by drug company employees; and worse.
Finally, we will see what can be done. While the deceit of a marketing drive can be ignored by an ethical doctor, the problems caused by distorted evidence affect everybody, without exception. The most expensive doctors in the world can only make decisions about your care on the basis of the evidence publicly available to them, and nobody has a special inside track. If this evidence is distorted, then we are all exposed to avoidable suffering, pain and death. The whole system needs to be fixed, and until it is, we are all, very truly, in this together.
How to read this book
I have set out to explain the flaws in our systems for assessing the benefits of treatments, and for disseminating the evidence we collect. Often, one specific drug is used as an example to explain a wider systemic flaw; but this is not an almanac of good and bad drugs, and you certainly shouldn’t change your medication based on what you read here. If you are concerned by what you read, there is advice on what you can do to improve things for yourself, and for others, at the end of the book. Most of the harms discussed arise from our failure to do the best we can, not from handing out treatments that are worse than nothing. If that disappoints you, if you want more melodrama, then I suggest you go and read a book by a quack.
I deliberately haven’t gone overboard to explain every medical term, to save space and avoid distractions: this doesn’t mean that you miss out. If a symptom, for example, isn’t explained or defined, that means you genuinely don’t need this detail to understand the story; but I’ve left the long word in to help medics or academics find their feet, and to anchor the general principle in a specific corner of medicine for them. Acronyms and abbreviations are defined as we go, and used in a haphazard way after that, because this is how people talk in the real world. There’s a glossary at the back for some common ideas, really just in case you read sections out of order, but there’s nothing in there that doesn’t come up in the main text.
Similarly, I haven’t given the full names of most clinical trials, because they are conventionally known by their acronyms, and most medical textbooks wouldn’t bother either: the ‘ISIS trial’, the ‘CAST trial’, in the minds of most doctors and academics, are the real names. If you’re very interested, you can search for them online or in the endnotes, but they’re not relevant to your enjoyment or understanding of the arguments in this book. Drugs present a different problem, because they have two names: the generic name, which is the correct scientific name for the molecule; and then the brand name used by the company manufacturing it in their packaging and advertising, which is usually a bit catchier. In general, doctors and academics think you should always use the scientific name, because it tells you a little about the class of the molecule, and is less ambiguous; while journalists and patients will more often use brand names. But everybody is inconsistent about which name they use, and in this book, so am I. Again, this simply reflects how people talk about medicines in the real world.
All the specific studies discussed are referenced at the back of the book. Where there was a choice, I’ve tried to select papers in open-access journals, so that they can be read for free by all. I’ve also tried to reference papers that give a good overview of a field, or good books on a subject, so that you can read more on whole areas if you want to.
Lastly: to an extent, this is a field where you need to know everything, to understand how it impacts on everything else. I’ve bent over backwards to introduce the ideas in the best order, but if all this material is completely new to you, then you might spot some extra connections – or feel greater outrage in your belly – reading it a second time. I have not assumed any prior knowledge. I have, however, assumed that you might be willing to deploy a little intellectual horsepower here and there. Some of this stuff is hard. That’s precisely why these problems have been ignored, and that’s why I’ve had to explain it to you here, in this book. If you want to catch people with their trousers down, you have to go into their home.
Enjoy.
Ben Goldacre August 2012
For this 2013 edition of the book, I’ve made occasional small changes to the text, many of them in light of helpful comments from readers: this was to disambiguate, improve, toughen and occasionally correct small errors (such as n/3 instead of 3/n here, which broke my heart). Over the past year, even more evidence has been published about the ongoing problems described in this book. I’ve resisted the urge to expand every section, but some of this new evidence is covered in the new Afterword, ‘What Happened Next’. For the key problem of withheld trial data, there has been an international campaign over the course of 2013, with some small forward movement; this is also described at the end, and I hope it will rouse you to action.
Ben Goldacre August 2013
1
Missing Data
Sponsors get the answer they want
Before we get going, we need to establish one thing beyond any doubt: industry-funded trials are more likely to produce a positive, flattering result than independently-funded trials. This is our core premise, and you’re about to read a very short chapter, because this is one of the most well-documented phenomena in the growing field of ‘research about research’. It has also become much easier to study in recent years, because the rules on declaring industry funding have become a little clearer.
We can begin with some recent work: in 2010, three researchers from Harvard and Toronto found all the trials looking at five major classes of drug – antidepressants, ulcer drugs and so on – then measured two key features: were they positive, and were they funded by industry?1 They found over five hundred trials in total: 85 per cent of the industry-funded studies were positive, but only 50 per cent of the government-funded trials were. That’s a very significant difference.
In 2007, researchers looked at every published trial that set out to explore the benefit of a statin.2 These are cholesterol-lowering drugs which reduce your risk of having a heart attack, they are prescribed in very large quantities, and they will loom large in this book. This study found 192 trials in total, either comparing one statin against another, or comparing a statin against a different kind of treatment. Once the researchers controlled for other factors (we’ll delve into what this means later), they found that industry-funded trials were twenty times more likely to give results favouring the test drug. Again, that’s a very big difference.
We’ll do one more. In 2006, researchers looked into every trial of psychiatric drugs in four academic journals over a ten-year period, finding 542 trial outcomes in total. Industry sponsors got favourable outcomes for their own drug 78 per cent of the time, while independently-funded trials only gave a positive result in 48 per cent of cases. If you were a competing drug put up against the sponsor’s drug in a trial, you were in for a pretty rough ride: you would only win a measly 28 per cent of the time.3
These are dismal, frightening results, but they come from individual studies. When there has been lots of research in a field, it’s always possible that someone – like me, for example – could cherry-pick the results, and give a partial view. I could, in essence, be doing exactly what I accuse the pharmaceutical industry of doing, and only telling you about the studies that support my case, while hiding the reassuring ones from you.
To guard against this risk, researchers invented the systematic review. We’ll explore this in more detail soon (p.14), since it’s at the core of modern medicine, but in essence a systematic review is simple: instead of just mooching through the research literature, consciously or unconsciously picking out papers here and there that support your pre-existing beliefs, you take a scientific, systematic approach to the very process of looking for scientific evidence, ensuring that your evidence is as complete and representative as possible of all the research that has ever been done.
Systematic reviews are very, very onerous. In 2003, by coincidence, two were published, both looking specifically at the question we’re