Smooth Pebbles

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

Slate asks: Are MDs shilling for pharma ... on public radio?

In a nifty bit of reporting, veteran health reporters Shannon Brownlee and Jeanne Lenzer revealed in "Stealth Marketers," a story on Slate, that a "Prozac Nation: Revisited," a radio piece on antidepressants and suicide that ran on many public radio stations recently, "featured four prestigious medical experts discussing the controversial link between antidepressants and suicide" who all reportedly have financial ties to the makers of antidepressants -- as does the radio series, known as "The Infinite Mind," that produced the show.

As the story notes, the extent of the financial ties are unknown because those involved won't reveal them. Still, Brownlee and Lenzer argue, the show in question, "Prozac Nation: Revisited," "may stand in a class by itself for concealing bias." (Then follows a troubling paragraph outlining the conflicts of interest involved.)

is that undisclosed financial conflicts of interest among media sources seem to be popping up all over the place these days. Some experts who appear independent are, in fact, serving as stealth marketers for the drug and biotech industries, and reporters either don't know about their sources' conflicts of interests, or they fail to disclose them to the public.

The story goes on to list several examples that point out out badly such influence compromises our ability to trust many news reports.

Conflicts of interest abound even in unexpected places. A recent survey of academic medical centers published in the Journal of the American Medical Association found that 60 percent of academic department chairs have personal ties to industry—serving as consultants, board members, or paid speakers, while two-thirds of the academic departments had institutional ties to industry. Such ties can be extremely lucrative. And according to these articles in the medical literature, researchers who receive funding from drug and medical-device manufacturers are up to 3.5 times as likely to conclude their study drug or medical device works than are researchers without such funding.

Brownlee and Lenzer put some focus on journalists as well. They cite one study of 544 science stories from top outlets (from 4/06 to 4/08) that checked whether the journalists quoted an independent expert and/or made some attempt to report researchers' potential conflicts of interest. "Half the stories failed to meet this requirement."

This doesn't surprise me. This story prompted a very lively exchange on a science writer listserve I participate in. That exchange confirmed that there's wide variation in how consistently researchers (and the institutions they work for) reveal their funding sources and in how often or consistently journalists ASK their sources about their funding resources. Science journalism is a field ever in tension between an excitement over the scientific discoveries in question and the more hard-nosed mission to vet the reported results and examine science as a social, political, and commercial activity. Most science journalists are ever balancing interest and enthusiasm with skepticism and critical thinking. They should do so conscientiously, of course; that's their job.

As Brownlee and Lenzer note, it's impossible to know at this point a) how much money some of the people involved actually got from drug companies and b) of course, how much it influenced them. But it's well-establshed that trust in scientific results -- especially in the much-tainted arena of psychiatric drugs -- depends on a transparency in funding that has been sorely lacking. This sort of thing -- undisclosed funding from pharm interest of a show that purports to EXAMINE the controversy over antidepressants and suicide -- can't help matters.

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

Psychiatry Handbook Linked to Drug Industry

From Well, Tara Parker-Hope's health blog at the NY Times:

More than half of the task force members who will oversee the next edition of the American Psychiatric Association’s most important diagnostic handbook have ties to the drug industry, reports a consumer watchdog group.

The Web site for Integrity in Science, a project of the Center for Science in the Public Interest, highlights the link between the drug industry and the all-important psychiatric manual, called the Diagnostic and Statistical Manual of Mental Disorders. The handbook is the most-used guide for diagnosing mental disorders in the United States. The guide has gone through several revisions since it was first published, and the next version will be the D.S.M.-V, to be published in 2012.

The American Psychiatric Association’s Web site has posted the financial disclosure of most of the the 28 task force members who will oversee the revision of the D.S.M.

It’s not the first time the D.S.M. has been linked to the drug industry. Tufts University researchers in 2006 reported that 95 — or 56 percent — of 170 experts who worked on the 1994 edition of the manual had at least one monetary relationship with a drug maker in the years from 1989 to 2004. The percentage was higher — 100 percent in some cases — for experts who worked on sections of the manual devoted to severe mental illnesses, like schizophrenia, the study found.

From Wall Street Journal: Rich, Not Poor, Are Crowding Emergency Rooms

It seems that the rise in ER use comes not from the poor uninsured but from a much more affluent income sector.

From the Wall St. Journal Health Blog:

Rich, Not Poor, Are Crowding Emergency Rooms:

This is the conventional wisdom: Priced out of health insurance, ever more Americans are crowding into emergency rooms because they can’t afford a trip to the doctor.

Yes, ERs are getting busier. But it’s not because of poor people or the uninsured, according to this analysis in the Annals of Emergency Medicine.

The study is based on national surveys conducted between 1996 and 2004. During that time, overall visits to the ER increased by 26% — but a disproportionate share of the growth came from those whose incomes put them at more than four times the poverty level, and who typically get their care at a doctor’s office. The percentage of uninsured ER patients remained flat, at roughly 15%.

The researchers did the study because the conventional wisdom didn’t seem to match the on-the-ground experience of ER docs. Instead, they saw a rise in ER traffic across the demographic spectrum, said Jonathan A. Showstack a study author based UCSF’s Institute for Health Policy Studies.

More at the Wall Street Journal Health Blog

Roundup of notables: The Certainty Epidemic, Dog Head Poetry, et alia

Some great stuff I've come across, lack time to blog on, but would hate for you to miss:

In On being certain, neurologist and novelist Robert Burton, who writes a column at Slate Salon, looks at the science of what makes us feel certain about things -- even when we're dead wrong about them. His book on the subject, which I read in advance copy a while back, is fascinating fun reading. The most startling (and disorienting) finding he describes is that, from a neurocognitive point of view, our feeling of certainty about things we're wrong about is pretty much indistinguishable from our certainty about things we're right about. Not something to think about when you're in the middle of an argument -- or maybe it is, because maybe it's the other guy who's certain but wrong. Hard to know!

Why are drug costs are going up?"Because they can," say the folks at Managed Care Matters

From Cognitive Daily, When we see a brain "light up," [most of] our brains shut off. How we are suckers for brain-scan pictures.

Mind Hacks drew attention to the wonderful poem below by Wislawa Szymborska, which is a reaction to a not-so-wonderful film, from 40s Soviet science, of a decapitated dog head that (supplied with blood) still reacts to many stimuli. Grim film, beautiful poem. Excellent commentary and links at Mind Hacks.

The Experiment
by Wisława Szymborska

As a short subject before the main feature -
in which the actors did their best
to make me cry and even laugh -
we were shown an interesting experiment
involving a head.

The head
a minute earlier was still attached to...
but now it was cut off.
Everyone could see that it didn't have a body.
The tubes dangling from the neck hooked it up to a machine
that kept its blood circulating.
The head
was doing just fine.

Without showing pain or even surprise,
it followed a moving flashlight with its eyes.
It pricked up its ears at the sound of a bell.
Its moist nose could tell
the smell of bacon from odorless oblivion,
and licking its chops with evident relish
it salivated its salute to physiology.

A dog's faithful head,
a dog's friendly head
squinted its eyes when stroked,
convinced that it was still part of a whole
that crooks its back if patted
and wags its tail.

I thought about happiness and was frightened.
For if that's all life is about,
the head
was happy.

We all seem convinced we're right about politics, religion or science these days. What makes us so sure of ourselves?

News

Feb. 29, 2008 | Certainty is everywhere. Fundamentalism is in full bloom. Legions of authorities cloaked in total conviction tell us why we should invade country X, ban "The Adventures of Huckleberry Finn" in schools, eat stewed tomatoes, how much brain damage is necessary to justify a plea of diminished capacity, the precise moment when a sperm and an egg must be treated as a human being, and why the stock market will revert to historical returns. A public change of mind is national news.

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).

What's Under the Rock: Full Data Shows SSRIs Barely Best Placebo

I've written before, both here in Smooth Pebbles and in print, about how FDA policy and drug company practices have allowed drug makers to publish (and the FDA to base approval on) only the most flattering drug-trial results while keeping less-flattering studies in the drawer. Today a New England Journal of Medicine report shows how things change when you include the results from the drawer: The effectiveness of many SSRIs dives to near placebo-level. This despite that the companies design and conduct most of these trials in a way calculated to produce positive results.

When I wrote on this a couple years ago, UCSF professor and Journal of the American Medical Association editor Drummond Rennie, told me, "If a company does ten trials on a drug and two show it helps but eight show it works no better than Rice Krispies, I'm not exactly getting a scientific view if they publish only the two positive studies.... How can we practice sophisticated medicine if the drug companies are hiding their results? That's not science. That's marketing."

The problem remains. Depressing. I recommend a good run.

Benedict Carey has a good story on it at the Times. And here's the meat of the abstract from the NEJM:

Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 study viewed as positive was not published. Studies viewed by the FDA as having negative or questionable results were, with 3 exceptions, either not published (22 studies) or published in a way that, in our opinion, conveyed a positive outcome (11 studies). According to the published literature, it appeared that 94% of the trials conducted were positive. By contrast, the FDA analysis showed that 51% were positive. Separate meta-analyses of the FDA and journal data sets showed that the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall.