Pharmageddon (40 page)

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.”
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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 the 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.
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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 ghostwritten
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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.
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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.
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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.
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We are at a fateful moment. The Internet is awash with sites taking a top-down approach. None of these sites are ever likely to discover anything. Many of them are likely to aggravate our problems while promising to empower us. They coexist with and indeed all but entrench the greatest failure of the free market on the planet—no where else is there so much important data pertinent to economic well-being that remains uncollected and unused. A bottom-up approach in contrast would offer a market-based solution to a growing market failure and in so doing would wrest control away from the “shadow government”
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that runs health care and would restore it to patients and doctors.

PATENTS ON DRUGS

When Senator Estes Kefauver attempted to come to grips with the pharmaceutical industry in the early 1960s, his bill ended up mandating randomized controlled trials without being aware he had done so, as one of his aides slipped these into the 1962 act. Kefauver maintained support for the prescription-only status of new drugs, despite expressing compelling doubts about arrangements in which one person orders what another will have to consume. But he couldn't muster the votes for the one thing he actively sought to change, the system of patenting drugs. Changing this system, he thought, was crucial to bringing down the prices of drugs.

The American—and now worldwide—system enables companies to take out product patents on drugs. A patent of this type offers companies a monopoly on a new drug for twenty years, effectively on a worldwide basis. We grant this privilege to companies in return for novel and truly beneficial compounds. But the system was put in place at a time when patents were restricted to a national territory and when the idea of a blockbuster drug was inconceivable.

The current arrangements have failed us—although they work wonderfully well for companies. They have failed in that companies are not producing novel drugs of the type we desperately need. We do not have the breakthroughs for cancers, dementia disorders, or for the neurological and rheumatoid conditions that still cripple and kill us—often from quite a young age.
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In fact we now have a situation, brought about in part by product patents, where, in principle, it is not in the interest of companies to improve our therapies—certainly not to the extent that would eliminate disorders. Treatments that cure rather than maintain disorders risk leading to a fall in company revenues and, as the example of using antibiotics to cure ulcers shows, companies will make efforts to block the adoption of cures that appear on the horizon. Getting rid of the incentive to develop a blockbuster that product patents offer would reorient drug development back to what most people think both medicine and pharmaceutical companies are trying to do, which is to eliminate the scourge of disease.