Pharmageddon
Page 34
But these hopes have not been realized. Rather than a bulwark against industry, prescription-only privileges have become a bulwark for physicians against competitors in the health domain, like homeopaths, psychologists, nurses, and others—a “precious” just like the Ring of Power in Lord of the Rings to be guarded jealously. A ring that puts physicians directly in the gun sights of the most sophisticated marketing on the planet. All the while, doctors seem be shrinking as did Gollum, the figure in J. R. R. Tolkien's novel who, under the influence of the Ring, became a twisted shadow of what he should have been. Given this, it is unbelievable that there does not appear to be a single medical course anywhere that offers physicians any education on marketing. The only doctors who seem to know something about marketing are those who have worked in the pharmaceutical industry. In the Lord of the Rings, in true market style, it was ultimately the self-interest of Gollum that saved everyone else. But that was only a fable—and while saving us, Gollum's self-interest destroyed him.
If we are to continue with prescription-only status as we have it now, our safety depends critically on doctors stepping up to the plate. They need to report on hazards and need to find a way to ensure their reports aren't airbrushed out of existence. They need to insist on companies undertaking adequate studies of drugs. Moreover, if companies are to be allowed to market their drugs under the banner of science, doctors need to ensure that companies adhere to the norms of science and make the data from these studies available, or else they need to undertake the appropriate studies themselves. They do, after all, report on the hazards of over-the-counter medicines and, funded by federal monies, doctors have undertaken research on drugs like tobacco, aimed at nailing down its hazards. Prescription-only arrangements once seemed like a mechanism to enhance the ability of medicine to interrogate the companies producing these “ethical” drugs. If it has become instead a mechanism that neuters medicine, it is time for medicine to take stock and then take action.
There are alternate arrangements to the current ones. We could make new medicines available by prescription only for a limited period before a decision was made as to whether they could be sold over the counter, during which time doctors would work hard to establish all the hazards of the new drugs. Alternatively, rather than have all new drugs available by prescription only, we could opt to make just highly toxic drugs available indefinitely by prescription only. We might distinguish between drugs used for traditional medical purposes and drugs for something closer to lifestyle enhancement, with the first group being available by prescription only and the second not.
The SSRIs offer an instructive example of what happens when essentially the same drugs are available by prescription only and over the counter. The SSRIs are antihistamines that inhibit serotonin reuptake. Available by prescription only, one set of selective serotonin reuptake inhibitors lead to agitation and suicidality, while very similar SSRIs available over the counter for allergies have occasionally been linked to irritability but appear in general to cause fewer problems than their prescription-only cousins. In part the differences likely stem from the difficulties described in chapter 7 in the case of Victor Motus: it is not easy to stop a treatment that doesn't suit a particular patient when a doctor has told that patient they need to remain on the treatment for several weeks before it “works.”
Doctors like Dr. Trostler, whom Victor Motus went to for help, have no training in the many things they do, aside from issuing a prescription for medication, that may enable or disable the people for whom they are trying to care from contributing to that care. They appear to have no feel for the fact that prescription-only arrangements put them in the position of a Roman emperor, with their patients in the role of tasters.
At a time when pregnant women have learned to shun over-thecounter drugs, even down to coffee, doctors have for over a decade dramatically increased their patients' prenatal consumption of SSRIs in the face of growing evidence these drugs double the rate of major birth defects and miscarriages. Drug companies like GlaxoSmithKline are aware that farmers have known for centuries to keep their herds out of fields in which the serotonin-reuptake-inhibiting St. John's wort grows as it leads to miscarriages, but these same drug companies have still manipulated doctors very successfully into herding women into the pastures in which their serotonin reuptake inhibitors grow.9
There are other benefits that might flow from lifting the prescriptiononly status of many drugs. The current arrangements constrain new drugs within a disease framework. If this were changed, a range of diseases from social phobia to osteopenia would vanish overnight. In the case of the antidepressants, for example, some that enhance appetite and sleep might be marketed as tonics rather than for depression. The SSRIs are more like St. John's wort and might be marketed similarly—for stress or burnout. At present, to get Prozac a person has to be labeled as suffering from depression or social phobia or obsessivecompulsive disorder first. If the drugs were marketed instead for stress or burnout there would be much less stigma in using them. In the case of the statins for cholesterol or biphosphonates for osteoporosis, the marketing would likely be aimed more for keeping arteries or bones young and not for supposed diseases. There might have been no fewer drugs sold but we would have fewer diseases. There would be a greater dividing line between medicine and daily life than there is now.
If many more drugs were available over the counter, company marketing would doubtless throw up a different set of abuses. It is doubtful, though, if the abuses could be any worse than the marketing of the proprietary panaceas that dominated the drug market in the late nineteenth and early twentieth centuries. But a century ago, when faced with these panaceas, there was a group of skeptics we could turn to— doctors. There are no skeptics now, and there need to be.
Where in the 1960s there was a gulf between the pharmaceutical and tobacco industries, partly owing to prescription-only arrangements, now it is increasingly difficult to distinguish between the two, except insofar as medicine supports one and not the other. If our current blockbusters were available over the counter, there is little doubt that the pharmaceutical industry would have marketed them as vigorously as the tobacco industry marketed cigarettes and likely caused as much damage with them as tobacco has. Would we be safer if our current blockbusters came with warnings that have the clarity of those found on tobacco products?
Abolishing prescription-only arrangements is a thought experiment. We have a tendency however to solve problems by opting for more rather than less regulation, and it is unlikely that this thought experiment is ever likely to be adopted. What we perhaps need to appreciate however is that these regulations are part of a growing apparatus within healthcare that Sam Sessions has referred to as a “Shadow Government.”10 Doctors are no longer free to follow the market for drugs on the basis of price or quality—they have to adhere to a variety of diktats in the form of guidelines and other instruments that have been fostered by companies. It is this range of instruments that pivot on the existence of prescription-only arrangements that effectively govern healthcare today. Whether in the United States or Europe, voices are increasingly raised against the involvement of government in healthcare—but when we look to Washington or other capitals for the culprits we are looking to the wrong place.
Another thought experiment might bring out what else could be done to make a prescription-only market work more efficiently than it does now.
RXISK.COM
In August 1973, a bank robbery at the Kreditbanken in Stockholm triggered a five-day siege with bank employees held hostage. After the siege ended, to the surprise of everyone many of the hostages, as if hypnotized, spoke well of their captors. “Stockholm syndrome” was born. Now recognized as common, the conditions that trigger this change in behavior seem to be isolation, a fear that your life is at risk, and kindness on the part of the hostage-takers.
Disease isolates us as profoundly as incarceration or anything else might. Our lives are at risk, and our doctors who control th
e exit to freedom are almost certain to be kind. But not a single doctor is trained to manage Stockholm syndrome, to suspect that our apparent insouciance or congenial conversation might conceal deep unhappiness with a proposed course of treatment or, even worse, alarm at new problems that have emerged on treatment.
From about the time of the 1973 Kreditbanken siege, doctors have become increasingly likely to suffer their own variant of Stockholm syndrome. If something goes wrong with a treatment a doctor gives, even though the label may concede that the drug can cause the problem, the makers of the drug and the doctor's colleagues will deny that it is likely to have done so in any particular case. Speaking up about a problem, once the material of medical advance, is now a recipe for professional suicide. A doctor attempting to rescue a patient is likely to be accused of being a persecutor who victimizes the patient by withholding effective treatment.
Offers to describe problems at professional meetings are turned down. Journals are ever less likely to accept publications outlining a new problem. Invitations to apply for better jobs, to attend conferences, or simply to go with colleagues to local eateries funded by drug companies are ever less likely to happen for doctors linked to adverse events. Those holding doctors hostage have been very kind indeed—there are ever fewer medical departments or medical conferences not awash with company support, when it comes to paying for meals with colleagues most doctors have forgotten what a credit card looks like, and of course in supplying drugs they supply the objects that make doctors desirable.
As a result bit by bit over the last forty years any of us seeking treatment have been disappearing in front of the eyes of our doctors, who in turn are increasingly inaudible and invisible to companies, academics, and regulators. A key component of the fog that envelopes both us and our doctors lies in the published trials that have hypnotized everyone. Individual observations, the logic goes, are unreliable, while trials supposedly offer reliable estimates about the consequences of treatment. When a doctor does report an adverse event to regulators, the report is invariably marked and filed as uncertain and unreliable information.
But we know that over 80 percent of the reports on the adverse consequences of treatment, dismissed as anecdotes, have turned out to be correct.11 We also now know that close to 30 percent of the clinical trials that have been undertaken remain unreported, and that of the 50 percent that are reported almost all will be ghostwritten12 and roughly 25 percent of the published trials altered to the extent that a negative result for a drug will have been transformed into evidence the drug works well and is safe.13 In 100 percent of cases, the data from trials remain inaccessible to scrutiny. Given these facts it is not reasonable to suggest that the observations of doctors or patients are any less reliable than clinical trial evidence.
Reporting the adverse effects of treatments has always been a delicate thing for doctors, because it involves recognition that they may have harmed a patient they intended to help and also because drugs once seen as poisons are now seen as fertilizers necessary to our growth and wellbeing rather than risky. There is also no feedback to doctors after they make report that would incentivize them to report further—nothing that recognizes that what they have done could be beneficial.
As a result doctors now report fewer than 5 percent of serious adverse events on treatment. Faced with this lack of reporting, American and European regulators have allowed patients to report on the adverse effects of drugs. But the new systems put in place for online reporting by patients are not user friendly. Minimal information is sought rather than the greatest amount of and richest possible details. Other than for altruistic reasons, or out of anger, there is very little incentive for a patient to report.
Consider what could be done. Roughly 25 percent of serious events have not been reported before, but whether reporting on a new problem or a problem already featured on a drug's label or elsewhere in the world literature, there is still a matter of deciding when I turn blue on a drug known to cause some people to turn blue, if in fact my blue hue is linked to treatment. There are standard ways to check out the likelihood of a linkage by noting the time of onset of the problem, what happens if the drug is stopped or the dose reduced, what happens if the drug is reintroduced or the dose increased, whether I have ever had reactions like this before on another drug, and whether anything else makes a difference. This approach can also help us decide if a drug might be linked to a problem never before reported.
Imagine if on making a report you were taken through these questions and then issued with a letter from an expert website to take to your doctor outlining the suspected reaction and the factors that in your case might help you and your doctor decide if there is a link to treatment. Imagine that this letter also lays out a case to your doctor that in-person, professional observations as to whether your treatment was likely to be linked to the problem are at the moment much more credible than the clinical trial data, and then invites your doctor to supplement or take issue with your report.
A few days later on the basis of the best possible input from both your doctor and you, when the reaction is coded and the database to which you've reported can assess how many other reactions like this there have been, imagine both you and your doctor get letters letting you know that a thousand other people have reported a similar problem and a hundred other doctors have endorsed a link between treatment and the effect. If 80 percent of medical reporting is likely to be correct, there comes a point where, even if the clinical trial data says otherwise, it is just not reasonable to say the problem can't be happening in at least some people. This compilation of individual reports offers your doctor and you a variation on an age old strategy—if you're going to owe the bank money, it is best to owe so much the bank has a problem—in this case it will be regulators and companies who have the problem. Far from being inaudible you and your doctor have been handed a megaphone.
Now take one more step. Hundreds of billions of dollars have been pumped into genomic research but very few genes have been found for major illnesses based on studies that have recruited tens of thousands of patients. Researchers have found small genetic risks contributing to common diseases like diabetes, hypertension, or mood disorders but little else. However in the case of clearly described adverse reactions to drugs, studies may only need to recruit fifty to a hundred people to find a gene coding for the treatment-induced problem. This makes sense as treatment effects have to be mediated biologically and a striking reaction to a drug is much more likely to be mediated through a single protein than is a complex condition like diabetes.
Getting us and our doctors to report on effects and work together to clarify the nature of the problem—whether turning blue on treatment involves two different conditions with one being turning blue from the waist up and the other blue from the waist down—will set up exactly the kind of conditions that make it possible to detect genetic inputs to such treatment effects. An effect tied to a gene is very difficult to dismiss as an anecdote. Health providers, insurers, and investors won't dismiss them. These are genes, moreover, that will reduce rather than increase our health insurance premiums—they point to risks we can avoid rather than risks waiting to happen.
Genes are just a tip of an iceberg. They code for proteins that are part of a biological mechanism. Even without knowing the gene, clear descriptions of problems will in many cases enable physiologists, pharmacologists, and others to pinpoint the larger mechanism producing an outcome, making it possible to state that X causes Y—the cholera bacillus causes cholera or SSRIs can causally trigger a suicide.14 It is in the laboratory rather than in a clinical trial we ultimately establish causes—in Koch's laboratory rather than Snow's epidemiology. But where Snow saw his epidemiology as paving the way for a hunt for causes, the exclusive turn to clinical trials in medicine today stops doctors and others from any effort to hunt for the mechanisms that make sense of the trial data.
There are new forces, like the Internet, emerging that will either swing us back
toward Koch or entrench a mindless turn to trials and guidelines. Seeking answers to health issues is now the second commonest reason to access the web. Many companies are gearing up to create electronic medical records, into which many of these Internet sites feed—sites offering to tell us for instance whether problems have been reported on our treatment. But all of the sites we might visit are at present linked to evidence-based medicine and current guidelines. The promise of companies providing these new technologies to healthcare organizations is that they will alert managers and doctors when prescribing if an electronic record strays from guidelines. This is sold as offering the organization a chance to ensure doctors give the best in medical care but in fact, unless medicine is driven by patients rather than guidelines, such electronic Big Brothers risk obliterating our individuality comprehensively.
This top-down approach aims at replacing individual judgments with the wisdom of experts supposedly relying only on the best available evidence. In contrast, the reporting model outlined above offers a bottom-up approach. It supplements the wisdom of experts with the wisdom of individual patients and doctors. This approach fits well with the ability of Google or social media like Facebook to track events.
If we are open to finding out what is really going on, we can get people not just to report events but to outline the impact of these events on their lives—the son who went off the rails on a stimulant and dropped out of college, the end of a marriage because of sexual dysfunction when taking an antihypertensive, the car crash because of temporary lack of coordination while on the heart drug amiodarone or many other drugs, the investigation for dementia because of cognitive difficulties on statins, the cost of a jail term following murder while on the smoking-cessation drug varenicline. We are aware these things can happen but have no idea how often they might be happening. We have no idea what the true costs of treatment might be, although we have hints that the cost of managing treatment-induced problems is more than the entire drugs budget.15