Bad Pharma: How drug companies mislead doctors and harm patients

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Bad Pharma by Ben Goldacre – review

Luisa Dillner praises a calmly outraged investigation into the drugs industry

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  • The Guardian, Wednesday 17 October 2012 12.26 BST
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Photograph: Joe Raedle/Getty Images

If you were shocked by the MPs expenses scandal, try this one: in America, a popular media doctor, Drew Pinsky, goes on air to praise the antidepressant Wellbutrin. What's so great about it? Whereas other antidepressants lower libido, this drug "may enhance" sexual arousal. What his loyal listeners don't know is that Pinsky has been paid $275,000 by GlaxoSmithKline "for services to Wellbutrin".

1. Bad Pharma: How drug companies mislead doctors and harm patients
2. by Ben Goldacre
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1. Tell us what you think: Star-rate and review this book

They might never have found out if the US Justice department hadn't taken GSK to court for illegal marketing and failing to report drug safety data. The nine-year investigation led to a $3bn fine. (Other pharmaceutical companies have been fined for similar misdemeanours.) This example doesn't make it into Ben Goldacre's Bad Pharma, his calmly outraged account of how the $600bn drug industry, doctors, academics, regulators and medical journals have let patients down. But it is by no means extraordinary.

Goldacre's previous book Bad Science is an easier read, since exposing charlatans can, at times, be played for laughs. Bad Pharma is altogether more sombre and grim – a thorough piece of investigative medical journalism. What keeps you turning its pages is the accessibility of Goldacre's writing (only slightly flabby in places), his genuine, indignant passion, his careful gathering of evidence and his use of stories, some of them personal, which bring the book to life.

His tales of drug companies buying the opinion of doctors is not the most alarming of his revelations. Goldacre sets out clearly what is wrong with the way drugs get on to the market. New drugs are tested by the companies that make them, often in trials designed to make the drug look good, which are then written up and published in medical journals. Unless, that is, the company doesn't like the result of the trial (maybe it shows the drug not working or having severe side-effects), in which case this result might be hidden. Regulators should have all the data on a drug's effects but they often don't share it, so researchers can't study the data. The book gives examples of regulatory bodies handing over page after page containing blacked-out results to academics trying to collect data from unpublished trials, the excuse for non-disclosure being commercial sensitivity. Companies pay doctors to extol the virtues of their drugs on the conference circuit (spelling out the sources of information they want doctors to use) and fund patient groups to lobby regulators to approve new drugs. Academic journals (I work for one, the BMJ) are sent research papers and comment pieces that may not always be written by the academics listed as the authors. If a journal does decide to publish a paper showing the benefits of a drug, it can be rewarded by the company which made it, who might buy up hundreds of thousands worth of reprints (glossy versions of the published paper) to distribute to doctors to encourage them to prescribe the drug.

Doctors generally want to do the best for their patients, but they can't know what that is if half of the data on clinical trials of drugs is missing and some of the rest is distorted. The editors of medical journals want to publish good research but know, as Goldacre says, that when companies test their shiny new drug against other treatments, they don't always play fair. The vital comparison may be made against a placebo (Goldacre gives a harrowing account of how such a trial led to children in India dying when there was a perfectly good drug to treat them) or against unusually low or abnormally high doses of the drug – to ensure suitable conclusions as to efficacy and the severity of side-effects. It's no surprise that most published trials funded by drug companies show positive results.

Poor trials you can at least analyse. Missing data, Goldacre says, poisons the knowledge-well for everyone. Consider rosiglitazone, a new type of diabetes drug, which was greeted with real enthusiasm in 2005-6. This was partly because, unlike most new pharmaceuticals, it wasn't a "me too" drug. (With "me too" drugs companies tinker with a product they already sell but that is coming out of patent – it's a cheaper way of making a "new drug" although its additional benefits may be minimal.) Rosiglitazone was lauded for reducing blood sugar levels in people with diabetes and so for reducing heart attacks. Before long, however, John Buse, a doctor from the University of North Carolina became concerned that instead of reducing heart problems, the drug was actually increasing them. His head of department was rung by GlaxoSmithKline, the company who made the drug; a US Senate Committee later released a report saying Buse had been subject to intimidation. Later, GSK added up results from many trials and found Buse was right. They released their results, but only after two years. Independently Steve Nissen, a cardiologist, did his own analysis and found a 43% increase in the risk of heart problems with rosiglitazone. In 2010 the drug was taken off the market.

What will be the response to Goldacre's book? Drug companies may say that the problems he identifies have now disappeared. New rules insist they register the details of trials, and publish the results – whether negative or positive. But as Goldacre points out, little has really changed, because no one checks up.

Poor research and bias cannot be placed simply at the door of drug companies. The BMJ revealed earlier this year that half of publicly funded research in America wasn't published within the required time period. Doctors are often resistant to the notion they could ever be influenced by ads and sponsorship, even though the evidence to the contrary is overwhelming. They also rely on education paid for by drug companies because (unusually among professionals) they are loath to pay for it themselves. At the BMJ we are revising our declarations of interest form to say we will seek to work with doctors who have not received financial hand-outs from drug companies (funding for research is different).

But pharmaceutical companies are, after all, not charities. They exist to make and sell drugs, some of which work well, and to make a profit for their shareholders. They may talk as if they want to improve healthcare and sometimes they mean it, but only proper regulation from external agencies will make any difference. There is evidence that companies spend much more on marketing than they do on research and development (in America 24.4% of the sales dollar is spent on promotion versus 13.4% on research and development). They also inflate the cost of developing new drugs – Goldacre cites companies claiming that it costs £550m to bring a new drug to the market but says others put it at a quarter of that cost.

Some of what Goldacre wants to see is indeed happening – in America the so called Sunshine Act will mean pharmaceutical companies must say how much they have paid doctors and for which activities. And websites such as ProPublica already enable any patient to see what his or her doctor has been paid by the industry. One of Goldacre's innumerable discoveries is that in 2010 a Dr Emert in West Hollywood ate $3,065 of food paid for by Pfizer. Since this book's publication GSK has already announced it will make all its trial data available. Perhaps Goldacre's medicine is already working.

http://www.guardian.co.uk/books/2012/oct/17/bad-pharma-ben-goldacre-review

The Drugs Don’t Work: A Modern Medical Scandal

October 22 2012 | 28,914 views | + Add to Favorites

By Dr. Mercola

When your physician writes you a prescription, you probably assume that it has been scientifically proven to be both effective and safe.

This is the basis upon which the modern medical paradigm revolves... break this revered tenet and the entire system comes crashing down.

Well, let me tell you, the walls are already crumbling; the system is nearing collapse, as all is not what it seems on the medical forefront as it pertains to science.

You see, those little blue pills, or red ones, or white ones or whatever color or shape they may be, may very well have been the subject of a multi-million-dollar, double-blind, placebo-controlled study. Perhaps even multiple studies.

But that means very little when it comes to protecting your health, as the system is set up so that drugs can virtually never fail.

Science is Regularly "Tweaked" in Favor of the Drugs – NOT Your Health

In an extract from his book Bad Pharma, Ben Goldacre highlights how drugs enter the market and are promoted as effective by pharmaceutical companies and doctors, even when trials have shown then to be ineffective and, often, unsafe.

He first used the example of reboxetine, an antidepressant. He had read the trial data, which suggested the drug was better than a placebo and as good as other antidepressants on the market. But that was because he had reviewed the one study that had been published in an academic trial.

There were six others as well, but none of the data had been published. Why? Because they all showed that reboxetine was no better than a placebo. Other unpublished data on the drug showed it was less effective than other drugs on the market, while posing a greater risk of side effects. No right-minded physician would prescribe this drug to a patient if he or she saw the whole picture. But the whole picture very rarely gets seen.

Goldacre writes:

"Nobody broke any law in that situation, reboxetine is still on the market and the system that allowed all this to happen is still in play, for all drugs, in all countries in the world. Negative data goes missing, for all treatments, in all areas of science. The regulators and professional bodies we would reasonably expect to stamp out such practices have failed us.

...Drugs are tested by the people who manufacture them, in poorly designed trials, on hopelessly small numbers of weird, unrepresentative patients, and analysed using techniques that are flawed by design, in such a way that they exaggerate the benefits of treatments. Unsurprisingly, these trials tend to produce results that favour the manufacturer. When trials throw up results that companies don't like, they are perfectly entitled to hide them from doctors and patients, so we only ever see a distorted picture of any drug's true effects."

Regulators See Most Trial Data – But Even That Doesn't Translate to a Safe Drug Market

Regulators are given access to most trial data from drug companies from early on in the drug's development. Trial data is often shared only behind closed doors with the regulators, who then make a decision about the drug's future. Conflict of interest, intimidation and fraud have all played a role in why various drugs have made it past regulators even when the data showed clear evidence of harm.

One of the most glaring was Avandia, which was on the market for years before a study by cardiologist professor Steve Nissen came out in 2007 showing a 43 percent increase in the risk of heart problems among patients taking the drug. This study was based on data that regulators had access to for years, and, in fact, the drug's maker, GlaxoSmithKline (GSK), had also conducted studies using this data in 2005 and 2006 – but conveniently didn't publish them until 2008.

"Nissen used the rosiglitazone (Avandia) data, when it became available, and found worrying signs of harm, which they then published to doctors – something the regulators had never done, despite having the information years earlier.  If this information had all been freely available from the start, regulators might have felt a little more anxious about their decisions but, crucially, doctors and patients could have disagreed with them and made informed choices. This is why we need wider access to all trial reports, for all medicines," Goldacre wrote.

Industry-Funded Studies Far More Likely to Have Positive Results

Overall, meta-analyses looking into whether industry funding is associated with positive results shows that an industry-funded study is about four times as likely to yield favorable results. One study even found that every trial they reviewed favored the drug of the study's sponsor.¹

What this means is that even if you scour the medical literature to determine what the consensus is on any given medical topic, what you'll find is an overwhelming preponderance of data in favor of the drug approach that in no way, shape or form reflects the reality of the scientific investigation that went into that specific drug.

The fact is, there are many ways to turn an otherwise negative study positive:

• Design bias or rigging the study to have more favorable results from the start, such as by comparing the drug to something you know doesn't work as well, such as a placebo or another drug at the wrong dose
• Choosing study participants who are more likely to benefit from the treatment
• Stopping the trial early if results look good (even if they would take a turn for the worse in a few more months or years)
• Hiding, or simply not publishing, negative results; in fact, researchers of industry-funded studies often sign gag orders that forbid them from publishing, discussing or analyzing data without permission of the funder

"Because researchers are free to bury any result they please, patients are exposed to harm on a staggering scale throughout the whole of medicine. Doctors can have no idea about the true effects of the treatments they give. Does this drug really work best, or have I simply been deprived of half the data? No one can tell. Is this expensive drug worth the money, or has the data simply been massaged? No one can tell.

Will this drug kill patients? Is there any evidence that it's dangerous? No one can tell. This is a bizarre situation to arise in medicine, a discipline in which everything is supposed to be based on evidence," Goldacre continued.

Drug Companies are Not Always Legally Obligated to Disclose Serious Side Effects

Drugs are oftentimes prescribed for so-called "off label uses," uses for which the drug hasn't been specifically approved, but which physicians can (legally) prescribe them for nonetheless. In order for the drug to become "official" for a certain off-label use, they must conduct additional safety studies to be submitted for approval.

But if serious side effects come up during those studies, the company is not legally obligated to notify anyone – even if the drug is being used extensively for that purpose.

For instance, GSK conducted trials of its antidepressant drug paroxetine (Paxil) on children between 1994 and 2002. The studies not only showed no benefit, but also suggested it may increase their risk of suicidal tendencies. But GSK made no mention of the findings, even though tens of thousands of children were receiving the drug off-label, until 2003 (and even then they mentioned it in passing at a meeting discussing another issue, Goldacre reported).

Time and time again, we're seeing that the drug industry is not concerned about protecting and bettering human health as they would have you believe, but rather is devoted to protecting their bottom line. The pharmaceutical industry as a whole has become the poster-child for fraud, deception, and manipulation of science for profit. Nearly 20 percent of the top 100 Corporate Criminals listed for the 1990s were in fact drug companies!

The Scientific "Well" Has Been Poisoned …

Getting back to my original point... when your physician prescribes you a medication, even if he or she has reviewed the relevant published data, there is virtually no way to know whether that drug is truly safe or effective. The well from which that data has been drawn has been "poisoned" so that it's nearly impossible to decipher what is real and what is a fabrication. Goldacre continued:

"Missing data poisons the well for everybody. If proper trials are never done, if trials with negative results are withheld, then we simply cannot know the true effects of the treatments we use. Evidence in medicine is not an abstract academic preoccupation. When we are fed bad data, we make the wrong decisions, inflicting unnecessary pain and suffering, and death, on people just like us."

Since it is very well established that most prescribed drugs do absolutely nothing to treat the cause of disease, it would be prudent to exercise the precautionary principle when eval‎uating ANY drug claim, as it will more than likely be seriously flawed, biased, or worse... And, of course, I always advise taking control of your health, which you can easily do by reviewing my comprehensive nutritional plan that summarizes my thirty years of clinical experience and treating 25,000 patients. I put this together so you can stay well and avoid falling into the dangerous, deceitful traps discussed in this article.

http://articles.mercola.com/sites/articles/archive/2012/10/22/modern-medical-scandal.aspx

Review: Bad Pharma, by Ben Goldacre

by Alice Bell

Bad Pharma: How drug companies mislead doctors and harm patients - Ben Goldacre. Fourth Estate. 2012

The dedication at the front of Ben Goldacre’s new book Bad Pharma reads, quite simply and quite beautifully, “To whom it may concern”. This reflects Goldacre's approach well; his outwardly-unassuming-yet-also-strident style, but also his philosophical position. It’s not who you know; it's what you know. It’s not the individual cherry-picked story; it’s the broader, more rigorously uncovered trend. It is the data; not an anecdote. Good data too. Good, big, full and thorough data.

And that’s largely what the book is about: when it comes to the drugs we are prescribed, the data isn’t quite what it could be. It’s not that it’s necessarily rubbish, just a bit patchy and not always efficiently applied. Dangerously patchy – worryingly so, scandalously so – even if it’s not always too obvious. The trials used to test drugs are too frequently badly designed, tested on small numbers of people, often unrepresentative people, and then analysed poorly, sometimes deliberately poorly. The result being that doctors do not know as much as they could about the effects of the treatments they prescribe.

The medical establishment knows they have gaps in their knowledge. It’s a sort of known unknown, or at least a loosely acknowledged one. Goldacre describes how medical students are advised not to prescribe a new drug till it’s been around a while; to check nothing bad happens. Think about that for a moment. I mean, you might choose to wait a few months after a new phone’s been released before you upgrade your current one; see what other people say and let the manufactures iron out problems. But that’s a phone. This is medicine. To blithely say “see how it plays out” when it comes to prescribing drugs is to turn the public at large into test-dummies, and makes rather a mockery of the whole medical trials business. The book might be called “Bad Pharma”, but Goldacre’s target is not just the pharmaceutical industry, but bad medicine, bad regulations and bad publishing too (for a taster on that, check out this column on medical ghostwriting). They’ve been covering up gaps for a while; not necessarily as a giant conspiracy, more a collective lack of vision interlaced with a few outright attempts to mislead.

Just as phone-hacking exposed blind eyes, mismanagement and corruption in the media and the recent financial crisis made us all look again at the sausage factory that makes the economy go round, Bad Pharma hopes to open a window into how medicine really works, and worry us enough into wanting to make it a lot better. I should stress the making it better part. It’s a depressing book – expect to wince in places – but it’s a hopeful one too. Goldacre’s quite clear about how he thinks we can fix things, with a neat set of ideas for ways out of these problems at the end of most chapters, and a clear afterword which recaps and pulls out what he feels are the most important problems and things we, the readers, can do.

I should also emphasise that at no point does Goldacre suggest we throw the whole system out. It’s not the idea of industrialised medicine that’s necessarily the problem, just that we’re not holding it up to strong enough standards. He is walking a tricky line here, as many use critique of “Big Pharma” quite loosely as reason to reject contemporary medicine entirely (the title Bad Pharma is as much a play on this well-worn phrase as it is a nod to his previous book and Guardian column, Bad Science). Indeed, many have called Goldacre a “Big Pharma” shill for his stance on homeopathy or vaccinations (rather harder to make that argument now…). On the other side, aspects of the medical establishment are sceptical that change can be as straightforward as he suggests (see, for example, Michael Rawlins’ review in the Lancet).

There’s also a more political critique to be made, as one might query Goldacre’s target here. For many, the various scandals of trust we’ve lived through the past decade – the City, MPs expenses or hacking – are symptoms of a larger broken system. Perhaps a larger economic change is what is required. Goldacre says he wants to make the pharmaceutical industry the sort of place people could be proud to work in, not critique the basis of its existence. This is not the more straightforward attempt to apply science in the justification of the status quo as you could find in, for example, the final chapter of Mark Henderson’s Geek Manifesto. Still, Goldacre’s reply to the first question in this interview with readers of the Observer might rile a few on the left. Whether you feel Goldacre’s warnings are a sign that more of medicine should be put under public control probably depends on your personal politics. Still, seeing as the privatization of medicine is such a topical issue, perhaps it is a failing of a book that this ideological question isn’t addressed more explicitly. 

There’s another problem too. It’s, honestly, a bit of a slog to read. Great as this book is, in many ways, a rip-roaring yarn to warm you on winter’s night this isn't. Even the kindest of reviews say it could probably do with a bit more of an edit. It can get a bit repetitive in places and is rather abstract. This is not necessarily Goldacre’s fault. This is complex stuff, it takes time to explain, which Goldacre does very well, with a gracious and generous style. The repetition and constant recaps are actually very useful, even if they aren’t especially gripping. Not for the first time, I found myself thinking Goldacre’s probably a brilliant teacher. I’m sure his students adore him. Still, I don’t always want to play student with a popular science book.

It’s a book about infrastructures and abstractions, not people. Or rather it is about people, but lots of them at once, and that’s sometimes hard to handle. It comes from people and goes back to them though. As the Economist review put it, the upshot of Goldacre’s prose is anything but abstract. It’s life or death in some cases. And it’s important. Our society runs on infrastructures and abstractions, it’s part of the benefits of modernity. But it can be hard to relate to people en masse (just ask the people who first tried to explain the welfare state, e.g. Isotype). One of Goldacre’s concluding points – that we can look at bad behaviour of characters like Richard Sykes or Mark Porter, but “These are meaningless, banal, lucky-dip examples: ignore them, forget their names, because they are not the norm” – is highly laudable in its own way. This attitude is part of the book's epistemological strength, but is also perhaps its rhetorical failing. This might depend on personal taste. Some readers will probably prefer patterns to characters, and it’s not as if the book is bereft of examples, it’s just more about the larger picture, that’s all.

In conclusion, I’d certainly recommend this book. You might well find yourself pulled in by Goldacre’s charm or simply the brave attempt to tell stories about modernity. I hope it finds a wide readership; more people should be at the very least talking about these issues, and preferably before a serious scandal compels us to have that conversation. The suggested solutions of the book might not suit everyone, but it’s worth taking time to see where he’s coming from. If you disagree with his methods, get involved and learn enough to critique them and offer alternatives that you would find more convincing. Even if you disagree with his suggestions for change, Goldacre offers a courteous introduction to the problems of the current way we make medicine.

Alice Bell is an academic and writer interested in science's relationships with the rest of society. She is currently researching science policy at the University of Sussex. She keeps a personal blog.

http://www.newleftproject.org/index.php/site/article_comments/review_bad_pharma_by_ben_goldacre