Check out Dr. Blumsohn's Latest

Aubrey Blumsohn has a very interesting new post about his saga over on his site. If you want a great case study of entanglement between academics and the pharmaceutical industry, you should really take a look at a good overview article of Blumsohn's predicament here. Then check out his latest post here. When you're done, feel free to scroll through his site, though it has quite a bit of info, so I suggest bringing your favorite beverage and a salty snack.

Olanzapine and Diabetes

A new study just published in the journal Progress in Neuro-Psychopharmacology & Biological Psychiatry found a significant increase in diabetes among patients taking olanzapine (Zyprexa), which is one of the second generation antipsychotics discussed yesterday here and here.

It would be quite ironic (at the very least) if the evidence continued to mount that olanzapine, which was often marketed as less likely to produce serious side effects than older antipsychotics, ended up causing as many or more health problems than the older and much cheaper medications. The results of the latest study should not be suprising, as other researchers have also found olanzapine use is related to significant health problems (especially diabetes), as can be seen here and here and here. Indeed, given the health risks associated with olanzapine, one is hard pressed to understand, rationally, why it is so often prescribed when safer agents are available.

Link to the most recent article's summary here.

If You're Looking for A Small Benefit -- Try Effexor for PTSD

The Archives of General Psychiatry had another interesting piece this month. In a rather large double-blind trial, venlafaxine (Effexor) was compared to placebo over a six-month period in the treatment of PTSD. Why so large (161 in the Effexor group and 168 in the placebo group)? Statistically, when you are likely to only find a small effect of treatment, make sure to have a large sample, so that you can find statistical significance.

How small the effect? The authors are to be commended for providing effect size data in Table 4, which indicate, across 17 measures, the highest effect size was .35 (in terms of Cohen’s d). I calculated the average of the effects across the 17 measures and came up with an average d of .256. So across 17 measures, the mean effect size was .256. This puts the effect just above small (generally recognized as d = .20), and well short of moderate (generally considered d = .50). In other words, not much to get excited about.

The authors receive credit for briefly (and I mean one sentence) mentioning that the effects were in the “low to modest” range, “in line with earlier reports for sertraline and paroxetine (p. 1163).” Using remission as an outcome, the authors found a number needed to treat of 8, meaning that for every eight people treated with venlafaxine, one additional patient would show remission relative to placebo treatment. This is described as a “moderate effect,” which seems like a stretch, but probably short of utter B.S. (p. 1164).

To sum up, venlafaxine (Effexor) showed a small advantage over placebo that was unlikely to be due to chance. The difference is so small that it is unclear why psychotherapy would not be indicated as opposed to pharmacotherapy in cases of PTSD since psychotherapy has a much lower incidence of side effects and likely longer lasting benefits. The longer lasting benefits guess is an extrapolation from research on treating anxiety disorders with medication, where once medication is discontinued, symptoms tend to recur, whereas the effects of psychotherapy tend to linger once treatment is discontinued (though not completely). The authors make not a single reference to nonpharmacological treatments.

Ghostwriter Watch: Dr. Michael P. Rennert is acknowledged for his “editorial assistance” with the paper. A simple Google query shows and ad of his placed in the American Medical Writers Association Journal in 2002 (Vol 17, No. 3). One can only guess who wrote what in this article, but it’s probably safe to believe that Dr. Rennert made a substantial contribution to the paper’s text.

Duplicate Presentation Watch: Right before the references sits a section titled “Previous Presentations.” This acknowledges that this study was formally presented at 13 conferences. THIRTEEN! In psychology, the general guide is to present findings at one conference, not a baker’s dozen. Maybe if it's a big study, split the findings between two or maybe three conferences at most. Apparently in psychiatry, anything goes in terms of duplicate presentations! Talk about marketing like crazy from a pretty meager finding. Perhaps this can make its way into multiple publications as well? Let's hope not.

The Future of Second Generation Antipsychotic Meds

My forecast: As evidence mounts showing that the second generation antipsychotics (SGA) are to first generation antipsychotics what SSRIs were to older antidepressants – a meager advance at the very best, look for SGAs to make up for declining schizophrenia market share by moving into bipolar disorder (despite being no more effective than lithium) and into child behavior problems and autism (where anything goes in treatment due to the general lack of treatment response). Look for more and more people to get labeled as bipolar. This will happen because of research using sloppily designed surveys which show "surprisingly high" prevalence rates for bipolar. The real market might come from Bipolar II, in which people are "just too darn energetic" at times despite generally having no functional impairment. There will of course be “disease awareness” campaigns and both direct to consumer and journal ads mentioning that bipolar is reaching epidemic proportions. Bipolar will be discussed as "undertreated," "underrecognized," and "tragic." Mind you, real cases of bipolar are indeed tragic and often undertreated. But when the bipolar II "epidemic" hits, mark my words, the scripts will be written quicker for these SGAs than you can believe.

The second use: Kids with behavior problems. If they're acting out, try an SGA. If that doesn't work, up the dose. If that doesn't work, add another SGA. Given enough SGAs, Genghis Khan would likely chill out, but at what cost? Add autism to the mix as well.

I see the trends already forming and within five years, bipolar disorder will have (allegedly) spread like the flu and those badly behaving children will increasingly swallow Zyprexa and other SGAs to control their behavior.

Of course, if SGAs go generic in the next few years, look for another new set of "miracle drugs" to replace them.

CUtLASS 1: Newer Antipsychotics Disappoint Again

In the Archives of General Psychiatry this month (October 2006), another blow is dealt to second generation antipsychotic medications. The study, known by the acronym CutLASS 1 indicated that outcomes, including quality of life as well as more traditional symptom-based measures such as the PANSS, were no different for patients taking first-generation antipsychotic medications (FGA) compared to those taking second-generation antipsychotics (SGA). Side effect data also indicated no differences between medication class. In fact, there was a nonsignificant trend favoring slightly better outcomes for those taking FGAs over SGAs.

Full text of the article is available free here.

The study is accompanied by two commentaries in the journal. I admit I was expecting at least one of them to come from an industry-entangled researcher whose conflicted interests would make for laughable pro-SGA flacking. I was wrong. Drs. Robert Rosenheck and Jeffrey Lieberman both aptly point out that the CUtLASS 1 findings are actually not particularly surprising. Indeed, when one considers the results of the CATIE trial (on which Lieberman and Rosenheck were both authors) as well as prior comparisons between FGAs and SGAs, the results from CUtLASS 1 meld in quite nicely. Rosenheck pointed out in a prior article (International Journal of Law and Psychiatry, Secp-Oct 2005) that two-thirds of trials comparing SGAs to haloperidol (Haldol; an FGA) did not allow prophylactic anticholinergic medication use for those taking Haldol. The problem is that Haldol, without concomitant anticholinergic meds, frequently causes side effects that result in early dropout “and can be mistaken for symptoms of schizophrenia” according to Rosenheck’s 2005 piece. Indeed, he pointed out that no study which allowed the recommended side effect control medication to be coadministered with Haldol has found it inferior to an SGA.

Rosenheck, in his current commentary, goes on to cite sources indicating that the cost of antipsychotic medications is currently over $10 billion annually, which is 70% paid by Medicaid (which is paid for by all of us). SGAs vary in cost, but at the extreme, they can cost 100 times as much as FGA’s, and in most cases, the difference is at least fifty-fold. Considering that they seem to have comparable efficacy and likely roughly equivalent safety (with the possible exception of extrapyramidal symptoms), one is left wondering why taxpayers are left footing such an exorbitant bill when equally efficacious medications are available at a fraction of the cost.

Lieberman was particularly quotable in his commentary, so let’s try on a few quotes for size:

First off, referring to the combined findings of CATIE and CUtLASS 1: “These studies found few differences in effectiveness between first-generation antipsychotics (FGAs) and second-generation antipsychotics (SGAs) in nonrefractory patients – a conclusion that runs counter to the impression of many clinicians and previous studies suggesting marked superiority of the SGAs and that belies the huge advantage in market share enjoyed by the SGAs in the United States and other parts of the world. However, the results are generally consistent with numerous meta-analyses carried out in the past decade in an effort to discern a clearer picture of the comparative effectiveness of antipsychotic drugs that could be derived from any previous individual trial (p. 1069).”

Next: “The second reason for the disparity in results between CUtLASS 1/CATIE and previous studies is that the claims of superiority for the SGAs were greatly exaggerated… the aggressive marketing of these drugs may have contributed to this enhanced perception of their effectiveness in the absence of empirical evidence (p. 1070).”

Lieberman also points out that many prior FGA-SGA comparison studies failed to allow concomitant anticholinergic medications for the FGA group and administered the FGAs at doses where side effects at moderate to high doses. This, of course, maximized FGA dropout and side effect rates while likely reducing efficacy.

One more eminent quote from Lieberman: “...any reasoned and objective view of the evidence in light of CUtLASS 1 and CATIE must lead to the conclusion that with the possible exception of clozapine, the SGAs are not the great breakthrough in therapeutics they were once thought to be; rather, they represent an incremental advance at best (p. 1071).”

My View: SGA = FGA. We’ll see how it pans out on the EPS issue, since SGAs were pimped heavily as being much less likely to induce movement disorders. The jury is still out on this issue, but more recent research seems to favor equivalence between classes. Crazy idea: Why not make a new class of antipsychotics rather than making a bunch of me-too’s in the SGA class? That would require a real investment in R & D, so don’t bet on it.

500 Hits

Open for business for less than a month and the site has now received 500 hits. Yes, I know that big name blogs receive that many or more in a day, but this is a new site and I'm pleased with traffic so far. I'll keep posting and you keep reading, adding your thoughts via comments or email. Thanks for your support!

To celebrate this meaningless number of 500 hits, feel free to subscribe to the site via email on the right.

Upcoming Posts

Wow, good stuff in a journal to be named later was just released. I'll be reading then writing shortly.

My Technorati Profile

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Pfizer: Treat Us Nice or Else We're Leaving!

In a somewhat explosive article in the Guardian (of course – as if a US paper would have the nerve to publish such rabblerousing), limited details of meetings between pharmaceutical executives and UK government officials were reported. A quote follows:

“The world's biggest drug company, Pfizer, warned ministers that it could take its business elsewhere. "Pfizer ... noted that there is complacency in some quarters of Whitehall regarding their continued investment in the UK," the minutes of the meeting record." That sounds like blackmail to me. – Aubrey Blumsohn.

Well, I’d have to agree with Dr. Blumsohn. Check out his excellent post here.

Yo Chuck, We Got Some Nonbelievers Out There (Corcept Plunges)

Remember Corecpt Therapeutics? They were testing mifepristone (aka RU-486 or Corlux) for psychotic depression. Well, again, things did not go exactly as planned. As indicated earlier, they found that the medication was no more efficacious than a placebo for depression in one trial, a result that was replicated by a second failed trial. One has to admire their ability to make excuses, as their press release states “As was the case in study 07 [the prior failed trial], there was an unusually high placebo response rate in Study 09.” When all else fails, blame the placebo! Two failed trials or not, Corcept marches on: They are enrolling patients in a third trial and plan to announce results in early 2007. Here at the CPP Blog, I will be watching anxiously. If they get one out of three, will the FDA give it a stamp of approval?

Of course, one can only guess how Dr. Charles Nemeroff felt about this latest turn of events. After all, he is on the scientific advisory board for Corcept and their stock really took a beating (down 34% in one day) upon release of the second negative trial. You may remember Chuck as the researcher who published positive comments in a review article regarding mifepristone based on a study containing a whopping sample of five patients. The article contained no disclosure of any conflicts of interests, such as the fact that he was on the advisory board for the company whose drug he was pimping based on very skimpy data. You can refresh your memory about the story here. Let’s hope, for his sake, he was able to move his shares before the latest press release was issued!

Plavix: Insight into Sticking it to the Consumer

To give a little insight into the greed of our friends in the pharmaceutical industry, consider that it is generally legal for drug manufacturers to pay generic drug manufacturers to not manufacture generic copies of their medications, even as patents set to expire.

From the latest New England Journal of Medicine:

“In August, pharmacies began selling a cheaper, generic version of the blockbuster antiplatelet agent Plavix (clopidogrel). This was good news for patients with cardiac disease or stroke who cannot afford to buy the medication at more than $4 a day. But to Bristol-Myers Squibb and Sanofi-Aventis, who produce and market the drug, it was a financial disaster. Plavix is the world's second-best-selling drug — 48 million Americans use it on a daily basis — and with sales of more than $6 billion last year, it accounts for about 30 percent of Bristol-Myers's total earnings. In an effort to keep the generic version off the market, Bristol-Myers and Sanofi had agreed to pay its Canadian manufacturer, Apotex, $40 million not to release it until 2011. If this agreement fell through because it was deemed unapprovable by government authorities, Bristol-Myers–Sanofi would pay a break-up fee of at least $60 million and they wouldn't take legal action in advance to stop Apotex from releasing the generic. If part of this payoff was late, Apotex would claim "interest at a rate of $20,000 per day," Chief Executive Officer (CEO) Barry Sherman informed a Bristol-Myers executive by e-mail after the companies' pay-off settlement was rejected by government reviewers…”

“…In the case of Plavix, after the authorities rejected the initial settlement between Apotex and Bristol-Myers–Sanofi, the companies reached a second settlement, but by the end of July 2006, it, too, had unravelled in the wake of revelations that the Department of Justice was launching a criminal investigation of the deal. A week later, Apotex began flooding the market with generic clopidogrel, and within days, more than 60% of Plavix prescriptions were being filled with the generic, priced up to 20% lower than the brand-name product. On August 31, Bristol-Myers and Sanofi won an injunction preventing further sales, but by then, Apotex had shipped quantities that industry analysts expected to last until 2007.

The case offers a rare glimpse of the high-stakes arrangements through which pharmaceutical companies delay sales of generics and keep drug prices high — all under the watchful eyes of the Federal Trade Commission (FTC) and the Department of Justice. Though the cash payments at the heart of this deal are shocking, such "reverse payments" from a brand-name drug producer to a generics company are not illegal. What's unusual about the case isn't the millions promised to Apotex, it's that the settlement fell apart and generic clopidogrel was released for sale. In recent years, such settlements have generally stuck, despite federal authorities' efforts to undo them, and generics have been kept off the market.”

The article goes on to describe that these arrangements are relatively common and end up costing consumers a fortune.

For much more on this topic, interested readers can do a quick search on PharmaGossip. There are dozens of relevant posts.

Manic Thinking Improves Mood?

Below I've copied a summary from a study in Psychological Science that cleverly studied the effects of speeded-up thinking on mood.

How 'Manic' Thinking Makes Us Happy, Energized And Self-confident

When people are made to think quickly, they report feeling happier as a result. They also say they are more energetic, more creative, more powerful, and more self-assured. In short, they reported a whole set of experiences associated with being "manic."

Fast thinking, or "racing thoughts," is most commonly known as a symptom of the clinical psychiatric disorder of mania. But, according to Princeton University psychologist Emily Pronin, most healthy people also have experienced racing thoughts at some point in time -- perhaps when they are excited about a new idea they have just learned, or when they are brainstorming with a group of people, or even when they lie in bed unable to fall asleep. Pronin and her Harvard colleague Daniel Wegner decided to explore whether inducing people to think fast might lead them to feel some of the other experiences also associated with the manic experience.

To examine this question, they experimentally manipulated the pace at which participants read a series of statements. Half of participants read the statements at a fast pace (about twice as fast as normal reading speed) and the other half read the statements at a slow pace (about twice as slow as normal reading speed). They then completed a questionnaire assessing their mood, energy level, self-esteem, etc., using standard psychological measures. As an added twist, some of the participants read statements that were very depressing in content (e.g., I want to go to sleep and never wake up) while others read statements that were very elating in content (e.g., Wow! I feel great!).

The researchers found that regardless of the content of the statements, people felt happier, more energetic, more creative, more powerful, and more grandiose when they read the statements at a fast rather than a slow pace. In fact, the effect of thought speed was just as powerful as the effect of the content of the thoughts. In other words, the speed of people's cognitive processing was just as important as what they processed in determining their mood. Even thinking sad thoughts at a fast pace made people relatively happy.

The article, titled "Manic Thinking: Independent Effects of Thought Speed and Thought Content on Mood" appears in the September issue of Psychological Science, and was co-authored by Emily Pronin of Princeton University and Daniel Wegner of Harvard University.

The reported effect of fast thinking on mood could have important applications in both clinical (psychiatric) and normal populations. The authors note that simple manipulations of thought speed could perhaps be used to improve individuals' mood, self-esteem, feelings of creativity, feelings of power, and energy level. Such manipulations could be useful in everyday situations, where people would like a quick mood, energy, or self-esteem boost on a day they are feeling tired or downcast. Manipulations of thought speed might also prove useful as part of treating depression, which is characterized by slow thinking, and also by the absence of things like positive mood, energy, feelings of power, and self-esteem.

The authors note that: "The results of our experiment suggest the intriguing possibility that even during moments when people feel stuck having depressed thoughts, interventions that accelerate the speed of such thoughts may serve to boost feelings of positive affect and energy."

Source: Association for Psychological Science

Hat tip: Robert Karl Stonjek

Venturing into Politics Briefly

I try to leave politics out of this blog, though I suppose some may label me a pinko for pointing out problems within the drug industry.

But, that being said, rushing through legislation that enables arbitrary (entirely at the president's discretion) detention, defines torture in a rather Oliver North sort of way, and gives the rubber stamp to kangaroo court proceedings brings two issues to mind:

1) It is a brilliant move by the Republican party, which can run this sort of rally around the flag balderdash to improve support among their base because…

2) Democrats already only nominal opposition to the Republicans has essentially vanished entirely. “Oh my God, they’ll say we’re terrorist sympathizers if we openly oppose this Stalinist legislation – and then we won’t regain control of the House and Senate.” News flash, you morons: You’re not going to gain control of anything if you never take a stand. When something is wrong, by God, explain why it is wrong and perhaps people will see you as something more than the party that sits around with dumb looks on their faces while the Republican Party is raping our Dear Republic in the name of Patriotism.

I will do my best to post nothing else on politics anytime soon. See the New York Times for a timely editorial on the topic (registration likely required).

Review of Doughnuts for Doctors

Doughnuts for the Doctors: Moynihan and Cassels on the pimping of antidepressants…

I was very much looking forward to their book, Selling Sickness, as I’ve been favorably impressed with much of Moynihan’s earlier work on disease mongering. The authors discuss depression in a chapter titled Doughnuts for the Doctors, in 18 short pages, which is unfortunately far too brief for the weighty topics tackled within. They point out that physicians are certainly influenced by contacts with drug reps, and that there are a litany of problems with SSRI’s (suicidality, small advantage over placebo, significant side effects such as sexual dysfunction, etc.), but the attention given to these points is unfortunately too brief.

I was more impressed with their description of the American Psychiatric Association’s convention, where the virtual orgy of drug promotion disguised as education (industry-sponsored symposia and those slick looking booths staffed by likely remarkable attractive cheerleaders, er, drug reps) was discussed again too briefly, but in a captivating manner. Loren Mosher, who quit the APA a few years ago in disgust, along with David Healy are discussed in passing. For Healy, especially, this is short shrift.

More interesting was the debate on the prevalence of mental disorders, including depression, which focused on the differing findings of Kessler versus Narrow in their estimates of the aforementioned problems. Certainly, Narrow found a lower prevalence for mental disorders than did Kessler, and the discussion is important and timely for all mental health practitioners and researchers.

My favorite line in the chapter is in the context of the finding that half of people receiving treatment for mental disorders were “either noncases or mild cases.” The authors opine cleverly, “The global obsession with “unmet need” – a notion that is constantly pushed by doctors and drug companies as the justification for aggressive drug marketing – may well be helping to create a strange new phenomenon: ‘met un-need.’” A great point when one considers how much energy (some of it indeed justified) goes into campaigns to get more people into treatment because [insert mental disorder here] is undertreated in the community. The authors then discuss a screening test from our friends at Bristol Myers Squibb which found that 49% of individuals had a “mental disorder." Later research showed, unsurprisingly that this test was a poor assessment of mental health. More (but still not enough) on marketing depression follows after this point.

A little more on the well-tread territory of antidepressant use in children follows, in which their insights are spot-on. What I found more interesting was the discussion of “thought leaders” and their development by the drug industry. Another great quote follows:

“Promising prospects might be singled out by a detailer as a potential thought-leader, and then given some small speaking engagement to test them out. Later, if they’ve proven their worth, they might be paid to speak regularly in small local settings about the latest new drug in the pipeline. With a bit of luck the thought-leader could eventually find themselves on a drug company’s ‘speaker’s bureau’ earning thousands of dollars for making presentations to their international peers about the latest new disease, at high-profile events like the APA congress in New York.”

More good stuff follows on “thought leaders," though yet again I wanted more.

Overall: If I had to assign stars, I’d give this chapter 4 of 5. Great source of references for the interested reader. The writing was solid and interesting, but it just went too quickly from topic to topic. Nonetheless, it is hard to disagree with their implicit conclusions that antidepressants are much more a miracle of marketing than science.

Hopefully time will arise for a brief synopsis of the ADHD chapter as well.

Merck: Only the Little People Pay Taxes

Ahhhh... Nothing like Merck getting caught evading taxes to start off the day. Pharmagossip has a summary of the story in the Wall Street Journal which details Merck's tricky accounting procedures related to this scandal.

"Thirteen years ago, Merck set up a subsidiary with an address in tax-friendly Bermuda, in partnership with a British bank. Merck quietly transferred patents underlying the blockbuster drugs to the new subsidiary, according to documents and people familiar with the transaction. Merck then paid the subsidiary for use of the patents.

The arrangement in effect allowed some of the profits to disappear into a kind of Bermuda triangle between different tax jurisdictions. The setup helped Merck slash $1.5 billion off its federal tax bills over roughly the next 10 years."

Check out the story on PharmaGossip or over at the Wall Street Journal.

Coming Soon... Selling Sickness Review

No time today. Hopefully on Thursday, I'll post my review of a couple of chapters from Selling Sickness by Ray Moynihan and Alan Cassels. I'll discuss the chapters on depression and ADHD in sticking with the psychiatry/psychology theme of the site.

Check out Rost's Site

If you haven't been following Peter Rost's trials and tribulations, this is a great time to start. There is something so refeshing about a whistleblower at a pharmaceutical company. I think everybody will enjoy his site.

Nemeroff: Another Lesson in Reviewing Literature

OK, OK. Enough about poor Charles Nemeroff already! Maybe he made a little mistake on the VNS thing. But, what if a similar problem occurred in another venue?

It did. Nemeroff & Owens were reviewing several treatments in the journal Nature Neuroscience (2002) and they came to the conclusion that both mifepristone and a transdermal lithium patch were likely solid treatment options for mood disorders.

Let’s start with mifepristone. To quote the review: “impressive studies [indicate] that the glucocorticoid receptor antagonist mifepristone is very effective in the treatment of psychotic depression.” The authors cite one study (not “studies”) to back up this claim. In this study, mifepristone was tested on five (yes, FIVE) individuals. So based on a study of five patients, Nemeroff and Owens state that the medication is “very effective.” That, my friends, is bad science! Oh, and incidentally (and not mentioned by the authors), mifepristone is better known as “the abortion pill.” I don’t know, but I think I might mention that in my review of mifepristone.

More on mifepristone/RU-486, the antidepressant: How about – It’s not an antidepressant. In a study of over 200 patients, mifepristone was found to be somewhat (mild to moderate effect size) more efficacious in alleviating psychotic symptoms of psychotic depression, but no more effective at alleviating depressive symptoms than a placebo. Granted, that was published years after Nemeroff and Owens’ dubious statement about its efficacy, but I thought readers may be interested to know that their statement on efficacy was quite overblown and has not been supported in a much larger study.

The rub: Nemeroff was reportedly a member of the scientific advisory board for Corcept Therapeutics, which was (and perhaps still is) developing mifepristone.

Now, about that lithium patch. The authors say “Changing the pharmacokinetic profiles of existing drugs has also proven beneficial. For example, controlled or sustained-release preparations of venlafaxine, buropion and paroxetine are now available, and methods to deliver a monoamine oxidase inhibitor and lithium via patch technology have been developed. These methods improve tolerability of the drug, as well as patient compliance.”

Sounds good, eh? The lithium patch improves tolerability and compliance, except that the authors provide not a single source to back these claims. When writing a review article, the point is to summarize scientific evidence, which is generally done through providing sources! Who needs a source, though, when you stand to profit handsomely from the use of the lithium patch. After all, Nemeroff is the co-patent holder for the device!

A related post on Nemeroff is available from the Alliance for Human Research Protection here.

VNS, Chuck, and Conflicts of Interest

Nemeroff Part 2

Suppose you are the paid chairman of the “Mechanism of Action Advisory Board” for a company that markets a device (vagus nerve stimulation or VNS) which treats depression. Is it ethical to slap your name on a very favorable journal article related to VNS without indicating that you (and several of your coauthors) have a substantial conflict of interest?

How about having a ghostwriter make substantial contributions to the aforementioned paper? And what do you think about making sure that this “scientific review” of VNS overlaps carefully with the marketing used for the device? At this point, I’ll quote directly from Health Care Renewal’s excellent post:

“There is no discernible difference between the corporation's press releases and the text of the review article on these topics. The review did not address the controversy surrounding the FDA approval process. In these respects, the review has the hallmarks of a ghostwritten article. As described by Leemon McHenry, who has written on conflict of interest issues in medicine, "I have ... seen contracts between the pharmaceutical companies and the ghostwriting companies with the plan of production and the budget. What is particularly interesting about these is the fact that it is clear that the company owns the manuscript until it is released to the "authors." The company's legal department reviews the manuscript and releases it at the end of the process. The first draft isn't even reviewed by the "authors." This is all internal until the second draft." It appears very likely that the VNS review was carefully screened by the corporation to ensure that the first draft was "on message" before being released to the "authors" for them to strengthen the hard science surrounding the stealth infomercial.”

Should your allegedly detached and scientific review skirt around any issues about the controversy of the device’s FDA approval for treating depression? To quote the NY Times: “…in the most carefully controlled trial, a group that had the device implanted but not turned on fared nearly as well as the group being stimulated. Critics also pointed out that long-term results indicated that 30 percent of the patients reported worsening depression similar to Ms. Coram’s, creating unanswered questions about potential harm.” Yeah, certainly don't mention any controversy!

As the lead author of the study, should you bother to mention that you are the chair of the Advisory Board for the corporation?

Better yet, should you publish this article in the journal where you are editor in chief? To top it off, make sure to be quoted in a press release by the VNS manufacturer, in which you describe how the latest article shows VNS is super-duper wonderful:

"After reviewing all the available data, taken together, it is clear that VNS Therapy is a promising treatment for patients living with TRD. Given the nature of TRD, it is exceptional that the antidepressant effect of VNS Therapy has been shown to improve over time and is sustained long-term for patients with TRD. Results of ongoing clinical and imaging studies will be critical to increasing our understanding of the mechanisms of action that mediate the beneficial effects of VNS Therapy for TRD.”

So, to summarize, a ghostwriter hired by Cyberonics pens a draft of an article (or at least writes quite a bit of an initial working draft) favorable to VNS therapy for depression. Eight academics, including Nemeroff, sign their names to it after perhaps adding some substantive content. The article is then sent to Neuropsychopharmacology, where Nemeroff is editor in chief, resulting in likely disproportionately favorable reviews and a relatively easy publication. In this publication, the financial conflict of interest of Nemeroff and colleagues is not mentioned. To celebrate this great triumph of marketing, er, science, Cyberonics issues a press release discussing how this “peer-reviewed” article provides support for their product. To top it off, Cyberonics reportedly ordered 10,000 reprints of this so-called study. Friendly representatives will be visiting a psychiatrist near you with this ironclad evidence of efficacy!

For more details, read Health Care Renewal’s post on the topic.

Is this a fluke for Dr. Nemeroff, a one-time occurrence. We’ll see…

Is Chuck Using a Ghostwriter?

There have been enough interesting stories about Charles Nemeroff, professor of psychiatry at Emory University, that I’m sure they warrant a posting or two.

Let’s start with ghostwriting and then move on to David Healy and then to conflicts of interest.

It is mentioned on Nemeroff's website that he has published “more than 750 research reports and reviews,” which is one impressive feat. In a quick Medline search, I turned up his earliest publication date as 1975. So, that’s about 30 years of publishing, putting him at 25 publications per year. I’m not saying the man is not legitimately prolific, but given his administrative responsibilities, major travel obligations (research and paid lectures across the country), and his time apparently spent trying to discredit David Healy (more on that coming soon), I wonder if he really had a legitimate role in 750-plus articles.

It appears that I’m not the only wondering if all of these publications are legit. Chuck had a recent publication in Neuropsychopharmacology where the wonders of vagus nerve stimulation were discussed. Let’s quote from Health Care Renewal’s great post on this subject:

“…the article acknowledged "editorial support" from a professional writer, who acknowledged to the Wall Street Journal that she was employed by the corporation for the task of writing a first draft. Although the authors claimed they provided substantive input after the first draft, it is ethically dubious to use a hired writer for a first draft.”

In other words, a ghostwriter wrote much (perhaps all) of the first draft, then Nemeroff and company added their pieces (or not) to the final draft. Who knows how many of the other 750-plus Nemeroff publications were, um, “assisted” by a ghostwriter? I’d have to defer to David Healy on that point.