by Ben Goldacre
When drug companies were asked about their attitudes and concerns in the same German study, only one expressed ethical worries, but only 20 per cent responded at all. They may not want to speak openly, but from a brief scan of the industry literature we can get a slightly clearer picture of how they view these educational sponsorship opportunities. This is from Pharmaceutical Market Europe, an industry publication, talking about how CME companies can get business. Again, this not a smoking gun: it’s just the everyday corporate reality of how the industry sees this teaching.
The overwhelming majority of support for European CME still comes from the pharmaceutical industry. Theoretically, anyone can be a supporter; but, as with any sponsorship however ‘hands-off’, it is the company which has the most to gain that will be supporting CME. An insistence that pharma companies support education in areas not of interest to them…will receive no backing.108
Of course there are regulations, to try to prevent malpractice, but these vary around the world, and commonly, as we see time and again, they are simply ignored. Norway is a wealthy country, with an efficient public sector, and industry is banned from funding any CME at all, whether directly or indirectly, without any problems. In the UK the pharmaceutical industry is allowed to support all CME. In the US there are various regulations and guidelines, which have the usual holes. In 2007 the Senate Finance Committee noted, for example, that drug companies are not compelled to follow these guidelines, and that no agency ever puts monitors in the audience to see what’s being taught, or engages in any kind of proactive assessment of content.109 Even if a CME provider is reported, found out, and has its accreditation revoked, this can take nine years.
The committee was witheringly clear on why the industry funds this activity: ‘It seems unlikely that this sophisticated industry would spend such large sums on an enterprise but for the expectation that the expenditures will be recouped by increased sales. Press reports and documents exposed in litigation and enforcement actions confirm these suspicions in some instances.’
They are referring, here, to an almost endless stream of leaked internal documents from legal cases which have revealed how the industry thinks, plans and acts. Many of these cases involve companies using CME to promote ‘off-label’ uses of drugs, expanding their prescription beyond the marketing authorisation, to other diseases where its use is not licensed. Warner-Lambert was accused of using ‘independent educational grants’ to fund CME programmes that taught doctors to use its drug Neurontin – licensed only for prescription in epilepsy – for completely different conditions, for which the drug has no licence at all. It paid $430 million to settle. Serono paid over $700 million to settle claims that it promoted its drug Serostim for uses for which it had no licence, through various methods including educational grants that funded ‘independent educational programmes’. Merck explicitly carried out an internal study to establish the ‘return on investment’ from discussion groups led by doctors, which was leaked in a court case.110 It estimated that for every dollar it spent on teaching, it got back almost $2 in revenue from doctors prescribing more of its drugs.
When ACCME reviewed the CME providers it accredits, it found that one in four were openly breaching its guidelines – not in clever, covert ways, but blatantly, not even bothering to hide it. These companies were fully accredited to teach doctors, and they allowed sponsors to influence decisions about content; allowed sponsors to choose who spoke; failed to check for conflicts of interest; repeatedly used the sponsor’s drug’s brand name to the exclusion of all others; and so on. This is hardly surprising – in fact, to imagine such transgressions wouldn’t take place is absurd. In a large, competitive and expensive market, which CME company is going to get the repeat business: the one that respects the rules? Or the one that gives the drug company what it wants?
Perhaps even more remarkably, doctors themselves recognise that the content of this teaching is biased. This includes – specifically – the ones who accept it. In a survey from 2011, 88 per cent of attenders of sponsored educational activities thought that commercial support introduces bias, but only 15 per cent thought such free teaching should be banned, and the majority were unwilling to pay properly for CME themselves.111 Reports from the American Medical Association, the Institute of Medicine, the Senate Finance Committee, the American Association of Medical Colleges and more have all called for commercial support of CME to be ended. They have all been ignored.
So there you have it. Doctors around the world – except in Norway – are taught which drugs are best by the drug companies themselves. The content is biased, and that’s why companies pay for it. For decades people have stood up, shown that the content is biased, written reports against it, demonstrated that weak guidelines fail to police it; and still it continues.
What can you do?
Ask your doctor if they accept industry-funded teaching.
If you’re a doctor, you could refuse to accept any industry-funded teaching, and refuse to give it, too.
Don’t be ashamed to ask colleagues whether they think it’s OK to attend or give industry teaching, and tell them about the research and legal cases demonstrating bias.
Receiving free teaching is a benefit in kind, of an expensive professional service. Doctors should be forced to declare publicly, to their colleagues and their patients, whether they accept free teaching from the pharmaceutical industry. Doctors who see patients should place a prominent notice in the waiting room and on their desk, stating exactly what companies they’ve accepted money or services from, and exactly what drugs those companies make.
It’s sad that individual doctors don’t volunteer to pay thousands of pounds a year, of their own money, for the continuing medical education that governments have made compulsory throughout the decades of their working lives, but they don’t. Governments need to think about forcing doctors to pay, or paying from state funds. There is no need for teaching to take place in expensive conference centres.
What does it mean to take money?
So now we enter the closing pages, and there are just a few loose ends to mop up. Many of the concerns we’ve seen in the preceding pages revolve around one idea: people who receive money from a company might have different views to those who don’t. This might seem like an obvious truth to you, but there are plenty of people who will angrily deny it, as they write another cheque for the school fees. Before we close, I will pick at this last open sore.
Firstly, we should be clear about what a conflict of interest means. The broadest definition says that you have a conflict of interest when you have some kind of financial, personal or ideological involvement that an outsider might reasonably think could affect your reasoning. It is not a behaviour, therefore, but rather a situation: to say that you had a conflict of interest doesn’t mean that you acted on it, but simply that you had one, and almost everybody has one, in one regard or another, depending on how you draw the lines.
For example: I don’t accept medical training sponsored by the pharmaceutical industry, I don’t do research or promotional work for industry, I don’t see drug reps, I’ve never been a KOL, or been flown anywhere nice with a pharmaceutical company. For the easy things, of medicine and academia, it’s a simple story. But if we broaden out, to the entirely unpoliced world of conflict of interest for popular-science writers, then the pharmaceutical industry could claim I’ve got an ideological position – that they are dodgy – and that I make money from selling this. Of course, I think I make fair arguments, giving a clear unbiased view of the evidence from systematic reviews, and I also don’t think I’d sell more books by exaggerating. But it is a conflict of interest: a situation, not a behaviour.
You could also argue the other way. For example, I have received two cheques that were partially related to the pharmaceutical industry. A decade ago, in my twenties, the Guardian entered me for the 2003 Association of British Science Writers prize. I arrived on the night and won: wandering drunkenly to the stage, I saw the prize wa
s partly sponsored by GSK, alongside some august scientific bodies. I took the cheque, with some muttering. Then, in 2011, I gave two unpaid talks to ghostwriters’ associations, explaining how their work harms patients. I give a lot of these ‘lion’s den’ talks, to groups whose work I criticise – angry quacks, journalists, academics, medics, and so on – explaining the harm done by their industries, and often picking up good stories from worried insiders. When the ghostwriters asked me to give the same talk a third time, a day’s travel away from London, I apologised and said I was busy. They offered money, I took it, and I gave the same talk again. Am I a stooge for the ghostwriters? I hardly think so, but you can disagree.
So it is important, in my view, to be clear about the importance of conflict of interest, but also, not to be unrealistic and shrill. To understand how much a conflict of interest matters, we need one basic, simple piece of evidence: overall, do academics and doctors with some kind of major interest have more pro-industry opinions than those without? We have already seen, from the very earliest pages of this book, that trials with industry funding are more likely to report positive results. We’re now talking about the next level, when people discuss the findings of other people’s trials, weigh up their strengths and weaknesses, or write opinion pieces, editorials and so on. In these kinds of discussion papers, do authors’ conclusions correlate with the extent of their industry funding? The answer, as you might expect, is yes.
As we have seen, the diabetes drug rosiglitazone has had an interesting and chequered history, with the FDA and the manufacturer, GSK, both failing to draw attention to the fact that it was associated with an increased risk of grave cardiac side effects. The drug was recently taken off the market, after billions of dollars of sales, because of problems spotted by academics which the regulators had failed to act on. One group of researchers recently pulled out all the academic papers discussing whether rosiglitazone is associated with an increased risk of heart attack.112 More specifically, they identified all 202 pieces citing and commenting on either of the two key publications examining this question: a meta-analysis by Steve Nissen, which showed that rosiglitazone does increase heart attacks; and the RECORD trial, which suggested that the drug was fine (although, you may now be concerned to hear, this trial was stopped rather early). The papers discussing these findings were from every category you can think of – review essays, letters, commentaries, editorials, guidelines and so on. As long as they discussed the link between rosiglitazone and heart attacks, and cited one of the two papers, they were in.
Around half of the authors had a financial conflict of interest, and analysing the findings by who said what gave a dismal but predictable result: people who thought rosiglitazone was safe (or, to be absolutely clear, who had a favourable view on the risk of heart attack after taking it) were 3.38 times more likely to have a financial conflict of interest with manufacturers of diabetes drugs generally, and with GSK in particular, when compared with people who took a dim view of the drug’s safety. Authors who made favourable recommendations about using the drug were similarly three and a half times more likely to have a financial interest. When the analysis was restricted to opinion articles, the link was even stronger: people recommending the drug were six times more likely to have a financial interest.
It’s important to be clear about the limitations of an ‘observational’ paper like this, and to think through alternative explanations for the observed correlation, just as we would with a research paper showing, for example, that people who eat lots of fruit and vegetables live longer. People who eat lots of vegetables tend to be wealthier, and are more likely to live healthier lives in all kinds of different ways, many of which have nothing to do with eating vegetables, so maybe that’s why they take longer to die. Likewise, in the case of favouring rosiglitazone and having a financial interest, maybe you buy stocks in a company, or go and work for it, or take a grant from it, after you’ve developed a favourable view about whether its treatment is good or bad. That may be the case for some people; but in the broader picture of all that we know about how financial interests impact on behaviour, it’s hard to believe that the findings are entirely innocent: and it certainly reiterates the fact that we need to be told, in detail, about people’s financial dealings with these companies.
How do we deal with this problem? In the most extreme view, anyone who has a conflict of interest in a particular area should be barred from expressing any view on it. Radio DJs, after all, were supposedly forbidden from accepting ‘payola’ from record companies, and their world didn’t collapse (though I’m sure there are other jollies for radio DJs).
A straight ban raises interesting problems, however. Firstly, in some areas of medicine you might struggle to find any experts at all who’ve never done any work with industry. Here we should pause for a moment to remind ourselves what we really think about the drug industry, and the people who work in it. Although this book is about problems, my goal is that pharma should be adequately regulated and transparent, to the extent that academics can feel positive and enthusiastic about collaboration with it. There is no medicine without medicines; companies can produce great products; and working with people who are focused on completing a project for profit, however distasteful you might find some aspects of that world, can be very exciting.
It’s also odd to take our frustrations out on individual doctors and academics, when they’re simply doing what governments have told them to do over the past three decades: get out there and work with industry. From the 1980 Bayh-Dole Act in the USA, which helped academics register patents on their ideas, to the Thatcher drive for ‘university entrepreneurs’, academics have consistently been told they must engage with industry, and find commercial applications for their output. Discounting all of these academics, having pushed them to engage with industry, and successfully convinced some of our finest minds to do so, would be bizarre.
There are other problems with a straight ban. Even if you can find experts with no conflicts, sometimes the people you most want to hear from are those from industry: they might have special inside knowledge of the processes that have shaped new medicines, for example. And once you start to go down the path of listening to their commercial insights, you run up against a new problem. Sometimes, though this is a very tricky area, it might be useful to allow industry people with huge conflicts of interest to speak discreetly, without attribution, on something like a medicines regulatory committee.
Journalists know that deep background, off the record, from a source inside a story they are trying to understand can be extremely valuable. Sometimes an industry person will speak more candidly, but unattributably, to a drug approval committee that doesn’t publish its minutes. I was told one story of an honorary professor of medicine, now working full time in drug development, standing up on an approvals committee to say, ‘Honestly? Everyone knows that drug is rubbish, it won’t last two years, and you’d save me some fuss if you killed it now.’ I’m not telling you this to persuade you that we should permit secrecy in regulation: I don’t think we should. I’m telling you so you can know that you’ve thought it through fairly.
On occasion, some journals have taken the view that industry is simply not to be trusted, even with declarations, and have then made rules accordingly. JAMA, for example, decided a few years ago that it would no longer accept industry-funded studies unless they had an independent statistician analysing the results rather than an industry one. It’s an interesting stipulation – it implies that the analysis is where the black magic happens – and it caused an interesting fuss. Stephen Evans is an eminent statistician who works in the same building as me: he is upright, an expert on fraud detection, and a movingly compassionate Christian (truly) in the way he talks about the dishonest academics he has exposed. He argues that we cannot simply discount the work of individual professionals out of hand, on the grounds that there is an observed association between working for industry and producing biased results:
Suppos
e that a biomedical journal invoked a new policy requiring that all authors based in western Europe or North America would receive ordinary peer review, but authors from other countries would receive a peer review with additional hurdles. This policy may seem unfair, but suppose the journal claimed that research has shown that there is a greater prevalence of fraud, bias, and sloppy work among papers coming from these other countries.113
I think he’s probably right, and that we should judge each paper on its merits, although I do slightly wish he was wrong. It’s also interesting to note that after JAMA brought in its ‘independent statistician’ rule, the number of industry-funded trials published in its pages dropped significantly.114
In general, the most common approach to conflict of interest is that it should be declared, rather than outlawed, and there are two reasons for pursuing this policy. Firstly, we hope it will allow the reader to decide whether someone is biased; and secondly, it is hoped that it might change behaviour. When I suggest that doctors should be forced to tell their patients, with prominent notices in their waiting rooms and on their desks, exactly what companies they’ve accepted money or services from, and exactly what drugs those companies manufacture, it’s partly because I think it might elicit a small amount of shame. Sunlight is a very powerful disinfectant, and has been proven to be so in many different areas. In Los Angeles, the simple act of posting every restaurant’s kitchen hygiene score in its window improved standards, and statistics on car safety led consumers to demand safer cars.
With medicine, however, declaration is more complicated than a single hygiene rating, or safety score, because it’s not always clear what should be declared. Conflict of interest, after all, goes well beyond simple drug industry payments to individual doctors. In the US – this will sound strange to readers in the UK – oncologists get more money if they treat their patients with intravenous drugs rather than simple pills: over half a community oncologist’s income comes from giving chemotherapy, so there is room for a conflict of interest. Similar problems may arise in the UK, with GPs managing the budget for their area, and taking a profit from some of the services they provide. And similar problems can arise when people are writing about a treatment they provide, even where there is no corporate involvement, simply through a vague sense of professional allegiance.