With thanks to the One Click Group 2.2.12 and the Financial Times‘ Science Editor, Clive Cookson:

UK research is plagued with misconduct, according to a survey of 2,700 scientists by the British Medical Journal. It found that 13 per cent had first-hand knowledge of UK-based researchers deliberately altering or fabricating data, while 6 per cent were aware of misconduct that had not been properly investigated.

The British Medical Journal released the results at a conference in London where experts pushed for stronger action to tackle what they said was a problem being ignored by many universities, hospitals and other scientific institutions. Fiona Godlee, BMJ editor, said the survey showed “that there is a substantial number of cases and that UK institutions are failing to investigate adequately, if at all. “The BMJ has been told of junior academics being advised to keep concerns to themselves to protect their careers, being bullied into not publishing their findings, or having their contracts terminated when they spoke out,” she added.

Speaker after speaker at the meeting said Britain should not be complacent just because the most publicised cases of fraud in recent years had taken place in other countries. “The British public do not know what is going on,” said Dr Godlee. “People need to realise that misconduct is affecting patients every day and it is a misappropriation of public funds.”

Journal editors were often the first to come across cases of misconduct, when they spotted inconsistencies in scientific or medical papers, said Elizabeth Wager, chair of the Committee on Publication Ethics, a forum for editors and publishers. “But they are not the right people to investigate misconduct,” she said. “That responsibility lies with the researchers’ institutions.”

“This BMJ survey chimes with our experience from COPE where we see many cases of institutions not co-operating with journals and failing to investigate research misconduct properly,” Dr Wager added.

Ginny Barbour, a senior editor with the PLoS group of journals, said one-third of authors could not find the original data to back up figures in scientific papers when these were questioned.

Unlike some other countries, the UK has no official national body to deal with research misconduct. The closest equivalent is the UK Research Integrity Office, established in 2006 as a voluntary body funded mainly by universities “UK RIO is a fairly modest organisation and we have had a bumpy ride [getting established] because some players wanted us to die a death,” said vice-chair Mike Farthing, vice-chancellor of Sussex University. But he hoped for more institutional support to expand its activities in future.

See http://avilian.co.uk/2012/01/reporting-of-research-ghosts-in-the-machine/

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…’

With thanks to the One Click Group Reporting of research: Ghosts in the machine 31.1.12:

By Peter T Wilmshurst, Consultant Cardiologist, Royal Shrewsbury Hospital, Shrewsbury SY3 8XQ 31 January 2012

If I tried to make money by deceiving people that a picture that I had painted was the work of some great artist, the law would call it fraud. Yet when pharmaceutical and medical device companies make money by deceiving doctors and patients that their articles were written by medical opinion leaders we call it ghost writing and gift authorship.[1]

This double standard is because this form of financial “fraud” is so prevalent amongst the most influential opinion leaders in the profession and so many journals and organisations profit from it that we have institutionalised this dishonesty in which everyone profits except perhaps the patients who may get inappropriate treatment and potentially those who pay for it – in the UK that is usually the tax-payer.

Dr Tony Rickards was a great cardiologist. His memory has been sullied because he was unusually both a “ghost” and a gift author on publications about the MIST Trial. He died in May 2004,[2] before the trial started in November 2004. He was not on the trial design committee: I know because I was. Despite satisfying none of the criteria for authorship of the most highly cited cardiology journal, Circulation, he was listed as an author of the paper.[3] One other member of the trial steering committee and I refused to be authors because of errors in the paper and because the sponsor refused to allow us to see all the data.

After persistent pressure from me Circulation eventually published a correction (700 words), data supplement (4 pages) and new version of the paper.[4-6] Before the correction was published the editors of Circulation knew that Dr Rickards had died and did not meet the criteria for authorship. They did not remove his name from the corrected version of the paper. Because Dr Rickards was dead, the sponsors could dispense with the customary payment to eminent gift authors.

Circulation published in 2009 a letter responding to correspondence about the MIST paper in which Dr Rickards had moved up to be the fourth author (from fifteenth author on the paper), even though the editors of Circulation knew that he had died 5 years earlier.[7] Dr Rickards was named as an author of a letter he had no part in writing, which responded to correspondence he had not read, about a paper he had not seen or written, which describing research in which he had not participated. If editors ignore their rules on authorship why should anyone else obey the rules?

References
1. Hendrick R. Ghosts in the machine. BMJ 2011;343:d7860.
2. Caroline Richmond. Obituary: Anthony Francis Rickards. BMJ 2004;329:234.
3. Dowson A, Mullen MJ, Peatfield R, Muir K, Khan AA, Wells C, Lipscombe SL, Rees T, De Giovanni JV, Morrison WL, Hildick-Smith D, Elrington G, Hillis WS, Malik IS, Rickards A. Migraine intervention with STARFlex Technology (MIST) Trial: a prospective, multicenter, double-blind, sham- controlled trial to evaluate the effectiveness of patent foramen ovale closure with STARFlex septal repair implant to resolve refractory migraine headache. Circulation 2008;117:1397-1404.
4. http://circ.ahajournals.org/cgi/content/full/circulationaha;120/9/e71
5. http://circ.ahajournals.org/cgi/content/full/CIRCULATIONAHA.107.727271/DC1
6. http://circ.ahajournals.org/cgi/content/full/117/11/1397
7. Dowson A, Mullen MJ, Khan AA, Rickards A, Peatfield R, Muir K, et al. Response to letter regarding article “Migraine Interventions with STARFlex Technology (MIST) Trial”. Circulation 2009;119:e194.

Competing interests: Peter T Wilmshurst says: My involvement is described in the letter. I have no financial conflicts.

With thanks to the One Click Group 30.1.12 ‘Scientific research emperor is marching around buck naked. The British Medical Journal’:

See Research misconduct The emperor is marching around buck naked. BMJ 2012; 344 doi: 10.1136/bmj.e541 (Published 24 January 2012) Cite this as: BMJ 2012;344:e541.

The validity and quality of research underpin the entire research enterprise worldwide. However, a number of studies have shown that many researchers take “shortcuts” and that perhaps 1-3% of research is grossly false, fitting into the category of research misconduct.

Research misconduct has been defined in US federal law as fabrication, plagiarism and/or falsification. Identified cases have been few, often limited to easy-to-identify falsified figures in published papers.

However, these may be the tip of the iceberg:

Godlee’s report of widespread research misconduct is disturbing and, I believe, generalises to the US.1 2 It’s not just the fact that it is happening, but that it reflects a culture within which new researchers are socialised. Previous research indicates the motivators for dishonesty include a high pressure achievement oriented environment, where “if everybody else is doing it, it must be OK.”3

The problem also underscores how important are reanalysis and replication of reported research, a recent topic on the US Institutional Review Board Forum (www.irbforum.org/forum/). But, get this, “Ginny Barbour, a senior editor with the PLoS group of journals, said one third of authors could not find the original data to back up figures in scientific papers when these were questioned.” I wonder how many journal editors seek to discover and reject such authors. I wonder how meticulous the US Food and Drug Administration is in policing the input it receives in support of marketing approval for new drugs and medical devices.

These behaviours are beyond the reach of surveillance by institutional review boards and research ethics boards, and they indicate the need for a new end product quality control system.4 The simplifying assumptions about the efficacy of peer review and professional ethics and responsibility fail miserably when the emperor is discovered marching around buck naked.

References

1. Godlee F. Research misconduct is widespread and harms patients [Editor’s Choice]. BMJ2012;344:e14. (5 January.)

   FREE Full Text
2. Martinson BC, Anderson MS, deVries R. Scientists behaving badly. Nature435;2005:737-8.
3. Vedantam S. Cheating is an awful thing for other people to do. Washington Post2006. www.washingtonpost.com/wp-dyn/content/article/2006/08/20/AR2006082000501.html.
4. Noble JH Jr. Peer review: quality control of applied social research. Science1974;185:916-21.

   FREE Full Text

See http://avilian.co.uk/2011/10/retractions-in-the-medical-literature-how-many-patients-are-put-at-risk-by-flawed-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 Research misconduct is widespread and harms patients, BMJ 2012; 344 doi: 10.1136/bmj.e14 (Published 5 January 2012), Cite this as: BMJ 2012;344:e14

See ‘…it is simply no longer possible to believe much of the clinical research that is published…‘

See The Whole Truth? Meta-Analysis of Reboxetine Trials Calls Into Question Veracity of All Industry-Sponsored Research

See Lies, Damned Lies, and Medical Science

See Science for Sale: Protect Yourself From Medical Research Deception

See British Medical Journal – now only 11% of NHS Treatments Backed by Evidence (was 13%)

See Big Pharma researcher admits to faking dozens of research studies

See CAM deaths 0 Iatrogenic deaths 999,936 annually

See Big Pharma Bias at Harvard Medical School

See Andrew Wakefield demands retraction from BMJ after documents prove innocence from allegations of vaccine autism data fraud

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

With thanks to the Journal of Medical Ethics  Med Ethics doi:10.1136/jme.2011.043133. 17.5.2011. R Grant Steen, President, MediCC, Medical Communications Consultants, LLC, 103 Van Doren Place, Chapel Hill NC 27517, USA; g_steen_medicc@yahoo.com 

Abstract: Background Clinical papers so flawed that they are eventually retracted may put patients at risk. Patient risk could arise in a retracted primary study or in any secondary study that draws ideas or inspiration from a primary study.

Methods: To determine how many patients were put at risk, we evaluated 788 retracted English-language papers published from 2000 to 2010, describing new research with humans or freshly derived human material. These primary papers—together with all secondary studies citing them—were evaluated using ISI Web of Knowledge. Excluded from study were 468 basic science papers not studying fresh human material; 88 reviews presenting older data; 22 case reports; 7 papers retracted for journal error and 23 papers unavailable on Web of Knowledge. Overall, 180 retracted primary papers (22.8%) met the inclusion criteria. Subjects enrolled and patients treated in 180 primary studies and 851 secondary studies were combined.

Results: Retracted papers were cited over 5000 times, with 93% of citations being research related, suggesting that ideas promulgated in retracted papers can influence subsequent research. Over 28 000 subjects were enrolled—and 9189 patients were treated—in 180 retracted primary studies. Over 400 000 subjects were enrolled—and 70 501 patients were treated—in 851 secondary studies which cited a retracted paper. Papers retracted for fraud (n=70) treated more patients per study (p<0.01) than papers retracted for error (n=110).

Conclusions: Many patients are put at risk by retracted studies. These are conservative estimates, as only patients enrolled in published clinical studies were tallied.

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

Research misconduct is widespread and harms patients, BMJ 2012; 344 doi: 10.1136/bmj.e14 (Published 5 January 2012), Cite this as: BMJ 2012;344:e14

See ‘…it is simply no longer possible to believe much of the clinical research that is published…‘

See The Whole Truth? Meta-Analysis of Reboxetine Trials Calls Into Question Veracity of All Industry-Sponsored Research

See Lies, Damned Lies, and Medical Science

See Science for Sale: Protect Yourself From Medical Research Deception

See British Medical Journal – now only 11% of NHS Treatments Backed by Evidence (was 13%)

See Big Pharma researcher admits to faking dozens of research studies

See CAM deaths 0 Iatrogenic deaths 999,936 annually

See Big Pharma Bias at Harvard Medical School

See Andrew Wakefield demands retraction from BMJ after documents prove innocence from allegations of vaccine autism data fraud

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

Results of medication studies in top medical journals may be misleading to readers. UCLA-Harvard study highlights 3 types of confusing outcome measures Contact: Enrique Rivero erivero@mednet.ucla.edu= 310-794-2273 University of California – Los Angeles Health Sciences Public release date: 25-Aug-2011

Studies about medications published in the most influential medical journals are frequently designed in a way that yields misleading or confusing results, new research suggests. Investigators from the medical schools at UCLA and Harvard analyzed all the randomized medication trials published in the six highest-impact general medicine journals between June 1, 2008, and Sept. 30, 2010, to determine the prevalence of three types of outcome measures that make data interpretation difficult.

In addition, they reviewed each study’s abstract to determine the percentage that reported results using relative rather than absolute numbers, which can also be a misleading. The findings are published online in the Journal of General Internal Medicine.

The six journals examined by the investigators— the New England Journal of Medicine, the Journal of the American Medical Association, The Lancet, the Annals of Internal Medicine, the British Medical Journal and the Archives of Internal Medicine — included studies that used the following types of outcome measures, which have received increasing criticism from scientific experts:

Surrogate outcomes (37 percent of studies), which refer to intermediate markers, such as a heart medication’s ability to lower blood pressure, but which may not be a good indicator of the medication’s impact on more important clinical outcomes, like heart attacks.

Composite outcomes (34 percent), which consist of multiple individual outcomes of unequal importance lumped together — such as hospitalizations and mortality — making it difficult to understand the effects on each outcome individually.

Disease-specific mortality (27 percent), which measures deaths from a specific cause rather than from any cause; this may be a misleading measure because, even if a given treatment reduces one type of death, it could increase the risk of dying from another cause, to an equal or greater extent.

“Patients and doctors care less about whether a medication lowers blood pressure than they do about whether it prevents heart attacks and strokes or decreases the risk of premature death,” said the study’s lead author, Dr. Michael Hochman, a fellow in the Robert Wood Johnson Foundation Clinical Scholars Program at the David Geffen School of Medicine at UCLA’s division of general internal medicine and health services research, and at the U.S. Department of Veterans Affairs’ Los Angeles Medical Center.

“Knowing the effects of a medication on blood pressure does not always tell you what the effect will be on the things that are really important, like heart attacks or strokes,” Hochman said. “Similarly, patients don’t care if a medication prevents deaths from heart disease if it leads to an equivalent increase in deaths from cancer.”

Dr. Danny McCormick, the study’s senior author and a physician at the Cambridge Health Alliance and Harvard Medical School, added: “Patients also want to know, in as much detail as possible, what the effects of a treatment are, and this can be difficult when multiple outcomes of unequal importance are lumped together.”

The authors also found that trials that used surrogate outcomes and disease-specific mortality were more likely to be exclusively commercially funded — for instance, by a pharmaceutical company. While 45 percent of exclusively commercially funded trials used surrogate endpoints, only 29 percent of trials receiving non-commercial funding did. And while 39 percent of exclusively commercially funded trials used disease-specific mortality, only 16 percent of trials receiving non-commercial funding did.

The researchers suggest that commercial sponsors of research may promote the use of outcomes that are most likely to indicate favorable results for their products, Hochman said. ”For example, it may be easier to show that a commercial product has a beneficial effect on a surrogate marker like blood pressure than on a hard outcome like heart attacks,” he said. “In fact, studies in our analysis using surrogate outcomes were more likely to report positive results than those using hard outcomes like heart attacks.”

The new study also shows that 44 percent of study abstracts reported study results exclusively in relative — rather than absolute — numbers, which can be misleading.

“The way in which study results are presented is critical,” McCormick said. “It’s one thing to say a medication lowers your risk of heart attacks from two-in-a-million to one-in-a-million, and something completely different to say a medication lowers your risk of heart attacks by 50 percent. Both ways of presenting the data are technically correct, but the second way, using relative numbers, could be misleading.”

Still, the authors acknowledge that the use of surrogate and composite outcomes and disease-specific mortality is appropriate in some cases. For example, these outcomes may be preferable in early-phase studies in which researchers hope to quickly determine whether a new treatment has the potential to help patients.

To remedy the problems identified by their analysis, Hochman and McCormick believe that studies should report results in absolute numbers, either instead of or in addition to relative numbers, and that committees overseeing research studies should closely scrutinize study outcomes to ensure that lower-quality outcomes, like surrogate makers, are only used in appropriate circumstances.

“Finally, medical journals should ensure that authors clearly indicate the limitations of lower-quality endpoints when they are used — something that does not always occur,” McCormick said.

###

The authors did not receive any internal or external funding for this research.

The Robert Wood Johnson Foundation focuses on the pressing health and health care issues facing our country. As the nation’s largest philanthropy devoted exclusively to improving the health and health care of all Americans, the Foundation works with a diverse group of organizations and individuals to identify solutions and achieve comprehensive, meaningful and timely change. For more than 35 years, the Foundation has brought experience, commitment, and a rigorous, balanced approach to the problems that affect the health and health care of those it serves. When it comes to helping Americans lead healthier lives and get the care they need, the Foundation expects to make a difference in your lifetime.

General Internal Medicine and Health Services Research is a division within the Department of Medicine at the David Geffen School of Medicine at UCLA. It provides a unique interactive environment for collaborative efforts between health services researchers and clinical experts with experience in evidence-based work. The division’s 100-plus clinicians and researchers are engaged in a wide variety of projects that examine issues related to access to care, quality of care, health measurement, physician education, clinical ethics and doctor/patient communication. The division’s researchers have close working relationships with economists, statisticians, social scientists and other specialists throughout UCLA and frequently collaborate with their counterparts at the RAND Corp and Charles Drew University.

Cambridge Health Alliance is an innovative, award-winning health system that provides high quality care in Cambridge, Somerville, and Boston’s metro-north communities. It includes three hospital campuses, a network of primary care and specialty practices, the Cambridge Public Health Dept., and the Network Health plan. CHA is a Harvard Medical School teaching affiliate and is also affiliated with Harvard School of Public Health, Harvard School of Dental Medicine, and Tufts University School of Medicine.

For more news, visit UCLA Newsroom and UCLA News|Week and follow us on Twitter.

See ‘…it is simply no longer possible to believe much of the clinical research that is published…‘

See The Whole Truth? Meta-Analysis of Reboxetine Trials Calls Into Question Veracity of All Industry-Sponsored Research

See Lies, Damned Lies, and Medical Science

See Science for Sale: Protect Yourself From Medical Research Deception

See British Medical Journal – now only 11% of NHS Treatments Backed by Evidence (was 13%)

See Big Pharma researcher admits to faking dozens of research studies

See CAM deaths 0 Iatrogenic deaths 999,936 annually

See Big Pharma Bias at Harvard Medical School

See Andrew Wakefield demands retraction from BMJ after documents prove innocence from allegations of vaccine autism data fraud

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

See http://avilian.co.uk/2011/10/in-honour-of-honest-scientists-hurrah-hurrah-hurrah/

With thanks to The One Click Group 16.6.2011:

By Dr. Marc-André Gagnon and Dr. Sergio Sismondo, Expert Advisors, EvidenceNetwork.ca. Dr. Marc-André Gagnon is assistant professor with the School of Public Policy and Administration at Carleton University. He is also an expert advisor with EvidenceNetwork.ca, a comprehensive and non-partisan online resource designed to help journalists covering health policy issues in Canada. Dr. Sergio Sismondo is professor of Philosophy and Sociology at Queen’s University. His current research is on the pharmaceutical industry’s relationships with academic medicine and practising physicians.

OTTAWA, and KINGSTON, ON, June 16, 2011/ Troy Media/ – The medical research world has been concerned about the problem of ghostwriting for more than a decade. The issue has been repeatedly raised in the mainstream media over the past few years, with most of the commentary focused on the ethics of academics serving as authors on papers they did not write and on some of the most egregious actions by pharmaceutical companies. But these efforts miss the ways in which Big Pharma has developed new forms of medical research to serve its own interests.

How ghostwriting feeds Big Pharma profits.

Big Pharma firms spend twice as much on promotion as on research and development (R&D). But it is worse than that: more and more medical R&D is organized as promotional campaigns to make physicians aware of products. The bulk of the industry’s external funding for research now goes to contract research organizations to produce studies that feed into large numbers of articles submitted to medical journals.

Internal documents from Pfizer, made public in litigation, showed that 85 scientific articles on its antidepressant Zoloft were produced and coordinated by a public relations company. Pfizer itself thus produced a critical mass of the favourable articles placed among the 211 scientific papers on Zoloft in the same period. Internal documents tell similar stories for Merck’s Vioxx, GlaxoSmithKline’s Paxil, Astra-Zeneca’s Seroquel, and Wyeth’s hormone-replacement drugs.

To promote the now-notorious Vioxx, Merck organized a ghostwriting campaign that involved some 96 scientific articles. Key ones did not mention the death of some patients during clinical trials. Through a class action lawsuit against Vioxx in Australia, it was discovered that Elsevier had created a fake medical journal for Merck – the Australasian Journal of Joint and Bone Medicine – and perhaps 10 other fake journals for Merck and other Big Pharma companies.

In another example, GlaxoSmithKline organized a ghostwriting program to promote its antidepressant Paxil. According to internal documents made public in 2009, the program was called “Case Study Publication for Peer-Review”, or CASPPER, a playful reference to the “friendly ghost”. Such strategies are not exceptions; they are now the norm in the industry. Most new drugs with blockbuster potential are introduced accompanied by 50, 60, or even 100 medical journal articles. Any firm that refused to play this game in the name of ethics would likely lose market share. Profits in the pharmaceutical industry depend on companies’ capacity to influence medical knowledge and create market share and market niches for their products.

A call for Evidence-Based medicine.

In 2008, research showed that pharmaceutical companies systematically failed to publish negative studies on their SSRIs, the Prozac generation of antidepressants. Of 74 clinical trials, 38 produced positive results and 36 did not: 94 per cent of the positive studies were published, but only 23 per cent of the negative ones were, and two-thirds of those were spun to make them look more positive.

Physicians reading the scientific literature got a biased view of the benefits of SSRIs. This helps to explain the huge number of antidepressant prescriptions, in spite of the fact that, according to a meta-analysis in JAMA in January 2010, for 70 per cent of people taking SSRIs, the drug did not bring more benefits than a placebo. Compared to placebo, however, SSRI antidepressants can result in serious adverse drug reactions.

There we see one of the problems with the ghost management of medical research and publication. Pharmaceutical companies want upbeat reports on their drugs. They design, write, and publish studies that are likely to show their drugs in positive lights – and there are myriad ways to do so. Ghosts sometimes bend the truth, and sometimes even commit fraud, with grave results.

Why do academics serve as authors on scientific articles they did not write, using research they did not perform? Because they are rewarded, both by their universities and by their colleagues for how much they publish and for its prominence. Pharmaceutical companies and their agents are very good at placing articles in prestigious journals, and then make them even more prominent by having their armies of sales reps circulate them and talk them up. Researchers who serve as authors on studies and analyses (perhaps scientifically correct) that are favourable to the industry can expect to see these articles increase their prestige and influence, and possibly even funding.

What happens, however, when a researcher produces studies and analyses (also scientifically correct) showing that some products are dangerous or inefficient, as some did about Vioxx before the scandal broke? Reading Merck’s internal e-mails, revealed during the class lawsuit, it was exposed that the company drew up a hit list of “rogue” researchers who needed to be “discredited” or “neutralized” – “seek them out and destroy them where they live,” reads one e-mail. Eight Stanford researchers say they received threats from Merck after publishing unfavourable results.

Corporate science.

In the ghost management of research and publication by drug companies we have a new model of science. This is corporate science, done by many unseen workers, performed for marketing purposes, and drawing its authority from traditional academic science. The high commercial stakes mean that all of the parties connected with this new corporate science can find reasons or be induced to participate, support, and steadily normalize it. It also biases the available science by pushing favourable results and downplaying negative ones – and sometimes through outright fraud.

As long as pharmaceutical companies hold the purse strings of medical research, medical knowledge will serve to market drugs, not to promote health. And as long as universities grovel for more partnerships with these companies, the door will remain wide open to proceed with the corruption of scientific research.

Legal Remedies for Medical Ghostwriting: Imposing Fraud Liability on Guest Authors of Ghostwritten Articles 2.8.11. Simon Stern 1, Trudo Lemmens 2. 1 Faculty of Law, University of Toronto, Toronto, Ontario, Canada, 2 Faculties of Law and Medicine, University of Toronto, Toronto, Ontario, Canada. There are persistent concerns about the influence of the pharmaceutical and device industries on the medical literature, and particularly on the reporting of clinical trials, which can include the distortion of the true evidence base of medical interventions and overestimation of the clinical benefit of a drug used to treat patients. An especially problematic issue involves the industry practice of publishing studies prepared by hired medical writers but signed by academic “guest authors” who are invited to add their names without fulfilling authorship criteria. In this case, “guest authorship” is accompanied by “ghostwriting,” which occurs when a published article fails to acknowledge the original writer or writers’ contributions

See ‘…it is simply no longer possible to believe much of the clinical research that is published…‘

See The Whole Truth? Meta-Analysis of Reboxetine Trials Calls Into Question Veracity of All Industry-Sponsored Research

See Lies, Damned Lies, and Medical Science

See Science for Sale: Protect Yourself From Medical Research Deception

See British Medical Journal – now only 11% of NHS Treatments Backed by Evidence (was 13%)

See Big Pharma researcher admits to faking dozens of research studies

See CAM deaths 0 Iatrogenic deaths 999,936 annually

See Big Pharma Bias at Harvard Medical School

See Andrew Wakefield demands retraction from BMJ after documents prove innocence from allegations of vaccine autism data fraud

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

With thanks to The Telegraph By Heidi Blake, Holly Watt and Robert Winnett 10:31PM GMT 03 Mar 2011:

Millions of NHS patients have been treated with controversial drugs on the basis of “fraudulent research” by one of the world’s leading anaesthetists, The Daily Telegraph can disclose.

Joachim Boldt is at the centre of a criminal investigation amid allegations that he may have forged up to 90 crucial studies on the treatment. He has been stripped of his professorship and sacked from a German hospital following allegations about his research into drugs known as colloids.

Experts described Mr Boldt’s alleged forgeries as possibly the biggest medical research scandal since Andrew Wakefield was struck off last year for falsely claiming to have proved a link between the MMR vaccine and autism.

Guidelines for British anaesthetists regarding colloids – used to boost blood volume in patients undergoing surgery – are being revised after it emerged that four of the key studies on which they were based are to be formally retracted.

Mr Boldt, 57, was regarded as a leading specialist in intravenous fluid management, and his work was published widely in British medical journals.

He claimed to have proved that colloids were as safe as other, similar treatments despite earlier studies showing them to be more dangerous. Mr Boldt’s alleged forgeries date back up to a decade.

The Consensus Guidelines on Intravenous Fluid Therapy, published by six British medical groups including the Association of Surgeons and the Intensive Care Society, were being withdrawn last night. Prof John MacFie, president of the Association of Surgeons, suggested that some British patients could have been put in danger. He said he would urge other medics to abandon colloids.

“We have withdrawn the guidelines from our website and we will need to rewrite the article,” he added. “The profession I represent does not want to be to be associated with potentially fraudulent research.

“Some people are comparing this to the Andrew Wakefield scandal. What Andrew Wakefield did had terrible implications on children’s lives, and the principle of this is the same.” As chief anaesthetist at Ludwigshafen Hospital in the Rhineland, Mr Boldt was the leading advocate of colloids, which are now commonly used across Europe.

He published dozens of papers “proving” their benefits and contradicting studies which suggested they could increase the risk of death in surgery and cause kidney failure, severe blood loss and heart failure.

German medical authorities are scrutinising 92 of his key publications and a criminal investigation is under way into allegations that he forged documents, tested drugs on patients without their consent and fraudulently claimed payments for operations he had never performed.

Mr Boldt received funding from manufacturers of hydroxyethyl starch (HES) – the colloid he most strongly advocated – including B. Braun, Baxter and Fresenius Kabi.

He was frequently paid to speak at international medical conferences where he hailed HES as “the holy grail” of fluid drugs.

HES and other colloids are up to 10 times more expensive than the alternative fluid management drugs, crystalloids, which some experts believe are safer as they contain smaller molecules and are more easily absorbed. Mr Boldt was sacked from Ludwigshafen Hospital last November. It has established an investigating commission to review 29 of the 92 papers which have been identified as “highly suspected” of containing forged or distorted data. The others will be examined if serious evidence of forgery is found.

Prof Eike Martin, head of the investigating commission, told The Telegraph: “At first we thought that all the studies were 100 per cent invented, but now we have found a huge amount of clinical data from trials that were conducted.

“Our suspicion is that the trials are not reported accurately in the papers. Prof Boldt was an advocate for colloids and that was the conclusion of his studies, but the data he published is different from the original data we have seen.”

Prof Martin said investigators examining one study, which purported to show that HES caused less inflammation than another fluid management drug, had found that the original data contradicted the conclusion.

The editors in chief of a consortium of medical journals which published Mr Boldt’s work are also reviewing the 92 publications.

Sources close to the investigation said that the editors would announce the formal retraction of 89 papers next month.

Rhineland state prosecutors are investigating Mr Boldt over allegations that he forged the signatures of his alleged “co-authors” on his studies, conducted drugs trials without official approval and claimed money for operations that he never performed. Police raided his home and his offices at the hospital in December and seized paperwork and computers.

Lothar Liebig, the state’s director of public prosecutions, said: “Boldt published certain studies about medical drugs in order to get them accepted.

“There there is a strong suspicion that he deliberately failed to obtain the approval of the institutional review board in Ludwigshafen, which is a criminal offence.”

Other medical research has contradicted Mr Boldt’s findings.

Research by Dr Gill Schierhout and Dr Ian Roberts of University College London found in 1998 that the use of colloids during surgery increased the risk of death by four percentage points – equivalent to four extra deaths in every 100 patients.

A review published 10 years later by Konrad Reinhart and Christiane Hartog of Friedrich Schiller University in Jena, Germany cited two large-scale clinical trials which found that HES could prevent the blood from clotting, which can cause heavy bleeding. Other studies have shown that some colloids can result in complications including heart and kidney failure, fluid entering the lungs and anaphylactic shock.

Suspicion first fell on Mr Boldt in October when readers of an article that he had published in the US journal Anesthesia and Analgesia, about the benefits of HES in bypass surgery, noticed that the pattern shown by his data was “too perfect to be believed”.

Dr Rupert Pearse, a senior lecturer in intensive care medicine at Barts and the London School of Medicine, and co-author of the British guidelines on fluid drugs, said last night: “I specifically remember looking at a paper of his last year and being surprised at how lucky he had been with his results.

“For me, it shakes the world I work in and makes me feel less confident in it, and if I were a member of the public I would feel the same.”

Mr Boldt was unavailable for comment.

See Beware the Ghost(writers) of Medical Research

See Health Journals May Force Reporting of Hedge Fund Ties

See ‘…it is simply no longer possible to believe much of the clinical research that is published…‘

See The Whole Truth? Meta-Analysis of Reboxetine Trials Calls Into Question Veracity of All Industry-Sponsored Research

See Lies, Damned Lies, and Medical Science

See Science for Sale: Protect Yourself From Medical Research Deception

See British Medical Journal – now only 11% of NHS Treatments Backed by Evidence (was 13%)

See Big Pharma researcher admits to faking dozens of research studies

See CAM deaths 0 Iatrogenic deaths 999,936 annually

See Big Pharma Bias at Harvard Medical School

See Andrew Wakefield demands retraction from BMJ after documents prove innocence from allegations of vaccine autism data fraud

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

With thanks to Bloomberg – article by Alex Nussbaum – Jan 19, 2011 9:53 PM GMT

The New England Journal of Medicine and 13 other research publications may force scientists who submit studies to disclose payments from hedge funds in the wake of insider-trading probes involving a drugmaker and technology companies.

Editors for the New England Journal, the Journal of the American Medical Association and 12 other periodicals will discuss during their annual meeting in June whether researchers must reveal investment-industry ties, said Karen Buckley, a New England Journal spokeswoman.

See Millions of surgery patients at risk in drug research fraud scandal

Existing rules on payments by drugmakers and device companies don’t cover arrangements with investors, Buckley said in a phone interview.

U.S. prosecutors in November said Yves Benhamou, a French researcher advising Human Genome Sciences Inc., leaked information about a drug study to a hedge-fund invested in the company. The case has focused new attention on doctors’ consulting work, said Jerome Kassirer, who was editor-in-chief of the New England Journal from 1991 to 1999.

“We have no idea what the doctors’ connections are, how much they know about new research, how much they’re talking to their friends about what the most promising drugs are,” said Kassirer, a professor at Tufts University Medical School in Boston, in a telephone interview today.

The journals publish peer-reviewed articles by scientists outlining their study results. They are followed closely by doctors and investors alike seeking insight into the value of medicines, devices and procedures, and their reports can move company stocks, Kassirer said.

Shares Jump. For example, Cepheid Inc., a maker of medical laboratory tests, jumped 7.2 percent in Nasdaq Stock Market trading on Sept. 1, after a study in The New England Journal of Medicine found a test developed by the Sunnyvale, California-based company could cut the time for diagnosing tuberculosis.

The International Committee of Medical Journal Editors meets in June and the question of whether to expand disclosure rules for researchers whose work is published in the journals is “on the agenda,” Buckley said.

Along with the Boston-based New England Journal, the panel includes editors from The Lancet of London and the Chicago-based Journal of the American Medical Association, also known as JAMA. Those three publications are the most influential, as measured by the number of times their articles are referenced in other publications. The rankings are compiled by Journal Citation Reports, a unit of Thomson Reuters Corp.

Discussion Needed. Jeffrey Drazen, the New England Journal’s current editor- in-chief and a member of the committee, declined to discuss the issue because it’s “premature” to say what the group will do, Buckley said.

While there’s no guarantee the editors will expand disclosure, Drazen said he felt “this is an issue that’s been in the news” and merited discussion, according to Buckley.

While the journals’ disclosure form required authors to reveal any financial activities that may be “broadly relevant” to research, instructions and editorials that accompanied the form’s release referred specifically to company connections.

The New England Journal’s editors recognize that scientists can play a legitimate role in helping the financial community, Buckley said. Investors “couldn’t operate without getting the professional opinion of someone in the medical community,” she said.

JAMA Comment. Catherine DeAngelis, JAMA’s editor-in-chief, declined to comment, said a spokeswoman, Jann Ingmire. JAMA “believes it has been quite clear in what it requires of authors,” Ingmire said in a telephone interview.

Benhamou, the adviser to Rockville, Maryland-based Human Genome Sciences, was charged Nov. 2 with allegedly leaking information to a portfolio manager at FrontPoint Partners LLC, a Greenwich, Connecticut-based hedge fund.

In separate cases, U.S. prosecutors last year filed insider-trading charges against employees at hedge funds, technology companies and expert-network firms that allegedly connected the two groups in cases involving secrets at Apple Inc., Dell Inc., Advanced Micro Devices Inc. and Taiwan Semiconductor Manufacturing Co.

The Human Genome case is another example of the “ubiquitous” ties between doctors and those who have a financial interest in their research, said Marcia Angell, a former New England Journal editor-in-chief who now teaches ethics at Harvard Medical School in Boston.

The journals should expand disclosures to cover the investment industry, she said.

“Conflicts of interest have real consequences and whenever there is a financial benefit to distorting the results of your work in some way, then that should either be prohibited or at the very least disclosed more broadly,” she said by telephone.

To contact the reporter on this story: Alex Nussbaum in New York anussbaum1@bloomberg.net.

To contact the editor responsible for this story: Reg Gale at Rgale5@bloomberg.net

With thanks to the One Click Group and to the International Academy of Oral Medicine & Toxicology:

CHAMPIONSGATE, Fla., Nov. 24, 2010 /PRNewswire-USNewswire/ — A new risk assessment report submitted by the International Academy of Oral Medicine and Toxicology this month to the U.S. Food and Drug Administration (FDA) warns that mercury from dental fillings is estimated to cause 67.2 million Americans to exceed the Reference Exposure Level (REL) of 0.3 ug/m3 established by the U.S. Environmental Protection Agency (U.S. EPA) in 1995.  

If the more protective REL of 0.03 ug/m3 established in 2008 by the California Environmental Protection Agency is used, then the current safe-dose is probably exceeded by 122.3 million Americans.

Dental fillings referred to by dentists as “amalgam” or “silver” are actually 50% mercury.  A 2006 Zogby poll indicated that 76% of Americans were not aware that silver fillings are half mercury.

Contrary to FDA’s 2009 ruling that exposure from mercury fillings presents no health risks, the latest assessment, by lead author G. Mark Richardson, Ph.D., of SNC-Lavalin, concludes that the mercury vapor continually emitted from these fillings is absorbed and distributed into every tissue and organ in the body including the brain.  Chronic (long-term) exposure to elemental mercury can cause kidney damage, crosses the blood brain barrier and is neurotoxic.

Prompted by four petitions challenging its 2009 no-risk classification, FDA scheduled public hearings December 14-15 to review the science related to the health risks of mercury fillings, particularly for pregnant women, children and other sensitive populations. The report states “Numerous studies have demonstrated that Hg levels in blood are increased in persons, including pregnant women, with amalgam.”

Dr. Richardson’s report explores how the release of mercury vapor from fillings in a mother’s mouth can cause harm to the fetus via cord blood and infant children via breast milk.

Adding to the significance of the SNC report, a review of more than 100 studies published November, 2010 in the Journal of Alzheimer’s Disease confirmed that mercury is likely a contributing cause of Alzheimer’s, a disease at epidemic proportions affecting an estimated 5.3 million Americans.

The Report concludes “….it is essential that precaution be applied in the determination of updated and revised reference exposure levels for the protection of public health.”  The use of mercury in dentistry has already been banned in Denmark, Norway and Sweden.

Amalgam Risk Assessments 2010
On December 14 and 15, 2010, the FDA will convene a scientific panel to re-examine the issue of mercury exposure from amalgam dental fillings.

Two private foundations, assisted by IAOMT, have commissioned G. Mark Richardson, PhD, of SNC Lavallin, Ottawa, Canada, formerly of Health Canada, to provide the scientific panel and FDA regulators with a formal risk assessment using the latest information from the scientific literature.

Previously published risk assessments dated from the 1990′s.  Meanwhile, newer studies have uncovered more toxicity produced by lower levels of mercury exposure, and various government agencies have been reducing their allowed exposure levels.

The final work is presented here in two parts.

Part 1 is titled UPDATING EXPOSURE, REEXAMINING REFERENCE EXPOSURE LEVELS, AND CRITICALLY EVALUATING RECENT STUDIES.  “…it was determined that some 67.2 million Americans would exceed the Hg dose associated with the REL of 0.3 ug/m3 established by the US Environmental Protection Agency in 1995, whereas 122.3 million Americans would exceed the dose associated with the REL of 0.03 ug/m3 established by the California Environmental Protection Agency in 2008.”

Part 2 is titled CUMULATIVE RISK ASSESSMENT AND JOINT TOXICITY: MERCURY VAPOR, METHYL MERCURY AND LEAD. This report will be made available in the coming weeks.

See Amalgam Risk Assessment Part !