My belief in honest science has been restored and my faith in human nature washed in cool waters!! A most heartfelt thank you to all the honest scientists and sceptics with whom I am privileged to share this world!!!
Can these honest people now make the leap to comprehend the way the pharmaceutical companies push out lies and misinformation (*see below) to destroy any perceived threat from the competition posed to them by homeopathy and alternative medicine?
Just how far does their honesty and integrity actually go?
Richard Smith was an editor for the British Medical Journal for 25 years. For the last 13 of those years, he was the editor and chief executive of the British Medical Journal Publishing Group, responsible for the profits of not only the British Medical Journal but of the whole group, which published some 25 other journals. He stepped down in July 2004. He is now a member of the board of the Public Library of Science, a position for which he is not paid. Richard Smith is Chief Executive of UnitedHealth Europe.
‘… Journals have devolved into information laundering operations for the pharmaceutical industry’, wrote Richard Horton, editor of The Lancet, in March 2004. 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’. 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, and the editors of PLoS Medicine have declared that they will not become ‘… part of the cycle of dependency…between journals and the pharmaceutical industry’. Something is clearly up.
‘The most conspicuous example of medical journals’ dependence on the pharmaceutical industry is the substantial income from advertising, but this is, I suggest, the least corrupting form of dependence. The advertisements may often be misleading and the profits worth millions, but the advertisements are there for all to see and criticise. Doctors may not be as uninfluenced by the advertisements as they would like to believe, but in every sphere, the public is used to discounting the claims of advertisers.
‘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.
‘Fortunately from the point of view of the companies funding these trials—but unfortunately for the credibility of the journals who publish them—these trials rarely produce results that are unfavourable to the companies’ products. Paula Rochon and others examined in 1994 all the trials funded by manufacturers of nonsteroidal anti-inflammatory drugs for arthritis that they could find. They found 56 trials, and not one of the published trials presented results that were unfavourable to the company that sponsored the trial. Every trial showed the company’s drug to be as good as or better than the comparison treatment.
‘By 2003 it was possible to do a systematic review of 30 studies comparing the outcomes of studies funded by the pharmaceutical industry with those of studies funded from other sources. Some 16 of the studies looked at clinical trials or meta-analyses, and 13 had outcomes favourable to the sponsoring companies. Overall, studies funded by a company were four times more likely to have results favourable to the company than studies funded from other sources. In the case of the five studies that looked at economic evaluations, the results were favourable to the sponsoring company in every case.
‘The evidence is strong that companies are getting the results they want, and this is especially worrisome because between two-thirds and three-quarters of the trials published in the major journals—Annals of Internal Medicine, JAMA, Lancet, and New England Journal of Medicine—are funded by the industry. For the British Medical Journal, it’s only one-third—partly, perhaps, because the journal has less influence than the others in North America, which is responsible for half of all the revenue of drug companies, and partly because the journal publishes more cluster-randomised trials (which are usually not drug trials).
‘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 good—and often better—than that of studies funded by others. 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” questions—and there are many ways to do this. 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, but this is a crude strategy—and 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. 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.
‘These strategies have been exposed in the cases of Risperidone and Odansetron, but it’s a huge amount of work to discover how many trials are truly independent and how many are simply the same results being published more than once. And usually it’s impossible to tell from the published studies: it’s necessary to go back to the authors and get data on individual patients.
‘Journal editors are becoming increasingly aware of how they are being manipulated and are fighting back, but I must confess that it took me almost a quarter of a century editing for the British Medical Journal to wake up to what was happening. Editors work by considering the studies submitted to them. They ask the authors to send them any related studies, but editors have no other mechanism to know what other unpublished studies exist. It’s hard even to know about related studies that are published, and it may be impossible to tell that studies are describing results from some of the same patients. Editors may thus be peer reviewing one piece of a gigantic and clever marketing jigsaw—and the piece they have is likely to be of high technical quality. It will probably pass peer review, a process that research has anyway shown to be an ineffective lottery prone to bias and abuse.
‘Furthermore, the editors are likely to favour randomised trials. Many journals publish few such trials and would like to publish more: they are, as I’ve said, a superior form of evidence. The trials are also likely to be clinically interesting. Other reasons for publishing are less worthy. Publishers know that pharmaceutical companies will often purchase thousands of dollars’ worth of reprints, and the profit margin on reprints is likely to be 70%. Editors, too, know that publishing such studies is highly profitable, and editors are increasingly responsible for the budgets of their journals and for producing a profit for the owners. Many owners—including academic societies—depend on profits from their journals. An editor may thus face a frighteningly stark conflict of interest: publish a trial that will bring US$100 000 of profit or meet the end-of-year budget by firing an editor.
‘How might we prevent journals from being an extension of the marketing arm of pharmaceutical companies in publishing trials that favour their products? Editors can review protocols, insist on trials being registered, demand that the role of sponsors be made transparent, and decline to publish trials unless researchers control the decision to publish. I doubt, however, that these steps will make much difference. Something more fundamental is needed.
‘Firstly, we need more public funding of trials, particularly of large head-to-head trials of all the treatments available for treating a condition. Secondly, journals should perhaps stop publishing trials. Instead, the protocols and results should be made available on regulated Web sites. Only such a radical step, I think, will stop journals from being beholden to companies. Instead of publishing trials, journals could concentrate on critically describing them.
Examples of Methods for Pharmaceutical Companies to Get the Results They Want from Clinical Trials:
- Conduct a trial of your drug against a treatment known to be inferior.
- Trial your drugs against too low a dose of a competitor drug.
- Conduct a trial of your drug against too high a dose of a competitor drug (making your drug seem less toxic).
- Conduct trials that are too small to show differences from competitor drugs.
- Use multiple endpoints in the trial and select for publication those that give favourable results.
- Do multicentre trials and select for publication results from centres that are favourable.
- Conduct subgroup analyses and select for publication those that are favourable.
- Present results that are most likely to impress—for example, reduction in relative rather than absolute risk.
This article is based on a talk that Richard Smith gave at the Medical Society of London in October 2004 when receiving the HealthWatch Award for 2004. The speech is reported in the January 2005 HealthWatch newsletter . The article overlaps to a small extent with an article published in the BMJ. http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0020138
Pharmaceutical company advertising in The Lancet The Lancet, Volume 378, Issue 9785, Page 30, 2 July 2011. Geoffrey Spurling University of Queensland, Brisbane, QLD 4029, Australia, Peter Mansfield Health Skepticism, Willunga, SA, Australia University of Adelaide, Adelaide, SA, Australia, Joel Lexchin chool of Health Policy and Management, York University, Toronto, ON, Canada.
‘The Editor of The Lancet, Richard Horton, is famously quoted (2004) as saying: ‘Journals have devolved into information laundering operations for the pharmaceutical industry.’ (Horton R. The dawn of McScience. New York Review of Books 2004; 51: 7. PubMed).
‘This sentiment is echoed by former New England Journal of Medicine Editor, Marcia Angell, who describes information from the pharmaceutical industry as coming, ‘… mixed with hyperbole, bias and misinformation, and there is often no way to tell which is which.’ (Angell M. The truth about the drug companies: how they deceive us and what to do about it. (New York: Random House, 2004). ((Marcia Angell was for 20 years editor of New England Journal of Medicine. Currently a professor at Harvard Medical School) 2004, quoted as ‘… The pharmaceutical industry is “primarily a marketing machine” which is willing to co-opt ‘… every institution that might stand in its way.’)
‘Both of these statements were cited by the Editors of the Journal of Emergency Medicine Australasia in their decision earlier this year to ban drug company advertising from their journal. (Jelinek GA, Brown AF. A stand against drug company advertising. Emerg Med Australas 2011; 23: 4-6. CrossRef | PubMed). We published a systematic review of 40 years of scientific literature dealing with the effect of information from pharmaceutical companies on physicians’ prescribing. (Spurling GK, Mansfield PR, Montgomery BD, et al. Information from pharmaceutical companies and the quality, quantity, and cost of physicians’ prescribing: a systematic review. PLoS Med 2010; 7: e1000352. CrossRef | PubMed).
‘Some studies found that journal advertisements were more strongly associated with prescribing than the scientific articles in the same journals; others found advertising associated with less rational prescribing and greater prescribing costs. However, none found associations between exposure to journal advertisements and improved quality of prescribing, reduced cost, or reduced prescribing overall. Our review was published in PLoS Medicine—a top-tier medical journal that does not accept pharmaceutical advertising. The Editors’ summary of our review concluded that ‘… the findings support the case for reforms to reduce negative influence to prescribing from pharmaceutical promotion.’ Is The Lancet prepared to take a stand against drug company advertisements similar to the Journal of Emergency Medicine Australasia? We declare that we have no conflicts of interest. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(11)61019-2/fulltext
Prescription for a Healthy Journal. PLoS Med 1(1): e22. doi:10.1371/journal.pmed.0010022. The PLoS Medicine Editors (2004), Virginia Barbour, James Butcher, Barbara Cohen, and Gavin Yamey. 19.10.2004.
‘We have decided not to be part of the cycle of dependency that has formed between journals and the pharmaceutical industry, an industry that focuses overwhelmingly on the most profitable drugs, thus sidelining many of the world’s health problems. Medical journals have allowed their interests to become aligned with those of the pharmaceutical industry by printing advertisements for drugs, publishing trials designed by drug companies’ marketing departments, and making profits on reprints used as marketing tools.
‘PLoS Medicine will not accept advertisements for pharmaceutical products or medical devices. Our open-access license allows free distribution of articles, so PLoS cannot benefit from exclusive reprint sales. And we consider as the lowest priority for publication papers that are simply aimed at increasing a drug’s market share without obvious benefit to patients. We will aim to have the highest levels of transparency in our published papers. We require authors to tell us of any possible competing interests; we in turn will tell readers about them. http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.0010022
See Reporting of Conflicts of Interest in Meta-analyses of Trials of Pharmacological Treatments. Michelle Roseman, BA; Katherine Milette, BSc; Lisa A. Bero, PhD; James C. Coyne, PhD; Joel Lexchin, MD; Erick H. Turner, MD; Brett D. Thombs, PhD. JAMA. 2011;305(10):1008-1017. doi: 10.1001/jama.2011.257
* So Just how far does the honesty and integrity of ‘honest scientists and sceptics’ actually go? Why are they so quiet about these abuses? Read on and wonder!!! http://www.huffingtonpost.com/dana-ullman/disinformation-homeopathy_b_969627.html Disinformation on Homeopathy: Two Leading Sources by Dana Ullman in The Huffington Post 10.3.2011
‘… Prior to actually conducting this research, the researcher wrote me saying, “Without agreement by all participants on the manner of how things were done, the outcome of the experimentation is indeed virtually meaningless.” And yet, he and the “20/20” team continued to conduct this junk science experiment with an outcome that indeed was meaningless…. It is further confusing that the “Amazing” James Randi or any of his many followers never commented about the quality of this study, even though they are known to ridicule virtually any and every study that has had a positive result from a homeopathic medicine. It certainly makes sense for a magician to want to expose frauds and charlatans. And yet, if Randi was truly serious about exposing frauds and charlatans, it is quite curious that he has chosen to go after alternative medicine rather than Big Pharma and Big Medicine when there are many more egregious frauds that occur regularly and with much greater impact on society….’ Continue reading if you dare…