No *other* conflict of interest, huh?

What’s wrong with this picture?

While continuing to search for information regarding the collective statistical illiteracy issue covered a couple of days ago, I found a brand new article in the New England Journal of Medicine.

As an exercise I decided to reorganize some of the paragraphs of the article, bringing to the top a couple of paragraphs that are located at the bottom of the original. FYI, the conclusion of the article is simple: “In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin (Note by G.F: Crestor, manufactured by AstraZeneca) significantly reduced the incidence of major cardiovascular events. ” Surprise, surprise! Crestor is good for you, even if you don’t have high cholesterol levels. Read the rest, it may explain:

“Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein”

by Paul M Ridker, M.D., Eleanor Danielson, M.I.A., Francisco A.H. Fonseca, M.D., Jacques Genest, M.D., Antonio M. Gotto, Jr., M.D., John J.P. Kastelein, M.D., Wolfgang Koenig, M.D., Peter Libby, M.D., Alberto J. Lorenzatti, M.D., Jean G. MacFadyen, B.A., Børge G. Nordestgaard, M.D., James Shepherd, M.D., James T. Willerson, M.D., Robert J. Glynn, Sc.D., for the JUPITER Study Group.

“Supported by AstraZeneca.

Dr. Ridker reports receiving grant support from AstraZeneca, Novartis, Merck, Abbott, Roche, and Sanofi-Aventis; consulting fees or lecture fees or both from AstraZeneca, Novartis, Merck, Merck–Schering-Plough, Sanofi-Aventis, Isis, Dade Behring, and Vascular Biogenics; and is listed as a coinventor on patents held by Brigham and Women’s Hospital that relate to the use of inflammatory biomarkers in cardiovascular disease, including the use of high-sensitivity C-reactive protein in the evaluation of patients’ risk of cardiovascular disease. These patents have been licensed to Dade Behring and AstraZeneca. Dr. Fonseca reports receiving research grants, lecture fees, and consulting fees from AstraZeneca, Pfizer, Schering-Plough, Sanofi-Aventis, and Merck; and Dr. Genest, lecture fees from AstraZeneca, Schering-Plough, Merck–Schering-Plough, Pfizer, Novartis, and Sanofi-Aventis and consulting fees from AstraZeneca, Merck, Merck Frosst, Schering-Plough,Pfizer, Novartis, Resverlogix, and Sanofi-Aventis. Dr. Gotto reports receiving consulting fees from Dupont, Novartis, Aegerion, Arisaph, Kowa, Merck, Merck–Schering-Plough, Pfizer, Genentech, Martek, and Reliant; serving as an expert witness; and receiving publication royalties. Dr. Kastelein reports receiving grant support from AstraZeneca, Pfizer, Roche, Novartis, Merck, Merck–Schering-Plough, Isis, Genzyme, and Sanofi-Aventis; lecture fees from AstraZeneca, GlaxoSmithKline, Pfizer, Novartis, Merck–Schering-Plough, Roche, Isis, and Boehringer Ingelheim; and consulting fees from AstraZeneca, Abbott, Pfizer, Isis, Genzyme, Roche, Novartis, Merck, Merck–Schering-Plough, and Sanofi-Aventis. Dr. Koenig reports receiving grant support from AstraZeneca, Roche, Anthera, Dade Behring and GlaxoSmithKline; lecture fees from AstraZeneca, Pfizer, Novartis, GlaxoSmithKline, DiaDexus, Roche, and Boehringer Ingelheim; and consulting fees from GlaxoSmithKline, Medlogix, Anthera, and Roche. Dr. Libby reports receiving lecture fees from Pfizer and lecture or consulting fees from AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Pfizer, Sanofi-Aventis, VIA Pharmaceuticals, Interleukin Genetics, Kowa Research Institute, Novartis, and Merck–Schering-Plough. Dr. Lorenzatti reports receiving grant support, lecture fees, and consulting fees from AstraZeneca, Takeda, and Novartis; Dr. Nordestgaard, lecture fees from AstraZeneca, Sanofi-Aventis, Pfizer, Boehringer Ingelheim, and Merck and consulting fees from AstraZeneca and BG Medicine; Dr. Shepherd, lecture fees from AstraZeneca, Pfizer, and Merck and consulting fees from AstraZeneca, Merck, Roche, GlaxoSmithKline, Pfizer, Nicox, and Oxford Biosciences; and Dr. Glynn, grant support from AstraZeneca and Bristol-Myers Squibb. No other potential conflict of interest relevant to this article was reported.[Emphasis added]

We thank the 17,802 study participants, their individual physicians, and the medical and clinical teams at AstraZeneca for their personal time and commitment to this project.

At this point are we supposed to:

  1. have our jaw drop to the floor?
  2. start laughing uncontrollably?
  3. keep on crying for hours?
  4. or, start saying out loud that enough is enough and that reform is essential and must happen urgently?

My personal choice is the last one.

In the age of transparency shall we assume that there is no scientific bias just because you publish at the very bottom of a long article the list of grants, consultancy and lecture fees?

It is definitely high time to promote a new paradigm of medical research and scientific reporting!

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Posted in: general | hc's problem list | trends & principles | understanding statistics

 

 

Comments

22 Responses to “No *other* conflict of interest, huh?”

  1. Makes me want to puke.

    The End of Medicine cites similar relationships in the people who generate the data and go around speaking, promoting their findings, funded by the companies whose products they’re promoting.

    On the one hand it’s good that those conflicts are disclosed. But having said that – oy, what a farce. Thanks for the specimen.

  2. As with grief, I believe we go through stages when we take a long hard look at the current state of affairs in healthcare. I very much like your list of options, which I might rephrase:

    1. Shock (Can this be?)
    2. Disbelief (No, it can’t!)
    3. Sadness (Yes, it is…)
    4. Determination to change things (We can change it!)

    But I think you’ve left one out that comes after sadness — denial or maybe it’s hopelessness, or perhaps even apathy. Unfortunately, we get stuck there and don’t focus our incredulity into action, but change is in the air ….

    I’m so glad e-Patients is here.

  3. Unfortunately we no longer have time for denial.

    The American healthcare system fiasco is the #1 fiscal issue for all Americans, even though most are unaware of this dark fact.

    The entire system needs profound reform, including how the pharmaceutical industry manipulates the drug approval process and even more how they get drug costs reimbursed by payers.

    This is one more reason to make a priority of promoting collective health & statistical literacy. Which will, in turn, lead to the rapid growth of participatory medicine.

  4. kirsti says:

    Ok so this is just absurd and we all know big Pharma loves this kind of activity. But here is my question – when it comes to user-designed medical devices – where do we draw the line?? Is this is a different ethical question? I often wonder when I read about medical devices and the relationships between providers, hospitals and the manufacturers. I remember when working in genetics, if you were a professional and you went to work for one of the test manufacturers you were assumed to have gone to the ‘dark side’ and no longer a colleague. It is a sad comment that this behavior is now normalized in big Pharma….

  5. Sarah Greene says:

    It was less than 10 years ago when full disclosure became a standard requirement in the scientific literature. It was huge victory for science – one of those lightbulb moments when you wondered why it took so long.

    I take a different view of whom to hold responsible in this instance and in the broader schema. It’s not the publishers or the authors or the pharmas to blame for the placement and font size of these passages. It’s irresponsible reporting. Journalism 101 teaches reporters to look at the fine print, but unfortunately there’s far more sensationalistic than responsible reporting. Careful journalism is much quieter than the fast and furious.

    More to the point, patients don’t get to wear that E-badge if they aren’t first Educated to understand Evidence. Two crucial elements, though, are prohibitive: first, most journal articles are not available to the public upon publication, thanks to the watered down open-access policy of the NIH. Second, how do we expect the average ’8th-grade-reading-level’ consumer to analyze and understand the scientific literature? This leads us to the pathetic state of U.S. science education at the junior high level – why shouldn’t an 8th grader be able to grasp it?

    But really, my shock-disbelief-sadness centers on the media. Can journalists be held accountable at a time when news organizations are pushing for more & faster & shorter, coupled with desperation for digital advertising dollars?

  6. The innumeracy of most readers or scientific reporters causes a host of misunderstandings, mostly because they can’t assess the relative unimportance of a change in rates versus a change in risk. And no one seems to pick up the problems for diabetics who make up a majority of those who qualify for statin therapy.

    From the study: “We did detect a small but significant increase in the rate of physician-reported diabetes with rosuvastatin, as well as a small, though significant, increase in the median value of glycated hemoglobin. Increases in glucose and glycated hemoglobin levels, the incidence of newly diagnosed diabetes, and worsening glycemic control have been reported in previous trials of pravastatin, simvastatin, and atorvastatin”

    About 20% more people got diabetes in the drug group. For every life “saved” by the drug, someone else got diabetes. Factor that into the “costs” of the drug.

    The results show a 20% reduction in mortality rate. This is reported in the press as a 20% reduction in risk. but since the odds of dying in the placebo group were only 2.77% and 2.22% in the Crestor group, the risk is only 0.55% lower. So 200 people would have to take the drugs for life, suffering from significant side effects as their innate CoQ10 is depleted for one life saved from heart attack (and proportionately increasing deaths from stroke or other endpoints.)

    If a person took a 30 minute walk per day they would have better results without the side effects or costs. Or if they followed an insulin resistance diet which helps anyone with metabolic syndrome. But of course they didn’t think of testing that.

  7. Susannah Fox says:

    To Sarah’s point about the responsibility of journalists: there was some potentially good news in the Herald-Tribune yesterday.

    Filling the gap in health journalism

    “The Kaiser Family Foundation is starting a news service to produce in-depth coverage of the policy and politics of health care, both for an independent Web site and in collaborations with mainstream news organizations.

    With a budget that is expected to reach $3 million to $4 million in two years, the project is one of the most ambitious in a wave of nonprofit online ventures that have emerged as mainstream newspapers and magazines cut jobs and budgets.”

  8. Susannah Fox says:

    And in case anyone missed Ted Eytan’s suggestion for another resource to combat misinformation:

    http://www.healthnewsreview.org/

  9. As an improvement to the disclosure policy, we should ask to see the conflicts of interest statements located before the articles, not after them. That was really the essence of this exercise. I am afraid too many people just don not have the patience to read the articles in their totality. If they don’t, they will probably never read about the potential conflicts of interests.

  10. NY Times editorial today: Expert or Shill?

    More evidence has emerged of appalling conflicts of interest that throw into doubt the advice rendered and the research performed by two prominent psychiatrists who have received substantial funding from the pharmaceutical industry.

    …Dr. Joseph Biederman, a world-renowned child psychiatrist at Harvard Medical School and Massachusetts General Hospital, had failed to report to Harvard at least $1.4 million in income from drug companies …

    …an unsavory collaboration between Dr. Biederman and Johnson & Johnson to generate and disseminate data that would support use of an antipsychotic drug, Risperdal, in children, a controversial target group.

    Controversial target group, indeed. Children?? Target??

    Again, I’m not asserting that all medical evidence is crooked. I am damn well asserting, though, that any e-patient or doctor needs to look at any journal article carefully before concluding that it’s written with our interests in mind.

  11. I’d also recomend the NHS Choices, Behind the Headlines site, for a UK perspective.
    http://www.nhs.uk/news/2008/11November/Pages/Newstatintrial.aspx

  12. Dan says:

    Facts Believed to be Associated With All Statin Medications:

    Adverse events associated with the statin class of pharmaceuticals are thought to occur more often than they are reported- with high doses of statins prescribed to patients in particular. However, ince this class of drugs has existed for use for over 20 years, statins are considered safe and effective for enhancing the clearance of LDL noted to be elevated in the lipid profiles of patients.
    Additionally, there is no reduction in cardiovascular morbidity or mortality, as well as an increase in a person’s lifespan, if one is on any particular statin medication for their lipid management over another, others have conclusion. So caution should perhaps be considered if one chooses to prescribe such a drug for a patient if they are absent of dyslipidemia to a significant degree, or are under the belief that one statin medication provides a greater cardiovascular benefit over another. In other words, the health care provider should be assured that any statin therapy for their patients is considered reasonable and necessary if the LDL in their patients need to be reduced perhaps at this time with the evidence that exists regarding statins.
    Abstract etiologies for those who choose to prescribe statin drugs on occasion for unindicated reasons , such as reducing CRP levels, or for Alzheimer’s treatment, or anything else not involved with LDL reduction may not appropriate prophylaxis at this point for any patient. All other benefits that appear to have favorable effects in such areas are speculative at this point, and require further research for disease states aside from dyslipidemia, according to many.
    Statins as a particular class of drugs that seem to in fact decrease the risk of cardiovascular events significantly, it has been proven. This may be due to the fact that statins improve endothelial function as well as they also have the ability to stabilize coronary artery plaques, which prevents myocardial infarctions. Statins also decrease thrombus formation as well as modulate inflammatory responses (CRP). For those patients with dyslipidemia who are placed on a statin, the effects of that statin on reducing a patient’s LDL level can be measured with the efficacy of the statin after about five weeks of therapy on a particular statin drug. Liver Function blood tests are recommended for those patients on continued statin therapy, and most are chronically taking statins for the rest of their lives to manage their lipid profile in regards to maintaining the suitable LDL level for a particular patient presently.
    As stated previously, in regards to other uses of statins besides just LDL reduction, there is evidence to suggest that statins have other benefits besides lowering LDL, such as reducing inflammation (CRP) with patients on statin therapy, those patients with dementia or Parkinson’s disease may benefit from statin medication, as well as those patients who may have certain types of cancer or even cataracts. Yet again, these other roles for statin therapy have only been minimally explored, comparatively speaking. Because of the limited evidence regarding additional benefits of statins, the drug should again be prescribed for those with dyslipidemia only at this time involving elevated LDL levels as detected in the patient’s bloodstream.

    Yet overall, the existing cholesterol lowering recommendations or guidelines should be re-evaluated, as they may be over-exaggerated upon tacit suggestions from the makers of statins to those who create these current lipid lowering guidelines. This is notable if one chooses to compare these cholesterol guidelines with others in the past. The cholesterol guidelines that exist now are considered by many health care providers and experts to be rather unreasonable, unnecessary, and possibly detrimental to a patient’s health, according to others. Yet statins are beneficial medications for those many people that exist with elevated LDL levels that can cause cardiovascular events to occur because of this abnormality. What that ideal LDL level is may have yet to be empirically determined.
    Finally, a focus on children and their lifestyles should be amplified so their arteries do not become those of one who is middle-aged, and this may prevent them from being candidates for statin therapy now and in the future, regarding the high cholesterol issue.
    Dietary management should be the first consideration in regards to correcting lipid dysfunctions,

    Dan Abshear

  13. [...] this blog has reported on the substantial conflicts of interest attached to some journal articles. Since those same journal articles are widely considered the gold [...]

  14. @serious_skeptic You should read http://bit.ly/48Tja. From last November: No *other* conflict of interest, huh?

  15. ePatientDave says:

    A @gfry classic RT @gfry: @serious_skeptic You should read http://bit.ly/48Tja. “No *other* conflict of interest, huh?”

  16. [...] our continuous series about undeclared conflicts of interest comes a great blog post from the Wall Street Journal. In it JAMA’s editor in chief, Catherine [...]

  17. [...] from Pfizer, Celebrex and Lyrica. No one paid attention to the fact that, like Dr Robinson and Dr. Ridker et al. Dr. Ruben was regularly paid by pharmaceutical companies. In fact he was active as a member of [...]

  18. Laurie says:

    Dear Gilles,
    Question for you? Could it be that “high cholesterol” is a made up condition to provide a continuous annuity for pharmaceutical companies? Is it possible that the makers of Lipitor, Crestor, Zocor, and the like are in cahoots???

  19. [...] No *other* conflict of interest, huh? (11/08) [...]

  20. [...] A Nothing” & I’m Proud Of It!, FDA Gives Light Scrutiny to Investigators’ Financial Ties, No *other* conflict of interest, huh? for a sample of why it would be so important for the FDA to hear the unbiased voice of some leaders [...]

  21. I was studying something else about this on another blog. Interesting. Your perspective on it is novel. – I tended to place my wife under a pedestal. – Woody Allen Born 1935

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