Dr. Oz takes a big bite of bad science

Mehmet Oz hosts a popular TV show that reaches millions of people.  He offers a constant stream of medical advice, and he is popular because he makes his topics sound dramatic, or exciting, or surprising, or all three.

Unfortunately, Dr. Oz sometimes has a poor understanding of science.  At least I hope so, because he promotes so many outrageous treatments, with such enthusiasm, that the only other explanation I can think of is that he is simply a fraud. I don't think that's true, so let's give him the benefit of the doubt and assume that when he makes a mistake, he is simply ignorant of the truth.  His latest startling revelation is that the metal fillings in your teeth are very, very bad for you.  Or are they?

Last week, Dr. Oz hosted a show called "Toxic Teeth: Are Mercury Fillings Making you Sick?  The show looked at silver amalgam fillings, which contain a small amount of mercury chemically bound within them.  Mercury is indeed a toxin.  Should you worry?  

One problem with taking a skeptical look at a Dr. Oz show is that he packs each episode with scientific claims, coming at you thick and fast, and it would take hours to critique them all.  Instead, I'll just pick a few, which illustrate Oz's lack of concern for accuracy, and his apparent ignorance of the underlying science about dental fillings.

Dr. Oz opens his show with a dramatic claim about mercury: 

"This thermometer contains mercury," he says, holding up a very small thermometer. "If I were to drop it, we would have to evacuate this entire studio immediately!" 

Now, this is complete nonsense.  If you drop a mercury thermometer, you should carefully clean up the mercury, which beads up into nice little silver-colored balls.  No one in the room is in danger, unless perhaps they try to drink it.*

This opening salvo should set off anyone's skeptical alarm bells.  Here's a guy who doesn't seem to mind exaggerating to make a point.  Why trust anything he says in the rest of the show?  I suspect, though, that after watching this episode, thousands of Oz's loyal viewers raced to the phone and made appointments to have the silver fillings in their teeth removed.

Dr. Oz continues his introduction by explaining that mercury is contained in silver tooth fillings.  No one knew, he claims, that mercury vapor could be released from these fillings, but this news:

"sparked a firestorm 30 years ago [here the show cuts to a graphic of a fireball exploding] when major news reports brought to light the potential TOXICITY of mercury fillings.  ... Now there's mounting new evidence showing mercury is released when you eat, and even when you brush your teeth."

Quick, run to the dentist!  Get this toxic mess out of my mouth!  

But hang on a minute.  Why aren't people dropping like flies from the fillings in their teeth?  With little effort, I determined that, contrary to Dr. Oz's statements, nothing new has been discovered lately about silver tooth fillings.  I found studies going back to the 1970s that shown that we've long known for decades that mercury is released from these fillings. But Oz ignores all these.  He even announces, a few minutes into the show, that 

"for the first time ever, I'm going to show you what happens when you brush your teeth with mercury fillings."  

No, this is not the "first time ever."  As a scientist, I find it worrisome that Oz seems quite comfortable claiming, incorrectly, that he's the first person ever to tell the world about this.

Perhaps the most outrageous - and unintentionally funny - segment of the show is the "demonstration," where Oz introduces an Oz-certified expert on mercury vapor, David Wentz, who has a gizmo that looks like it was built by a sideshow huckster.  The device is a plexiglass box that looks like it was meant to handle biohazards, with black rubber gloves that let you manipulate its contents.  In the box: a set of fake teeth containing... silver fillings!  And a toothbrush!  

As he walks over to the device, Oz says "I work with Dave Wentz and his Ph.D. dad."  This goes by really fast, so you would be excused for not realizing that Dave Wentz himself doesn't have a Ph.D., and for not knowing whether he has any credentials at all.  Dr. Oz conveniently omits the fact that Wentz and his father run a highly profitable nutritional supplements company, USANA http://www.usana.com/dotCom/about/index, which happens also to donate money to Oz's nonprofit corporation, HealthCorps.  Hmm.

Dr. Oz then reaches into the box, and while the audience watches in hushed excitement, he brushes the teeth, right on top of those silver fillings!  Right on cue, Wentz proclaims that the mercury vapor reading hits 61 in just a few seconds. 

"Anything over zero is toxic," Wentz proclaims.  "And we're at 61."
"Oh my goodness, 61!" Dr. Oz exclaims.
"That mercury is coming off the fillings, into your mouth, going across the blood-brain barrier, into your brain," says Wentz dramatically.

Wow.  I've been brushing my teeth (which have several fillings) for years.  How can I not be dead?

As Dr. Oz should know, "the dose makes the poison."  Even water can kill you if you drink too much of it.   Wentz is clearly wrong to say that "anything over zero is toxic."  

How much mercury is safe, then?  

According to the EPA, 0.1 micrograms of mercury per kilogram of body weight per day is safe.  For an adult who weighs around 150 pounds, that's about 7 micrograms.  A 6-ounce can of tuna has about 20 micrograms of mercury, about 3 times the safe amount per day.  Scientists do have real concerns that mercury in tuna and other fatty fish might present a health hazard.   

Dr. Oz's device seemed to show that 61 micrograms of mercury were released from brushing teeth, which would be about 9 times the exposure that is considered safe.  Is there really a risk here?

Well, no.  The EPA has found that "nearly all methylmercury exposures in the U.S. occur through eating fish and shellfish."  (Admittedly, though, this is not mercury vapor.) The precise question that Oz claims to be explaining "for the first time" has been examined in multiple studies, and the evidence is that silver fillings are harmless.  (See the FDA summary here.)  

A thorough scientific review in 2004 concluded that:

"The current data are insufficient to support an association between mercury release from dental amalgam and the various complaints that have been attributed to this restoration material. ... Individuals with dental amalgam-attributed complaints had neither elevated HgU nor increased prevalence of hypersensitivity to dental amalgam or mercury when compared with controls. The findings of these studies suggested that individuals with complaints self-attributed to dental amalgam should be screened for underlying dental, physical, and psychiatric conditions."

So no, there's no evidence that mercury from silver fillings causes any health problems.  None.

But what about that device on Dr. Oz's show, which showed 61 micrograms being released in just a few seconds of brushing the teeth?  My conclusion is that the device in Dr. Oz's studio was either wildly inaccurate or simply fraudulent.  The setup was almost a parody of what real scientific instruments look like, and nothing about it gave me any confidence that it was reliable.  I would suggest to Oz that before making a claim like this, he should ask rigorously trained scientists to make the measurements using properly calibrated equipment.  A TV studio is no substitute for a real lab. 

But wait: Mehmet Oz is a Professor of Surgery at Columbia University - he must know his science!  Plus he has an M.D. from the University of Pennsylvania, and he did his undergrad studies at Harvard.  By all appearances, he is a very smart guy.  If his show were about heart surgery - his specialty - it would no doubt be professional, accurate, and probably far too technical to attract an audience.

Here's the rub: despite his credentials, Oz is not an expert on mercury amalgam fillings.  He probably could have read and understood the science, but he appears to be unaware, or too busy to  be bothered by, the many scientific studies on this subject. Had he done his homework, he might not have presented such a spectacularly overblown episode that seems intended to scare people into removing the silver fillings from their teeth.  

So there's no need to go out and get your silver fillings replaced.  It's too bad that a highly educated surgeon like Mehmet Oz, with such a big audience, prefers to present wild exaggerations rather than telling people the truth.  Perhaps, though, the truth just isn't that exciting.

*Note added on followup: Even swallowing is rarely harmful.  From J. Dodes: "Acute toxic exposures to  elemental mercury are rare but there have been cases of elemental mercury being accidentally released directly into the  bloodstream from broken rectal thermometers and when elemental mercury had been swallowed intentionally in an attempt at suicide.  In all these cases there was no long-term effects from the mercury."  Dodes, JE.  The Amalgam Controversy:an evidence-based analysis.  JADA, 132:348-56, 2001.

Why we want to believe chocolate makes us smarter

Eat chocolate, win Nobel Prize?

The New England Journal of Medicine published a study two weeks ago showing, amazingly, that eating chocolate might make you smarter.  To be precise, the author, Franz Messerli, was wondering if chocolate consumption might be correlated with the overall cognitive function of a population.  He couldn't find any data on national intelligence, so instead he used the total number of Nobel prize winners per capita.  The correlation between chocolate consumption and Nobels is remarkably strong, with a p-value less than 0.0001, meaning that the odds that this is due to chance are less than 1 in 10,000.

Ha ha! Dr. Messerli was just kidding.  Or was he?

The article itself reads like almost any science paper.  It includes a straight-faced presentation of the data and scholarly references suggesting that the brain-enhancing effect of chocolate might be due to flavanols, which may be "effective in slowing down or even reversing the reductions in cognitive performance that occur with aging."

In fact the entire article appears to be dead serious until the end, where Messerli makes the wry comment that

"The cumulative dose of chocolate that is needed to sufficiently increase the odds of being asked to travel to Stockholm [where the Nobels are awarded] is uncertain."

And then, in his disclosure of conflicts of interest, he reports "daily chocolate consumption, mostly but not exclusively in the form of Lindt's dark varieties."  Hmmm, this doesn't seem like a serious science paper after all.

Word of this article swept through the halls of academia the day after it was published.  I heard it being discussed among my colleagues, who were concerned that NEJM had published yet another example of misleading statistics.  It took a couple of days for us to realize that it was a joke - based on real data, but a joke nonetheless.

The media reported the story widely, and a few reporters figured out the ruse, but the parody was just too subtle for most.  Reuters wasn't fooled, as reported on their own site and on Fox News. They reached Messerli by phone, who confessed that

"the whole idea is absurd, although the data are legitimate and contain a few lessons about the fallibility of science."

The Associated Press reporters were slightly suspicious, opening with "take this with a grain of salt." But they went on to report it as straight news, and their story appeared on CBS News, the Huffington Post, and elsewhere.

Larry Husten, my fellow columnist at at Forbes, reported it as straight news with the headline "Chocolate and Nobel Prizes Linked in Study." Time magazine fell for it too.

Two medical websites, Medical News Today and WebMD, not only took the story seriously, but also bought into the explanation that the effect is caused by flavanols, which are found not just in cocoa, but also in red wine and green tea.  Sounds like an ideal diet to me.

Slate's Brian Palmer had an interesting angle. He reported the story as straight news, but then investigated why the Swiss eat so much chocolate.  (Answer: innovation in chocolate-making, and wealth.)

Why do we want to believe chocolate makes us smarter?  Well, obviously because we'd love for it to be true.  And as Messerli points out, there have been some serious studies linking flavonoids to better health and cognitive function.  But the notion that chocolate leads to Nobel prizes is a little too good to be true.  I'm reminded of the study that I wrote about back in April that claimed chocolate would help you lose weight - which was little more than wishful thinking masquerading as science.

Still, with Halloween just past, many parents are probably wondering how much to let their kids eat.  Those Nobel-champion Swiss consume about 11 kilograms per year, about 30 g (1 ounce) per day.  That's 3 of those little mini-chocolate bars.  And parents, maybe you should have a few too - just in case Messerli is right.

Multivitamins and cancer: a mixed bag

A major new study published this week in the Journal of the American Medical Association (JAMA)  came to the surprising conclusion that

"daily multivitamin supplementation modestly but significantly reduced the risk of total cancer."

The report included some caveats, such as the fact that all 14,641 participants were healthy male physicians.

But the result is still surprising, because other recent studies, some of them even larger, have concluded that vitamin supplements do not provide any significant health benefits.  On the contrary, some studies found that supplements could actually be harmful.  As I wrote last year, a very large study of 38,772 older women, who were followed for 25 years, showed that the risk of death INCREASED with long-term use of multivitamins, vitamin B6, folic acid, iron, magnesium, zinc, and copper.  That's death, not just cancer.  The authors of that study, Jaakko Mursu and colleagues, concluded that there is

"little justification for the general and widespread use of dietary supplements."

The new study, PHS II (Physicians' Health Study II) looked at overall death rates as well as cancer, and found that men on a daily multivitamin had fewer deaths, but too few to be statistically significant.

So we have a large study in men showing that multivitamins seem to reduce overall cancer, and maybe even death, but an even larger study in women showing the opposite effect.

A second study from last year, in 35,533 men, looked at vitamin E and selenium supplements. That study, also published in JAMA, found that risk of cancer INCREASED for men taking vitamin E, selenium, or both.

The media reports aren't helping to clarify things.  The NY Times proclaimed "Multivitamin use linked to lowered cancer risk, and the Wall St. Journal reported that "Multivitamin cuts cancer risk, large study finds."  Bloomberg News went right for the business angle, announcing that "Pfizer multivitamin reduces cancer 8% in men, study finds."

Compared to Bloomberg news, Pfizer's own website was remarkably restrained, saying only

"Centrum Silver was part of the recently published landmark study evaluating the long-term benefits of multivitamins."  

No claims about reducing the risk of cancer - surprisingly, the independent media made far stronger statements than Pfizer.  Not true of supplement manufacturer GNC, which was flashing a pop-up headline that "Taking a daily multivitamin could cut cancer risk", linking to a news article at the Boston Herald.

So what do we make of this new study?  Are multivitamins good for you after all?

The new JAMA study appears to be very well done.  It's a double-blind, placebo-controlled study in which half of the physicians received a daily multivitamin, Centrum Silver, and half received a placebo.  The participants didn't know if the pill they were taking was a vitamin or a sugar pill.  The authors report some minor conflicts of interest, but none of them work for or received major funding from Pfizer (PFE, the manufacturer of Centrum).  So how to explain the seeming contradiction with two larger studies published only a year ago?

To answer this question, we must look at the details of the study itself.  This study looked at 21 different types of cancer risk.  For most cancers - colon cancer, prostate cancer, lung cancer, pancreatic cancer, lymphoma, leukemia, melanoma, and others - multivitamins did not provide a benefit.  But when all the numbers were added up, the effect was just large enough to be "significant", at a level of p=0.04.  More on that in a moment.

Here are the raw numbers: among the 7,317 men who took a daily multivitamin, there were 1,290 cases of cancer over the 11-year study.  Among the 7,324 men who took a placebo pill, there were 1,379 cases.  That's about 1.2% more - far less than the 8% reported by Bloomberg News. The statistical analysis showed that this difference had a p-value of 0.04, a result the authors considered significant. When the authors looked only at men with no history of cancer, the effect was smaller, and not statistically significant.

One explanation of the new finding is that the effects were indeed due to chance. Let's look at that p-value of 0.04. In much of the scientific literature, any p-value below 0.05 is considered "significant," but this has been widely criticized, in part because it encourages binary "true, false" thinking that is not the way scientists actually think. Also, the "0.05 threshold actually represents evidence much weaker than the number "0.05" suggests. A back-of-the-envelope Bayesian calculation shows that if the cancer-preventing power of multivitamins was a 50:50 proposition before this study, then after this study there is still a 10-26% chance that the cancer prevention claim is wrong. If we thought that prior evidence made this effect less than 50:50, (say 25:75), then the study has roughly a 25-50% chance of being wrong.* Either way, I won't be stocking up on Centrum Silver anytime soon.

Looking at this small effect, and at the contradictory results from other studies, neurologist Steven Novella writes in his blog that

"About the only thing we can say with a high degree of confidence is that there is no large risk or benefit from taking a multivitamin. There may be a small benefit, no benefit, or even a small harm."

That's a good summary.  So should men take a multivitamin?  Well, it's your money, but if you don't have a vitamin deficiency, it's probably not worth it.  Should women?  The evidence still says no.

*Thanks to Stanford biostatistician Steven Goodman (formerly of Johns Hopkins University) for crunching some numbers to produce Bayes factors.

Eat more chocolate! Lose weight!

It's a holiday weekend, and many of us will be eating chocolate, especially chocolate bunnies and chocolate eggs.  (Where does that come from, anyway?  Bunnies don't lay eggs.) We don't really need an excuse to eat chocolate.  But isn't it wonderful when a scientific study tells us that we should?  Even the skeptics among us really want to believe that eating chocolate is good for you.

Last week, a new study in the Archives of Internal Medicine claimed that eating chocolate more frequently is associated with a lower body-mass index, or BMI.  The study's authors carefully stated their results as a "link," but then they went on to say that other evidence would "suggest the association could be causal."

Of course the media ate this up (pun intended), with headlines like "The Chocolate Diet?" at The New York Times.  The Times story was filled with caveats, pointing out that it was frequency of chocolate consumption (how many times per week you eat it) that was associated with lower body weight,  and that people who simply eat more chocolate tend to be, well, fatter.  Surprise!

Beatrice Golomb, the lead author of the study, explained to the Times that:

“It’s not the case that eating the largest amount of chocolate is beneficial; it’s that eating it more often was favorable.”  

Because the thinner people in the study ate less chocolate overall, they must have eaten much less at each sitting.

Alas, this is just a bad study.  The biggest problem is that it was based entirely on questionnaires, in which 1018 men and women answered questions about how often they excercise and how often they eat chocolate.  Here are some key features of these subjects:

• Their average BMI was 28.  So they are kind of fat. (A BMI of 25-30 is overweight.)
• They claim to exercise 3.6 times per week, on average.
• They report eating chocolate 2 times per week.

We all know how this works. Even though the questionnaire is anonymous, we still want to look like we're doing the right thing.  So we over-state how often we exercise (3.6 times per week? ha!) and we under-state how often you eat unhealthy foods.  The entire result can be explained by a tendency of thinner people to admit eating chocolate more often.  Observational studies like this one are notoriously unreliable.

On this note, I have to give kudos to Gary Taubes at Discover magazine, who isn't buying any of this.  Taubes explains that:

"Both of these studies were classic examples of what is known technically as observational epidemiology, a field of research I discussed at great length back in 2007 in the New York Times Magazine.  I made the argument that this particular pursuit is closer to a pseudoscience than a real science."

Taube looked at multiple observational studies done at Harvard's School of Public Health, by one of the top epidemiology groups in the country.  But when observational studies "discovered" a causal relationship, it never seemed to pan out, says Taube:

"I pointed out that every time that these Harvard researchers had claimed that an association observed in their observational trials was a causal relationship—that food or drug X caused disease or health benefit Y—and that this supposed causal relationship had then been tested in experiment, the experiment had failed to confirm the causal interpretation—i.e., the folks from Harvard got it wrong. Not most times, but every time."

A zero percent validation rate - it doesn't get any worse than that.  Taube makes a very good case that the whole "nutritional epidemiology business" is pseudoscience.  You just can't go around asking people what they eat and expect to get reliable answers.

So nope, it just isn't so, no matter how much we'd like to believe it.  Eating chocolate isn't going to lower anyone's BMI.  But the really important question is, which part of the chocolate Easter bunny do you eat first?  I go for the ears.

The Skeptical Optimist

Some readers of this blog may be surprised to learn that I'm very optimistic about the future of science and medicine.  Over the past few years, I've criticized many different frauds, fakes, bad scientists, bogus claims, quack medical practices, and scam artists.  I will continue to do so.

But deep down, I'm an optimist.  Science has transformed our lives over the past century, thanks to a list of discoveries far too long to write down, including cures and vaccines for many childhood diseases, better ways to heat and light our homes, and faster ways to travel and communicate. I'm confident science will continue to make progress on all sorts of problems affecting our species. One reason I focus my criticism on pseudoscience is that every minute spent on bad science is a minute that could have been spent on real science, moving us closer to genuine treatments or real scientific discoveries.

I also write on occasion about true breakthroughs, such as the recent success using stem cells to treat damaged hearts, or last year's development of a vaccine against the Ebola virus.  It's good to remind ourselves that good stuff is happening despite all the nonsense being pushed by quacks out there.

But I'm a skeptical optimist.  All real scientists must be skeptics: we know that initially exciting results often turn out to be statistical flukes, experimental errors, or just plain randomness.  We have to check and double-check our results before publishing, and even then we sometimes make mistakes.  Our training makes us skeptical whenever we hear about some amazing new breakthrough, even when we are hopeful that the results are true.

But we can't let pseudoscience take precious resources away from real work.  So it's back to the front lines in the ongoing battle against the anti-science forces: watch this space tomorrow for my choice for the worst quackery of 2011.

Battlefield acupuncture: pseudoscience for wounded troops

In times of war, it’s tough to cut the military budget. Unthinkable, really. But what if the military is spending money on something that actually harms wounded military men and women coming back from war? Unbelievable? It should be. Today’s article describes a practice that is so bizarre, so obviously ridiculous, that some readers may think I’m making this up. I’m not.

Doctors in our military are now treating severely injured soldiers with “battlefield acupuncture,” a technique where they stick short needles into five points on the ear. Air Force doctors admit that they are using battlefield acupuncture to treat severely wounded troops as they are taken from the battlefield to Andrews Air Force Base and to Walter Reed Army Medical Center. This includes soldiers with brain injuries, severed limbs, burns, and penetrating wounds.

The Air Force news website Military.com reported on this nearly two years ago when Major (Dr.) Conner Nguyen began treating wounded soldiers at Landstuhl Air Force Base in Germany, after he received training from Stephen Burns and Richard Niemtzow, military doctors from Andrews Air Force Base in Maryland. Niemtzow has trained hundreds of military doctors in battlefield acupuncture, a method that he invented in 2001. Niemtzow also boasted in an interview last year that “if the military is using it, then it must be good for the civilian world."

The worst scientific idea of the decade: vaccines cause autism

The year and the decade are coming to an end, and top-10 lists are everywhere. These are hard to put together if you want to do it right. I’m opting for a simpler list: the top 1, and I’ll make it for the entire decade.

Of all the bad science, bad medicine, and pseudoscientific nonsense that human beings have come up with over the past decade, which is the worst? Of course, scientists have bad ideas all the time, and most of them never make it out of the lab. So for me, “worst” means a bad scientific notion that has emerged into the public domain and done more damage to civilization, or to public health, than any other idea of the past decade.

To answer this question, I wanted a belief or practice that rose to prominence during the past 10 years, which eliminates a large number of pseudoscientific practices and quack treatments that have been around much longer, including acupuncture, chiropractic, and homeopathy. So what idea has taken hold only recently?

And the worst scientific idea of the 2000's is: vaccines cause autism. This idea has caught on and spread like wildfire during the past ten years, thanks largely to the well-funded, well-publicized efforts of organizations such as Generation Rescue, led by the notoriously mis-informed celebrities Jenny McCarthy and her even more famous boyfriend, the actor Jim Carrey.

Strictly speaking, this terrible idea was first published more than a decade ago, in a now-discredited, notorious 1998 paper in The Lancet by Andrew Wakefield, a British gastroenterologist. This very small study of 12 children seemed to show a link between the measles, mumps, rubella (MMR) vaccine and autism, but it later turned out that the study had multiple flaws: Wakefield recruited the children to the study through a lawyer who was trying to build a case against vaccine makers, Wakefield himself received over $750,000 in consulting frees from the same lawyer, Wakefield didn’t tell his co-authors any of this, Wakefield had filed for a patent on an alternative, “safer” vaccine, and on and on. Although his co-authors repudiated the paper publicly and withdraw their conclusions in 2002, Wakefield has continued to this day to stand by his original claims. (See journalist Brian Deer’s website for a good summary of the Lancet scandal.) He moved to the U.S. after being forced out of his job at a London hospital, and he set up a private business in Texas from which he continues to promote his anti-vaccination claims.

Alcohol and cancer: journal editors say they got it wrong

In a recent editorial in the Journal of the National Cancer Institute, three scientists point out that I was correct in my February blog post, where I pointed out the errors - and the mistaken scare-mongering - in press reports of a new study on alcohol and cancer.

The JNCI editorial, titled "Promoting Healthy Skepticism in the News: Helping Journalists Get it Right" focuses on two studies, one of which is the article I wrote about. Journalists at the time, including Sanjay Gupta at CNN, reported "there is no level of alcohol consumption that can be considered safe when it comes to cancer." As the editorial points out, the journalists got it wrong. The authors point out that other explanations (other causes besides alcohol) might explain the increased risk. And it's nice to see that even though their own journal was partly to blame for the hype back in February, at least they're making an effort to correct it now.

They could have done more, though. They didn't dig into the article and report, as I did, that the minimum risk levels in the study were for light drinkers, who had 1-2 glasses of wine per week and who had a lower risk than non-drinkers. But at least they pointed out that the absolute increase in risk, even for heavy drinkers, was very small. In fact, they go on to say that under-reporting of absolute risk is a major failing of many biomedical journals.

So my advice for the holiday season is: drink up! The evidence for heart-healthy benefits of wine, especially red wines with high levels of procyanidins (as described in this article from Nature 2006), probably outweighs any risks. Happy holidays!

Crestor gets an undeserved boost from the FDA

The FDA planted a big, wet sloppy kiss on AstraZeneca this week. An FDA scientist told reporters that the benefits of Crestor, a cholesterol-lowering drug, outweighed the risks even for otherwise healthy people. Essentially, millions of healthy people with normal cholesterol levels could find themselves taking Crestor, if they listen to this anonymous FDA scientist and to Crestor’s manufacturer, AstraZeneca. This new recommendation was widely reported on Friday, appearing in the Wall St. Journal, in a widely carried AP report, and in a more skeptical Reuters report.

The new report isn’t based on anything new, though. It’s based on a study published a year ago – a seriously flawed study that I dissected at length on this blog in November 2008. The FDA took a year to review this study and then said yep, we agree. I should mention that the 2008 study has one condition before recommending Crestor: that the patients should have elevated levels of C-reactive protein (CRP). I described in earlier blog post the problems with this recommendation – including the fact that they study’s leader has a patent on the CRP diagnostic test.

Does it matter that, as I explained a year ago, the study was funded by AstraZeneca? How about the fact that this huge study found only a tiny benefit? That’s right: the benefit is so small that you’d have to treat 95 patients for 2 years in order to prevent one heart attack. As I wrote last year, and as others have pointed out, when the number needed (NN) to treat is over 50, the result is probably just statistical noise. Or to put it another way, if you take Crestor for 2 years, you have about a 1% chance of getting any benefit. Compare that to, say, taking vitamin C to treat scurvy, where the NN is about 1. With any decent drug, if you take it, you should have a very high likelihood of benefit.

We know who’s going to benefit here: AstraZeneca. Does it matter to them that there is a significantly higher risk of diabetes in people who take Crestor? There was also a higher number of deaths in the placebo group caused by gastrointestinal disorders, but the FDA dismissed this number because it didn’t reach statistical significance. (Kudos to the WSJ and Reuters reporters for highlighting these problems.) And no one besides me (see my Nov 2008 blog post) seems to have noticed some of the other problems with the study, such as the fact that the placebo group contained an excess in the number of patients with conditions that raise the risk of heart disease.

Does it matter that, as the FDA reported in 2005, “Rhabdomyolysis (serious muscle damage) has been reported in patients taking Crestor as well as other statin drugs.” Or that, as the same report said, “Kidney failure of various types has also been reported in patients treated with Crestor as well as other statins”?

So who the heck are these FDA scientists? After considerable searching, I found the lengthy FDA report here. It’s a “briefing document” for a FDA advisory committee that will meet on Dec. 15. It basically reviews the study in great detail and simply repeats the study results. What became clear to me once I downloaded the document, though, was that it was written by AstraZeneca! [Note: thanks to the first commenter on this blog, I also found the separate FDA-sponsored document - see comments.]

The reports from the AP, Reuters, and the WSJ I cited above mention an anonymous FDA reviewer, but apparently this “reviewer” did not want to be named on the record. It's too bad none of the reporters revealed the name of this anonymous FDA scientist, but the roster of the FDA panel reviewing Crestor is here.

It’s a shame that the FDA’s own scientists can’t take a more critical look at the evidence. Look for AstraZeneca stock to go up next week. Let me close with a video from Stephen Colbert, who had a great skeptical spoof of this last year on his show. Skip forward to about the 2-minute mark in this video to see the Crestor segment.

The Colbert Report	Mon - Thurs 11:30pm / 10:30c
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www.colbertnation.com
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As Stephen says in the video, "this is a great breakthrough in the battle to find things to prescribe to people who don't need them".

Nice.

Science, medicine, and politics mix in new mammography and stem cell guidelines

Today's news included two stories that both illustrate how politicians almost always get science wrong. It never seems to be a good thing when politicians sink their teeth into a scientific or medical question: they are only too happy to distort the facts to achieve their political goals.

First, the new mammography guidelines. This was all over the news two weeks ago: an official federal advisory panel, the U.S. Preventive Services Task Force, recommended that women between 40 and 50, who had no risk factors for breast cancer, not have annual mammograms. This caused a firestorm of criticism from many quarters, because the previous guidelines recommended annual screening. The panel determined, after looking at data from the past decade and more, that the risks of excessive screening (many more false positives, and the resulting biopsies and even surgeries) were not justified by the small number of additional cancers detected.

This is a complex issue, and many other bloggers wrote about it, so I'm not going to discuss it in detail. My overall impression was that the panel weighed the evidence and made their recommendations based on the best available science, and I think their decisions were good ones. I'd also note something that the media seems to have missed: about ten years ago, when another panel was debating similar recommendations, there was tremendous political pressure to make annual screening the official policy.

Merck paid Elsevier to create fake medical journal

In a delightful case of hypocrisy, the mega-academic publisher Elsevier produced a fake medical journal - with the superficial appearance of legitimacy - for money. Apparently the pharmaceutical company Merck needed another journal to publish favorable articles about Vioxx, and Elsevier was happy to oblige. This is on top of Merck's activity paying doctors to list their names as authors on studies favorable to Vioxx - studies that the doctors had little or no involvement in - which I blogged about in May and October of last year.

The new findings were reported recently in The Scientist (free subscription required), and they came to light in The Australian a few weeks prior to that. We only learned about this fraud - and that's what it is - because of a lawsuit filed by an Australian man who suffered a heart attack while on Vioxx. In testimony at the trial, a medical editor testified that

"Only close inspection of the journals, along with knowledge of medical journals and publishing conventions, enabled me to determine that the Journal was not, in fact, a peer reviewed medical journal, but instead a marketing publication for MSD[A]." (MSDA is a subsidiary of Merck.)

The fake journal is called The Australasian Journal of Bone and Joint Medicine, and it is published by Elsevier.

Why is this especially hypocritical? Well, it shows that large publishers, including Elsevier, who have been opposing open access so vigorously, are, well, just blowing smoke in our eyes (to put it politely). Elsevier and others claim that they are guardians of academic quality and integrity, and that they provide an invaluable (or at least very expensive) service by editing the many journals that they sell to libraries and scientists around the world. As the open access movement has gained momentum, they even created an anti-open-access lobbying group, PRISM which they claim will help "to safeguard the scientific and medical peer-review process."

Right.

Now it turns out that this is just the tip of the iceberg. As The Scientist reported last week, Elsevier published not one, but at least 6 fake journals since the year 2000, all sponsored by (still-unnamed) pharmaceutical companies. Remarkable.

As a fellow blogger commented:

"The bitter irony is that Elsevier, along with the other major academic publishers, have spent the last few years ceaselessly lobbying against the open access movement, on the grounds that open access journals can’t be trusted to maintain the high quality of peer review that the commercial publishers provide."

The hypocrisy is breathtaking. It's stories like these that feed the paranoia of anti-big-pharma groups and other conspiracy theorists. Once in a while, there really is a conspiracy.

p.s. the blogosphere has many posts on this episode. See Jonathan Eisen's post, which has links to others.

Parents: ADHD drugs don’t work

If you want to start an argument, try telling a parent – any parent – how to raise their kids. So I'm going to preface this by saying that I'm just trying to make parents aware of something that might concern them. One of the most controversial issues among parents of school-age children today is the shockingly large number of children who are being treated with drugs to control their behavior, especially those children who have been diagnosed with attention-deficit hyperactivity disorder (ADHD). Now it appears that these drugs simply don’t work, except in the short term. The results of a scientific study reported this past week showed that long-term use of drugs to children with ADHD doesn’t provide any benefit over behavioral therapy. Not only that, but children who took medication ended up, on average, one inch shorter than children who didn’t. That’s right: ADHD drugs stunt children’s growth.

This seems to be rather shockingly bad news for the ADHD drug manufacturers. The news was reported on the front page of the Washington Post and in many other media outlets. The study, an 8-year followup of the Multimodal Treatment Study of Children With ADHD (MTA), was reported in the Journal of the American Academy of Child and Adolescent Psychiatry (JAACAP). The study divided children into 4 groups: medication (M), behavior therapy (B), both treatments (M+B), or no treatment. The authors of the study had reported in 1999 – with great fanfare – that children who received drugs (M and M+B) did better than children who only had therapy (B) after 14 months and at 2 years followup. In other words, over the short term, the drugs seemed to work. As the Washington Post reported: “Because children given drugs alone appeared to do about as well as those treated with both drugs and talk therapy, the study skewed treatment in the direction of medication.”

However, over longer time periods, the drugs (including Adderall and Concerta, two of the most commonly prescribed drugs for ADHD) didn’t help at all – and they stunted growth. Children who took ADHD drugs for 3 years or longer were an average of one inch shorter than children who didn’t take drugs. The study looked at “grades earned in school, arrests, psychiatric hospitalizations, [and] other clinically relevant outcomes,” and found no differences in children given drugs compared to children given only behavioral therapy.

What should be even more disturbing is that this isn’t really news at all – it was reported two years ago, in 2007. The same authors reported then, in a 3-year followup study, that “treatment groups did not differ significantly on any measure at 36 months.” In other words, the benefits of drugs disappeared by 3 years after treatment started. Some of the scientists involved have downplayed these results, but one, William Pelham, was quoted in the Post saying his colleagues are “embarrassed to say they were wrong and we led the whole field astray.”

Another scientists leading the study, Peter Jensen, shot back that Pelham was biased against drugs. However, Jensen has been pushing drug therapy quite publicly for years. In the press release from the National Institute of Mental Health after the 2007 report, he said that “medication can make a long-term difference for some children if it's continued with optimal intensity.” This despite the fact that the 2007 results indicated that medication was not providing any benefit over behavior therapy, results that appear even stronger now. In contrast, William Pelham was already saying in 2007 that ADHD drugs were “all risk and no reward.”

It’s worth noting also that NIMH heavily promoted the initial results of this study back in 2000, and its website still states that “combination treatments as well as medication-management alone are both significantly superior to intensive behavioral treatments and routine community treatments in reducing ADHD symptoms.”

Reporter and blogger Maggie Mahar tried to draw attention to the story in 2007, but the U.S. media simply didn’t pick up on the story. Mahar also pointed out that “drug manufacturers have a serious interest in keeping the U.S. discussion on ADHD married to the medical-disease model.”

All of this made me wonder if Peter Jensen, who seems determined to continue to support the use of drugs to treat ADHD, might have ties to pharmaceutical companies. It took me only a few minutes to discover that he has received funding or grants from: UCB-Pharma, Cephalon, Novartis, McNeil Consumer & Specialty Pharmaceuticals, and Janssen Pharmaceutica. I found confirmation of these ties here. Novartis and UCB-Pharma are manufacturers of ADHD drugs (Ritalin or methylphenidate), and Cephalon makes Provigil, which they attempted to promote as an ADHD drug for years until the FDA rejected it.

Far too many of our children – primarily boys, who are diagnosed with ADHD 3-4 times more often than girls – are being medicated for ADHD. There is ongoing controversy, which I won’t get into here, over whether ADHD is grossly overdiagnosed. Whether ADHD is correctly diagnosed or not, though, it now seems clear that putting children on drug therapy might cause them long-term harm (stunting their growth) while only providing temporary, short-term changes in behavior.