America's biggest prescription drugs, and the patients taking them, were reeling today after reading headlines about the second of two disturbing medical reports to appear this week.
We hope that these findings prove decisive in energizing the public to insist that legislators enact urgent data-disclosure reforms.
And they should fund more clinical research into lifestyle/diet measures that already possess a preponderance of strongly positive evidence with regard to America's biggest "prescription conditions": heart disease and depression/anxiety.
Two major cholesterol drugs prove worthless; one appears dangerous
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Key Points
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Major cholesterol medicine worsens clogs in artery to the brain, and does not reduce heart risks.
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Review reveals drug companies’ attempts to hide negative research on leading anti-depressants.
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Including negative trials reduces the alleged benefits of anti-depressants dramatically. |
Even people who don’t watch much TV have found it hard to escape the ubiquitous ads for Vytorin, a drug that combines a cholesterol-lowering statin drug called Zocor (simvastatin) with a different kind of cholesterol-lowering drug called Zetia.
At least until this week, doctors prescribed Zetia to about one million people a week. About 60 percent of patients who take Zetia take it with Zocor as Vytorin.
Statins reduce the amount of LDL (“bad”) cholesterol formed in the liver, while Zetia blocks intestinal absorption of cholesterol from foods.
Unlike Zocor and some other statin drugs, which have demonstrated the ability to reduce adverse heart events, Zetia has never been shown to prevent heart attacks or other life-threatening events.
In published clinical trials, Zetia lowers cholesterol by 15 percent to 20 percent in most patients.
But the results of a new clinical trial showed that arterial plaques grew almost twice as fast in patients taking Zetia along with Zocor (in the form of Vytorin), versus those taking Zocor alone.
(This was not a statistically significant change: it simply showed that Vytorin worked no better than Zocor alone.)
The trial lasted two years and involved about 720 patients with very high cholesterol, mostly in Holland. Patients taking Vytorin in the newly published trial suffered expansion of the fatty plaques in their carotid arteries, compared with those taking Zocor alone.
The trial lasted two years and involved about 720 patients with very high cholesterol, mostly in Holland. Patients taking Vytorin in the newly published trial suffered expansion of the fatty plaques in their carotid arteries, compared with those taking Zocor alone.
The New York Times quoted Dr. Steven Nissen, chairman of cardiology at the Cleveland Clinic, who said the results were “shocking.” As he told the Times, “Patients should not be prescribed Zetia unless all other cholesterol drugs have failed.” (Berenson A 2008)
(We question the wisdom of Dr. Nissen’s comment, which reveals a disturbing tendency for doctors to rely on synthetic drugs, even when they appear useless and downright dangerous.)
The companies that make Zetia and Zocor only released the trial’s highly negative results after news reports highlighted a long delay in its publication.
As we’ve reported, there is substantial evidence that omega-3s are as effective as statin drugs when it comes to reducing death rates in heart patients, and that the cholesterol theory of cardiovascular disease is seriously flawed. (See “Omega-3s Seen Rivaling Statins at Reducing Risk of Death”, “Does Fish Oil Lower Cholesterol? Does it Matter?”, and “Can Radical Cholesterol Cutting Raise Cancer Risk?”.)
Sadly, the US regulatory system is rigged against nutritional interventions, which cannot be patented, and therefore can provide no profits to drug makers.
Anti-depressant makers suppressed negative studies
If the statin story doesn’t make your blood boil, this one should.
Psychiatrist Erick H. Turner, M.D., is a former clinical reviewer of mood-altering drugs for the FDA, who’s worked at Oregon Health and Sciences University for several years.
In 2004, he wrote an essay calling for the U.S. Food and Drug Administration (FDA) to share more information provided by pharmaceutical companies regarding their clinical drug trials.
As Dr. Turner said then, drug trial registries usually aren't coordinated and participation is voluntary. Consequently, not all clinical trial results are listed and those that are may be incomplete (OHSU 2004).
His team’s report in today’s edition of The New England Journal of Medicine puts the main issue front and center, in the first sentence: “Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased. Selective publication of clinical trials – and the outcomes within those trials – can lead to unrealistic estimates of drug effectiveness and alter the apparent risk–benefit ratio.”
Their new analysis reviewed data from 74 trials involving 12 drugs, and is the most thorough study of its kind published to date.
And their review made deeply disturbing findings: some 94 percent of anti-depressant trials with positive outcomes (i.e., effects superior to placebo pills) were published, while only 14 percent of trials with negative or unclear results appeared in any public form.
And according to the FDA’s own study reviewers, the results of many of the “positive” studies were not as good as their authors claimed.
Of the 74 FDA-registered studies analyzed by Dr. Turner’s team, 31 percent were never published.
Dr. Turner’s team also found a strong correlation between the outcome of studies and whether and how they were published: studies that showed benefit were far more likely to see the light of day.
These were their detailed findings (Turner EH et al 2008):
- “A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published.
- Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies).
- According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive.
- Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall.”
The last two points imply that the authors of trials sponsored by drug companies routinely overstated the degree of benefit, compared with the evaluations made by more objective FDA reviewers, or simply decided not to publish studies with negative outcomes.
And this failure to publish negative trials means that the benefits of anti-depressants like Prozac have been substantially overstated for years.
As Dr. Turner told The New York Times, “The bottom line for people considering an antidepressant, I think, is that they should be more circumspect about taking it, and not be so shocked if it doesn’t work the first time and think something’s wrong with them.” (Carey B 2008)
And he said that doctors often end up asking, “How come these drugs seem to work so well in all these studies, and I’m not getting that response?” (Carey B 2008)
Iron triangle of FDA revolving door, campaign finance and Wall Street
Despite these twin fiascoes regarding multi-billion-dollar cholesterol and depression drugs, we won’t hold our breath waiting for major changes in the way the US regulates drugs, or treats nutrients with comparable or greater benefits.
Sadly, the campaign finance system and revolving door that leads from the FDA to drug companies make it unlikely that things will change soon. And Wall Street firms are heavily invested in big pharma, so they will exert pressure to keep things just as they are.
It’s enough to make you sick.
Sources
- Berenson A. Cholesterol Drug Has No Benefit in Trial. The New York Times, January 14, 2008. Accessed online January 17, 2008 at http://www.nytimes.com/2008/01/14/business/14cnd-drug.html
- Carey B. Researchers Find Bias in Drug Trial Publishing. The New York Times, January 14, 2008. Accessed online January 17, 2008 at http://www.nytimes.com/2008/01/17/health/17depress.html
- Turner EH, Matthews AM, Linardatos E, Tell RA, Rosenthal R. Selective Publication of Antidepressant Trials and Its Influence on Apparent Efficacy. NEJM. Volume 358:252-260 January 17, 2008 Number 3. Accessed online January 17, 2008 at http://content.nejm.org/cgi/content/short/358/3/252
- OHSU. Researcher says FDA could broaden access to results of clinical drug trials. December 28, 2004. Accessed online January 17, 2008 at http://www.ohsu.edu/news/2004/122804turner.html
