Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients (42 page)

What can you do?

1. Lobby for your university to develop a strong and unambiguous code forbidding academic staff from being involved in ghostwriting. If you are a student, draw parallels with the plagiarism checks that are deployed on your own work.

2. Lobby for the following changes in all academic journals you are involved in:

•
A full description of ‘film credit’ contributions at the end of every paper, including details of who initiated the idea for the publication.

•
A full declaration of the amount paid to any commercial medical writing firm for each paper, in the paper, and of who paid it.

•
Every person making a significant contribution should appear as a proper author, not ‘editorial assistance’.

3. Raise awareness of the issue of ghostwriting, and ensure that everyone you know realises that the people who appear as authors on an academic paper may have had little to do with writing it.

4. If you teach medical students, ensure that they are aware of this widespread dishonesty among senior figures in the academic medical literature.

5. If you are aware of colleagues who have accepted guest authorship, discuss the ethics of this with them.

6. If you are a doctor or an academic, lobby for your Royal College or academic society to have a strong code forbidding involvement in ghostwriting.

Academic journals

We put a lot of trust in academic journals, because they are the conduit through which we find out about new scientific research. We assume that they take scientific articles based on merit. We assume that they make basic checks on accuracy (though we’ve seen that they don’t prevent misleading analyses of trial data being published). And we assume that the biggest, most famous journals – which are read regularly by many more people – take the better articles.

This is naïve. In reality, the systems used by journals to select articles are brittle, and vulnerable to exploitation.

Firstly, of course, there are the inherent frailties in the system. There is a huge amount of confusion for the public – and for many doctors – around what ‘peer reviewed’ publication actually means. Put very simply, when a paper is submitted to a journal, the editor sends it out to a few academics who they know have an interest in a particular field. These reviewers are unpaid, and do this work for the good of the academic community. They read the paper, and come to a judgement about whether it’s a newsworthy piece of research, a well-conducted study, fairly described, and whether its conclusions broadly match its findings.

This is an imperfect and subjective set of judgement calls, standards vary hugely between journals, and there’s also room to stick the knife into competitors and enemies, since most reviewers’ comments are anonymised. That being said, the reviewers are often not very anonymous, because a comment like ‘This paper is unacceptable because it doesn’t cite the work of
Chancer et al
. in the introduction’ is a pretty good sign that Professor Chancer himself has just peer reviewed your paper. In any case, good journals often take papers that aren’t perfect, on the grounds that they have something, of some small scientific interest, in their results. So the academic literature is a ‘buyer beware’ environment, where judgement must be deployed by expert readers, and you cannot simply say, ‘I saw it in a peer reviewed paper, therefore it is true.’

Then there is the clear conflict of interest. This problem is now openly discussed for academics – their industry grants, their drug-company stock portfolio – and every scientist is compelled by journal editors to declare their financial interests when publishing a paper. But the very editors who impose this rule on their contributors have, for the most part, exempted themselves from the same process. That is odd. The pharmaceutical industry has global revenues of $600 billion, and it buys a lot of advertising space in academic journals, often representing the greatest single component of a journal’s income stream, as editors very well know. In some respects, taking a step back, it’s odd that journals should only take adverts for drugs (and the occasional body scanner): the rates in
JAMA
are cheaper than those in
Vogue
, taking circulation into account (300,000 against a million), and doctors buy cars and smartphones like everyone else. But journals do like to look scholarly; and it was only recently that they were trying to persuade the government that drug adverts are educational content, and should therefore be tax exempt. You will remember, I hope, just how educational these adverts are, from the discussion earlier in this chapter of how often they make claims that are not supported by the evidence.

To reduce the risk that this income strand will pervert decisions on whether to publish an article, journals often claim that they introduce ‘firewalls’ between editorial and advertising staff. Sadly, such firewalls are easily burnt through.

In 2004, for example, an editorial was submitted to the respected journal
Transplantation and Dialysis
, questioning the value of erythropoietin, or ‘EPO’.
⁹²
Although this molecule is made by the body, it can also be manufactured and given medically, and in this form it is one of the biggest-selling pharmaceutical products of all time. It is also, unfortunately, extremely expensive, and the editorial was submitted in response to a call from Medicare, which had asked for help in reviewing its policy on giving the treatment to people in end-stage renal disease, since there were fears that it might not be effective. The editorial agreed with this pessimistic stance, and was accepted by three ‘peer reviewers’ at the journal. Then the editor sent the following unwise letter to the author:

    I have now heard back from a third reviewer of your EPO editorial, who also recommended that it be published…Unfortunately, I have been overruled by our marketing department with regard to publishing your editorial.

        As you accurately surmised, the publication of your editorial would, in fact, not be accepted in some quarters…and apparently went beyond what our marketing department was willing to accommodate. Please know that I gave it my best shot, as I firmly believe that opposing points of view should be provided a forum, especially in a medical environment, and especially after those points of view survive the peer review process. I truly am sorry.

The letter was made public, and the journal reversed its decision. As ever, it is impossible to know how often decisions like this are made, and how often they are hidden. All we can do is document the scale of the financial incentive for journals, and the quantitative evidence showing a possible impact on their content.

Overall, the pharmaceutical industry spends around half a billion dollars a year on advertising in academic journals.
⁹³
The biggest –
NEJM
,
JAMA
– take $10 or $20 million each, and there is a few million each for the next rank down. Strikingly, while many journals are run by professional bodies, their income from advertising is still far larger than anything they get from membership fees. In addition to the large general journals, and the small specialist ones, some journals are delivered to doctors for free, and subsidised entirely by advertising revenue. To see whether this income has an impact on content, a 2011 paper looked at all the issues of eleven journals read by GPs in Germany – a mix of free and subscription publications – and found 412 articles where drug recommendations were made. The results were stark: free journals, subsidised by advertising, ‘almost exclusively recommended the use of the specified drugs’. Journals financed entirely through subscription fees, meanwhile, ‘tended to recommend against the use of the same drugs’.
⁹⁴

Advertising is not the only source of drug company revenue for academic journals; there are several other strands of income, some of which are not immediately apparent. Journals often produce ‘supplements’, whole extra editions outside of its normal work. These are often sponsored by a drug company, based on the presentations at one of its sponsored conferences or events, and have much lower scientific standards than are found in the journal itself.

Then there are ‘reprints’. These are special extra copies of individual academic papers that are printed off and sold by academic journals. These are then handed out to doctors by drug reps to promote their drugs, and are bought in huge quantities, with spends of up to $1 million to buy crates of copies of just one paper. Those are the sorts of figures that haunt editors’ imaginations when they try to choose which of two trials they should publish. Richard Smith, a former editor of the
British Medical Journal
, framed the dilemma: ‘Publish a trial that will bring in $100,000 of profit, or meet the end-of-year budget by firing an editor.’
⁹⁵

Sometimes the implicit reasoning behind these choices can find its way into the public domain. A recent investigation from the UK Prescriptions Medicine Code of Practice Authority, for example, ruled that the company Boehringer Ingelheim was responsible for the content of an article making unacceptable claims for its diabetes drug linagliptin, even though it was written by two academics, and appeared in the Wiley Publishing academic journal
Future Prescriber
, because ‘although Boehringer Ingelheim did not pay for the article per se, it in effect commissioned it through an agreement to pay for 2,000 reprints’.
⁹⁶

For the most part, however, even the most basic numbers on this huge source of income are hard to obtain. A research project I was involved in found that the biggest and most lucrative reprint orders come overwhelmingly from the pharmaceutical industry (this was a lot of work, and we’ve just had it published in the
BMJ
,
⁹⁷
though it might have happened faster with a commercial medical writing firm handling the legwork for us). This simple finding is exactly what you might expect, but there was something else that happened during this study, which many people found much more concerning. We asked all the leading journals in the world for information about their income from reprints, but only the
BMJ
and the
Lancet
were willing to give us any data at all: the
Journal of the American Medical Association
said this information was proprietary; the vice president of publishing for
Annals of Internal Medicine
said they did not have the resources to provide the information; and the managing director of publishing for the
New England Journal of Medicine
said it would conflict with their business practices to tell us. So this huge source of pharmaceutical industry income, paid to the gatekeepers of medical knowledge, remains secret.

Is there any evidence to show that journals are more likely, on a fair comparison, to take industry-funded studies?

This has been studied only rarely – because, as we need to keep reminding ourselves, this whole area has hardly been a research funding priority – but the answer appears to be yes. A paper published in 2009 analysed every study ever published on the influenza vaccine
⁹⁸
(although it’s reasonable to assume that its results might hold for other subject areas). It looked at whether funding source affected the quality of a study, the accuracy of its summary, and the eminence of the journal in which it was published.

Academics measure the eminence of a journal, rightly or wrongly, by its ‘impact factor’: an indicator of how commonly, on average, research papers in that journal go on to be ‘cited’ or ‘referenced’ by other research papers elsewhere. The average journal impact factor for the ninety-two government-funded studies was 3.74; for the fifty-two studies wholly or partly funded by industry, the average impact factor was much higher, at 8.78. This means that studies funded by the pharmaceutical industry were hugely more likely to get into the bigger, more respected journals.

That’s an interesting finding, because there is no other explanation for it. There was no difference in methodological rigour, or quality, between the government-funded research and the industry-funded research. There was no difference in the size of the samples used in the studies. And there is no difference in where people submit their articles: everybody wants to get into a big, famous journal, and everybody tries them first. If they get rejected they will try lesser and lesser journals, until someone takes the paper. It’s possible that the industry-funded researchers were simply more dogged, or more shameless; and that maybe, when they were rejected by one major journal, they hawked their paper to other equally large ones. It’s possible that they could do this more rapidly than those without industry funding, because they had administrative assistance from professional writers to deal with the tedious bureaucracy of each journal’s submission system, and tolerated the long delay in publication that this strategy would cause. Or perhaps lucrative industry-funded studies are simply favoured by editors.

Either way, getting published in a higher-impact journal is a huge advantage, for a number of reasons. Firstly, it is prestigious, and implies that your research is regarded as higher-quality. But secondly, papers in bigger journals are simply more likely to be read. As we’ve already seen, our systems for disseminating knowledge are ad hoc and antiquated, built on centuries-old platforms where science is presented in essay form, and printed on paper, with no clear mechanism for getting the right information to the right doctor at the right time. In a world where the information architecture of medicine is so massively flawed, simply getting under someone’s nose counts for a lot.