Results tagged “Media” from Pathophilia

Another Winter Solstice, another anniversary for the Pathophilia blog. Today marks 2 years of up-and-running blog time, which is 3½ years in Hollywood-marriage time.

And because anniversaries and a closing year prompt reflection, here are Pathophilia's top 10 stories for the year in medicine, pharma, and film noir on DVD. (Ho-ho-ho! So rare that I get to use the blog's strikeout feature as lame joke.)

No. 10: More Dumping on Merck's Vytorin, Zetia

The year began with continued debate (to put it nicely) about how to assess emerging cancer data from clinical trials of the anti-cholesterol combo drug Vytorin (ezetimibe/simvastatin; Merck). (For lots of necessary background, start at last year's No. 6 story.)

In a Smackdown: New England-Style, prominent cardiologist Steven Nissen essentially charged Sir Richard Peto and his colleagues with unethical behavior, when they separately analyzed cancer data from the SEAS trial (which suggested an increased drug-related cancer risk) and data from the ongoing SHARP and IMPROVE-IT studies (which did not). Nissen believed that data from all 3 studies should have been combined for the analysis (which would have affirmed a cancer risk); but Peto, a statistician and epidemiologist, stressed the importance of separating data in a hypothesis-generating study (eg, the SEAS trial) from data in hypothesis-testing studies (eg, SHARP and IMPROVE-IT). His analysis did not indicate an increased cancer risk with the drug.

At the same time, the FDA attempted to quell some of the anti-Vytorin sentiment and downright company-directed schadenfreude caused by the delayed results of 2008's troubled ENHANCE study. (And if you still don't know what the ENHANCE study is, go back to last year's No. 6 story.) The agency emphasized the importance of lowering the LDL cholesterol level (which Vytorin does) to reduce cardiac risks, like MI. The FDA also weighed in on why the ENHANCE study did not show a reduction of another surrogate marker for vascular disease, CIMT, with the addition of ezetimibe to simvastatin. Speculation included the selectiveness of the study population.

Months later, an Abbott-sponsored phase 4 trial (ARBITER 6-HALTS), which pitted the company's Niaspan (extended-release niacin) against Zetia (the ezetimibe half of Vytorin) was terminated early—and not because of safety concerns. The Street speculated that Abbott's drug had outperformed Zetia in the open-label study of high-risk adults. The Street was right.  

At the Scientific Sessions of the American Heart Association in November, results of ARBITER 6-HALTS showed that Niaspan outperformed Zetia in 5 of 7 outcomes, including a composite clinical outcome. Many media reports played up Niaspan's effects on CIMT at the expense of Zetia, while downplaying tolerability issues (eg, flushing) and the fact that the study population was small (N = 208) and selective: enrollees were statin-treated adults who had already attained target LDL levels (<100 mg/dL) and had moderately low HDL levels. Niaspan in such patients would be expected to elevate HDL, and Zetia would be expected to further lower total cholesterol and LDL levels—which is what the investigators found.

Relatively minimal attention was given to another small placebo-controlled study of extended-release niacin, also presented at the AHA sessions, in which changes in carotid-wall plaque (via MRI) were comparable in the 2 treatment groups.

Merck's Zetia/Vytorin-related troubles, vis-a-vis 2-plus years of media coverage, were epitomized in an end-of-year article by Forbes reporter Matthew Herper—who showed his continued disdain for the drugs and their marketing in a less-than-objective synopsis of results from relevant clinical trials.

Herper and others like him have 2 more years to capitalize on the controversies surrounding Zetia and Vytorin. At that time, results of the long-running IMPROVE-IT study, in which Vytorin is compared with simvastatin monotherapy in at-risk adults, will be available. The primary and major secondary endpoints in this study aren't surrogate markers, like LDL and CIMT, but actual clinical events. 

ARBITER 6-HALTS = ARterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6 - HDL and LDL Treatment Strategies in Atherosclerosis; CIMT = carotid intima-media thickness; ENHANCE = Effect of Combination Ezetimibe and High-Dose Simvastatin vs Simvastatin Alone on the Atherosclerotic Process in Patients with Heterozygous Familial Hypercholesterolemia; HDL = high-density lipoprotein; IMPROVE-IT = Improved Reduction of Outcomes: Vytorin Efficacy International Trial; LDL = low-density lipoprotein; SEAS = Simvastatin and Ezetimibe in Aortic Stenosis; SHARP = Study of Heart and Renal Protection.

Public-domain image of Hamilton-Burr duel, which admittedly took place in New Jersey (not New England), from Wikipedia.

12/22/09 update: The FDA says it's "unlikely" that Vytorin and Zetia increase the risk of cancer; although the agency can't rule out the possibility, according to today's WSJ. The agency's announcement comes after its own review of cancer data from the SEAS trial.

And I write the title of this post without qualifying it with a phrase like "in my opinion."

The dramatic "Inside Edition" video can be found here; but any neurologist worth his or her salt would recognize that the young woman's filmed condition is factitious. I fully suspect that the Hopkins neurologists who reportedly made the diagnosis of "dystonia" believe that it represents a profound case of malingering also.

Jennings claims that her movement disorder appeared 10 days after getting a seasonal flu shot in August—so the obvious secondary gains would appear to be attention and financial compensation.

Other bloggers, like Orac and neurologist Steve Novella, have commented extensively on this case.

For the record, Jennings appears to have recovered with questionable treatments from the questionable Rashid Buttar, a controversial osteopath in North Carolina. God knows, she couldn't have kept it going forever.

11/24/09 update

Two Losers Find Each Other Thanks to a Third Loser

Jenny McCarthy's Generation Rescue evidently recommended Buttar to Desiree Jennings, the Washington Redskins cheerleader ambassador (whatever the hell that is). According to this recent Fox News affiliate report (which, once again, demonstrates that local news reporting simply sucks), Buttar diagnosed Jennings with something he calls "acute viral postimmunization encephalopathy" and "secondary mercury toxicity"—both of which he attributes to the flu shot.

But if Jenning's vaccination delivered any mercury,* she would have received no more than 25 micrograms of ethylmercury in the form of the preservative thimerosal.

And all injected seasonal flu vaccines contain inactivated (ie, split) virus, which is incapable of causing infection.

* And if the vaccine was in the form of a single-use syringe, it did not have ethylmercury-containing thimerosal.

The payoff of pseudoscience and why it's so damned attractive are explored by writer Amy Wallace for Wired in her comprehensive profile of infectious-disease specialist Paul Offit (aka Satan incarnate to anti-vaccinationists).

Some kind of solace is what the otherwise rational Bill "All-I'm-Saying-Is-That-We-Should-Have-a-Debate" Maher must be seeking in his faith-like embrace of anything that's not "Western medicine"—a term that he has used liberally, disparagingly, and without explanation on his HBO show.* On the show's season finale, Maher once again maligned vaccination to an otherwise incredulous guest panel of Chris Matthews, Alec Baldwin, and Maryland Governor Martin O'Malley. Among the many illogical, non-sequitor, and/or flat-out wrong claims made by the host is this gem.

I also would like to say that I do understand the theory of inoculation. Yes, you give someone a little bit of the disease, and it fools your body into providing antibodies, which fight it. Brilliant. Bravo. Maybe there's some occasions where an inoculation is a wise thing to do. I hope not. I hope I would never have to have one, because, you know, to present it just as this genius medical advancement—no, it's actually a risky medical procedure that begs long-term cost-benefit analysis. I mean, if you don't believe me, look on the CDC web site as to what is in the swine-flu vaccine. You know, aluminum, insect repellant, formaldehyde, mercury. You know, that's right on their web site. Don't take it from a talk-show host.

Maher's last statement is the only one worth heeding. He continues to require education about the actual process of modern vaccination, given his statement "you give someone a little bit of disease...," and wrongly implies that vaccine advocates deny any risk whatsoever from vaccination.

As Maher indicates, the CDC web site offers some answers to FAQs about the ingredients of the 2009 H1N1 vaccine. The most obvious relates to the vaccine's mercury content, which has been falsely associated with the risk of autism. The truth of the matter: Only vials of the vaccine, not the prefilled syringes, contain measurable (but very tiny) amounts of ethylmercury (25 microg/dose), which is part of the thimerosal preservative. The seasonal flu vaccine is also available in thimerosal-free versions.

Data on other purported 2009 H1N1 vaccine ingredients, or lack thereof, are more easily found from online sources other than the CDC web site, including the FDA web site. Aluminum hydroxide is evidently used as an adjuvant in the low-dose Chinese vaccine,** but the US vaccine does not contain it.

Formaldehyde is used during vaccine production—to harvest and inactivate the cultivated virus from the chicken-egg medium, specifically the allantoic fluid. The virus is then chemically split by using a noninonic surfactant, polyethylene glycol p-isooctylphenyl ether, or Triton X-100. According to the package insert for the sanofi-pasteur 2009 H1N1 vaccine, "Each 0.5 mL dose may contain residual amounts of formaldehyde (not more than 100 microg), [Triton X-100] (not more than 0.02%), and sucrose (not more than 2.0%). It's not clear to me if the "insect repellant" that Maher refers to is supposed to be Triton X-100 or some other substance.

* The alternative, logically, is Eastern medicine--which is generally understood to encompass any idea of illness or medical therapy that's unproven. Adherence to Eastern medicine therefore requires faith. It could be said that Maher, who famously eschews religion, ironically places a religious-like faith in the benefits of these non-evidence-based ideas and practices.

** Hey Bill Maher, you still like Eastern medicine?

It's one thing to bury your missed primary endpoint, but nobody entertains like a renegade PR writer who's sky-high on his own fumes.

Epeius Biotechnologies, a privately held, California firm, evidently employs one such maverick (yes, I wrote "maverick")—as evidenced by some seriously entertaining press releases. Props for discovering the purple prose go to Trista Morrison at bnet.

The clumsy hyperbole concerns the firm's front-runner drug, Rexin-G, an antitumor molecule in stage 1/2 development.

Amongst the high-larity*:

October 14, 2009

The outstanding results of this advanced US clinical trial...demonstrate beyond contestation that Rexin-G...exhibits profound anti-tumor activity...

The success of landmark studies is a tribute, not only to the clinical investigators who "held the course" and the "cause" of a better medicine as a high standard, but to the US FDA who, by allowing across-the-board dose escalations in ongoing trials...served to expedite the achievement of these effective doses, and thus these heartening results. [quotation marks sic]

October 12, 2009 (regarding 3 case studies)

...Rexin-G has once again accomplished what standard cancer treatment and even much-touted biologics have failed to do: that is, to bring forth the benefits of remission in otherwise intractable metastatic cancers.

Even more remarkable, perhaps, are the profiles of...two patients, which signal the advent of Rexin-G as the vanguard of a new class of exceedingly precise, selective, and effective anti-cancer agents, and which typify a newfound societal acceptance and acknowledgement of the real-world promise and potential of this uniquely-targeted genetic medicine.

Remarkably, a Catholic priest, who was previously bedridden and in withering pain, suffering from end-stage prostate cancer that had spread to his bones, received successive courses of Rexin-G, during which time the bone pain was relieved, the PSA tumor markers fell, the bone tumors stopped growing, and even the previously inoperable primary tumor disappeared on follow-up CT scans.

As the priest’s bones began to heal and strengthen, he arose from his bed and is currently saying daily Mass and delivering lectures in the seminary. What is even more remarkable is that this revered man of the cloth was over ninety years old at the time of his treatment and remission.

...the latest good news comes from the trenches of Stage IVb pancreas cancer...

Indeed, as the unprecedented single-agent efficacy of Rexin-G is incontrovertibly demonstrated...the progressive steps of these intrepid pioneers may provide a rational basis of hope and expectation...

June 22, 2009

Epeius...stuns the medical and scientific communities...

Yet the progressive development strategy has finally paid off with real dividends...The dividends for the cancer patient can now be measured in terms of overall survival...

June 17, 2009

Rexin-G is the flagship of tumor-targeted genetic medicine: "smart," "stealth," "selective" and "potent" nano-medicine...

June 9, 2009

...Rexin-G is the world’s smallest hero! Imagine if you will, a tiny particle that can travel freely within the human body seeking out cancerous tissues and metastatic tumors that have spread far and wide. Imagine an entire army of these tiny nano-particles seeking out and accumulating to high concentrations within the flagrant, otherwise intractable tumors with one goal in mind: to destroy the metastatic cancers from the inside. Guided by nature’s own disease-seeking factors (ie, pathotropic targeting), armed with a powerful tumor-killing designer gene, and trained in the art of efficient gene delivery over aeons of evolutionary engineering, these tiny therapeutic particles represent a new paradigm in drug delivery and a new class of anti-cancer agents that exhibit profound and unprecedented single-agent efficacy in many cancers.

...these tiny nano-particles are inherently "smart." In performing a vital cancer surveillance function, they are uniformly "vigilant." By taking on a broad spectrum of cancers that are determined to be refractory to standard chemotherapy (ie, ineffectual apothecary), they are exceedingly "valiant." By reducing the cancer patient’s body burden and extending overall survival, they are truly "heroic." In a manner of speaking, these tiny nano-particles may well be the smallest heroes in all the world. [boldface sic]

December 18, 2007

...such individual accomplishments are rarely heralded by the intrepid physicians and scientists at Epeius Biotechnologies whose mission runs contrary to so many blue-sky biotechnology companies that are quick to "sell (ie, promote) the story," only to disappoint the patients, who remain the most vulnerable of society.

June 4, 2007

Epeius Biotechnologies Corporation today announced the publication of a historic landmark in medical oncology and a definitive benchmark in the emerging field of cancer gene therapy...In other words, this paper documents the unprecedented efficacy of targeted gene delivery in the tragic battlefield of metastatic cancer...  

Frederick Hall, President and CEO of Epeius, is on my short list of suspect writers, given the ex-squeeze-me style of his quotes:

It is most fitting that Rexin-G receives its first product registration in the Philippines which brought forth the stellar physician-scientist whose drive and determination to engineer a better medicine made Rexin-G possible, and also it was first in the Philippines where the dedicated clinicians, oncologists, regulatory authorities, and medical institutions worked tirelessly for years to bring this targeted genetic medicine to the bedside.

In each and every cancer patient extends their very own impedimenta, which deepens and exacerbates with time and ineffectual apothecary. The scientists and physicians at Epeius Biotechnologies are proud to have participated in the historic events that brought these first targeted genetic medicines safely and conscientiously across the threshold of history, bringing hard science gently to the bedside.

* Because of the relative sobriety of the press releases during 2008 and the first part of 2009, I conclude that the writer was either on extended vacation, forcibly restrained from contributing to the PR process, or receiving effective psychiatric medication.

N.B. The puffed-up leadership of Epeius is also suggested by a literary explanation of the company name—a tribute to the little-known architect of the Trojan Horse.

Like white on rice, rational bloggers have been all over Bill Maher's goofy ideas about vaccines and vaccination. It's too bad, though, that the man has a nationally televised show, HBO's "Real Time With Bill Maher," which affords Maher an opportunity to influence potentially gullible viewers in front of (like many a talk/variety/comedy show) an audibly fawning studio audience.

Nevertheless, begrudging props may be given to Maher for inviting retired Republican Senator and physician Bill Frist on Friday to discuss vaccination. In this segment, it's not entirely clear that Maher "gets schooled" by Frist about vaccines (despite the clip's title). Schooling requires that Maher's thick skull be penetrable. And schooling requires time—much more time than television typically allows.

But a blog provides an enduring, leisurely format for dissecting and refuting some of the utterly fallible anti-vaccine statements that Maher made on Friday and that Frist didn't have the chance to challenge.

Maher comment #1: Conservatives always say, about healthcare especially: You gonna let the government run healthcare? They screw everything up. So why would you let them stick a disease into your arm? I would never get a swine flu vaccine or any vaccine. I don't trust the government, especially with my health. [Applause.] And that seems to be a conservative opinion: not to trust the government.

Dissection: The usually liberal Maher tries to create a bit of oh-gosh irony here by aligning himself with traditionally government-distrusting conservatives. He then jumps to make a very broad and loose association between government incompetence and government-recommended vaccination. However, if Maher were familiar with the monumental benefits of historical vaccination programs (eg, against smallpox and polio), the association actually supports organized intervention into healthcare (whether instigated by a government or some other authoritative entity, like the World Health Organization).

At the same time, Maher indicates that vaccination is a process whereby "disease" is injected into the body. First "disease" is a clinical manifestation of bodily dysfunction; it is not something that can be confined in a syringe. But we sort of know what Maher's means here, so we'll give him a pass on this semantic point. What Maher is really implying is that disease-causing virus is injected during vaccination. But that idea is also false.

With respect to the injected 2009 H1N1 (swine flu) vaccine, the inoculant is a killed (actually chemically "split") virus—which is incapable of causing infection (but is capable of inducing protective immunity). The nasal-spray vaccine from MedImmune contains live, attenuated H1N1 virus. The attenuated virus is engineered (ie, cold adapted and temperature sensitive) so that it can replicate in the cooler confines of the nose to induce immunity, without causing influenza-like illness.

Maher indicates that he would never get the swine flu vaccine, which is fine (assuming that Maher isn't at baseline risk for influenza complications and doesn't care for an infant younger than 6 months of age*). The 53-year-old isn't a CDC-recommended candidate for the 2009 H1N1 vaccine (although he should get a seasonal flu shot).

Maher comment #2 (in response to a Frist anecdote about a patient dying of swine flu): I cannot believe that a perfectly healthy person died of swine flu. That person was not perfectly healthy. Medical—Western medicine misses a lot.

Dissection: Maher's just flat-out wrong here. Regardless of what he believes, serious H1N1-related disease preferentially affects persons younger than 65 years of age, and about 45% of Americans who have died of swine flu were healthy, according to the CDC. With his last sentence, Maher also betrays a broad, inherent distrust of Western (really, allopathic) medicine. 

Maher comment #3: Let me read you a quote from the former control officer at the US FDA. His name is Dr. J. Anthony Morris. He said, "There is no evidence that any influenza vaccine thus far developed is effective in preventing or mitigating any attack of influenza. The producers of these vaccines know they are worthless, but they go on selling them anyway."

Dissection: By quoting J. Anthony Morris, Maher reveals a lazy reliance on an ostensibly authoritative source, about which he probably knows nothing. 

Finding reliable information on Morris (at least on the web) is a challenge; at first blush, he appears to be a quotable favorite among anti-vaccinationists—probably because of the specious appeal-to-authority angle (ie, Morris reportedly has/had a PhD in bacteriology and was an FDA employee). An archived newspaper search reveals that Morris was a virologist in the Division of Biologic Standards, which was part of the NIH until 1972 when the division was transferred to the FDA.

In the fall of 1971, Morris made news by arguing to Congress that influenza vaccines were not just useless, but dangerous (see Lyons RD. Influenza shots held ineffective. NYT. October 15, 1971). He claimed that "not only has there been little or no benefit from the use of influenza vaccine in man, but harm has resulted." However, a federally appointed, 12-person scientific committee rejected Morris's claims of incompetence within his NIH division; although the committee did concede, in ho-hum fashion, that "inactivated influenza vaccines are imperfect instruments for the prevention of influenza." (The committee may have been referring to subpotent lots of influenza vaccine that were distributed in the 1960s.) The committee then proceeded to reject Morris's claims that influenza vaccines are harmful (see Lyons RD. Charges of poor vaccine regulation rejected. NYT. November 30, 1971).

A related news story in June 1972 indicates that Morris had been demoted within his division, which was now (presumably) a part of the FDA. But later news reports indicate that Morris was appointed director of the Slow and Temperate Virus Branch of the agency.

In July 1976, Morris, then 57, was finally fired from the FDA for "insubordination" and "inefficiency." Morris claimed that he was sacked from his $35,000-a-year job because he opposed President Ford's swine flu vaccination program. FDA officials acknowledged, at the time, that it was very unusual for an FDA employee to be fired, but the process that led to Morris's departure began long before anybody recognized the swine flu threat. Later Morris showed up on fear-mongering talk shows like "Phil Donahue" and provided anti-vaccine quotes to news reporters as recently as 1988. 

A phrase search of various archived newspapers fails to return a source for the exact quote cited by Maher, except in 1 instance: Donald Harte, in a November 2007 editorial for the Marin Independent Journal ("Is there a vaccine that protects against non-science?") requotes Morris from a citation in a contemporary issue of Health & Fitness magazine. The quote was described as being 30 years old, but the original source was not identified. 

Morris, if alive this year (and I haven't been able to confirm whether he's alive or dead), would be about 90. 

Maher comment #4: But a virus is always mutating. You would agree with that? [Frist: Yeah.] So, so the vaccine that they produce back in March—that's not really what's gonna prevent what's, what's going on now. Because—I know a lot of people on the conservative side don't believe in evolution—but—and you can't see evolution in advanced species, but you can see—[Frist interrupts: We know this vaccine is 98% effective...]

Dissection: Here Maher tries to discount the efficacy of the swine flu vaccine by implying that the virus has mutated so much since the creation of the vaccine (in March) that it will evade whatever immunity is produced by inoculation. However, on October 9 (the same day that Maher's show aired), the CDC reported that the 2009 H1N1 viruses "have not undergone substantial antigenic change since they were first characterized in April 2009 and should be well-matched to the monovalent vaccine strain." 

Last month, data published in the NEJM indicated that significant antibody titers were generated in 97% of adults after 1 dose of the inactivated vaccine. Rates of antibody production among children aged 6-35 months, 3-9 years, and 10-17 years were 25%, 36%, and 76%, respectively. These data are the foundation for recommending 2 vaccine doses in children younger than 10 years of age. The suboptimal immune response in younger children is probably related to their limited immune experience with influenza viruses and is clearly not the result of viral mutation.

There have been scattered reports of 2009 H1N1 virus that is resistant to oseltamivir (Tamiflu), but all of these isolates were susceptible to zanamivir (Relenza).

Maher comment #5: Dr. Jonas Salk: "Live virus vaccines against influenza and paralytic polio, for example, may in each instance cause the disease it's intended to prevent."

Dissection: Another appeal to authority by Maher. Salk, as everyone knows, was the creator of the inactivated polio vaccine. The quote cannot be confirmed and, again, appears to be a favorite among online anti-vaccinationists. An archived newspaper search fails to return relevant hits, and without context, it's useless to interpret a statement that Salk may or may not have made.

* And don't we all hope that's the case.

A warning to pharma execs who are inclined to bury missed primary endpoints of clinical trials in press releases: You are personally at risk of federal indictment and conviction. No more hiding behind the company shield.

Case in point: Scott Harkonen

The former CEO of InterMune, was found guilty of wire fraud last week in a San Francisco federal court, reported the DoJ in a September 29 statement.* As a result, Harkonen faces up to $250,000 in fines and 20 years in prison. The jury-trial conviction relates primarily to a press release issued by InterMune on August 28, 2002, and reportedly at Harkonen's direction. 

The InterMune press release in question (reprinted here) claimed, in blatant up-front fashion, that the company's drug Actimmune (interferon gamma-1b) improved overall survival in a phase 3 study of patients with mild-moderate idiopathic pulmonary fibrosis (IPF). However, the trial results failed to show a statistical difference in progression-free survival, the trial's primary endpoint, between Actimmune and standard corticosteroid treatment. News of the missed primary endpoint was buried in the first paragraph of InterMune's press release and overshadowed by follow-up praise for the trial results provided by Harkonen and the study's lead investigator, Ganesh Raghu.

In January 2004, Raghu and his scientific colleagues published the results of the same trial in the NEJM. There the peer-reviewed data failed to show that Actimmune significantly improved progression-free survival, pulmonary function, or quality of life. Later that year, the DoJ launched an investigation of InterMune and its promotion of Actimmune for the off-label indication of IPF. The investigation culminated in InterMune paying a $37-million settlement to the government in October of 2006 (for a detailed timeline of InterMune's troubles, go here).** Harkonen was separately indicted by the DoJ in March of last year.

Harkonen resigned from InterMune in June 2003 and is currently President and CEO of Comentis, a San Francisco-based biotech. Notably, in his legal defense, Harkonen claimed that the InterMune press release should be protected by the free-speech clause of the First Amendment. Harkonen argued that he was engaging in "scientific debate"; the judge, however, failed to buy the argument, possibly because she found the press-release statements to be misleading.

* Harkonen was simultaneously acquitted of a misbranding charge.

** In 2007, the clinical investigation of Actimmune in IPF was abandoned by InterMune after interim results of another phase 3 trial showed no survival benefit with drug. InterMune is currently investigating pirfenidone in IPF.

Two days ago, I posted a somewhat snarky response (although this is a blog) to the NYT's expose of Forest's 2004 marketing plan for Lexapro (which was drafted in 2003). Contained within the company's leaked, abridged marketing plan was a proposal to use "reporters" from selected psychiatry journals, including "CNS News"—which was probably meant to be written as "CNS Spectrums"—to cover Lexapro data at major psychiatry meetings. (CNSNews is a conservative, mainstream, online news source.) The reports would be included as supplements in the journal and provide continuing medical education (CME) credit.

CNS Spectrums is a monthly neuropsychiatric journal published by MBL Communications, Inc, which offers some CME-certified articles in conjunction with its accredited partner, the Mount Sinai School of Medicine. The general reputation of the journal among clinicians is that of a "throwaway" publication. To wit, I used to receive unsolicited, free issues of CNS Spectrums by mail; I'd glance at them and then throw them away. Nevertheless the journal, despite its lackluster reputation, is included in the National Library of Medicine's PubMed database.

So as a follow-up exercise (and because I'm slightly nuts), I examined the articles that made it into the supplemental issues of CNS Spectrums during 2004. The objective was to determine to what extent Forest's Lexapro marketers realized their described plan, at least with respect to this particular tactic. My methods consisted of 1) a PubMed search within the confines of the year 2004 and the search term "CNS Spectr"[Journal]; 2) a directed search of the CNS Spectrums web site; and 3) a review of clinical supplements listed at the CNS Spectrums web site.

Here are the results:

At least by my search, there is no evidence that a Forest-sponsored article made it into a supplement of CNS Spectrums during the 2004 calendar year. In 5 cases, however, the supplements could not be accessed by using the search function provided at the publication's web site** or through the PubMed link (when provided). Nevertheless, in these cases, it is unlikely that Forest sponsored the supplements (ostensibly to promote the antidepressant Lexapro), given the designated topics—for instance, Alzheimer disease, antipsychotic use, or bipolar disorder.

There is also no evidence that any of these supplements were certified for CME, given the absence of designated learning objectives and other ACCME-required language. Although in 2 cases, the supplements were supported by an "unrestricted, educational grant" (both from GlaxoSmithKline). Whether any or all of these 2004 articles, all of which have clinician authors, were ghostwritten by "reporters" is just about anybody's guess. 

2004 Supplement	Topic	Sponsor	CME	Faculty Disclosures
February	Rapid-cycling bipolar disorder (panel discussion)	AstraZeneca	No evidence	No
April	Anxiety disorders (panel review)	UCB Pharma	No evidence	Yes
June	Mood and anxiety disorders (4 articles)	GSK	No evidence*	Yes
July	Alzheimer’s disease (5 articles)	No data**	—	—
August	Bipolar disorder in women (1 article)	GSK	No evidence*
August	Antipsychotic-associated hyperprolactinemia (1 article)	No data**	—	—
August	Anxiety disorders (1 article)	No data**	—	—
September	Antipsychotic use (4 articles)	No data**	—	—
October	Psychosis/schizophrenia (4 articles)	No data**	—	—
November	Bipolar disorder (3 articles based on data presented at the 2004 APA meeting)	None indicated	No evidence	No

* Although funded by an "unrestricted, educational grant."
** An "error" occurred when attempting to access the article at the CNS Spectrums web site. The error message advises contacting the web designer, which has the unfortunate name of spinindustry.com.

A review of listed clinical supplements at the CNS Spectrums web site reveals only 1 that was sponsored by Forest: "Bridging the Clinical Gap: Managing Patients with Co-occurring Mood, Anxiety, and Alcohol Use Disorders." Published in April 2008, the supplement consists of 5 articles (including an introduction), none of which appear to offer CME credit. Faculty disclosures are provided with each article, and "editorial assistance" is acknowledged by name (Eileen McGee, Marsha Kellar, and Joyce Waskelo) and company (Hudson Medical Communications, which is described as a promotional firm at the web site of its parent company). The acknowledgement appears to be an attempt at editorial transparency and to undermine accusations of ghostwriting. But given the suspicion that McGee, Kellar, and Waskelo actually drafted the articles, they should have been defined as coauthors.

In the 5 articles, "escitalopram" (ie, Lexapro) is mentioned exactly 4 times in the text bodies and in conjunction with other antidepressants (eg, citalopram [Celexa], fluoxetine [Prozac], and paroxetine [Paxil]).

ACCME = Accreditation Council for CME; APA = American Psychiatric Association.

I got carsick on my couch last night watching CNN's John King mess around forever with that touch-screen map of Indiana. There are really only so many times that anyone should have to watch Lake County being enlarged and shrunk.

Perhaps trying to justify how it spent the last 5 months, the AP follows up its throw-up-your-hands-to-the-skies "exposé" of trace-trace-trace pharmaceuticals in drinking water by reporting the reactions to its story. "Test it, study it, figure out how to clean it—but still drink it," is how the AP begins its follow-up. Did the AP—perhaps now substituting alcohol for all of its drinking water—expect that we would or should avoid consuming water on the basis of its arguably useless report?

 

"There is no wisdom in avoidance," advised one Washington-based environmental lawyer as quoted by the AP. No freekin' shit, Sherlock. Whatever risks may be posed by drinking infinitesimal amounts of pharmaceuticals—and nobody knows if there are any—lack of water will kill in no time. Trust me. They teach that stuff in medical school.

 

The AP water story reminds me of those ridiculous signs in California hotels that warn of the dangers of breathing the building's air. What in a supreme being's name am I supposed to do with that information? Not breathe? Run outside, where the air's even filthier?

 

Next thing you know the AP's going to tell me that saliva causes cancer, but only if swallowed in small quantities over an extended period of time. No wait. Chevy Chase already reported that information on SNL in nineteen-dickety-two. It's the cycle of news to parody, back to news again.

 

Photo: www.saturday-night-live.com