Smooth Pebbles

Measles is back, and it's because your kids aren't vaccinated: Scientific American Blog

This one's causing a dust-up over at the Scientific American's "60-Second Science" blog

Measles is back, and it's because your kids aren't vaccinated
David Biello

If you didn't vaccinate your kids, you too could find yourself partly responsible for the resurgence of a disease thought eliminated in 2000.

Measles—a highly contagious disease-causing virus—is making a comeback in the U.S., thanks to parents fears over vaccines. Fifteen children under 20, including four babies, have been hospitalized and 131 sickened by the red splotches since the beginning of this year in 15 states and the District of Columbia, according to the U.S. Centers for Disease Control.

The CDC had announced in 2000 that the disease was eliminated in the U.S. thanks to a vaccine that can completely control it. But fears of autism have led some parents to forego this treatment and at least 63 of the sickened children were unvaccinated.

Peditrician Pauline Filipek of the University of California, Irvine told ScientificAmerican.com this spring that parents who don't vaccinate their kids are putting the tykes at risk of long-forgotten diseases, like measles. What they're not doing: preventing autism.

"Many, if not most, of the younger siblings [of autistic children] never have any vaccinations," says Filipek, who believes that autism is not caused by vaccines. "And they are as autistic as the day is long."

Catch more at:

Measles is back, and it's because your kids aren't vaccinated: Scientific American Blog

Tags: measles, vaccines, autism, health, epidemiology, Scientific American

A Fine Flap Over Pharma Influence on Medical Reporting

A couple weeks ago Slate ran a piece asking "Are doctors shilling for drug companies on public radio?", which I took brief note of in a previous post.

Now I've written up a longer reaction (actually a reaction to the reaction to the Slate story) for Columbia Journalism Review's "Observatory" blog, which covers science journalism. The gist:

If journalists ... want the information they present to the public to be taken as credible, they need to err on the side of transparency, presenting not only the voices but also the relevant financial interests of the experts they feature. Failing to do so only damages message and messenger alike. But in the wake of the repeated scandals about drug-company concealment of drug-trial data, it’s strange that I have to spell this out.

As expected, this generated some blowback from people less worried than I about the trust problems created by failure to disclose potential conflicts of interest in experts quoted in medical stories. I expected, for instance, to be accused of trying to end all links between doctors and drug and device developers or to shush doctors with such ties from public discussion, and I was, at least indirectly. Yet as I noted in the comments column:

I am not proposing that doctors or researchers with financial ties to industry be excluded from press stories or public discussion of medicine. That would be destructive. I am arguing that the relevant financial ties of quoted experts should be disclosed so that the public can consider those in considering their positions. Butterworth appears averse to this idea. But it's one that the leading medical journals have embraced, and it seems to have raised rather than eroded faith in the studies published in those journals.

The issue of industry influence on medical opinion is a rich one; may this little squabble shine a bit of light on it. Check it out at "To Disclose or Not to Disclose."

Technorati Tags: Brownlee, Jeanne Lenzer, journalism, Lilly, pharma, Slate

Did Antidepressants Depress Japan?

The Kirsch study published a few weeks ago has stirred much discussion of the placebo power of antidepressants (or is it the antidepressant power of placebos?); it's clear that the act of taking a pill that you expect to help you often does help you.

But can the availability of a pill meant for depression make you feel (or think of yourself as) depressed? That's the question behind another part of the drug debate, regarding whether the drug industry encourages us to medicalize ordinary experience.

In pondering these things I ran across this fascinating New York Times >article from 2004, "Did Antidepressants Depress Japan," about the introduction of the concept of depression in Japan beginning in the late 1990s. Before then, the article asserts, Japanese culture concerned itself little with depression outside of professional psychiatry and medicine. But when drug companies started pushing antidepressants beginning in 1999, a cultural awareness of depression grew -- and with it, the number of people who considered themselves depressed.

All arguments about the reality of severe depression aside, this says remarkable things about how cultures define -- and individuals experience (or not) -- a state of ill-being. The story is excerpted below the break, or read the whole thing here.

Drugs in Your Drinking Water

This one's getting a lot of play: There are traceable levels of prescription drugs in many public water supplies.

The Times includes the AP story, which is both long and good. I bumped into it first on the Wall Street Journal Health Blog:

Health Blog : Big Pharma is in the Water Big Pharma is in the Water Posted by Sarah Rubenstein

It's not so expensive to get pharmaceuticals after all: Just drink water.

An investigation by the Associated Press found trace amounts of scads of drugs in drinking-water supplies around the country. For a list of what was found in the watersheds of 28 metro areas, click here. Among the water's offerings were antibiotics, anti-convulsants, mood stabilizers and sex hormones. There were traces of sedatives in water serving the city that never sleeps.

The drugs get in the water via our own waste.

Clive Thompson looked at the ability to trace drugs in water supplies -- a "community urinalysis," as he called it -- in a brief item in the NY Times Magazine's "Ideas" issue.

Do these drugs have any effects? The drug content is pretty low, but as one scientist points out in the Times story, these drugs are meant to have effects at low doses. As the Times story notes in signing off:

''We know we are being exposed to other people's drugs through our drinking water, and that can't be good,'' says Dr. David Carpenter, who directs the Institute for Health and the Environment of the State University of New York at Albany.

From Wall St Journal: "Employers Pick Workers’ Pockets on Health Insurance"

Why aren't your wages going up? Maybe because you're the one paying for the health insurance your boss is supposedly paying for.

That's the gist of a new commentary in JAMA, which I'd missed till the Health Blog at the Wall Street Journal brought it to my attention: "Who Really Pays for Health Care?," the recent commentary by bioethicist Ezekiel Emanuel and economist Victor Fuchs,  argues that employer-provided health care is not as valuable a benefit as it is cracked up to be because employers basically pull it from pay raises employees would get otherwise. The result, the article says, is that you get flat or declining real wages, which is exactly what many workers have received the last decade or two. Thus along with management taking an increasing share of company income, rising health premiums are a main reason wages have been flat.

"Why does this myth matter?" ask the WSJ Health Blog --

Emanuel says that people’s belief that they’re getting a free benefit is a big reason why they are resistant to a major overhaul of the health care system. But employer-based health care is economically inefficient, Emanuel tells the Health Blog. A substantial chunk of the money goes to pay for things that have nothing to do with health care, such as underwriting, sales and marketing.

Uwe Reinhardt, a Princeton health economist, likens the employer-based health insurance to a garden party where a very slick pickpocket steals your wallet and then buys you roses and chocolates. “You’d be very grateful,” Reinhardt tells the Health Blog. Employers “are pickpockets who very skillfully take it out of your paycheck. Then they say, ‘Now genuflect.’ ”

The JAMA article is here, behind a paywall; the WSJ blog piece is here.

Tags: heath_insurance, health_care

"No more scavenger hunts," says Nature of SSRI-placebo study

A quick heads-up: Nature weighs in on the flap over the Kirsch SSRI study that found antidepressants no more effective than placebo. I've given a lot of attention to the placebo issue. Nature stresses another point: That the Kirsch study underscores the need for clinical trial data to be public. At present it is not, as the drug companies have persuaded the FDA that releasing all trial data might reveal trade secrets. Nature argues -- as have many -- that what's being hidden is not proprietary trade secrets but information vital to public health:

No more scavenger hunts

The recent media flap over antidepressants highlights the need for data to be transparent %u2014 and for a mandatory database of all clinical trials.

It was not the media's finest hour. When a study was released last week challenging the effectiveness of several popular antidepressant drugs, some news outlets, particularly in the United Kingdom, responded with headlines blaring 'the drugs don't work' %u2014 even though the drugs often do work. Yes, the study showed that the drugs often performed no better than a placebo. But what many of the media missed was that the placebo effect can be remarkably strong in psychological and neurological disorders, especially in mild depression. Doctors scrambled to assure patients that they should not abandon treatment.

Almost buried in the hubbub, though, was a more important story. To access the data needed for this study %u2014 a meta-analysis of 35 clinical trials %u2014 the researchers had to file a Freedom of Information Act request with the US Food and Drug Administration. And the information they finally received was incomplete: crucial data were missing for several studies that failed to find a significant benefit of the drug compared with the placebo. The missing data limited the analysis, and forced the researchers to abandon their investigation of two drugs altogether.

Such data chaos has become all too familiar in the world of clinical trials. And that fact, combined with recent scandals about antidepressants, diabetes drugs and cholesterol medications, has spurred an outcry to make clinical-trial registries mandatory.

More at the Nature website.

Slippery Ground: SSRI-Study Fallout Spreads

photo © iStockPhoto/AnikaSalsera

The ripples from the PLOS Medicine antidepressants-don't-work study by Kirsch et alia, which I covered below, just keep spreading. Those who want to follow it can do well by visiting or bookmarking this search I did (an ingenious Google News search for "Kirsch SSRI"). It seems to be tracking the press coverage pretty well. Note that the heavier and higher-profile coverage comes mainly from UK. As far as I can tell, none of the top 3 or 4 US papers have yet covered it.

This blog search should help as well.

Some of the more notable responses since yesterday:

Science weighs in. The Times Online (UK), with a hat top to SSRI as antidepressant, opines that "If it's all in the mind, fine."

The searches above will find more.

As many have noted, that antidepressants barely best placebo is not big big news; other studies have found that the drugs barely best placebo. But the starkness of Kirsch's "no effect" finding -- and the paper's assertion that there seems no reason to prescribe except for the deeply, dangerously depressed -- seems to have sparked a deeper examination of this issue than previous studies have. The anguish you see in many posts and comments, especially by doctors and depression sufferers, is that of an entire discipline and patient base having to confront the profound ambivalence of the data and the plain wierdness of the way in which psychiatric drugs work. Many drugs depend heavily on a placebo effect, of course. But the mind-body mystery raised by placebo effects in antidepressants presses itself more insistently, since "the body" doesn't seem so much in play.

This is slippery territory; not surprising that many are having trouble finding their footing.

Drug Bust Paper Blowback: Responses and implications to the Kirsch antidepressant study

The Kirsch study I wrote about a couple days ago, which found that antidepressants seem to have no more effect than placebo, has generated a wide variety of reactions in the blogosphere and press. Several things of note here:

1) In a pattern I've noticed repeatedly of late about other types of stories about things in the U.S., this story got much more attention in the British press than it did here in the U.S. (The authors were from the UK, but the paper was published in a U.S.-based journal, and antidepressant use is a huge issue in the U.S.)

2) The responses -- some by bloggers, writers, and other critics, some by doctors -- are a fascinating mix of hard-line rhetoric (from both sides) and more nuanced points about the difficulties of drawing definite conclusions from meta-analyses that are by their nature heavily statistical. Pointers to a few are below. Most intriguing is the exchange on the the PLOS Medicine site itself (where the paper was published), which involves mainly doctors. My thoughts on that are at bottom, below a far-from-complete annotated list of responses here and there

My thoughts on that are at bottom, below this shorter list of worthwhile responses:

Ben Goldacre, who writes the column "Bad Science" for the UK's Guardian, points out some of the more troubling implications of this study.

The Washington Post's Kevin Drum drew brief notice to it. His post is notable mainly for the lively and long string of reader comments it produced -- an exchange that suggests reader interest in the U.S. is perhaps more intense than editorial interest.

The journalist/blogger James Hrynshyn, of North Carolina, wrote a thoughtful post on his blog at Seed, as did Jonah Lehrer at his Seed blog The Frontal Cortex.

The Socratic Gadfly takes a shot at some of the study's limitations.

PsyBlog takes a measured, educational approach.

Among posts noting the study's limitations, the most damning I came across is perhaps that of Henry Gee, an editor at Nature. Gee is one of several writers who point out that a major caveat of this study is that it is limited to patients taking the drugs over only about 8 weeks or less, thus missing anyone who would have benefited from taking the drug for a longer period. He finds this completely damning:

This will affect the conclusions of the study, as every doctor (and patient) knows, antidepressants are drugs for the long haul. It takes weeks for them to have much effect, and this study seems to have had a cutoff before any such effect could be manifested. The results of this study are therefore compromised, and people who have been distressed by it have, I think, been misled....

So, shame on PLoS Medicine for touting what looks like a sensationalist story that grabs headlines on the distress of others; and shame (as usual) on the hog-whimperingly low standards of science news editing and reporting that have failed to pick up on this important flaw.

I think Gee goes too far. SSRIs do sometimes take weeks to kick in; but in most cases, they kick in inside of 8 weeks -- and some users get an initial lift then that then fades. So this time limit (created primarily by the drug companies who nevertheless repeatedly claimed to find high benefit during that period) strikes me as one of several limitations on the study rather than a fatal flaw. And the criticism ignores the fact that the drug companies repeatedly claimed to find a significant therapeutic effect inside that 6- to 8-week window. I'm not sure why we're supposed to accept on one hand that the drugs have proven themselves effective within an 8-week window ... but reject a study that finds they were not effective in that window because the drugs supposedly aren't effective till later. If they're not effective till later, how did the drug companies ever find an effect inside of 6 or 8 weeks? Strange logical territory.

As Gee notes, however, quite a few people, many of them doctors, lodged similar critiques at the PLOS Medicine "responses" site, as well as other objections more substantive. This is the juiciest reading on the paper I've found -- well worth perusing to get a sense of the debate and an education in the problems with meta-analyses, especially as applied to placebo effects. It's a serious debate even among doctors.

One doctor, for instance, says the study is a needed wake-up call to doctors who have been essentially falling for a placebo effect themselves; another doctor argues that "dozens of clinicals trials plus decades of clinical practice plus millions of content patients can't be that wrong. Whatever the bias in whatever the study, common sense clearly says: the sum of the parts attesting antidepressants efficacy blatantly outnumbers the evidence showing the opposite. The use of these antidepressants is now deeply rooted and well-established in medical society worldwide, it's safe, it works, and there's no shadow of doubt about it. Instead, this study insists in a different truth."

Overall, the discussion among doctors on the PLOS Medicine Responses page is The meta-analysis is a strange animal, in some ways more reliable than individual studies, since it looks at many; but problemmatic for the same reason, because it has to use some sometimes sophisticated (even obscure) statistical methods to extract (hopefully) reliable, consistent information from studies that may differ in structure and method.

How this all sugars out (no pun intended), I'm not quite sure myself. Two paradoxes jump to my mind, however. One is that the drug companies, with nods from the FDA, dug much of this hole themselves by structuring studies and often filtering results in ways designed to highlight advantages and minimize disadvantages. The short timespan of these studies is an example: When psych drugs work, they generally work their best early on, and the 6- or 8-week drug trial took advantage of that. That's just one way in which the drug companies created a clinical trial system that pretty much begs for harsh criticism; it worked for a while, but now it has cast the industry's credibility into question, making it extremely difficult to ferret out what really works and what does not.

The other paradox, even more painful, is that many, many people, both clinicians and patients, have found these drugs genuinely helpful. In a highly limited but important sense, whether these drugs help through biological mechanisms or through placebo effect is almost a moot point for those they help: They've given quite a few people the buoyancy to float atop life again instead of getting tugged under. The question I tried to raise in my earlier post remains: If these drugs lack a genuine biological effect (or if they have that effect only for a very few) but work well as placebos, how the heck do we replace them?

*update later 2/28/08: Another interesting thread of comments from doctors is this one at the Herald (the one from the UK).

The Drug Bust II: Big New Study Shows Antidepressants Have No Significant Effect

[This is a revised, expanded version of the original heads-up I put up last night.]

A large new meta-analysis of SSRI antidepressant trials concludes that the drugs have essentially no therapeutic effect at all. The study, in PLOS Medicine today, comes on the heels of another study published a few weeks ago (I blogged on it here) showing that SSRIs have little therapeutic effect if you include the (unflattering) clinical trials the industry had previously hidden.

The PLOS study is a meta-analysis of 47 clinical trials that account for almost all full data on clinical trials of SSRIs such as Prozac and Paxil. It showed that "compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression" -- and that (as the editors write) "the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective."

If this holds up, this is a huge development. Many people who take SSRIs say they help them, and they know they have a physiological effect because of subtle or more blatant side-effects -- everything from itching, dry mouth, and sexual problems to slight tingling or numbing of the lips or a sort of spacey feel. Those things often kick in within a few days. Then, for those who do feel better, the improvement follows 3 to 6 weeks later. But is the improvement a placebo effect and/or the result of attentive treatment via psychotherapy? The association of the felt physiological changes with improvement makes it seem clear the drug helps. This study appears to argue -- adamantly -- otherwise -- or, at best, that SSRIs work because the drug's felt physiological side-effects strengthen the placebo effect.

This is a profoundly consequential finding. Millions of people take these drugs, spending billions of dollars to do so. And many feel they are helpful. Are they being hoodwinked? Fooling themselves? All of the above? The finding that the drugs have no statistically significant effect is not necessarily the same as saying they don't help anyone. It is saying that the drugs help about the same number of people as placebos do. And placebos help a fair number -- generally between 30 and 50 percent in antidepressant trials. What's producing the placebo effect? The power of expectancy comes into play here, as does the value of even a little bit of official attention to one's despair. Back in 1963, Claude Levi-Strauss proposed some mechanisms behind the magic of placebo:

First, the sorcerer’s belief in the effectiveness of his techniques; second, the patient’s or victim’s belief in the sorcerer’s power; and, finally, the faith and expectations of the group, which constantly acts as a sort of gravitational field within which the relationship between sorcerer and bewitched is located and defined.

Whatever the mechanism, it's clear that placebos have an effect. If SSRIs are helping some people -- and they are, though apparently no more than placebo does -- then they may be helping via a placebo effect. THis is valuable, of course. But is it worth the side-effects (and incredible expense)? An SSRI makes a pricey placebo whether from a medical or an economic perspective. But it carries the placebo's effectiveness, which in depression seems to run about a third to a half.

Be nice, of course, if doctors could just prescribe placebos. But hoodwinking patients -- telling the they're getting a drug when they're getting a placebo -- violates informed consent, at least if the patient asks very many questions. A few years back, a NY Times Magazine article explored just this question -- If placebos work so well, why can't doctors use them?

This is not to suggest we should keep prescribing physiologically powerful, side-effect-heavy drugs just for a placebo effect. That's not conscionable. But most therapists feel it's clear that SSRIs, precisely BECAUSE they were so hyped and create such positive expectancy, have provided a tool that has helped many patients feel better and saved quite a few lives. What do we replace that with? This won't be an easy question to answer.

It'll be interesting to see how this plays out.

Some of the editors' summary is below. The paper itself is here, and free.

What Did the Researchers Do and Find?

The researchers obtained data on all the clinical trials submitted to the FDA for the licensing of fluoxetine, venlafaxine, nefazodone, and paroxetine. They then used meta-analytic techniques to investigate whether the initial severity of depression affected the HRSD improvement scores for the drug and placebo groups in these trials. They confirmed first that the overall effect of these new generation of antidepressants was below the recommended criteria for clinical significance. Then they showed that there was virtually no difference in the improvement scores for drug and placebo in patients with moderate depression and only a small and clinically insignificant difference among patients with very severe depression. The difference in improvement between the antidepressant and placebo reached clinical significance, however, in patients with initial HRSD scores of more than 28—that is, in the most severely depressed patients. Additional analyses indicated that the apparent clinical effectiveness of the antidepressants among these most severely depressed patients reflected a decreased responsiveness to placebo rather than an increased responsiveness to antidepressants.

What Do These Findings Mean?

These findings suggest that, compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression, but show significant effects only in the most severely depressed patients. The findings also show that the effect for these patients seems to be due to decreased responsiveness to placebo, rather than increased responsiveness to medication. Given these results, the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective. In addition, the finding that extremely depressed patients are less responsive to placebo than less severely depressed patients but have similar responses to antidepressants is a potentially important insight into how patients with depression respond to antidepressants and placebos that should be investigated further.

Meta-Analysis Shows Antidepressants Have No Significant Effects

I've not had time to thoroughly read this yet. But on the heels of another study published a few weeks ago (I blogged on it here) showing that SSRIs have little therapeutic effect if you include the (unflattering) clinical trials the industry had previously hidden, PLOS Medicine now publishes a larger study -- a meta-analysis of all available data on clinical trials of SSRIs -- that shows that "compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression" -- and that (as the editors write) "the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective."

If this holds up, this is a huge development indeed. Many people who take SSRIs say they help them, and they know they have a physiological effect because of subtle or more blatant side-effects -- everything from itching, dry mouth, and sexual problems to slight tingling or numbing of the lips or a sort of spacey feel. Those things often kick in within a few days. Then, for those who do feel better, the improvement follows 3 to 6 weeks later. But is the improvement a placebo effect and/or the result of attentive treatment via psychotherapy? The association of the felt physiological changes with improvement makes it seem clear the drug helps. This study appears to argue -- adamantly -- otherwise -- or, at best, that SSRIs work because the drug's felt physiological side-effects strengthen the placebo effect.

It'll be interesting to see how this plays out.

Some of the editors' summary is below. The paper itself is here, and free.

These findings suggest that, compared with placebo, the new-generation antidepressants do not produce clinically significant improvements in depression in patients who initially have moderate or even very severe depression, but show significant effects only in the most severely depressed patients. The findings also show that the effect for these patients seems to be due to decreased responsiveness to placebo, rather than increased responsiveness to medication. Given these results, the researchers conclude that there is little reason to prescribe new-generation antidepressant medications to any but the most severely depressed patients unless alternative treatments have been ineffective. In addition, the finding that extremely depressed patients are less responsive to placebo than less severely depressed patients but have similar responses to antidepressants is a potentially important insight into how patients with depression respond to antidepressants and placebos that should be investigated further.