That’s a lot to stand up, and the details are much more horrific than that paragraph makes it sound. There are some individual stories that will make you seriously question the integrity of the individuals involved; some that will make you angry; and some, I suspect, that might make you very sad. But I hope you will come to see that this is not just a book about bad people. In fact, it’s possible for good people, in perversely designed systems, to casually perpetrate acts of great harm on strangers, sometimes without ever realising it. The current regulations – for companies, doctors and researchers – create perverse incentives; and we’ll have better luck fixing those broken systems than we will ever have trying to rid the world of avarice.
Some people will say that this book is an attack on the pharmaceutical industry, and of course it is. But it’s not only that. Firstly, as you will see, the problems are diffuse, and doctors, regulators, academic journals, pharmacists, patient groups and many more all play their part. Secondly, it’s not unbounded. I suspect that most of the people who work in this industry are fundamentally good-hearted, and there is no medicine without medicines. Drug companies around the world have produced some of the most amazing innovations of the past fifty years, saving lives on an epic scale. But that does not allow them to hide data, mislead doctors and harm patients.
Today, when an academic or doctor tells you that they are working for the pharmaceutical industry, they often do so with a look of quiet embarrassment. I want to work towards a world where doctors and academics can feel actively optimistic about collaborating with industry, to make better treatments and better patients. This will require big changes, and some of them have been a very long time coming.
To that end, because the stories I am telling you are so worrying, I’ve tried to go beyond simply documenting the problems. Where there are obvious fixes, I’ve set out what they are. But I’ve also included, at the end of each chapter, some suggestions on what you can do to improve things. These are tailored to whoever you might be: a doctor, a patient, a politician, a researcher, a regulator or a drug company.
More than anything, though, I don’t want you to lose sight of one thing: this is a pop science book. The tricks and distortions documented in these pages are beautiful, and intricate, and fascinating in their details. The true scale of this murderous disaster only fully reveals itself when the details are untangled. Good science has been perverted on an industrial scale, but this has happened slowly, and evolved naturally, over time. This has all been perpetrated by ordinary people, but many of them may not even know what they’ve done.
I want you to find them, and tell them.
What’s coming
The book follows a simple trajectory.
We start by defending our central claim: industry-sponsored studies are more likely to produce results that flatter the sponsor’s drug, which has now been demonstrated, beyond any doubt, by current research. In this section we also encounter the idea of a ‘systematic review’ for the first time. A systematic review is an unbiased survey of all the evidence on a given question. It is the best-quality evidence that can be used, and where they exist, systematic reviews are used for evidence throughout this book, with individual studies described only to give you a flavour of how the research has been done, or how mischief has been made.
Then we look at how the pharmaceutical industry manages to create all these positive trials for its drugs. Our first stop is to review the evidence showing that unflattering trial data can simply be withheld from doctors and patients. Companies are perfectly entitled to conduct seven studies, but only publish the two positive ones, and this behaviour is commonplace. What’s more, it happens in every field of science and medicine: from basic laboratory research, where selective publication fills the literature with false positive findings, wasting everyone’s time; through early research trials, where evidence that drugs might be dangerous is hidden from view; and on to major trials used to inform everyday clinical practice. Because so much trial data is withheld from doctors and patients, we can have no clear idea of the true effects of the treatments that we use every day in medicine. The stories in this section go from antidepressants, through statins, cancer drugs, diet pills, and right up to Tamiflu. Governments around the world have spent billions of dollars to stockpile this flu drug, in fear of a pandemic, and yet the evidence on whether it reduces the rate of pneumonia and death is being withheld right now, to this day.
Next, we take a step back, to look at where drugs come from. We cover the drug development process, from the moment someone dreams up a new molecule, through tests in labs, on animals, the first tests in humans, and then the early trials necessary to show that a drug works on patients. Here you will find, I suspect, some surprises. Risky ‘first-in-man’ drug tests are conducted on homeless people; but more than that, full clinical trials are being globalised, a new development that has arisen very suddenly, in only the last couple of years. This raises serious ethical problems, because trial participants in developing countries are often unlikely to benefit from expensive new drugs; but it also raises interesting new problems for trusting the data.
Then we look at regulation, and the hoops you must go through to get a drug onto the market. We will see that the bar is very low: that drugs must only prove that they are better than nothing, even when there are highly effective treatments on the market already. This means that real patients are given dummy placebo pills for no good reason, but also that drugs appear on the market which are worse than the treatments we already have. We will see that companies break their promises over follow-up studies, and that regulators let them do this. We will also see how data on side effects and effectiveness can be withheld from regulators, and that regulators, in turn, are obsessively secretive, withholding the data they do have from doctors and patients. Lastly, we will see the harm done by this secrecy: ‘many eyes’ are often very powerful, to spot problems with medicines, and some of the most frightening harms have been missed by regulators, and only identified by academics who were forced to fight hard for access to data.
Then we take a tour through ‘bad trials’. It is tempting to believe that a simple clinical trial is always a fair test of a treatment: and if done properly, it is. But several tricks have been introduced, over the course of many years, which allow researchers to overstate and exaggerate the benefits of the treatments they are testing. When you get here, you might think that some of these are innocent mistakes; in all seriousness, while I doubt that, I’m more interested in how clever they are. More importantly, we will see how obvious these tricks are, and how people who should know better at every step of the chain, from ethics committees through to academic journals, have allowed companies and researchers to engage in these shameful, outright distortions.
After a brief detour to discuss how some of the problems around bad evidence, and missing evidence, could be addressed, we move on to marketing, which is where most previous books on drug companies have focused their attention.
Here we will see that pharmaceutical companies spend tens of billions of pounds every year trying to change the treatment decisions of doctors: in fact, they spend as much on marketing and advertising as they do on the research and development of new drugs. Since we all want doctors to prescribe medicine based on evidence, and evidence is universal, there is only one possible reason for such huge spends: to distort evidence-based practice. All of this money comes directly from patients and governments, so we ourselves are paying for this privilege. Doctors spend forty years practising medicine, with very little formal education after their initial training. Medicine changes completely in four decades, and as they try to keep up, doctors are bombarded with information: from adverts that misrepresent the benefits and risks of new medicines; from sales reps who spy on patients’ confidential prescribing records; from colleagues who are quietly paid by drug companies; from ‘teaching’ that