With thanks to the One Click Group 5.4.12
TRANSPARENCY AND MEDICINE – A series examining issues from ethics to the evidence in evidence-based medicine, the influence of medical journals to the role of Big Pharma in our present and future health.
Here Adam Dunn discusses his research into authorship networks, which revealed the position of industry researchers in academic publishing. There’s growing concern that large pharmaceutical companies are capable of undermining the truth about the published evidence doctors use to treat patients. The suspicion is that pharmaceutical companies may be trading lives for profits.
Clinical trials are one of the main sources of information that guide doctors when they treat patients. But controversial drug withdrawals have given doctors good reasons to be sceptical about the evidence that reaches them, and eroded their trust in the evidence base.
Vioxx gave us the quintessential story of what can go wrong when a big pharmaceutical company exerts influence over the evidence base. The arthritis drug was prescribed millions of times in Australia before it was revealed that it doubled the risk of heart attack. Vioxx was withdrawn in 2003 but the evidence showing its harmful effects was available years earlier.
So when looking for someone to blame, the fingers of prominent academics point directly at the pharmaceutical industry. But are their views justified?
With colleagues from the Centre for Health Informatics, I used network analysis to investigate clinical trial collaboration for a selection of widely prescribed drugs. Much like the way network pictures of Twitter or Facebook are drawn, we connected researchers who had worked together in a clinical trial.
We wanted to see how important each researcher was in their network, especially those who were affiliated with pharmaceutical companies that manufacture the drugs they study.
Our results showed that industry-based authors of clinical trials held more influential positions in their collaborative networks. These authors also received more citations than their non-industry peers.
We concluded that when it comes to clinical trials about drugs, industry researchers occupy influential positions, and their work is more widely cited. These conclusions left us feeling very uneasy about clinical evidence. It appears that pharmaceutical companies are disproportionately powerful in coming up with the evidence to support the safety and efficacy of their own drugs.
Those familiar with clinical trials might ask how this could happen when clinical trials are registered under strict protocols and published after rigorous peer-review processes. In other words, if clinical trials are so tightly controlled, how can they be manipulated to show a drug is safe when it’s not?
The simple answer is that industry groups do trials differently. Industry-sponsored trials are less likely to publish negative results and more likely to design trials that will produce positive results in the first place. On top of that, industry is responsible for more evidence now than ever before – over a third of registered clinical trials each year are now funded by pharmaceutical companies.
When important evidence is designed to provide only positive conclusions, the data proving a drug’s safety is simply not made available. This is exactly what happened when diabetes drug Avandia was shown to increase the risk of heart failure in 2007. Even after a decade in the market, there were simply not enough data available to show the long-term risks or benefits.
Avandia was a key piece of the evidence puzzle for our research because it revealed the clear and direct negative effect of industry influence. An analysis of articles about the drug revealed that researchers with financial conflicts of interest continued to write favourably about the drug even after the negative evidence was published.
And although Avandia was withdrawn in the United Kingdom and New Zealand, it remains available (albeit under much tighter controls) in Australia and the United States.
So it seems that the lessons from this case may not have been learned. How can we know where and when industry influence will next tip the evidence balance in the favour of another harmful drug?
We’ll need to know more than whether or not clinical trials demonstrate safety and efficacy – we need to know if the right kinds of clinical trials were done in the first place.
See Why Most Published Research Findings Are False Ioannidis JPA (2005) Why Most Published Research Findings Are False. PLoS Med 2(8): e124. doi:10.1371/journal.pmed.0020124 ‘… There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias. In this essay, I discuss the implications of these problems for the conduct and interpretation of research…’
See A key player in stoking this Swine Flu hysteria was Dr Iain Stephenson, a Consultant at University Hospital of Leicester NHS Trust who has been found guilty of vaccine research fraud on a grand scale by the General Medical Council (GMC).
See Thirteen per cent of scientists or doctors have said they know of colleagues who have fabricated data in order to get research published. More than one in ten (13%) scientists or doctors have witnessed colleagues intentionally altering or fabricating data to get published or during their research, a poll suggests. The survey of almost 2,800 experts in the UK also found 6% knew of possible research misconduct at their institution that has not been properly investigated. The poll, for the British Medical Journal (BMJ), is being presented at a meeting aimed at tackling research misconduct in the UK. 13 January 2012
See Mental scores decline precipitously at 30 months after anthrax vaccine, but CDC spins study to say vaccine safe Thursday, January 12, 2012
See http://www.theoneclickgroup.co.uk/news.php?id=6732#newspost Patient No. 28665 was helping a Chesterfield company test a drug dubbed the “female Viagra” but stopped showing up for exams in December 2007. That didn’t stop a staffer of the company, PPS Clinical Research STL, from claiming that six months later the patient came in for an exam, was diagnosed with medical conditions, had undergone tests and even had given a urine sample. That admission was made in the company’s guilty plea to a federal felony charge of obstructing a proceeding of a federal agency. The drug the company helped test, aimed at women who suffered from an unexplained lack of sexual desire, never made it to market. As part of the plea, PPS admitted that it “corruptly influenced, obstructed, and impeded” an inspection by the Food and Drug Administration by providing false patient records in May 2010. During the trials, the drug’s manufacturer faulted PPS for failing to have a trained investigator conduct some exams, for back dating records and for failing to properly oversee one patient’s selection for the study, according to prosecutors. Boehringer did not respond to emails seeking comment.
See http://www.theoneclickgroup.co.uk/news.php?id=6610#newspost A well-known psychologist in the Netherlands whose work has been published widely in professional journals falsified data and made up entire experiments, an investigating committee has found. Experts say the case exposes deep flaws in the way science is done in a field, psychology, that has only recently earned a fragile respectability.
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