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Journals have devolved into information laundering operations for the pharmaceutical industry, wrote Richard Horton, editor of the Lancet, in March 2004 [1]. In the same year, Marcia Angell, former editor of the New England Journal of Medicine, lambasted the industry for becoming primarily a marketing machine and co-opting every institution that might stand in its way [2]. Medical journals were conspicuously absent from her list of co-opted institutions, but she and Horton are not the only editors who have become increasingly queasy about the power and influence of the industry. Jerry Kassirer, another former editor of the New England Journal of Medicine, argues that the industry has deflected the moral compasses of many physicians [3], and the editors of PLoS Medicine have declared that they will not become part of the cycle of dependencybetween journals and the pharmaceutical industry [4]. Something is clearly up.
The much bigger problem lies with the original studies, particularly the clinical trials, published by journals. Far from discounting these, readers see randomised controlled trials as one of the highest forms of evidence. A large trial published in a major journal has the journal's stamp of approval (unlike the advertising), will be distributed around the world, and may well receive global media coverage, particularly if promoted simultaneously by press releases from both the journal and the expensive public-relations firm hired by the pharmaceutical company that sponsored the trial. For a drug company, a favourable trial is worth thousands of pages of advertising, which is why a company will sometimes spend upwards of a million dollars on reprints of the trial for worldwide distribution. The doctors receiving the reprints may not read them, but they will be impressed by the name of the journal from which they come. The quality of the journal will bless the quality of the drug.
Why are pharmaceutical companies getting the results they want? Why are the peer-review systems of journals not noticing what seem to be biased results? The systematic review of 2003 looked at the technical quality of the studies funded by the industry and found that it was as goodand often betterthan that of studies funded by others [8]. This is not surprising as the companies have huge resources and are very familiar with conducting trials to the highest standards.
The companies seem to get the results they want not by fiddling the results, which would be far too crude and possibly detectable by peer review, but rather by asking the right questionsand there are many ways to do this [10]. Some of the methods for achieving favourable results are listed in the Sidebar, but there are many ways to hugely increase the chance of producing favourable results, and there are many hired guns who will think up new ways and stay one jump ahead of peer reviewers.
Then, various publishing strategies are available to ensure maximum exposure of positive results. Companies have resorted to trying to suppress negative studies [11,12], but this is a crude strategyand one that should rarely be necessary if the company is asking the right questions. A much better strategy is to publish positive results more than once, often in supplements to journals, which are highly profitable to the publishers and shown to be of dubious quality [13,14]. Companies will usually conduct multicentre trials, and there is huge scope for publishing different results from different centres at different times in different journals. It's also possible to combine the results from different centres in multiple combinations.
I view the highly controversial but real issue of medical journals' relationships with pharmaceutical companies in the context of the dilemma facing academic medicine as a whole. There are three colluding parties involved: the journals, which are usually published by the professional soceities; the pharmaceutical companies, which are usually multinational industries with enormous funds; and last but not least the academics who form the editorial boards of the journals. They also act as reviewers for the journals and as authors and co-authors of the papers submitted to the them, and they serve as academic promotion reviewers in medical academic institutions the world over. There are seemingly intricate connections between these three parties which mutually sustain one another in that part of modern medicine which we call academic medicine.
Richard Smith's generally well-argued essay on the indirect use of medical journals for pharmaceutical marketing was all the more impressive in coming from someone who did so much - albeit inadvertently - to create the situation he now deplores.
During his editorship of the BMJ, the journal acted as the major source of positive propaganda for the Evidence-Based Medicine (EBM) movement [2], which firstly popularized the view that large randomized controlled trials (megatrials) were the 'best' evidence concerning therapeutic effectiveness, then later the view that they were the ONLY valid evidence of effectiveness. Yet the intrinsic superiority of the RCT methodology was merely asserted and never demonstrated, for the excellent reason that it is not true [4, 5]. Indeed it is a ludicrous idea that one particular experimental methodology should possess intrinsic superiority over other methodologies.
The dogma of RCTs as the gold standard has led to the present situation in which those who control trials control clinical practice. The consequent abuses and distortions have been thoroughly documented in psychiatry [6,7, 8], although Smith -inadvertently - delayed awareness of this work [7]. 'Ghost' authorship of industry research by respected scientists from prestigious institutions is managed by public relations agencies to optimize pharmaceutical marketing [8].
The box listing the methods that Pharmaceutical companies use for getting the results they want from clinical trials is very similar to one that I have developed in a lecture that I am currently writing up on "how to cheat in clinical trials" based on game theory (design games, analysis games, write-up games and publication games).
Design games include: avoiding active comparators, choosing an obscure comparator, using the comparator at the wrong dose, and selecting outcome measures that inflate the treatment effect.
Analysis games include torturing that data with lots of statistical tests (only some of which are reported), torturing the data again with unspecified subgroup analyses, using relative as opposed to absolute changes to sound impressive, only testing change in score for each treatment separately but not against each other, and not performing an intention-to-treat analysis.
Write-up games include misinterpreting inconclusiveness with therapeutic equivalence, avoid mentioning adverse effects in abstract, ignoring patient-generated outcomes, inflating the scales on figures and emphasising clinically meaningless composite scales.
The publishing games are fairly straightforward ie don't publish "negative" studies, delay publishing negative studies, publish such studies in obscure journals, and duplicate and salami publishing of "positive" studies.