mosholder was only looking at studies conducted, approved and released by drug companies, and there is evidence that at least one of these companies has suppressed data that could keep their products off the market. In 1998, a confidential memorandum from SmithKline Beecham (now GlaxoSmithKline Plc) concluded that one study on the antidepressant Paxil “failed to demonstrate a statistically significant difference from placebo in primary efficacy measures,” and that a second study “showed a high placebo response rate and failed to demonstrate any separation of Paxil from placebo.” The memo concluded that these results were “insufficiently robust” and “will therefore not be submitted to the regulatory authorities.” (I found this document especially interesting because it was Paxil that my friend had been taking just before he came to believed he was Bruce Willis, and SmithKline that threatened me with the aforementioned lawsuit.)
The memo shows how the FDA allows drug companies to more or less regulate themselves, letting them determine which drugs are and are not safe and which studies will and will not be reported. And they are doing so in the face of allegations suggesting that the psychiatric drug industry is rarely interested in any science that might harm investor expectations of future drug production pipelines and profit margins. Some of these charges are coming from members of the psychiatric field itself, such as the Welsh psychiatrist David Healy. Before becoming known as one of the world's most outspoken critics of antidepressants, Healy was a paid consultant to the pharmaceutical industry, authored 120 peer reviewed articles and twelve books, and served as Secretary of the British Association of Psychopharmacology. He is an expert on the science and business of the drug industry, and a talk he gave in 2001 in Toronto on the subject is worth quoting at length: "No SSRIs, not even Prozac, are available on the Japanese market for depression. The era of depression that we have lived through in the 1990s in the West has arguably been a politically and economically constructed era that bears little relationship to any clinical facts. An era that has changed popular culture by replacing a psychobabble of Freudian terms with a new biobabble about low serotonin levels and the like … Aside from the inadequacy of our clinical trial methods, professors are in jail for inventing patients. A significant proportion of the scientific literature is now ghostwritten. A large number of the clinical trials done are not reported if the results don't suit the study's sponsoring company … to call this ‘science' is misleading. When you consider that we are now treating children from the ages 1 to 4 with Prozac and Ritalin, you will see that we are not treating diseases here."
Healy went on to analyze eating disorders and hyperactivity in terms of the creation of markets and the control of behavior for the benefit of industry. Finally, Healy delivered his punchline: “I happen to believe that Prozac and other SSRI drugs can lead to suicide. These drugs may have been responsible for one death for every day that Prozac has been on the market in North America.”
Healy's cautious wording about how antidepressants “may have been responsible” speaks to the complexity of precisely measuring the effects psychiatric drugs on their users. The efficacy of a drug for fever, for example, can be measured by taking the subject's temperature, just as the safety of an automobile can be measured with a crash test. A psychiatric drug, on the other hand, treats a condition that leaves much room for interpretation, and is diagnosed in part by the patient's input as well as the psychiatrist's observations. A healthy test subject is determined to be such, in part, through his or her own answers to standardized questions about a condition. Healy's new book, Let Them Eat Prozac, describes every niche of this process and shows how a company's stock price and product development deadlines can impact the way the interpret data.
Money allows companies to come to terms with the victims whenever things fall apart. The Johnson family has retained the Bristol, Pa. firm of Cordisco, Bradway and Simmons as their counsel. The family has requested that the Indianapolis coroner perform a second test on Johnson's blood to determine if duloxetine was in her system at the time of her death. Should the Johnson family decide to file suit, they will likely end up receiving a large settlement—perhaps as much as $10 million or even $100 million. But these amounts do not seem so large beside the $2 billion or more in annual sales that analysts have estimated Cymbalta could make on the U.S. market; in fact paying off the family of the occasional dead guinea pig or patient could be considered a cost of doing business. Unless the FDA changes the ways in which it collects and audits information from drug studies, it's unlikely the production of new disorders and new drugs will stop, with each scientific breakthrough timed to coincide with the expiration of a patent.
Lilly can afford to hire the best crisis managers, public relations representatives, and, if necessary, defense attorneys that money can buy. But Rev. Barnaby said money won't be enough to silence Traci Johnson's family. “They are greatly concerned that no further harm be done to anyone else as a result of taking this drug,” he said. “This is not about money. Traci died with some honor and with dignity. Eli Lilly needs to show some respect for her memory.”
Robert P. Helms is the editor and principle author of Guinea Pig Zero: An Anthology of the Journal for Human Research Subjects available from Garrett County Press. Formerly of University City, he now lives in Paris.
|
|
|
|
|
|
|
|
|
|
|
|
