Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients (33 page)

More than this, I think we need a cultural shift in the way we all, as patients, view our reciprocal relationship with research in medicine. We only know what works because of trials, and we all profit from the participation of patients before us in these trials; but many of us seem to have forgotten this. By remembering, we could create a social contract whereby everyone expects their health service to be constantly conducting trials, simple A/B tests, comparing treatments against each other to see which is the best, or even the cheapest, if they’re both equally effective. A doctor failing to take part in such tests could be regarded as an oddity who is harming future patients. It could be obvious to all patients that participating in these trials is a normal reflection of the need to produce better evidence to improve medical treatments, for themselves in future, and for the others in the community with whom they share their medical system.

In almost every developed country in the world, medicine is provided free at point of access, by the community, funded through taxation. From the perspective of the community, this whole process could be regarded as a simple bargain: we provide medicines free at point of access; in exchange, you need to let us find out what works best for you and others. The NHS could be in a constant cycle of testing and learning, improving its performance, and improving outcomes for everyone in the country, and everyone in the world, by creating better knowledge on what works.

It’s a quirk of history that has been largely lost to most doctors and academics, but this was essentially the dynamic around the first ever truly modern randomised trial. In 1946 the antibiotic streptomycin had just been discovered, and after huge effort, 50kg was produced for the UK. It was hoped that this drug could be used to treat tuberculosis, but it was incredibly expensive, and we needed to find out if it actually worked. Patients with TB meningitis, in the brain, weren’t a problem: they would die in front of you, and fast, almost every time; so if
any
of these patients survived after being given streptomycin, you knew the drug was probably effective. For pulmonary TB, in the lungs, the story was more complicated: people would often recover by themselves over time, without any medication, so it would be harder to tell if the drug really had improved their chances, or hastened their recovery.

In the US this drug was available on the open market, at huge prices. If you wanted to try it, you simply bought some, took it, and hoped for the best. But the UK Medical Research Council was in sole charge of our 50kg supply, and decided it was going to use this expensive new drug efficiently, in a randomised trial, to find out whether it really did make any difference to survival (and also whether it caused any unpredictable side effects). Doctors weren’t pleased, but in the immediate post-war environment, with rationing still commonplace, the notion of central control for the sake of the greater good was not so unusual. The first proper modern randomised trial went ahead, and the whole world’s understanding of streptomycin’s effectiveness was generated, essentially because the MRC forced our hands.

If that whole story sounds uncomfortably Stalinist, then I apologise, but you may have misunderstood. I’m not proposing that we coerce every patient to participate in a trial, wherever there is uncertainty about which is the best treatment for them, by exploiting the opportunity that the state has to ration supply: I’m simply suggesting that trials should be routinely embedded in all clinical practice, as the norm, as an everyday act. If people really want to opt out, and take drugs of unknown effectiveness without generating any new knowledge, then of course I accept their desire to be antisocial for no personal gain.

But this is a need that becomes more pressing with every day. Health care is cripplingly expensive, trials are the best tool we have to make our treatment decisions more cost-effective, and they can be run on many of the most important questions in medicine at very little cost, inflicting no harm at all on participants. Irrational prescribing costs lives, and it costs money; while the cost of research to prevent irrational prescribing is trivial in comparison, and large simple routine trials would swamp the bad evidence that has polluted medical practice, in just a few years. Our extreme effort, aiming to run trials at almost no cost in routinely collected electronic health records, is just one example of how this could be done.

Instead, we have occasional, small, brief trials, in unrepresentative populations, testing irrelevant comparisons, measuring irrelevant outcomes, with whole trials that go missing, avoidable design flaws, and endless reporting biases that only persist because research is conducted chaotically, for commercial gain, in spuriously expensive trials. The poor-quality evidence created by this system harms patients around the world.

And if we wanted, we could fix it.

6

Marketing

So far, we have established that the evidence gathered to guide treatment choices in medicine suffers from a huge number of avoidable biases and problems. But that is only part of the story: this poorly collected evidence is then disseminated, and implemented, through chaotic and biased systems, which adds a whole extra layer of exaggeration and error.

To understand what is happening here, we need to ask a simple question: how do doctors decide what to prescribe? This is a surprisingly complicated issue, and to feel our way through it we need to think about the four main players exerting pressure: the patient; the funder (which in the UK means the NHS); the doctor; and the drug company.

For patients, things are simple: you want a doctor to prescribe the best treatment for your medical problem. Or rather, you want the treatment that has been shown, overall, in fair tests, to be better than all the others. You will probably trust your doctor to make this decision, and hope that there are systems in place to ensure that it is done properly, because getting involved in every single decision yourself would be enormously time-consuming.

That’s not to say that patients are locked out, either by tradition or by design. It’s true that it’s rare for patients to make decisions about which treatment is best
entirely
for themselves, by reading the primary research literature, and spotting the strengths and flaws in each trial for themselves. I feel bad about that, and wish that this book could teach you everything you need to know, but the reality is that medical decision-making requires a lot of specialist knowledge and skills, which take time and practice to acquire at a safe level of competence, and there is a serious risk of people making very bad decisions when it’s not done well.

That said, doctors and patients do make decisions together all the time, when medical practice is at its best, in discussions where doctors act as a kind of personal shopper, eliciting the outcomes a patient is most interested in achieving, and communicating the best existing evidence clearly, to allow an informed decision. Some patients might want a longer life at any cost, for example, while others might hate the hassle of taking a pill twice a day, and prefer to tolerate a greater risk of a bad long-term outcome. We will discuss how this can best be done later, but for now we will settle on the fact that in most cases, patients just want the best treatment.

Our next players are the funders, and for them, the answer is also fairly simple: they want the same thing as the patient, unless it’s insanely expensive. For common drugs, and common decisions, they might have a set ‘pathway’ that dictates to GPs (more commonly than to hospital doctors) which drug is to be used, but outside those simple rules for simple situations, they rely on doctors’ judgements.

Now we come to our core player in the individual treatment decision: doctors. They need good-quality information, but they need it, crucially, under their noses. The problem of the modern world is not information poverty, after all, but information overload, and even more precisely, what Clay Shirky calls ‘filter failure’. As recently as the 1950s, remember, medicine was driven almost entirely by anecdote and eminence; in fact, it’s only in the past couple of generations that we have collected good-quality evidence at all, in large amounts, and for all the failures in our current systems, we suddenly now have an overwhelming avalanche of data. The exciting future, for evidence-based medicine, is an information architecture that can get the right evidence to the right doctor at the right time.

Does this happen? The simple answer is no. Although there are many automated systems for disseminating knowledge, for the most part we continue to rely on systems that have evolved over centuries, like the long, meandering essays in academic journals that are still used to report the results of clinical trials. Often, if you ask a doctor whether they know if one particular treatment is best for a particular medical condition, they’ll tell you they certainly do, and name it. But if you ask them how they know it is the best, their answer might scare you.

They might say: that’s what I learnt at medical school; that’s what the person in the office next door told me she uses; that’s what I see the local consultant prescribing in his letters on patients I’ve referred; that’s what the local drug rep told me; that’s what I picked up on a teaching day two years ago; that’s what I think I read in a review article somewhere; that’s what I remember from some guidelines I looked up once; that’s what the local prescribing guidelines recommend; that’s what a trial I read said; that’s what I’ve always used; and so on.

In reality, doctors can’t read every scientific article that’s relevant to their work, and that’s not just my opinion, or even a moan about my own reading pile. There are tens of thousands of academic journals, and millions of academic medical papers in existence, with more produced every day. One recent study tried to estimate how long it would take to keep up with all this information.
¹
The researchers collected every academic paper published in a single month that was relevant to general practice. Taking just a few minutes for each one, they estimated it would take a doctor six hundred hours to skim through them all. That’s about twenty-nine hours each weekday, which is, of course, not possible.

So doctors will not be going through every trial, about every treatment relevant to their field, meticulously checking each one for the methodological tricks described in this book, diligently keeping their knowledge perfectly current. They will take shortcuts, and these shortcuts can be exploited.

To see how bad doctors are at prescribing efficiently, we can look at national prescribing patterns. The NHS spends £9 billion a year on drugs. You know by now that many of the drugs on the market are ‘me-too’ drugs, which are no better than the drugs they copy, and that often the branded ‘me-too’ drugs could be replaced with equally effective drugs from the same class which are old enough to have come out of patent.

In 2010 a team of academics analysed the top ten most highly prescribed classes of drugs in the NHS, and calculated that at least £1 billion is wasted, every year, from doctors using branded me-too drugs in a situation where there was an equally effective off-patent drug available.
²

For example: atorvastatin and simvastatin are both equally effective, as far as we currently know (we keep returning to statins, because so many people take these drugs), and simvastatin came off patent six years ago. So you would expect that everyone should be taking simvastatin, instead of atorvastatin, unless there’s a very good idiosyncratic reason to choose the unnecessarily expensive one in a specific patient. But even in 2009 there were still three million prescriptions a year for atorvastatin, not much down from the six million in 2006: this cost the NHS an unnecessary £165 million a year. And all those prescriptions for atorvastatin were despite major national programmes to try and get doctors switching.

The same pattern can be seen across the board. Losartan is an ‘ARB’-type blood-pressure drug: there are lots of me-too drugs in this class, and because high blood pressure is so common, this class of medicines is the fourth most expensive for the NHS. In 2010, losartan came off patent: it is clinically almost indistinguishable from other ARB drugs, so you would expect the NHS to have switched everyone onto it, ready for the big price drop. But even after the price drop came, only 0.3 million of the 1.6 million people taking an ARB were on Losartan, so the NHS lost £200 million a year.

If we can’t manage rational prescribing decisions even for these incredibly common medicines, then that is good evidence that prescription is a haphazard affair, where clear information is not efficiently disseminated to the people making the decisions, on either effectiveness or cost-effectiveness. I can honestly say, if I were in charge of the medical research budgets, I would cancel all primary research for a year, and only fund projects devising new ways to optimise our methods for disseminating information, ensuring that the evidence we already have is summarised, targeted and implemented. But I am not in charge, and there are some much more powerful influences out there.

Now let’s think through a doctor’s prescribing decision from the perspective of a drug company. You want the doctor to prescribe your product, and you will do everything you can to make that happen. You might dress this up as ‘raising awareness of our product’, or ‘helping doctors make decisions’, but the reality is, you want sales. So you will advertise your new treatment in medical journals, stating the benefits but downplaying the risks, and leaning away from unflattering comparisons. You will send out ‘drug reps’ to meet doctors individually, and talk up the merits of your treatment. They will offer gifts, lunches, and forge personal relationships that may be mutually beneficial later.

But it goes deeper than this. Doctors need ongoing education: they practise for decades after they leave medical school, and looking back from today, medicine has changed unrecognisably since, say, the 1970s, which is when many currently practising doctors came out of medical training. This education is expensive, and the state is unwilling to pay, so it is drug companies that pay for talks, tutorials, teaching materials, conference sessions, and whole conferences, featuring experts who they know prefer their drug.