Pharmageddon
Page 30
Invoking Maudsley had an effect, perhaps because owing to an accident of history his name had ended up on Britain's most distinguished psychiatric research facility—the Maudsley Hospital. But in fact Maudsley disliked clinical practice and had very little experience with serious mental illness. He preferred writing. And the book in which a throwaway sentence about diabetes appears had been written when he was twenty-nine, so that even if he had been interested in patients he would not have had time to form a seasoned judgment about their condition, especially as patients with type-1 diabetes did not then live more than a few months from the onset of their illness, and type-2 diabetes was rare.
In North Wales, we had access to over three thousand consecutive admissions to the local asylum from 1875 to 1924, covering Maudsley's career. During this time over twelve hundred patients were admitted with a psychosis but not a single one had diabetes. We also identified every single one of the 396 patients with a psychosis who had presented for the first time to the modern services between 1994 and 2006—not a single one had type-2 diabetes. But the modern group, once on treatment with antipsychotic drugs, went on to develop diabetes at double the normally expected rate.45 These figures show how ridiculous the Maudsley quote is, but for most doctors the anecdote, told repeatedly by a drug company, will continue to work.
FACTORY DOCTORS
In medicine up until the 1960s, if some doctor discovered a new disorder or described a body part, it was commonly named after him—so we have Bright's, Hashimoto's and Grave's diseases, Duchenne muscular dystrophy, Epstein-Barr virus, Nissl bodies, and Mullerian ducts.46 It was the height of ambition for many male doctors to have their name linked in this way to a new observation or finding, and many of our most distinguished journals became well known because they published these new syndromes. Our brave new pharmaceutical era should be a golden one for doctors who have even a scrap of motivation in this direction.
Since the breakthrough with smoking and lung cancer, there is been a widespread recognition that many of our diseases are environmentally caused.47 From chemicals in the air we breathe leading to respiratory disorders; to pesticides or other toxins leading to cancers, Parkinson's, and other neurological disorders; or aspects of the food we eat leading to cardiovascular disorders or gut cancers—across all these disorders lies the common factor of people ingesting some chemical or toxin.
But there is no other walk of life in which people ingest chemicals to the same extent, or in such concentrated forms, as happens among those treated in the modern practice of medicine. Unfortunate though it might be to put it in this way, medicine increasingly provides the perfect natural experiment to track the effects of poisons in the human body. Even if many of their colleagues disapproved, if the medical market were a free market working as Adam Smith described it, some doctors at least might be expected to hover around their patients like gulls around a trawler or robbers around a bank, because their career interests in reporting any new diseases and the concerns of patients at risk of suffering adverse reactions from treatment should coincide.
But this doesn't happen. It doesn't happen because companies rather than doctors run clinical trials. Moreover, companies sequester the data from those trials, so no one can use these data to determine what the hazards of treatment might be. Also, in their ghostwritten articles appearing in the very best journals, apparently authored by the most distinguished academics, companies have been able to interpret data pointing to marginal benefits from treatments as evidence that these treatments are remarkably effective, thus casting doubt on any remaining data that might point to the existence of hazards.
Locked into the distribution channel for prescription-only drugs, hemmed in by the science, doctors increasingly resemble the employees of the occupational health department of a factory that in the course of business exposes its workers to disability-inducing aerosols. These are doctors who are all too aware that their ongoing employment depends first on keeping mum about problems the workers may be having and second on being willing to recommend laying off workers at the first signs of any ill health—having persuaded them that they aren't fit for the job rather than conceding that job conditions might be the problem. The characteristic portrayal of a factory doctor like this, as opposed to the best of family doctors, lies precisely in the degree to which the one cares about patients and is prepared to speak out and the other can't.
The pressure on individual doctors in these situations can be forbidding, but we would still expect medical organizations to speak out about the hazards of treatment. Yet even after the FDA had finally conceded that antidepressants could cause suicide and required the drug companies involved to place warnings on their drugs to this effect, the American Psychiatric Association (APA) could still pose the question, “Do antidepressants increase the risk of suicide?” and answer it, “There is no evidence that antidepressants increase the risk of suicide,”48 stating instead that “antidepressants save lives.”49
At a time when healthcare is becoming standardized, when clinical prescribing is being constrained by guidelines, if drugs save lives, and hazards aren't worth mentioning, then why not let nurses—who are much less expensive—prescribe them? Nurses are much more likely to adhere to best practice, as embodied in guidelines. The APA statement amounts to a professional suicide note.
What does it take to back a profession into this kind of a corner? Some hints come from the kind of session held behind closed doors and without minutes that I was invited to attend in October 2005. It was convened by Britain's Royal College of Psychiatrists in the wake of the scandal over the suicide-inducing effects of antidepressants on children, to review whether the college needed more firewalls against pharmaceutical influence.50 Most American medical associations have looked at their policies vis-à-vis industry in similar fashion in recent years.
The invited audience was small and included most of the officers of the college. The first half of the day was taken up by presentations about the pharmaceutical industry's view of its current position within the British economy—that half the day was handed over to industry was itself remarkable. These presentations claimed that the pharmaceutical industry was the largest funder of research in Britain, providing nearly 40 percent of all corporate monies in industrial research and development and 70 percent of Britain's medical research funding. Getting drug trials started in the UK was slow, however, we were told, and Britain was the most expensive place in Europe to do research. While the quality of research in Britain had been excellent, the rest of world was catching up, and clinical trials were moving to Russia, India, and China—a similar message to one delivered repeatedly to American academics for over a decade.51
There was a “we're all consenting adults” tone to the presentations. Company personnel made it clear that the pharmaceutical industry was a business whose bottom line was profit. The clinicians were told that if they had been to a sponsored meeting or seen a company representative they had worked with industry. And if they had read the scientific literature they would have been influenced by the pharmaceutical industry. The issue now, in the pharmaceutical industry's view, was how to put a framework in place to support the contribution industry could make to Britain's health and prosperity and enable medicine, the regulatory apparatus, and the pharmaceutical industry all to work in partnership.
The scandal of company suppression of clinical trial data showing that antidepressants made children suicidal had come to light the year before. Because of this, many of the clinicians present felt that however pharmaceutical companies dressed up their material, nothing about the claimed benefits to patients could be taken at face value. Some recognized the larger dilemma, namely, that we doctors were in the same business as the pharmaceutical industry. We never told patients when we felt industry's treatments weren't very good, because that would be saying that some of the treatments we were giving weren't very good. Were we professionals whose interests really diverge all that much from those of industry?
Though the British rarely state anything plainly, these concerns among the attendees were expressed clearly enough. In response, industry took off its gloves. Padraig White, working for GlaxoSmithKline, told those assembled that current policies were in fact the result of the closest cooperation between industry and the most senior figures in British medicine. When it came to issues like our asking for the data from clinical trials, these notables would not be putting their knighthoods on the line to insist upon access to raw data from clinical trials. Within academic psychiatry alone, he went on, there were twenty-five senior figures in Britain each earning in excess of $200,000 a year out of links with industry, so academia was unlikely to side with their clinical colleagues. And finally, we clinicians all needed to note that 40 percent of British life insurance policies were invested in the pharmaceutical industry. Whether we liked it or not, we were shareholders in the industry, and rocking the boat would not be in our interest.
There was a time, not so long ago, when even senior figures from the pharmaceutical industry attending a meeting involving senior officers of a national medical association would have appeared grateful to be present and would have held their tongue when issues such as these were raised. But the balance of power and position had changed so much that a relatively junior official from the pharmaceutical industry felt able to tell a professional medical association to “Get real.”
In such a world, what scope is there for professionalism? How can clinicians “get real”? A start might be to shift the focus represented by statements like the American Psychiatric Association's “antidepressants save lives” to something more in the spirit of “doctors can save lives.” How would they do this? Well, if they have a good knowledge of the natural history of the conditions they treat and use agents of limited effectiveness and uncertain safety with care while enlisting their patients' support in monitoring the effects of any interventions, lives might then indeed be saved.
Industry monitors the prescribing habits of every doctor in the Western world. Data on who prescribes what is used by industry to shape tomorrow's sales pitch to produce an increase in prescriptions of their compounds or to determine why they are losing market share to one of their competitors.
In contrast, doctors record almost none of the problems that develop when they put patients on a drug. The FDA and other regulatory websites make it clear that doctors in the United States and Britain report only one in a hundred serious adverse events on drug treatment to the regulator. The postal service, in other words, does a vastly better job in tracking the fate of parcels than clinicians do in tracking their patients. Rather than becoming evidence-based, medicine is monitoring and quantifying exactly the wrong things. It quantifies hints that the latest snake oil has some benefits, helping drug companies smuggle their products through the regulations designed to prevent undue injuries to patients. But in the face of a growing series of premature deaths and other injuries induced by drug treatments, it does nothing.
THE RULE OF DOUBT
The question of whether Prozac was in fact causing serious problems unleashed on the FDA a set of public and media concerns to rival those that had broken around tolbutamide in 1970. In 1991 the agency organized public hearings on the issue, which gave rise to a dramatic clash between the personal histories of a range of patients and randomized trial data supplied by Lilly, the makers of Prozac. But in marked contrast to their handling of tolbutamide, the FDA introduced an extraordinary argument that would have brought howls of medical outrage in the 1970s but produced not a peep of protest in the 1990s.
If the FDA did the right thing and warned about risks, agency representatives argued, it might paradoxically increase the number of deaths. Even if some people became suicidal on Prozac, senior officials within the FDA and academics linked to Lilly claimed, their numbers would be smaller than the number of deaths likely to occur among people who because of the existence of a warning would be deterred from seeking treatment in the first place. Prominent warnings about risks of suicide, in other words, might lead to an increase in the number of deaths.52
There is an astonishing ethical calculus here. In the case of the antidepressants, even the FDA had doubts about whether the drugs worked. There was absolutely no evidence they reduce suicides—all the clinical trial evidence pointed to an increase in risk, so much so that the major companies were engaged in various subterfuges to minimize public attention on the problem.
Given the completely predictable vigor of pharmaceutical company marketing that has led doctors to switch patients to the latest branded drugs, such as from ibuprofen or naproxyn to Vioxx or from hypoglycemics such as metformin to Rezulin and Avandia almost from the day they are launched, not warning patients appropriately in these cases amounts to a covert vaccination program—we want to see as many people on these new drugs as possible. But unlike vaccination, as the use of blockbuster drugs has spread, whether for osteoporosis, lowering blood sugar, or mood stabilization, the human cost that clinical trials of these drugs point to is increasingly paid by people who do not stand to benefit.
When it comes to the injuries produced by other industrial products, it is now clear that companies have been quite prepared to sponsor studies designed to bring in results that cast doubt on claims that chemicals from vinyl chloride to lead pose any health risks. Recent legal actions involving Paxil and birth defects have unearthed documents suggesting that lawyers for GlaxoSmithKline have liaised with academics to generate studies that could in similar fashion be used to counter any claims that Paxil might cause birth defects.53 This suggests that tactics honed in the battles over industrial pollution in the 1950s are being deployed within medicine today.
The most striking example of company willingness to put profits before all else came at the end of the 1960s, when in response to concerns about smoking and lung cancer, the tobacco companies sponsored a series of papers showing that from 1900 to 1960 respiratory and cardiac deaths fell and life expectancy rose in tandem with increased tobacco consumption. This use of apparently scientific data (but misleading analysis) was part of a campaign to sow doubt about a link between smoking and disease, caught exquisitely in company admissions that “doubt is our product.”54
But the ultimate use of the “doubt is our product” strategy faces us now in the form of company arguments that doubt about a hazard means it can be disregarded. As long as the data do not point to a statistically significant increase in heart attacks on Vioxx or deaths on statins or biphosphonates, the companies argue that doubt remains, and while doubt remains the drug must be regarded as being, in effect, free of hazards. The FDA and most doctors join them in this argument—to add warnings would, according to the American Psychiatric Association, have “a chilling effect on appropriate prescribing for patients.”55
A PREEMPTIVE STRIKE
When it comes to other chemicals and the problems they pose, no company can buy up all doctors and hence they have to cope with the abilities of doctors to spot new hazards and their preparedness to speak out about these hazards. But when it comes to drugs, the interests of doctors, regulators, and companies are now so closely allied that pharmaceutical companies have been able to deploy an extraordinary legal maneuver.
When in 1991 the FDA talked about the public health consequences of deterring patients from treatment with antidepressants, it was a view aired in the course of a public debate. It wasn't public policy. The regulators and drug companies were still notionally managing the labels on drugs rather than determining the trea
tment of patients. A few years later a case in Southern California, the Motus case, made it clear that efforts were underway to shift public policy in the direction of actively supporting treatment with drugs.
In early November 1998, Victor Motus, a prominent member of the Filipino community in Southern California, had a few nights of poor sleep. He owned an architectural firm, was president of the local school district board, and had just launched his campaign for a seat on the Cerritos city council. He was due to go to Washington to receive an award from President Clinton for work done for the local school. With his wife, Flora, he owned numerous rental properties, an antique store, and he held an 80 percent ownership interest in two restaurants. Even without all this, a few nights of poor sleep were hardly surprising in a fifty-one-year-old man.56
The only health problem Motus had was type 2 diabetes that he managed by a combination of diet and medication. When he developed problems sleeping, Flora made an appointment with a general practitioner, Dr. Trostler, on November 6, 1998 for her husband to obtain sleeping pills. During the visit, mention was made of financial problems with one of his restaurants, and even though there was no prior medical history to point to depression and little wrong clinically, educated by companies like Pfizer to think that sleep difficulties commonly pointed to a depressive disorder, in which case antidepressants would be a more appropriate treatment than hypnotics, Trostler gave Victor a sample pack of the antidepressant Zoloft—something unlikely to help his sleep. The Motuses were told that Zoloft might take several weeks to work.