Statin-Cholesterol Guidelines–Industry influenced?

Wed, 14 Jul 2004

Scientific journal editors are scrambling about how to react to bad publicity emanating from public disclosure that the scientific reports they have published are likely to be biased because the authors’ had financial ties to the companies whose drugs / devices they report on favorably-and that information was withheld from readers.

A newly released survey by the Center for Science for the Public Interest (CSPI) looked at articles that appeared during a 3 month period–between December 2003 and February 2004–in four premier scientific journals–the New England Journal of Medicine, the Journal of the American Medical Association, Environmental Health Perspectives and Toxicology and Applied Pharmacology–finding that even in these journals, 8% of authors failed to disclose conflicts of interest.

Among the reports cited by CSPI whose authors failed to disclose their financial conflicts: “Frank D. Kolodgie and Renu Virmani, two scientists at the U.S. Armed Forces Institute of Pathology, failed to disclose their consulting relationships with 20 companies in the heart-disease treatment field in a December article in the New England Journal of Medicine about the formation of plaque in coronary arteries.” [Ref. 1]

Inasmuch as biased science affects public health policies and misleads treating physicians who may be unwittingly doing harm to patients, is it not the responsibility of science journals to ensure that they provide accurate, full information to readers?

Here are two modest recommendations: Journal editors should make an effort to publish an update, listing articles whose authors failed to disclose their financial ties to drug companies.

Furthermore, it is essential for journals to retract clinical trial reports that were based on only partial–favorable-data. The results are false and misleading, and may be leading physicians to prescribe medications whose risks outweigh any benefits. [References 2]

The same day that CSPI’s survey was reported in the press, the journal, Circulation, published a report announcing new federally endorsed recommendations for the treatment of heart disease–more accurately, recommendations for the increased use of cholesterol lowering drugs. The recommendations were made by a panel convened by the National Cholesterol Education Program on the supposition that they will prevent heart disease. The recommendations will dramatically increase the use of statins to control cholesterol levels.

Statins sales for the current 26 million Americans taking them reach $15 billion. The new recommendations will increase the number of users to 36 million and increase sales to $20.8 billion.

The Wall Street Journal reports today, that the FDA is about to approve Vytorin, a drug, “which packs two cholesterol fighters into one pill. It combines Zetia, a cholesterol-blocker from Schering-Plough Corp., with Merck & Co.’s Zocor, the second-most-prescribed brand in the class of powerful drugs known as statins: “Just as heart patients and their doctors are grappling with updated government guidelines for dramatically lowering cholesterol, a new drug is about to be approved that is sure to deepen the confusion over choosing proper treatment.” [Ref 3]

Since the NIH recommendations clearly provide statin drug manufacturers with a mega-billion dollar profit enhancement-and the rationale is controversial–isn’t a bit of skepticism in order?

For starters, why has no one questioned the absence of financial disclosure by the panel members that recommend the new guidelines? Have editors of the journal Circulation not heard about disclosure requirements? [Ref. 4]

Why have reporters failed to ask about possible financial conflicts of interest that may have a bearing on these recommendations? [Ref. 5]

Why has no one in the mainstream media seen fit to inform the public that there are scientists around the world who are skeptical about the intensive statin-cholesterol push, calling it “massive hype” by “Rent-A-Quote” Doctors? [Ref. 6]

Doesn’t good science depend upon open debate?

The new recommendations were immediately endorsed by the National Heart, Lung and Blood Institute (NHLBI); the American Heart Association (AHA); and the American College of Cardiology (ACC). But these institutions have a checkered record of endorsing expensive treatments that were no better than cheaper ones, and potentially made matters worse.

For example, the ALLHAT study conducted by NHLBI (“antihypertensive and lipid lowering to prevent heart attack trial”) tested the effectiveness of both antihypertensive and lipid treatments. It was published in JAMA (2002) and is cited in the journal, Circulation. The ALLHAT study was critically reviewed in the British Medical Journal (2003), noting that in BOTH arms of this government sponsored study neither expensive treatment endorsed by the AHA and ACC demonstrated better results than cheaper treatments which proved safer. [Ref 7]

Indeed, a cheap diuretic proved safer and more effective against heart attack than either expensive calcium channel blockers and ACE inhibitors or lipid lowering statins which “showed no statistically significant reduction in cardiovascular disease event rates or in deaths.”

Of special note is that this study tested statins in patients with higher risk of heart disease–because such patients had generally shown a greater benefit from statins than do lower risk patients–yet the outcome was negative.

However, the negative ALLHAT study findings were never publicized and the PR firm handling Pfizer’s marketing of the expensive drug, of Cardura, didn’t challenge the findings because “The reality is no one promotes a diuretic. So you’ve got one study that says yes, you should [use a diuretic], then starting the day after, you’ve got a $10bn [sic] industry. . . and 55 promotional events . . . for an ACE inhibitor…” [Ref 7]

Incredibly, none of the journalists in the major media–including Gina Kolata (NYT), Rob Stein (Wash Post), Ron Winslow (WSJ), among others–saw fit to even mention the serious risks associated with statins. These include: a potential increase in liver enzymes, muscle aches, weakness, immune system suppression, an increase in cancer risk, and a serious degenerative muscle tissue condition called rhabdomyolysis-and the depletion of Q10, the co-enzyme for the production of cellular energy.

What is Q10? Dr. Peter Langsjoen, an expert cardiologist who has done original research into Q10, says this co-enzyme “is responsible for over 80 per cent of energy and if you knock the level of this essential nutrient down, nothing works as well. Those tissues and organs that use a lot of energy are the first to be affected. The heart, for example, uses a huge amount of juice and if you cut it back with the use of a statin, what you start having first and foremost is lack of energy -you start getting sluggish. So the clinical consequences come about gradually and this weakening – fatigue, getting winded when you’re walking up the stairs.It’s extremely widespread. If you look for it, you’ll see it in just about every single new patient who has been on a statin.” [Ref. 8]

Science journalists seem to have very short memories about universally recommended preventive treatments that turned out to increase harm-the hormone replacement therapy debacle seems to have taught them nothing.

The 2003 BMJ report uncovered evidence of Pfizer financial largesse-not surprising, the beneficiaries were the endorsers of Pfizer’s high priced cholesterol lowering drugs. Even the NHLBI investigators walked away from their negative study findings, insisting: “we know [statins] work.” Is this science or faith? The NHLBI scientists went on to raise questions about their own methodology.

But Dr. Marcia Angell noted that questions about study results should be “hypothesis generating” and cannot be assumed as fact until they are tested. She suggested that what’s true of the ALLHAT drug study “may be true of an awful lot of drugs. A lot of newer drugs may not only not be better-they may be worse.” The problem arises, Dr. Angell said, because “most drug companies don’t want a head to head [study]. And the FDA allows trials to run that are rigged where a drug is tested against placebo or a drug of the same class that is inadequately dosed, or they look at the wrong group of people or the wrong endpoints so their drug looks good.” [Ref. 7]

Why, then, have healthcare journalists who reported about statin-sales boosting recommendations fail to raise questions about the risks of statins, or to inform readers how much financial support / grants the manufacturers of statins provide to the three institutions that endorsed the recommendations?

Must we always have to wait for the British to publish reports that raise serious questions about healthcare promotions? Must we wait for the BMJ to investigate unacknowledged financial incentives that may have persuaded those who promote the increased use of statins and other expensive new drugs?

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References:

1. THE WALL STREET JOURNAL. Research Conflicts Go Undisclosed Study Says Medical Journals Don’t Effectively Monitor Financial Ties of Authors. By ROBERT TOMSHO, July 13, 2004; Page D3 http://online.wsj.com/article/0,,SB108967337655561782,00.html

2. British Medical Journal. Efficacy and safety of antidepressants for children and Adolescents. Jon N Jureidini, et al. online free at: http://bmj.bmjjournals.com/cgi/content/full/328/7444/879?

See: The Lancet. Selective serotonin reuptake inhibitors in childhood depression: systematic review of published versus unpublished data. Craig J Whittington, et al. Volume 363, Number 9418, April 24, 2004, online free at: http://www.thelancet.com/journal/journal.isa

3. THE WALL STREET JOURNAL. New Option for Fighting Cholesterol FDA Is Expected to Approve Pill That Mixes Two Drugs; What the Lower Target Means By SCOTT HENSLEY , July 14, 2004; Page D1

4. NCEPAT Panel: Scott M. Gundy, James I Cleeman, Noel C Mertz, H. Bryan Brewer, Luther T. Clark, Donald B. Hunninghage, Richard C. Pasternak, Sidney C. Smith, Neil J. Stone,

5. The New York Times. Experts Set a Lower Low for Cholesterol Levels By GINA KOLATA July 13, 2004, A-1. http://www.nytimes.com/2004/07/13/health/13heart.html?hp=&pagewanted=print&position=

WASHINGTON POST. Lower Cholesterol Targets Urged By Rob Stein http://www.washingtonpost.com/wp-dyn/articles/A44702-2004Jul12.html

THE WALL STREET JOURNAL. New, Lower Goal Is Set for Cholesterol High-Risk Patients Are Urged to Consider Getting Their LDL Below 70 as Opposed to 100 By RON WINSLOW July 13, 2004; Page D1

6. See articles and reports by members of The International Network of Cholesterol Skeptics: “The International Network of Cholesterol Skeptics (THINCS) is a steadily growing group of scientists, physicians, other academicians and science writers from various countries.” http://www.thincs.org/Malcolm.htm

7. British Medical Journal. Spin doctors doctors soft pedal data on antihypertensives. By Jeanne Lenzer, BMJ 2003;326:170 ( 18 January ) http://bmj.bmjjournals.com/cgi/content/full/326/7381/170/DC1

8. See: Nicholas Regush interview Dr. Peter Langsjoen, a pioneering researcher and cardiologist who has brought considerable attention to a mighty nutrient called “Co-Enzyme Q10” about the hazards of statins. Langsjoen has been involved in some of the key original work showing the link between Q10 depletion and heart disease. His concerns and warnings about statin use come at a time when statin therapy is being very aggressively promoted by the drug industry http://redflagsweekly.com/RFD_Interviews/index.html

Contact: Vera Hassner Sharav
Tel: 212-595-8974

http://www.usatoday.com/news/health/2004-07-12-journal-conflicts_x.htm

Journals, authors cited for conflicts of interest
By Robert Davis, USA TODAY

Some leading scientific and medical journals do not always enforce their conflict of interest policies with the authors of published studies, according to a new report. The Center for Science in the Public Interest found that in some cases the journals did not disclose contributing authors’ financial conflicts of interest even though the journals’ own rules require such disclosures.

“There is a consistent pattern here,” says Merrill Goozner, CSPI project director. “This is an unacceptable level, and the journals need to take action.”

The findings come amid growing concern over the influence that private industry has on scientific research. For example, journal editors, including those responsible for some of the content that was studied by CSPI, are considering requiring drug companies to register all clinical trials in a database for more accountability.

The study examined 163 articles in The New England Journal of Medicine, TheJournal of the American Medical Association (JAMA), Environmental Health Perspectives, and Toxicology and Applied Pharmacology and found that the authors of 13 articles had relevant conflicts of interest that were not reported to readers.

The most obvious conflicts were reported, such as when the research was funded by a company that employs the author. But the CSPI researchers found hidden conflicts in what Goozner calls “the margins,” in which there was no direct link, but the researcher stood to benefit from the same industry.

One author of a study on heart disease, for instance, failed to reveal relationships with 20 companies that made cardiovascular drugs or devices. “This is important for the general public and the scientific community because full disclosure gives you another piece of information for evaluating these studies,” Goozner says. “If you hide the fact that there is a conflict of interest with the researcher, then you are deceiving people.”

CSPI is a consumer advocacy organization. It says that journal editors should: .Require all authors to disclose all financial arrangements made with private firms within the past three years, whether or not those arrangements are directly related to the subject of the article. Patents, patent applications and an intention to apply for a patent also should be revealed.

.Impose sanctions against authors who fail to disclose conflicts of interests, perhaps banning the author from publishing in the journal for three years.

The study found the highest incidence of unreported conflicts of interests at JAMA, where six of 57 articles, or 11%, failed to disclose a financial conflict of interest. In most cases, the authors of the JAMA studies in question told CSPI that they had not disclosed the information to the journal editors.

Phil Fontanarosa, JAMA’s executive deputy editor, said Monday that he had not yet seen the study and could not comment on it. But he said the study “will help keep the issue on the front burner.” “We all want the same thing, which is transparency of reporting of conflicts of interests,” he said.

“These journals were picked because they have the best policies,” Goozner says. “Imagine what is happening at the lesser journals.”

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