Pharmageddon (37 page)

Members of the public were then given three-minute slots to present views—seventy-three of them. Among these, a series of doctors made presentations—almost all male and all warning against the issuing of warnings. These were intermingled with a series of mothers, a modernday set of Demeters. Demeter was the Greek goddess of the Earth and of fertility whose daughter, Cora, was forcibly abducted and carried off to the underworld by Hades. Demeter protested to Zeus, who professed himself helpless, until Demeter threatened Earth with permanent winter. Zeus intervened and restored Cora to her mother as Persephone. Because Persephone had eaten some pomegranate seeds while in the underworld, however, she was obliged to return to Hades for the several months of winter each year.

These modern-day Demeters similarly aimed at shaming the heavens to take action. In a presentation with mythic resonance, in the 72
^nd
slot Mathy Downing confronted Tom Laughren:

On January 10th, 2004 our beautiful little girl, Candace, died by hanging four days after ingesting 100 mg of Zoloft. She was 12 years old. The autopsy report indicated that Zoloft was present in her system. We had no warning that this would happen. This was not a child who had ever been depressed or had suicidal ideation. She was a happy little girl and a friend to everyone. She had been prescribed Zoloft for generalized anxiety disorder, by a qualified child psychiatrist, which manifested in school anxiety…. She had the full support of a loving, caring, functional family and a nurturing school environment.

Her death not only affected us but rocked our community…. When Candace died her school was closed for the day of her memorial service, a service that had to be held in the school gym in order to seat the thousand or so people who attended. How ironic, Dr. Laughren, that your family attended Candace's memorial service. Our daughters had been in class together since kindergarten. How devastating to us that your daughter will graduate from the school that they both attended for the past eight years and that Candace will never have the opportunity to do so.

Candace's death was entirely avoidable, had we been given appropriate warnings and implications of the possible effects of Zoloft. It should have been our choice to make and not yours. We are not comforted by the insensitive comments of a corrupt and uncaring FDA or pharmaceutical benefactors such as Pfizer who sit in their ivory towers, passing judgments on the lives and deaths of so many innocent children. The blood of these children is on your hands. To continue to blame the victim rather than the drug is wrong. To make such blatant statements that depressed children run the risk of becoming suicidal does not fit the profile of our little girl.
⁶⁰

A few minutes earlier, Mary Ellen Winter had also confronted Laughren and the FDA about her twenty-three-year-old daughter, Beth, and brought a new player into the frame:

Beth was looking forward to a career in communication and was experiencing some anxiety and having trouble sleeping when she consulted our family physician. He prescribed Paxil and said she would start feeling better in two weeks. Seven days later Beth took her own life.

We, like most of you in this room, grew up with confidence in the strides made in medicine and accepted with faith antibiotics and vaccinations prescribed. We believed the FDA would always act to protect our family's well being. When my daughter went to our family GP last year, we trusted that our doctor was well educated and informed. We were wrong. We now know that pharmaceutical sales are a high stake business, driven to increase shareholder wealth. The consolidation of pharmaceutical companies like GlaxoSmithKline has resulted in increased sophistication in the quest to market and distribute pharmaceutical products. Priority has moved from health to profit. Not all doctors are equipped to understand the marketing targets they have become. The FDA has allowed our daughter to be the victim of a highly commercial enterprise that selectively releases clinical data to maximize sales efforts and seeks only to gain corporate profits….

As residents of the State of New York, we thank our Attorney General, Elliot Spitzer, for addressing issues that the FDA has been unwilling to address….
⁶¹

A few weeks before, the attorney general's office in New York had opened a fraud action against GlaxoSmithKline. The brief had been prepared by the unlikeliest of heroines, Rose Firestein. Firestein was blind and in poor health, but she had a passionate concern for the abuse of children. She charged GlaxoSmithKline with fraudulent interference with the practice of medicine. The company had engineered sales of Paxil for use in treating children who were depressed through the publication of ghostwritten papers that had concealed the drug's hazards and portrayed the outcome of studies, like Study 329, as positive even though this and other clinical trials had failed to show the drug worked. Her trump card was the internal GlaxoSmithKline document I had made public at an FDA hearing on pediatric suicidality on antidepressants six months earlier that showed the company deliberately setting out to present the good bits of the evidence and suppress the rest, and to publish papers in influential journals that would lead doctors to prescribe a drug that the company had already internally recognized did not work.

When faced by GSK's lawyers with the argument Troy made in the Motus case, that the FDA's views preempted any views a state might have, Firestein responded that New York was not attempting to argue the toss with the FDA on the labeling of the drug. When it came to the practice of medicine in the state of New York, however, the state and not the FDA had primacy. GlaxoSmithKline settled, and as part of the settlement posted on their website details of all of their clinical trials.

Ultimately, Mary Ellen Winter, Mathy Downing, and others who testified played a part in forcing the FDA to bow and issue warnings that antidepressants might lead to suicide in children, warnings that were extended to adults in 2006. These mothers did not win because their pleas were impassioned. They won because the FDA, although still giving every sign of willingness to ignore the nineteenth bullet in the twenty-bullet gun barrel, faced with nineteen bullets there could see no way out of issuing warnings. The FDA have since gone further and issued suicide warnings for anticonvulsants and antipsychotics, as well as Champix and Zyban for smoking cessation, Roaccutane for acne, Tamiflu for flu, and Singulair for asthma, and have withdrawn from the market Rimonabant for weight loss and Cymbalta/Yentreve for urinary incontinence for this reason.

Legal actions against pharmaceutical companies are almost nonexistent outside the United States. In part this is because patients in Europe and other countries have universal healthcare and there is much less or no need to recover the costs of treatment for an injury from a pharmaceutical company. A great deal of what the world knows therefore about how pharmaceutical companies do business—how they market drugs, ghostwrite articles, ensure trials recruit just the right number of patients so that the results for serious hazards cannot become statistically significant—stems from legal actions in the United States.

The attempted preemptive strike engineered by Malcolm Wheeler and Dan Troy in the Motus case—that of claiming that federal regulatory agency statutes preempted any action, state or federal, against a pharmaceutical company—aimed at removing one of the few remaining impediments in the world to company abilities to do business. Although Pfizer won the Motus case by other means, other companies began to use preemption with increasing frequency, and success. A series of SSRI-induced suicides, Vioxx-induced heart attacks, and Avandia- and Rezulin-induced deaths were thrown out on this basis.

As the argument raised was legally unprecedented, it was taken all the way to the Supreme Court.
⁶²
When preemption had first been raised in 1998, it had seemed inconceivable to most legal minds that such a defense might succeed as a matter of principle, but a decade of company arguments and lobbying had made a difference. In attempting to come to a resolution, the Supreme Court scheduled two cases. The first involved Pfizer's Rezulin, which had been approved in 1997 as a treatment to lower blood sugar and then withdrawn from the market in 2000 after being linked with an excess of deaths from liver failure. In this case in 2008, the nine justices tied 4 to 4, Chief Justice Rehnquist having recused himself on the basis that he held shares in Pfizer.
⁶³

A second case heard in October 2008 involved phenergan, a Wyeth drug, given for nausea, which when given by injection caused an arterial spasm that led to Diana Levine losing her right arm. At the heart of the case was the issue of whether this loss stemmed from a lack of warnings regarding its proper administration.
⁶⁴
The issue was not whether Wyeth knew about the hazard, but rather whether the FDA had or had not specifically instructed the company to warn about the hazard and if not, whether this exculpated Wyeth—even if the company did know about the hazard. On March 4, 2009, the Court came to a 6–3 verdict against Wyeth and against preemption.
⁶⁵

For the moment therefore, the kind of documents on which Firestein based her case in New York may still occasionally come to light in actions taken by plaintiffs against drug companies. For the moment, companies remain somewhat limited in their abilities to interfere with the practice of medicine in whatever way they see fit. For the moment, the FDA has not unequivocally become the de facto regulator of medicine rather than just medicines.

As this was happening another drama was unfolding. As part of their settlement with New York State, GlaxoSmithKline agreed to post details of all their clinical trials. This sounds better than it is: the company only posted internal study reports, not the actual data. These differ little from ghostwritten articles. They do not let anyone establish, for instance, whether a dropout from a trial was really a dropout for noncompliance or whether the child had attempted to commit suicide.

But it is difficult to hide deaths. In 2007, Steve Nissen, a cardiologist at the Cleveland Clinic, combed through the data from trials on Avandia (rosiglitazone), GlaxoSmithKline's latest blockbuster, a successor to tolbutamide in the treatment of adult-onset diabetes, and found that, while no one trial of Avandia showed an excess of cardiac deaths, in all trials combined the drug was linked to a marked increase in such deaths.
⁶⁶

The Avandia story repeats all the elements of drug disasters from tolbutamide to Paxil. When first licensed by the FDA in 1999, there was no evidence that it saved lives, but influential academics lobbied regulators and other decision makers to ensure favorable treatment for this must-have drug. The American Diabetes Association came out strongly in favor of the drug even before it was approved.
⁶⁷
Over the next five years, Avandia moved rapidly to blockbuster status despite warnings by the World Health Organization (WHO) in 2004 of an increased risk of death. Internal GlaxoSmithKline analyses also found increased—but nonsignificant—rates of cardiac events on Avandia in their clinical trials, but in public the company continued to argue that the drug was absolutely safe and sales continued to boom. In the face of Nissen's analysis, the company fast-tracked a major study of cardiac safety on the drug, the RECORD study, and published it claiming that it demonstrated that Avandia was safe.
⁶⁸
Both the FDA and European regulators agreed. But mounting concerns led to hearings at the FDA, and further investigations by FDA staff, one of whom, Thomas Marciniak, found a pattern of concealment of serious events on Avandia in the RECORD study that echoed the hiding of deaths and other serious events on SSRIs and Vioxx.
⁶⁹

These events led a Senate committee to investigate GlaxoSmithKline and issue a damning report.
⁷⁰
Legal cases have been instituted. These reveal extensive ghostwriting of the medical literature as part of the marketing of Avandia, comparable to that found in the marketing of Hormone Replacement Therapy (HRT)
⁷¹
or oral contraceptives such as Yaz. These cases reveal that the pattern of using evidence-based medicine to drive prescribing is now all but universal. Apparently rational prescribing in such circumstances is close to certain irrationality.

Zeus responded to Demeter that he was helpless to do anything about her daughter. Once, if our daughters were threatened by Hades, doctors from Philippe Pinel two centuries ago, to Alfred Worcester and Richard Cabot a century ago, and Dr. Lapin who looked after my father a quarter of a century ago, might have intervened on our behalf, but for the moment all we have standing between us and Hades is a small group, comprised of mothers and wives like Mathy Downing and Mary Ellen Winter and a dwindling number of Lapins, Worcesters, and Pinels. It is these who do the job of alerting us to the hazards of treatment, a job that one might have thought lay at the heart of good medical care. How long they can hold on before the Heavens answer is not clear.

8

Pharmageddon

Nothing more
But the sense
Of where we are

That seeks to find, to rescue
Love to the chill
Upper world, and to speak

A substantial language
Of Dignity
And of respect.

—George Oppen, “Orpheus”
 

Medicine as we have known it is at death's door. Real disease brings the specter of death with it, and every medical journey to some extent follows in the steps of Cora into the underworld, leaving Demeter to implore heaven to restore her to some measure of life.

Over the last quarter of a century, what was medicine has increasingly turned into healthcare, part of a vast global market in healthrelated products. Pharmaceuticals are exemplars of the goods in this modern health products market, but entire services can be packaged and managed as commodities, just as drugs are.

Only the market can guarantee efficient production, we're told, and we must surrender to it. The industrialization and marketization of healthcare has entailed a gamut of changes similar to those that have been seen in other industries. We see a standardization of care, with practices geared to treating patients in the same way as a service station handles a car that comes in for servicing—albeit with appropriate expressions of concern that wouldn't be necessary with a car. Meanwhile, the labor of taking risks in trials of new drugs has been outsourced to the Third World, Enron-scale scandals with drugs like Vioxx and Zyprexa have erupted, and to sell the products, healthcare advertisers now promise what automobile and shampoo advertisers have promised for years with purchase of their products—an enhanced life.

The corporate world of today's health services industry is a long way from the clinics in which nurses, doctors, and others working with those who are suffering try, often against the odds, to produce health. Ads for healthcare products that portray patients as vigorous and embracing life, as if drugs were just another set of consumer goods at the mall, conflict with the reality of diseases that shorten and compromise lives. People with diabetes are taught to prick the side of their fingers to get blood samples because the disease brings a risk of blindness and they may need the pulp of their fingers to remain touch-sensitive—good care does not deny these possibilities or put them in the small print of an advertisement. Medicine aims at a myriad of adjustments, with as much assistance as possible from technology, in order to cope with the frailties of the human body and mind; it aims at producing as much health as possible out of mankind's most debilitating afflictions.
¹
This is quite a different project than the enhancements health products offer.

At the heart of medicine is an act of care by doctors who talk, look, listen, and do something for patients who come to a clinic acutely ill with an abdominal problem, a heart attack, or a broken limb, or druginduced injury where every patient is different and care necessarily has to reflect this. While today's rhetoric is more and more about personalized medicine, the practice of dispensing health products has moved increasingly to standardized screenings for risk factors with treatments like the statins, or drugs for osteoporosis, nervous problems, or blood sugar control that clinical trials suggest in many cases are at least as likely to harm us as to help—a practice that is as far from caring as it is possible to get.

Generations of revolutionaries have talked about the alienation market forces and industrialization produce, the loss of jobs and skills, of values and ways of life, but many of us in the economically developed world have seen our material circumstances improve and have shrugged. Why should we expect anything less than comparable improvements in medical care—especially as we seem to hear of ever more medical breakthroughs in the media?

There are a few reasons why things are different now. One is that drugs and other services in the medical market physically act on the stuff of which we are made and may reconfigure us quite dramatically in ways we are not told about. Unlike short courses of antibiotics, which do not substantially change us, chronic courses of treatments aimed at managing risk factors do change us. Whether it be a cholesterollowering statin, an anti-inflammatory such as Celebrex, a treatment for osteoporosis such as Actonel, or a psychotropic cocktail, these drugs do not just have the action we are told about but often have much greater effects throughout the body than the one the company markets, potentially leading to an increased risk of dementia in the case of Vioxx and Celebrex, an enduring susceptibility to heart attacks in the case of Fosamax and Actonel, or changes in our ability to make love in the case of Paxil, Cymbalta, or Zoloft. Beyond these specific problems, the indiscriminate actions of many of these drugs on our physical constitution quite probably alter both our susceptibility to various diseases and our personalities too in subtle ways.

A second reason things are different now is that unlike other industrial processes, many of which have led to tangible benefits, the logic of healthcare marketing may block real benefits. Companies initially attempted to play down the evidence that ulcers were linked to a bacterium that could be eliminated, because this information wasn't good for business. They have similarly been extraordinarily successful at replacing older generations of antibiotics, psychotropic drugs, and anti-inflammatories with less effective and more hazardous agents such as Celebrex, Prozac, and Cipro. As a result some of us are now dying earlier than we should, and many more are suffering needlessly. By taking us away from productive work any premature deaths and incapacity come at a cost to the economy, and so it is in the interest of all of us to pay attention to the medical care each of us gets.

A third and perhaps most important reason is that these drugs also serve as a screen for a set of processes that act on us just as potently as the drugs themselves do. Companies take our inner aspirations and fears and mold a strategy designed to readjust our identities and get us to consume drugs more faithfully than we would do if we were living in a totalitarian regime and required to consume.
²
The changes in the way we live can be so mundane as to be almost invisible. Take the case of Josephine, a fit sixty-year-old who had been told she had osteopenia—a normal state for a woman of her age that comes with no risk of a fracture. But led to believe she has an illness, and put on Actonel or Fosamax, she is now afraid to mow the lawn for fear of falling and breaking a hip—though mowing the lawn instead of taking the drugs is a better way of reducing her risk of a fracture. Josephine's sixties are being shaped in ways she could not easily guess by the patents on a group of drugs. Our very ideas of ourselves are now subject to change at intervals coinciding with the fall of off-patent and rise of newly patented compounds.

Macbeth's unmet desires for fame and power left him vulnerable to seduction by the witches. Many of us can live without fame and power, but we are almost all vulnerable to seductions that offer us freedom from disease, with possible enhancements of our potency or beauty. Just as reaching for what was on offer produced disaster for Macbeth, so also our reaching seems to have left us with potentially reduced life expectancies, a growing discontent with who we are, and an atrophied ability to care for others.

If we fall prey to the witches' seduction in the health domain, our abilities to resist the industrial processes now encroaching on teaching and farming and other domains are also likely to crumble. Ultimately even the rearing of children may be affected. The hour is already late; just as patients have been eliminated from medicine in favor of medical consumers, so teachers have been replaced by educators whose brief it is to make available a range of educational products to their clients rather than to try and foster the growth of a person. We may not be far from a time when, for the sake of ensuring quality upbringing, mothers (and fathers) will be encouraged to look after their young clients in standardized ways. If as a society we cannot care for patients, it is not clear that we can care for children or for the planet.

It doesn't have to be like this. Ironically, indeed tragically, our new medical systems now produce as many perverse outcomes as they do in part because of some mechanisms we have put in place that stem from our recognition of how central health is to everything that counts for us. Given this centrality, it seemed important to Senator Estes Kefauver to control the pharmaceutical industry, and he, on our behalf, attempted to do so by making new drugs available by prescription only and then only letting them on the market once they had been through controlled trials. These safeguards, which were designed to bolster the role of doctors and contain industry, have in industry's hand been turned to do just the opposite. Increasingly alienated, doctors are not the force they once were and it is very difficult to view them as a body likely to rise up and demand change.

If, however, there is a path down into Hades, there must also be a path up. And there is hope in the knowledge that life often teems even in the most inhospitable environments. The first step back is to decide what kind of society we want to live in, what kind of economy we want.

At present we are trained from infancy to believe that the key things we produce are cars, computers, pharmaceuticals, and other goods. No one would accept that these are the things we care about the most, but we have slipped into a de facto acceptance that these things have a primacy largely because they can be readily commodified and quantified. The problems with the kind of system we have ended up with become very clear when we find that the cleanup of an oil spill like the
Exxon Valdez
, because it leads to a quantifiable increase in the consumption of commodities, adds to our economic wealth. As the service sector of the economy has grown, we produce units of service rather than old-style goods and this is what Western economies now depend on to an ever greater extent.

When it comes to health and education, the dangers in this model become ever more apparent. Just as with the
Exxon Valdez
in measures of gross domestic product, so in health, the side effects of treatments are at present (a lawsuit or two aside) an unalloyed good for pharmaceutical companies. They tend to lead to treatment with ever more drugs to manage side-effect problems rather than to a reconsideration of the original treatment; for instance Avandia and Lipitor are given to manage the diabetes and raised cholesterol triggered by a guideline-mandated drug like Zyprexa rather than rejecting this newer drug and returning instead to older, off-patent, less expensive drugs that would be much less likely to cause these problems. Increasing rates of treatment-induced mortality so far have had little effect on these practices. Instead, we have increasing efforts to standardize treatment delivery through the development of guidelines, which happen to recommend the latest onpatent medications that in many cases clinical trials have suggested may increase rather than reduce mortality. In this way the side effects of our latest blockbuster drugs have become one of the primary drivers of health system growth.

Is there an alternative to these “diabolical” scenarios?

One option is to put a fostering of persons at the center of the economic
(oikos nomos)
stage. Just as in a home
(oikos)
, it makes more sense to view our family or our people, rather than any provisions, the furnishings, or money salted away, as the ultimate source of our wellbeing, including our economic well-being. The trick will lie in redesigning the rules
(nomos)
of our collective home to reflect this. This would not mean turning our back on the production of goods. The problems we face do not come from technical advances—few among us would not welcome more effective treatments for dementia or cancer, and technical advances now seem a crucial component to saving life on the planet—the home of our homes.

The problems come from the social arrangements, the rules, through which at present all developments in health are filtered. It is these rules that give rise to our alienation and also increasingly block the emergence of the developments we need. Senator Kefauver adjusted the rules one way, perhaps the right way for his time, but in a manner that seems to be contributing to our problems now. Are there any adjustments that might steer medicine back toward what it could be and at the same time give us a glimpse of what a properly human economy
(oikumene)
might look like? There may be other steps to take, but following Kefauver we can look at company practices of sequestering clinical trial data that inhibit the ability of doctors to practice data-based medicine, the availability of medicines by prescription only, and the current patenting arrangements for drugs.

Reforms in these areas will require wisdom—having good intentions is not sufficient. Social arrangements have a great capacity to deliver exactly the opposite outcomes to those their proponents intended, as perhaps Kefauver's 1962 Act demonstrates better than anything else. But our intentions are also important. There must be some attempt to answer just what it is we want or need in order to determine whether our arrangements are likely to facilitate this or not. In the following pages I will review changes in terms of whether they are likely to foster an ability to care or not.

Our story will end on the wider shores of myth, where by myth I mean our more general orientation to the unknown. But it is in specific changes to the social arrangements that govern our way of life on the planet and vis-à-vis each other that the survival of medicine is likely to lie.

DATA-BASED MEDICINE

In the 1960s randomized controlled trials appeared to be an almost perfect way both to harness the benefits that industry could bring to the common good and to contain or even eliminate the evils of pharmaceutical marketing. In the 1990s, in response to growing commercial pressures on medicine, this medical turn to controlled trials evolved into a commitment to what came to be called evidence-based medicine. Far from resisting these moves that were meant to constrain it, industry embraced them, and from the 1990s has proselytized for evidence-based medicine. Few seem to have noticed the irony, and among those who do there is bewilderment as to how to manage this Hydra who grows new heads no matter what efforts are made to prune it back.