The Cholesterol Debate And Journal Disclosures
27 CommentsBy Ed Silverman // June 30th, 2010 // 8:42 am
Earlier this week, the Archives of Internal Medicine published a few articles and editorials about statins, although one, in particular, generated some heat - a review of the controversial Jupiter study from 2008. The study, which focused on AstraZeneca’s Crestor cholesterol pill, measured levels of a protein called CRP that can indicate arteries are inflamed and point toward heart disease.
The results prompted debate over the extent to which CRP should be used as a guideline for treating cholsterol and the wisdom in prescribing Crestor and other statins to people with low cholesterol. This week’s revisitation (see here) stirred anew the controversy, but also focused on allegations of poor methodology, bias and conflicts of interest (see here).
However, as was noted yesterday, two of the nine authors are members of The International Network of Cholesterol Skeptics, a group that argues against the use of statins and maintains high cholesterol is not a health issue. Other members have written books explaining this view (see here and here). The connection was not mentioned in the author affiliations, although this is not a perceived financial conflict either. In any event, we asked Rita Redberg, the journal’s editor, for her thoughts. She acknowledged that neither she nor her editorial team were aware of their membership, but also noted the journal’s disclosure form requests info about financial or personal relationships.
“I and the rest of my editors feel strongly that conflicts needs to be disclosed…but they belong to a group, which basically shares an intellectual feeling about cholesterol. People belong to all kinds of groups they don’t reveal to us and it’s not generally listed as a conflict…I’m not clear this is an undisclosed conflict. The policy mentions a personal realtionship that could influence one’s work. I think that could be a big stretch,” Redberg tells us. “…My initial impression is the group has an intellectual message, but doesn’t fit as a personal relationship that could effect the authors’ work…I agree not all conflicts are financial and can still have personal gain, but even expanding it to that definition, I’m not sure that group fits into that category…I will probably talk to some of our ethics expets and see what they think…In general, we would rather err on the side of disclosure, but I thought the piece did deal with the science of the study and not anything else.”
We also reached out to the two authors who belong to THINCS. Michel de Lorgeril wrote that, “if it is, indeed, very important to disclose financial conflicts of interest that can influence our way of working and thinking about cholesterol and statins, there is so far no obligation to provide a CV each time we publish any thing…Why should I disclose what is publically available? As a matter of fact, you obtained the information without my help. May I underline the fact that being a member of THINCS - not a group of terrorists, mainly a club of very kind retired scientists with whom I have interesting and open discussion - is not a conflict of interest?” And Harumi Tomohito, didn’t quite answer our question about disclosure, but wrote that “I have been trying to convince scientists that high serum cholesterol (both the total and LDL-C) is a predictor of longevity, and the cases for which statins are applicable should be extremely limited.”
There are obviously some subtleties at work here. Would it have mattered if those two authors had disclosed their membership? Would disclosure somehow have provided readers with a greater understanding of the paper? Should disclosure have been made based on principle? Are their views irrelevant to the subject of their paper? What do you think?
Should The Authors Have Disclosed Membership In THINCS?
- Yes (70%, 107 Votes)
- No (32%, 48 Votes)
Total Voters: 152
Loading ...
Justice in MI
I don’t think this is a complex issue. The two authors, so far as I can tell, would gain nothing through the publication but publication itself. We already know that there are those who hold strong views (on whatever bases) about most categories of drugs–especially vaccines, psychotropics, statins, et. al..
To require disclosure of such affiliation
with like-minded others seems
to me to be the equvalent of requiring disclosure of religious affiliation, political associations, whether one is a vegetarian, etc.
Justice in MI
As a further example, David Graham would include the fact that he is a devout Catholic in what drives his commitment to drug safety. Should he “disclose” his Catholicism on each publication?
Paul
“In this world, no matter how clear and blue the sky is, there will always be people who look up and see nothing but rain”
StacceyT@cholesterol
I don’t understand why they would not disclose this information. It would seem to make the argument a little less substantial with the types of contributors. It’s like saying that more people are for pro-choice, but you only interview pro-choice people.
Tim B
The challenge with competing interests is that we focus all too narrowly on FINANCIAL and tend to ignore EMOTIONAL ones.
Take a look at the ICMJE COI form that they present as a new standard (http://www.icmje.org/coi_disclosure.pdf) - it correctly provides the opportunity to present non-financial conflicts.
Yes, of course they should have disclosed these conflicts.
Bruce Wilson
Anyone who belongs to an organization that may influence their point of view on a topic should disclose their membership in that organization. Being a Catholic has no relevance to issues of drug safety, but being a Scientologist does. (Scientology opposes the use of pharmaceuticals.)
As humans, everyone has a bias. There is no such thing as absolute objectivity. But the more disclosures we have, the more we know where people are coming from.
What I’d like to see are more disclosures from journalists who their information from industry PR materials. That is a group that is supposed to be objective and is just isn’t so anymore.
Justice in MI
Hey, Stacey–Of course, 7 of the 9 authors were not from this group (as I understand it), and it was not an opinion piece, but a study.
Diclosure. I myself take a statin and am happy about it.
Nevertheless, there are a number of folks who aren’t flat earthers–John Abramson, for example–who has raised serious questions about benefit/risk when it comes to statins and primary prevention.
Anecdotal but….I was once at a world-class cardio center for a consult. Re: statins, when of the nurses said off-handedly to me (as though I’d “get it”) that “cf course, none of the docs here use a statin themselves if they can avoid it.”
So it goes….
Karl in FL
It seems to me that if these two gentlemen had disclosed their affiliation with Thincs, then the paper seems stronger, since this group does not seem to be a particular fan of statin use.
Justice in MI
re: Bruce’s comment, of course, I am not against more info in general. Far more relevant than disclosure of group affiliation would be transparent access to all data that the publication repesents (potentially selectively), whether a ghostwriter involved, etc.
Nevertheless, I do think it is sensible to distinguish between affilitations that influence what hypotheses one is likely to test versus affiliations that stand to benefit commercially–potentially, enormously–from a particular publication.
The Jupiter study, in itself, had the potential to yield, literally, billions of dollars for AZ and other statin manufacturers. This study in Archives has the potential to yield, as far as I can tell, nothing of commercial interest to its authors.
To me, that remains a relevant distinction re: disclosure. In the meantime, studies will rise or fall on their own merits and the extent to which they are, indeed, based on full disclosure–not of affiliations–but of data, endpoints, conflicting and unpublished studies of which the authors and their company are aware, etc..
Justice in MI
Having now looked at the author disclosure form and requirements that Ed links (and which include sublinks), I believe there is no question that the two authors’ affiliations were not of the sort for which disclosure was necessary or relevant, “interesting” as they might otherwise be.
Most conflicts aren't financial
People can be driven more by fame and ego rather than money. Frankly people in academic medicine don’t make much money and are more apt to be biased based upon their paradigms and hypotheses rather than their wallet. Ridker has both biases at play. He does not have a dog in the fight over crestor, he does have a dog in the fight over crp. When crp tests are performed, this does inure to his benefit. Frankly, it is very discouraging that the negative results relating to CRP’s inability to “relative risk stratify” were not presented earlier. By releasing the results late, he and the Brigham and Women’s Hospital may have intentionally profited from the large number of people that had their crp tested. They care about the crp testing and the money from this, not the number of prescriptions filled.
Justice in MI
Of course, people have all kinds of biases, interests, and affiliations. A given.
The question is–which sort ought to be disclosed and in what contexts?
I would disagree with the suggestion above that being a Scientologist, however interesting, ought to be required to be disclosed in a study oublished in a peer-reviewed journal. (As opposed to an editorial or opinion piece dressed up to be otherwise.)
vince
To argue that this is a conflict of interest is simply ridiculous the study not the first study to find a lack of benefit on mortality in statin trails stands or falls on it’s owe merit. Membership in a group which has its own public website and freely publishes opinions from its members is simply not equatable to a paper written by someone with a hidden economic stake in the results. You want real conflicts of interest look like just look at the Cholesterol advisory board ‘http://www.usatoday.com/news/health/2004-10-16-panel-conflict-of-interest_x.htm As USA reported “……But when these famous doctors advised the government recently on new cholesterol guidelines for the public, something else they had in common wasn’t revealed.
Eight of the nine were making money from the very companies whose cholesterol-lowering drugs they were urging upon millions more Americans. Two own stock in them. Two others went to work for drug companies shortly after working on the guidelines. Another was a senior government scientist who moonlights for 10 companies and even serves on one of their boards. …….”
NOW THAT IS CONFLICT OF INTEREST.
Justice in MI
Go, Vince! So how come we’re getting creamed in the vote?
I would genuinely love to hear a compelling argument on the other side. I don’t think there’s any way that the Archives author guidelines could be interpreted to require, or even encourage, disclosure of the sort being discussed here.
So the issue would be a purely ethical one. And the question, as usual, would be where you draw the line and why.
vince
The vote really does not surprise me. Most I do not believe know how unnecessary it is . Most anyone interested in the field understands that a fairly large segment of Docs doubt the cholesterol hypothesis they have been outspoken. The conflict of interest here is is a false equivalency. Soon the cholesterol hypothesis will face another obstacle. A very interesting study …..http://eurheartj.oxfordjournals.org/content/early/2010/06/01/eurheartj.ehq181.abstract
“Ezetimibe alone or in combination with simvastatin increases small dense low-density lipoproteins in healthy men: a randomized trial”
…..Aims The predominance of small dense low-density lipoproteins (sdLDLs) has been associated with increased cardiovascular risk. The effect of ezetimibe on LDL subfraction distribution has not been fully elucidated. This study assessed by gradient gel electrophoresis the effects of ezetimibe alone, simvastatin alone, and their combination on sdLDL subfraction distribution……….
……Conclusion In healthy men, treatment with ezetimibe alone is associated with the development of a pro-atherogenic LDL subfraction profile. Potentially atheroprotective effects of simvastatin are offset by ezetimibe. This study is registered with ClinicalTrials.gov, identifier no. NCT00317993.
PMID: 20525999 [PubMed - as supplied by publisher]
Stephen Guy-Clarke
There is a natural bias one way or the other regarding the use of statins. I have two general points which are facts and should be taken into account;
Cardiologist Peter Langsjoen notes that statin treatment may lead to heart muscle weakening and failure. ‘It occurs because statin drugs block the production of coenzyme Q10, vital for the production of cell energy,’ says Langsjoen. ‘Evidence to the FDA shows marked reduction of CoQ10 in patients on statin drugs.’
Another point to be borne in mind is the use of long term drug therapy to lower cholesterol levels, where it is unclear what the full effects might be over a 30 year period. In spite of this, the Food and Drug Administration (FDA) gives approval for this class of drugs on the basis of less than 10 years’ clinical trials.
Justice in MI
Indeed. As noted, I use a statin myself, but not without concerns as articulated. A very distinguished colleague–an MD/Ph.D. pharmacologist with expertise in drugs and cardio–is now suffering from both debilitating rhabdo and heart failure secondary to long-term statin use. There could be no better informed pt. in the world.
We take our chances…
Kaia
De Lorgeril’s research and publications are related to the Mediterranean diet which does not endorse a high animal fat content. This research looks at what diet and non-drug interventions can accomplish in cardioprotection and has found health benefits independent of targeted cholesterol levels. Many others including popular analysts of diet and health as diverse as Michael Pollan and Gary Taubes have argued against the relevance of dietary cholesterol without being labeled cultists.
Perhaps de Lorgeril’s association with THINCS should be deemed a commendable example of collegiality considering their differing views on diet.
Or perhaps, those who adhere to a guilt-by-association model of COI desire even more stringent parameters.Should authors disclose what they had for lunch?
Uffe Ravnskov
The consequence
If Michel de Lorgeril and Tomohito Hamazaki should have told about their membership of THINCS, then all scientists who present a new hypothesis or explanation must declare a conflict of interest: I do not believe in the current view on this issue.
Uffe Ravnskov
Spokesman of THINCS
Malcolm Kendrick
D.O.I. (disclosure of interest)
My D.O.I is that I am also a member of thincs.
A conflict of interest is something that might mean you are biased towards something due to financial pressure. However, it is hardly a conflict of interest for someone who does not believe in the diet/heart cholesterol hypothesis to write an article critical of the hypothesis. What are they supposed to do? Never write anything. Write articles in conflict with their own views?
As proposed at the start of this message. It may be of interest to people to know what the views of the author are, on the subject in hand.
But having a point of view is very different from being paid hundreds of thousands of dollars a year by a company with a vested financial interest in a certain outcome
Michael Barker
Identifying what school of thought one comes fromf thought, ad hoc or not, to my knowledge has never been required for discourse. If this is a new standard, Mr. Silverman, who authored this article should give his. I would, as well, require that those who have authored other papers on diet and nutrition do so as well. What is good for the goose is good for the gander.
Jeff Cable
D.O.I: I am unwilling to support or acknowledge any ‘research’ which was funded by individuals or institutions which have any vested interest in manipulating the outcome, usually to improve the prospect of making more pharmaceutical sales… either for the usual quid pro quo provided by pharmaceutical companies or where the ‘research’ is a blatant advertorial for the product and was based upon junk science.
The obvious solution (to questionable ‘research’ being proffered as novel and compelling) is to refuse to accept papers that were funded by vested interests. Advertising revenues for medical journals may suffer as a result but integrity is just like virginity, when it is lost, there is no recovery. Be in no doubt; several fake journals, published by Elsevier, were an indicator of pharmaceutical company intrusion into medical practice and clinical judgement.
Prospective authors, who are in the paid employ of pharmaceutical companies, should automatically forfeit their right to submit research to medical journals… by dint of a career choice which they have made by accepting honoraria and more, from the pharmaceutical industry.
As for the potential conflict of interest in holding a contrarian viewpoint… piffle! Where there is no opportunity for pecuniary gain, it is an irrelevance as to what school of thought a person subscribes. The hope is always that they will believe in the value of independent thought and testing their beliefs.
Josh
Mr. Barker,
Obviously you are not a frequent visitor to this site or you would know that Ed is certainly not in the employ of pharma companies. He is a journalist asking a very fair question, so no need to be so defensive.
I just noted an interesting dynamic on this site…someone questions something anti-pharma, they are labeled “shills for the industry”, but when the shoe is on the other foot, people are mounting the .50 cal.
Marilyn Mann
More on Dr. de Lorgeril:
http://cardiobrief.org/2010/07/08/authors-of-jupiter-attack-committed-self-plagiarism/
NP
Malcolm Kendrick, do you earn royalties on your book? If so, why would this not be considered a “conflict of interest”? Would it be fair to say that if the controversy over statins and/or cholesterol were to die down, there may be less interest in your book?
Lorraine Johnson
The issue of disclosing non-financial conflicts of interests is new. IOM has interesting book on conflicts exploring all this in depth. (Institute of Medicine (Committee on Conflict of Interest in Medical Research E, and Practice), . Conflict of interest in medical research, education, and practice. Washington, DC: National Academies Press., 2009.) It’s available on line. The reason that non-financial are not normally considered disclosable is that the “line drawing” exercise inherent in COI management becomes quite difficult–everyone has a bias.
COI requires a different approach from bias. For instance, the IOM(ish) answer to financial conflicts of interest on guidelines panels would be to avoid them entirely or barring that limit them (no more than 20% on panel say) and contain them (no chairmanships, no writing, maybe no voting).
The answer to bias on a guidelines panel, on the other hand, is to make sure that stakeholders are represented and that views are not suppressed by dominant players. This is to ensure that treatment options are preserved and that where science is lacking and viewpoints are divided the default is to clinical judgment and patient autonomy.
DOI Activist on minority side of medical debate in Lyme disease.
Marilyn Mann
Dr. de Lorgeril and his co-author Patricia Salen do not seem to be opposed to industry-funded research in general. They are on the scientific advisory board for The Columbus Paradigm Institute SA, a BNLfood Group (Belovo) company.
http://www.columbus-concept.com/aboutus/aboutus.php?cat_ID=2
The purposes of the SAB include:
•review and evaluate studies in progress funded by Belovo
•consider new proposals
•generate research proposals
•develop collaborative research
•review statements developed by Belovo for scientific accuracy (i.e. Common Statement)
•ensure that marketing is based on scientific concepts and principles
•establish an international network of scientists for the presentation of the scientific aspects of the Columbus Concept to the press
BNLfood Group (Belovo) produces foods such as eggs with a high Omega-3 content. So, naturally, BNLfood Group is interested in funding research on its products.
http://www.bnlfood.com/
So, Dr. de Lorgeril and Ms. Salen are apparently fine with studies funded by industries that they approve of.