Pfizer wants you to make a New Year’s resolution

“80% of you will fail to quit smoking with Chantix. “ That’s what the ad should say, but it doesn’t. Instead, it shows a smiling woman who “quit smoking with Chantix and support in June ’07” and it promises “with Chantix you can smoke during the first week of treatment.” Nowhere does it say how likely you are to quit smoking.

This is from a very large, full-page ad that’s been running for weeks, almost every day, in the Washington Post and other newspapers. The top 1/3 of the page is the “sell,” and the rest of the page contains the required safety information, which tells you some of the problems, including hostility, depression, suicidal thoughts or actions, and nausea. Naturally, the top of the page is in a larger font with a colorful picture.

Why is Pfizer (Chantix’s manufacturer) running these ads now? Well, quitting smoking is a very popular New Year’s resolution. It’s on many top-10 lists, even one from the U.S. government. Pfizer is trying to grab smokers’ attention now, so they’ll ask their doctors for a prescription, which I have no doubt they’ll get. These direct-to-consumer ads work, big time, and the drug makers know it. The U.S. should never have allowed drug makers to advertise directly to consumers – and Congress should re-institute laws prohibiting these ads.

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
Cheating Death - Women's Health
www.colbertnation.com
Colbert Report Full Episodes Political Humor U.S. Speedskating

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.

Read this if you like shrimp

Shrimp are tasty little morsels, but for years I’ve limited my shrimp intake because they’re high in cholesterol, or so I heard. Recently, though, I heard that they might good for you, so I decided to investigate. The results are a bit surprising.

First, shrimp is high in cholesterol, very high in fact. The American Heart Association recommends no more than 300 mg per day for a normal adult, but a 5-ounce serving of steamed shrimp contains 590 mg. For comparison, 2 large eggs contain about 580 mg of cholesterol.

On the other hand, shrimp is quite low in fat. That same 5-ounce (150g) serving of shrimp has just 1.7 grams of fat, while the same amount of beef has 14 grams of fat. So it’s low in fat, but high in cholesterol. What’s a shrimp-lover to do? Luckily, there’s a bona fide scientific study that attempted to answer this question – but with a catch, as we’ll see.

Searching the Web for shrimp and cholesterol, it’s easy to find lots of pages offering health and nutrition advice telling you that shrimp are good for you. But most of these webpages are from dietary advice “experts” who want to sell their books and diet plans, or from shrimp producers. Uh oh.

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.

Stimulus funds are promoting pseudoscience at Harvard Medical School

Another in an ongoing series of blog posts about wasteful spending by NCCAM, the National Center for Complementary and Alternative Medicine

In today’s competitive research environment, if the government offers money for something, then someone will do it – even if the research is worthless. This even happens at Harvard (where, it so happens, I got my Ph.D.).

Let's look at how, just recently, NIH funnelled more money to acupuncture. Bruce Rosen of the Massachusetts General Hospital and Harvard Medical School has secured two stimulus grants totalling $1.8 million to study acupuncture’s effects on brain activity. This was clever in two ways: first, Rosen took advantage of the fact that the National Center for Complementary and Alternative Medicine (NCCAM), the home of pseudoscience within NIH, had some stimulus funds that it had to spend quickly. Second, his studies simply use imaging techniques (fMRI) to look at patients’ brains during acupuncture. This virtually guarantees that he’ll find something: if you stick a needle into a person’s body, then of course the brain reacts! It hurts, doggone it! And if you compare this to sham acupuncture, where the pain is a bit different, then voila! you find that the fMRI looks different! Ergo, acupuncture must be activating some special brain functions. Clever!

Specifically, here are the stimulus funds that Rosen just landed:
2P01-AT002048-06 “Neuroimaging Acupuncture Affects on Human Brain Activity, $1,200,061
1P30-AT005895-01 , “Core Center for Multimodal Evaluation of Acupuncture Mechanisms”, $593,196

Here’s how Rosen introduces one of these projects:

“Acupuncture, a component of traditional Chinese medicine, has been used for thousands of years to treat a multitude of ailments. Recent scientific evaluation has suggested that this therapy may demonstrate clinical benefit for a number of conditions including chronic pain, though the mechanisms of action have not been well understood.”

Here we have, in his very first sentence: a classic logical fallacy (the “argument from authority”), right at the beginning of the proposal. Even if a treatment has been used for thousands of years (and let me note here that this is not true of acupuncture, despite numerous claims to the contrary), that doesn’t mean that it works. And of course, in ancient times people had a life expectancy of about 30 years, so we don't exactly want to go back to those days. Rosen follows this fallacy with the “suggestion” that acupuncture might work – and note how vague his claim is, using the phrase "may demonstrate" – despite the fact that all the properly-controlled studies show the opposite. In fact, recent studies show quite convincingly that “sham” acupuncture works just as well, even if the needles don’t penetrate the skin! And with placebo treatments, you get the benefit (such as it is) without the risk of infection from needle sticks.

Rosen has impressive credentials, with a Ph.D. in physics from MIT and an M.D. from Hahnemann Medical College. And he’s probably a really smart guy - who got taken in by pseudoscience somewhere along the way. A look at the publications on his acupuncture center’s website reveals almost no publications in the peer-reviewed literature since 2005. OK, maybe his web page is out of date, so I looked on PubMed and found two – only two – publications by Rosen on acupuncture and MRI in the past two years. Both were small, poorly controlled studies, and one appeared in BMC Complementary and Alternative Medicine, a rather pathetic excuse for a journal. With this kind of productivity, no wonder NCCAM gave him another $1.8 million!

But NCCAM loves this stuff. They even feature a picture from one of Rosen’s (two) studies on their website in their latest newsletter. It doesn’t matter if acupuncture works, as long as you can generate cool MRI images of people’s brains. Hey look, it’s an MRI – it must be science!

So Bruce Rosen is getting $1.8 million in stimulus funds to take worthless MRI images of patients’ brains while someone sticks them with needles. And this $1.8 million is merely a supplement to his ongoing NCCAM work – he’s been funded by NCCAM since at least 2003, (see the “06” at the end of that first grant number above? That means it’s in its 6th year of funding) and he proudly states that “our well-established group has been a leading force in acupuncture mechanism research for over a decade.” Great.

Finally, if Bruce Rosen reads this and feels I’m unfairly attacking him, well, he can reply on this blog (comments welcome!), or he can talk to me in person in February, when I’ll be giving a talk at Harvard Medical School, his home turf.

Merck hiding negative results about drugs, again

You’d think that after the Vioxx fiasco, Merck might be a little more careful about pushing drugs that don’t offer much benefit. Well, if you did think that, you’d be wrong. A new study in the New England Journal of Medicine this week shows that two very, very profitable cholesterol drugs are pretty much useless. Merck has been at least partly aware of this for 3 years, but they still don't want to admit it – not surprising given that sales of these drugs by Merck last year totalled over $4.5 billion. That’s “billion” with a "b." Merck has also been advertising these drugs heavily since they were approved by the FDA in 2002, and it has paid off.

So what are these drugs? They’re called Vytorin and Zetia, and first of all, they’re not statins (which many of you may have heard of), which are indeed useful at lowering cholesterol. The newer drug is called ezetimibe; Zetia is the brand name, while Vytorin is a combination of ezetimibe and a statin drug. Merck makes statins too, and they have been enormously profitable, but with statins I’d say the drug makers have earned their profits (at least some of them).

What did the new study find? Well, to quote the article itself, “niacin is superior to ezetimibe”, and the NEJM editors wrote that, “the findings, obtained in a modest sample of 208 patients, followed for only 14 months, show a clear superiority of niacin over ezetimibe.” That’s right, the use of inexpensive, non-prescription niacin (vitamin B) was clearly better that Zetia. It’s worth noting that the study wasn’t measuring the rates of heart attack; instead, it measured the thickness of the common carotid artery as a surrogate, on the assumption that thickening of the arteries leads to heart attacks. But there were also more heart attacks, and more deaths, in the patients on Zetia – not enough to reach statistical significance, but perhaps that was only because of the small number of subjects. The trial was halted early when it became clear that niacin worked better, and it might be harmful to the subjects to continue giving them Zetia (ezetimibe) instead.

I found another NEJM article from April 2008 that showed that combining Zetia with statins was no better than statins alone.

So what did Merck have to say? Astonishingly (or not?), they are continuing to promote Zetia aggressively, and they issued this statement a few days ago: “"The results of the small ARBITER 6 study do not, in any way, change our view of Zetia and Vytorin as effective medicines for fighting high LDL cholesterol," said Peter S. Kim, Ph.D., president, Merck Research Laboratories. “We encourage patients to continue taking their medication as prescribed by their physicians.” Really? The results don't change his view in any way?

This latest news comes just 3 months after Merck and Schering-Plough agreed to pay $41.5 million to settle a lawsuit that accused them of sitting on unfavorable results about Zetia and Vytorin for two years. That lawsuit was based on results released in January 2008, describing a study that ended two years earlier.

This is the kind of greedy, evidence-be-damned behavior that encourages conspiracy theorists to make wild accusations about drug companies. The problem is, sometimes their accusations are true, even if the drug companies do produce many beneficial products. One thing the U.S. should do is put a stop to direct-to-consumer marketing of drugs, ads like the one below, which claims that Vytorin is better than statins alone. Note how it doesn’t directly claim that Vytorin will reduce your risk of heart attacks, but it cleverly implies that it will:



Now that is insidious. We should never have allowed direct marketing of drugs, and we can still put a stop to it.