Smooth Pebbles

Rumblings and worries about Obama's FDA options

As Obama solidifies his teams on science, education, and environment, attention -- and not a little worry from the drug industry -- is turning toward his hunt for a new FDA commissioner. The WSJ Health Blog reports that the FDA Commissioner Coalition, which is heavy with groups financed by the drug industry, appears increasingly concerned that Obama will appoint outspoken critics of drugmakers and the FDA, such as Cleveland Clinic cardiologist Steven Nissen or Baltimore health commissioner Joshua Sharfstein, who is heading Obama's FDA assessment team.

While the coalition prominently talks about the need for an FDA chief who can withstand some kinds of outside pressure, there’s no mention of an ability to withstand pressure from industry. Yet undue industry influence is at the heart of concerns from both parties in both houses of Congress, from FDA officials, from doctors and many medical researchers.

A copy of the Coalition's letter (to Secretary of Health Designate Tom Daschle) can be found at Pharmalot.

Antidepressant toll on sex worse than thought

As time goes on, it seems the benefits offered by modern antidepressants seem to drop while the downsides seem to expand. A story in today's Boston Globe -- excerpted below -- suggests that up to half of people who take SSRIs suffer significant sexual side-effects.

Sexual "numbness." Lack of libido. Arousal that stalls.

Such sexual symptoms have long been known side effects of the popular Prozac class of antidepressants, but a growing body of research suggests that they are far more common than previously thought, perhaps affecting half or more of patients....

Current warnings on the labels of selective serotonin reuptake inhibitors, or SSRIs, cite early studies in which the prevalence of sexual side effects was lower: 4 percent for Prozac, for example, and ranging from 0 to 28 percent for Paxil.

But more recent studies, in which patients were more likely to be asked about specific sexual side effects and thus more likely to report them, suggest that the ballpark range of those affected by SSRIs is between 30 percent and 50 percent, said researchers including Dr. Richard Balon, a psychiatry professor at Wayne State University who studies the symptoms.

That would translate into millions of affected sex lives among the estimated 1 in 8 American adults who have tried these antidepressants in the past decade or so. Some studies have found the range still higher.

Why the rising costs and flattening benefits? Among other things, it's becoming clear, as the wide use of these drugs runs through time, that many drugs prove less effective and more troublesome when prescribed to sick people (many of whom have other health problems and take other drugs) than when used in clinical trials, which usually take care to use patients with fewer problems. It doesn't help that drug companies often fail to report or publish their less flattering results -- and that they didn't investigate the sexual side-effects more aggressively during the trials.

In this case the differences between side effects in trials and in real life is startling, both for the scale of the difference and, of course, for the high-impact nature of sexual side-effects. As Aline Zoldbrod, a Lexington psychologist and sex therapist quoted in the Globe article notes:

"This is such an upsetting issue. There are people for whom SSRIs are really life-saving, I think, but the idea that someone would have to choose between getting out of the darkness of depression and having a good sex life is horrible."

Hat tip: The ever-watchful Furious Seasons

More pebbles: items I (wanted to but) didn't get to

Boing boing spots Virgin Mary in MRI

Bird flu round-up, from Great Beyond touches a few stories reporting some unsettling human deaths from bird flu. I think people are scared to cover bird flu these days: There was so much about it 2-3 years ago, then the epidemic didn't come (we're so impatient!), and now a lot of journalists feel they were out shouting wolf. Maybe wolf is still out there.

Jonah Lehrer on Governor "Show Me the Money" Blagojevich, greed, and a version of the ultimatum game called -- I love this -- the dictator game. "When the dictator cannot see the responder - they are isolated - the dictator begins acting with the kind of unfettered greed expected by economists." (Special bonus: Andrew Sullivan's Quote of the Day is also about Blagojevich.)

Daniel Carlat on "It's not about Goodwin. It's about disclosure."

The Extensible Obama: How the POTUS-elect will use web tools to power his next presidency. From MIT's Technology Review.

Survey the Slippery Slope of Cognitive Enhancement

There's been a lot of buzz on the Net* about the Nature commentary on cognitive enhancement I blogged about yesterday, in which I noted that you need only think about coffee to realize what a slippery slope the cog enhancement issue presents.

If you want to experience first-hand just how slippery, take this survey, which reader Michael Lanthier kindly drew my attention to. It starts with a question about coffee and pulls you inexorably, um, downhill from there.

It's hard to take that survey without concluding the issue of enhancement offers no bright lines. if someone knows of a rigorous argument to the contrary, please chime in.

*NB this one from a chess site.

Pebble Collection

A few that rolled away with the tide ...

PsychCentral not impressed with Outliers

Look Who's in the Operating Room

From the Deutches Museum, tractors as core culture

And from Boing Boing, a Studley tool chest. And I was all excited to get my little canvas toolbag yesterday.

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Technorati Tags:
Malcolm Gladwell, Medtronics, Deutsches Museum, Wildlife

Pebble collection

A few that keep slipping out of my hands:

It's All in Your Head -- Sally Satel, in the Wall St Journal, on a recent study showing about half of American doctors use placebos in practice. Satel, who wrote an interesting piece NY Times Magazine piece a while back on her search for a kidney donor, also has an interesting piece on a Senate bill designed to allow states to reward organ donors.

PhamaLot on Pharma's Influence on the Media.

On a related note, a Columbia Journalism Review piece on Science Reporting by Press Release

Andrew Sullivan on The AP's Cowardice.

Hospitals Fail to Take Basic Steps to Stop MRSA’s Spread, from the Wall St Journal's Health Blog. MRSA -- the antiobiotic resistant germ -- killed my uncle on October 1. Man had survived being shot down and crashing in Vietnam, but was no match for MRSA.

Boing boing on awareness after decapitation

Mouse bites snake to death. I also watched a video where a wild pig turned tables on a lioness and butted her till she ran away ... but I can't find it now.

I better stop there.

Technorati Tags:
Sally Satel, Big Pharma, Columbia Journalism Review

Jerome Kagan on The Meaning of Psychological Abnormality

Jerome Kagan, a highly prominent developmental psychologist, weighs in the Dana Foundation's Cerebrum on the roots of the skyrocketing rates of diagnosis of childhood bipolar disorder, autism, and ADHD. "[it] is important ... to ask," he writes

whether this troubling [increase] reflects a true rise in mental illness or is the result of changes in the definition of childhood psychiatric disorders. The latter explanation is likely because the concept of psychopathology is ambiguous, and physicians have considerable latitude when they classify a child as mentally ill. Because a diagnosis of ADHD, bipolar disorder, or autism allows parents to obtain special educational and therapeutic resources that would not be forthcoming if the child is called mentally retarded, incorrigible, or uninterested in academic progress, doctors are motivated to please the distraught parents who want to help their child.

As Kagan notes, a disorder is often declared mainly because the child is disorderly, rather than really sick. If the parents think the child needs help, the doctor usually goes along - and the solution is far more often pharmacological than family-based. This comes into play most seriously in the accelerating diagnosis of bipolar disorder in children in the U.S.

Equally serious, if not more so, is the dramatic rise (more than 40 percent in the past decade) in diagnoses of bipolar disorder in young children, based on parental complaints of chronic levels of extreme disobedience, impulsive bursts of aggression, and an inability to control emotion. These symptoms can in part be the product of permissive socialization practices by parents who are reluctant to induce anxiety or guilt in children placed in surrogate care because both parents are working. Most children classified as bipolar do not display the cycles of manic excitement and depression that define this disease in adults. Thus it is a diagnostic error to call children who cannot regulate their moods “bipolar” simply because they seem to have a single feature in common with the adult disorder: uncontrolled behavior. I do not believe that psychiatrists have detected a new childhood disorder; they have used a new term for a serious rise in poor regulation of emotion that is probably a result of experiential rather than genetic factors.

The setting aside of family issues in favor of focusing on genetic "causes" and pharmacological solutions gets overlooked in most of the writing -- both academic and mainstream media -- about pediatric bipolar disorder. Why don't doctors more often focus on the family and home environment? A slew of reasons -- little time, the desire for a quick fix, the awkwardness of bringing up the issue of family dysfunction and the difficulty of treating it or of getting the family to sign on to a solution that requires them to change behavior rather than just medicate the child.

At a panel about pediatric BPD at the first Neuroethics Society conference earlier this month, Hastings Center bioethicist Josephine Johnston suggested a major reason family issues aren't brought up is the "schizophrenogenic phantom" -- the memory that in the 1970s, schizophrenia, which usually shows itself in late adolescence, was blamed on harsh or cool upbringing by the patient's mother: the "blame the mom" etiology. Was quite a backlash against this when heavy genetic components were found underlying schizophrenia -- a backlash, Johnston suggested, that now keeps the touchy subject of family dysfunction off the table when parents bring deeply troubled or disruptive to doctors seeking help.

Kagan doesn't touch on this, but he covers much else. It's well worth reading the entire article -- and worth a peek at Vaughn's commentary on this piece at Mind Hacks, which gets the hat tip on this one.

The Dana Foundation - The Meaning of Psychological Abnormality:

Psych Problem #2: Cooking the Books

Lisa Bero

Critics of the FDA drug-trial process have often complained that the drug companies are free to publish only the trials that are flattering to their cause (that is, only those that show effects above placebo and relatively low side-effects). As explained in Wired Science, UC San Francisco health policy expert and Cochrane Collaboration co-director Lisa Bero has been picking this process apart:

The difference between what drug companies tell the government and doctors suggests that they're cooking the books, which could mislead doctors making prescriptions.

Of 33 new drugs approved by the Food and Drug Administration in 2001 and 2002, one-fifth of supporting clinical trials were not published in medical journals, according to a new study. And those results that were published were often more positive than what companies presented to the FDA in their applications. As a result, potentially unreliable data is being used to promote drugs on which billions of dollars and thousands of lives may ride.

"Some studies aren't published at all. Then, when they are, there are little changes that make the papers look more favorable towards the product," [said Bero].

Among the things Bero found:

Among the differences between results submitted to medical journals and to the FDA were trials that didn't favor a company's product, Bero found. Only half of 43 such outcomes were reported in the literature. More subtly, but just as importantly, key pieces of trial data vanished.

"The main thing that jumped out at me was the addition and deletion of primary outcomes. Those are the most important outcomes of a trial. To find that one disappeared from a paper, or just appeared in a paper, is pretty amazing to me," said Bero.

How to fix this? The FDA does things this way partly because the drugs companies are paying for the studies, and so get to control them. But there is a healthier model:

Bero calls for the FDA to be overhauled to run clinical studies itself, as is done by comparable agencies in Italy and Spain.

"The Italian FDA collects money from every drug company that sells drugs in Italy, pools that, and funds drug trials. They fund the sort of head-to-head drug comparisons that companies don't like to fund. And they have independent people peer-reviewing the trials. It's a great model," she said.

Bero's study is at PLOS Medicine.

Who's Driving the Psych Bus? [was 'Psychiatry at a crossroads']

Sen. Charles Grassley, R-Iowa

As the Times reported Friday, Senator Charles Grassley's pharma-money sweep has taken down another huge player in psychiatry: Grassley revealed that Fred Goodwin, a former NIH director who has long hosted the award-winning NPR radio show "The Infinite Mind," which frequently examined controversies about psychopharmacology, had taken in over $1.3 million consulting and speaking fees from Big Pharma between 2000 and 2007 and failed to report that income to the show's listeners and, apparently, to its producers. (For rundowns on this, see Furious Seasons, Huffington Post, WSJ's Health Blog, PsychCentraol, and PharmaLot

The expansion of Grassley's investigation into journalism throws a new kind of light on the lines through which Big Pharma seeks to shape opinion about powerful psychopharmaceuticals. And the mounting body count from Grassley's campaign -- and the fear in psych departments across the country -- adds to the sense that psychiatry stands near some sort of crisis point.

A Bit o' Background

Goodwin's reported $1.3 million in pharma income is an iceberg the tip of which was exposed in May in a Slate article by Shannon Brownlee and Jeanne Lenzer; I wrote about that article -- and about the counterattack it produced from Pharma and Infinite Mind producer Bill Lichtenstein - in an article at Columbia Journalism Review's science blog. As I noted then, Lichtenstein's counterattack, which seemed to treat failure to disclose conflicts as a hassle that is optional, ignored that drug-industry-related conflicts of interest in psychiatry have have become so big a problem that they are central and relevant to any discussion of any psychiatric disorder.

If journalists like Lichtenstein 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. 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.

Not Getting It

This same tone deafness saturated Goodwin's reported response to Grassley's revelations. If the Times quoted Goodwin accurately, he argued that he suffered no conflict of interest because the various payments from different drug companies "cancelled each other out" -- as if the only concern was whether a particular company, rather than an entire industry, might win his favor.

Carlat: How Drug Companies Hid Millions in Physician Payments in Vermont

This one hits close to home, as I live in Vermont. As Daniel Carlat notes, Vermont is one of the few states to actually require drug companies to disclose drug-company payments to MDs, but the state allowed exception for payments related to 'trade secrets.' The companies apparently made the most of this.

The Carlat Psychiatry Blog: How Drug Companies Hid Millions in Physician Payments in Vermont:

Vermont is one of a handful of states that requires drug companies to disclose their payments to physicians. But the law contains a loophole as big as the Ritz%u2014companies are allowed to withhold information on payments that they consider %u201Ctrade secrets.%u201D

Ever since the Vermont law was passed, many have wondered what on earth these %u201Ctrade secrets%u201D might be. A research letter published in this week%u2019s edition of JAMA (Journal of the American Medical Association) finally provides the answer.

The non-profit group Public Citizen sued to obtain information on the trade secret payments, and here it is. During the two year period from the summer of 2002 to the summer of 2004, drug companies made 21,409 payments, primarily to doctors, totaling $4.90 million. 42.9% of these payments, totaling $2.72 million were labeled %u201Ctrade secrets.%u201D

The researchers, led by Dr. Joseph Ross at Mt. Sinai School of Medicine in New York, focused their analysis on those payments to physicians of more than $100 (the Vermont law requires disclosure of all payments of at least $25). There were 4743 payments that exceeded $100, totaling $3.2 million. 49% of these larger payments were trade secrets. The median trade secret payment was $500 per doctor, far greater than the median non%u2013trade-secret%u2013designated payment of $177.

What kinds of payments were considered trade secrets? One would assume these would be for consulting arrangements in which doctors give advice about secret new products in the pipeline. But %u201Cconsulting%u201D constituted only 8.2% of trade secret payments.

By far the majority of trade secret payments were for promotional speaking (43.2%) and for %u201Ceducational%u201D activities%u2014presumably CME (41.7%). Most such gigs are well-publicized by mailings to doctors' offices, and they are typically for products that are already FDA-approved.

Calling promotional speeches and CME events %u201Ctrade secrets%u201D is Orwellian double-speak at its finest. Luckily, the Physician Payment Sunshine Act, likely to be passed by Congress in the coming year, does away with this loophole.