Monday, April 30, 2007
Apparently drug marketers are making drug names to appeal directly to humans (duh), but in a manner that is more direct. Think about drugs for humans, like Prozac -- well, Pro is good, but what the hell is Zac? But new doggie drug names like Reconclie (doggie Prozac), Slentrol (for fat pooches), and Serenia (to prevent dogs from puking) -- pretty straightforward. After all, it's easier to be serene when one's dog is not yakking all over the floor. Slentrol (uh, slender-control), and Reconcile (no, you're a GOOD doggie parent -- reconcile with your sad dog with dog-Zac) are likewise easy to figure out.
Hat tip to Pharmalot and Name Development.
The irony is that Lilly claims that the documents which paint a rather awful picture of its off-label marketing (here, here, here, and here) are taken out of context, yet they refuse to make any additional information available. If the documents are out of context, why don't you provide some context? Indeed, they are suing those who tried to disseminate information pertaining to the drug. And let's also not forget about the email exchange where a Lilly employee discussed ways in which a study casting dispersions on the "safety" of Zyprexa could get deep-sixed through nefarious means.
Very sad news to report. Pharma Giles, easily the most entertaining pharma-related blog, has decided to call it quits. I wish he were just pulling a Peter Rost and retiring for a week, then coming back, but Giles strikes me as pretty serious. That being said...
PLEASE DON'T GO!!! PharmaGossip and Peter Rost agree with me, as I'm sure do others. You can't possibly leave. Who will fill your shoes?
Friday, April 27, 2007
Once again, Berenson uses the "one paper out of several thousands of documents" approach to depict Lilly as a criminal corporation.Further, it is added
On the heels of intense criticism of the NYT coverage of the Duke rape case and the paper's falling earnings, the Berenson reporting is another example of the Times decline.OK. Here's my challenge. I'd like Drug Wonks or, well, anyone to read the following posts. Read the Lilly documents that are freely available and are linked within said posts. Then talk about how Lilly is a good corporate citizen, and did not promote Zyprexa off-label. Here you go...
- Demented Marketing of Zyprexa?
- Marketing Zyprexa as the New Mood Stabilizer...
- Zyprexa Off-Label Promotion (?)
- Zyprexa Off-Label Marketing (?): Part 2
A preliminary ruling has indicated that GlaxoSmithKline should pay out $63.8 million to make amends for making misleading claims about its antidepressant Paxil (Seroxat) in kids. Of course, the company admits no wrongdoing.
I wonder if the authors who stamped their names on the the main ghostwritten "scientific" publication for Paxil in kids should also be shelling out some cash. After all, it was the paper (chock full of HUGE misinterpretations of the study data) with their names on it that was doubtlessly used as part of the Paxil in kids marketing campaign. Were these "independent" academics innocent parties who were misled by the corporate meanies at GSK? Or, conversely, were these academics an integral part of the marketing team and should they also be held accountable for making false claims? Like these claims made in the infamous GSK study 329 (from an earlier post)...
What counts as safe and effective on Planet Paxil passes as ineffective and dangerous to us Earthlings. So while I'm glad to see that it appears GSK will be shelling out some dough to compensate its , consumers, the systemic problems of ghosted science and outright lying are not addressed. What is $64 million to GSK? Roughly a drop in the bucket. And the "key opinion leaders" who pimped Paxil escape unscathed.
Article: Paroxetine is generally well-tolerated and effective for major depression in adolescents (p. 762).
Data on effectiveness: On the primary outcome variables (Hamilton Rating Scale for Depression [HAM-D] mean change and HAM-D final score < 8 and/or improved by 50% or more), paroxetine was not statistically superior to placebo. On four of eight measures, paroxetine was superior to placebo. Note, however, that its superiority was always by a small to moderate (at best) margin. On the whole, the most accurate take is that paroxetine was either no better or slightly better than a placebo.
Data on safety: Emotional lability occurred in 6 of 93 participants on paroxetine compared to 1 of 87 on placebo. Hostility occurred in 7 of 93 patients on paroxetine compared to 0 of 87 on placebo. In fact, on paroxetine, 7 patients were hospitalized due to adverse events, including 2 from emotional lability, 2 due to aggression, 2 with worsening depression, and 1 with manic-like symptoms. This compares to 1 patient who had lability in the placebo group, but apparently not to the point that it required hospitalization. A total of 10 people had serious psychiatric adverse events on paroxetine compared to one on placebo.
What exactly were emotional lability and hostility? To quote James McCafferty, a GSK employee who helped work on Study 329, “the term emotional lability was catch all term for ‘suicidal ideation and gestures’. The hostility term captures behavioral problems, most related to parental and school confrontations.” According to Dr. David Healy, who certainly has much inside knowledge of raw data and company documents (background here), hostility counted for “homicidal acts, homicidal ideation and aggressive events.”
Suicidality is now lability and overt aggression is now hostility. Sounds much nicer that way.
Please read the fine post at Health Care Renewal about how academics might be brought to think twice before becoming drug pimps. I also think that giving out sarcastic awards to academics who participate in ghosted science is a good idea, so here goes...
Awards? I'd like to nominate Dr. Karen Wagner for a Golden Goblet, or perhaps a Krusty the Klown award for her pimping of Paxil as well as her stalwart work on the "SSRIs are great for kids" report authored on behalf of the American College of Neuropsychopharmacology. Her reports of clinical trials that overstated the efficacy and hid serious side effects of Zoloft also merit special mention. Overstating the efficacy of citalopram in kids was also nice work. While she was co-authoring the report saying that SSRIs are great for kids, she was also busy conducting trials of SSRIs for kids. Sound like a conflict of interest? Worry not, because she was also sitting on the conflict of interest committee at her own university!
Please feel free to add your nominations.
Oh, and as for the latest version of SSRIs are great for kids report (in JAMA). I'll hopefully get on that sometime in the near future. Suffice to say that it is highly misleading for now.
Wednesday, April 25, 2007
The FDA has questions about a Lilly document from February 2000 in which the company found that patients taking Zyprexa in clinical trials were three and a half times as likely to develop high blood sugar as those who did not take the drug.But worry not, Lilly is claiming the above was just an honest mistake. Kind of a large mistake, eh? After the data were analyzed accurately, then Zyprexa did not appear nearly as risky. Of course, we can be sure Lilly is being honest, just like when they said that they never marketed Zyprexa as a treatment for dementia. Or the time they said that Zyprexa does not cause diabetes. Or maybe when Lilly decided to sell Zyprexa as a "safe, gentle psychotropic." I think you get the point... It is indeed possible that Lilly is being truthful, but I personally doubt it.
That document was not submitted to the agency. But a few months later, Lilly provided data to the FDA that showed almost no difference in blood sugar between patients who took Zyprexa and those who did not.
On a side note, good to see that Alex Berenson is back to writing about Zyprexa.
Thursday, April 19, 2007
Oh, and another study found that using behavioral sleep management techniques resulted in higher quality sleep than did taking Lunesta. So keep that butterfly out of my bedroom!
With that, I close. I'll be away for a few days. Enjoy your weekend.
I bow down to Peter Rost. Why? Let's see... He broke the latest AstraZeneca Arimidex off-label marketing scandal. Rather than being a one-time story, it has continued to unfold, looking worse and worse for AZ. Rost continues to serve up hot AZ insider information, as the scandal grows wider in scope. He has also backed up his brand of investigative journalism with evidence (here and here) that points quite directly at AZ marketing their product in an off-label fashion. And the plot continues to thicken, as you can see here.
Keep up the good work Peter!
OBJECTIVE: The safety, efficacy, and tolerability of venlafaxine extended release (ER) in subjects ages 7 to 17 years with major depressive disorder were evaluated in two multicenter, randomized, double-blind, placebo-controlled trials conducted between October 1997 and August 2001. METHOD: Participants received venlafaxine ER (flexible dose, based on body weight; intent to treat, n = 169) or placebo (intent to treat, n = 165) for up to 8 weeks. The primary efficacy variable was the change from baseline in the Children's Depression Rating Scale-Revised score at week 8. RESULTS: There were no statistically significant differences between venlafaxine ER and placebo on the Children's Depression Rating Scale-Revised in either study. A post hoc age subgroup analysis of the pooled data showed greater improvement on the Children's Depression Rating Scale-Revised with venlafaxine ER than with placebo (-24.4 versus -19.9; p = .022) among adolescents (ages 12-17), but not among children (ages 7-11). The most common adverse events were anorexia and abdominal pain. Hostility and suicide-related events were more common in venlafaxine ER-treated participants than in placebo-treated participants. There were no completed suicides. CONCLUSIONS: Venlafaxine ER may be effective in depressed adolescents. However, its safety and efficacy in pediatric patients has not been established. Prescribers should monitor for signs of suicidal ideation and hostility in pediatric patients taking venlafaxine ER.
Here are my gripes...
- OK, so the studies were conducted in 1997 and 2001. And they're just getting published NOW? How's that for delaying the bad news? Were the studies positive in their findings, they would have been published years ago.
- Suicidal ideation/suicidal attempt/suicide preparation: 8 of 182 taking venlafaxine, 0 of 179 taking placebo (these numbers come from the latest JAMA analysis, table 3).
- Grasping at straws: One analysis finds that adolescents do a bit better on the drug, and you decide to run with it? Was this finding consistent across various rating scales or was it just one one scale? My initial guess is that the difference was also of a rather small magnitude.
One blogger (Pharmalyst) has estimated that Lilly's new doggie Prozac could bring in $270 million annually in US sales. Sounds over the top, but maybe it could happen. I looked for the clinical trials, because I really want to know how one measures canine depression, but I couldn't find any information.
Wyeth on Thursday said low doses of its experimental drug Pristiq were effective against both depression and hot flashes and caused less nausea than seen in prior studies of higher doses, boosting prospects for the company's most important experimental drug.Well, good. With antidepressants, we all know by now that "effective" means "slightly better than placebo" on average. Pristiq, a knock-off of Effexor, is hoping to nab FDA approval early in 2008. Can't wait to see the ad campaign. Depression Hurts is already taken, so with the depression/hot flash combo, I have the following idea:
Does Depression Make You Hot? Let Pristiq Cool You Down.
Hat tip: Pharmalot
The DSM has had a dehumanizing impact on the practice of psychiatry. History taking—the central evaluation tool in psychiatry—has frequently been reduced to the use of DSM checklists. DSM discourages clinicians from getting to know the patient as an individual person because of its dryly empirical approach. Third, validity has been sacrificed to achieve reliability. DSM diagnoses have given researchers a common nomenclature—but probably the wrong one. Although creating standardized diagnoses that would facilitate research was a major goal, DSM diagnoses are not useful for research because of their lack of validity.Ouch. Training in psychiatry programs as well as (sigh) some psychology programs has often been reduced to memorizing symptoms and asking yes-no questions from a checklist. See what diagnosis a person has by asking a bunch of structured questions then whip out a prescription pad. Talk with the patients about their problems, develop a relationship? Nah, we never learned about that in our graduate/medical training.
Hat tip: AHRP.
Monday, April 16, 2007
In any case, the letter then goes on to make some astounding claims, including [bold font in original letter]
The clinical profile of Lexapro and citalopram are distinct, as illustrated by the following:
- Lexapro is effective in the treatment of major depressive disorder (MD) and generalized anxiety disorder (GAD). In contrast, citalopram is not indicated for GAD, or for any other anxiety disorder. [citations were to the respective drug labels.]
- There is clinical evidence for the greater efficacy of Lexapro vs. Celexa
...among others. For a very nice analysis of why these claims are misleading, please read the full post at Health Care Renewal. My two cents on why the claims are misleading is as follows:
- Since its patent was running out, Forest opted to not seek FDA approval for any anxiety disorders. No study has ever compared the two compounds in treating anxiety. While true that citalopram is not FDA-indicated, this should not be taken as a sign that it would perform worse than escitalopram in anxiety. Indeed, across the class, SSRIs are efficacious (in the short-term, and not a lot better than placebo) for anxiety.
- The evidence cited to support the greater efficacy of escitalopram over citalopram is very weak. It comes from looking only at the few instances where escitalopram showed a very small advantage over citalopram and ignoring the great majority of the evidence that suggests equivalent efficacy of the two compounds. An excellent article by Svensson and Mansfield laid this issue to rest years ago. Here's what they said regarding Forest's prior advertising claims that Lexapro is more effective than Celexa:
"The advertising claims are not justified because they are based on secondary outcomes, non-intention-to-treat analyses and arbitrarily defined subgroups. The subgroup results are inconsistent. Methodological flaws in the trials could account for the differences found. Even if the differences claimed were real they appear too small to justify higher prices."
My thought is that the letter may have something to do with managed care policies, but it is also a stealth advertisement for Lexapro as being the most efficacious SSRI. After all, if it is "better" than Celexa, then maybe it is "better" than other SSRIs. Of course, this would not be the first time that something Lexapro-related was looking at the scientific evidence through rose colored glasses.
According to Bloomberg, Lilly is planning to ramp up marketing of Cymbalta and Zyprexa. Can you say Viva Zyprexa Strikes Back? How about Anxiety Hurts (1, 2)? I wonder to whom Lilly will market Zyprexa? Seriously -- they've tried primary care, psychiatrists, and likely the geriatric market, so who's next? How about pediatricians? Tantrum = Zyprexa?
Friday, April 13, 2007
Lest you forget, AZ also makes Seroquel, and the lawsuits have already begun about the, um, liberal, marketing of that product. More on Seroquel's ever-expanding market here and here.
- AHRP notes that the FDA review panel which will examine the risks associated with Merck's new COX-2 inhibitor, etoricoxib (Arcoxia), is stacked to find that the drug is safe. How? Well, as AHRP said:
The arthritis specialists who voted to keep the COX-2 inhibitors on the market were reappointed. But the four most vocal critics of the COX-2 pain killers were NOT to reappointed. FDA apparently wants to avoid a full examination of the safety issues when considering approval of Merck's Vioxx replacement drug.
- But the good news is that with the exception of one member (and who the hell was that one member?), Arcoxia got voted down by a 20-1 margin. GoozNews has a great post that mentions how the advisory committee decided getting fooled twice was not an option. David Graham, unsurprisingly stepped up the the plate yet again. Incredibly, Merck decided to compare Arcoxia to another drug that has an elevated risk of causing heart problems. And the IRB that approved that study was...? By comparing it to a risky drug, Merck could attempt to claim that Arcoxia didn't increase cardiovascular risk. That's like comparing a drug to getting hit by a sledgehammer. "Well, the drug was actually less risky than being brained with a large blunt object; therefore, it is clearly safe." Nice to see that the FDA didn't fall for it this time.
- Pharmalot also has a nice summary of the Arcoxia debacle.
- No surprise here -- Pharma Giles is guilty of causing me to nearly suffer the same fate as those who took the ill-fated drug Uleak due to my Def Comedy Jam type laughter at two of his recent posts. Here's the one on Uleak and here's one thinly disguised parody of the latest developments at AstraZeneca.
- Peter Rost received some information, allegedly from an Astra Zeneca insider, stating that they were tired of AZ's unethical practices, specifically referencing the marketing of Arimidex (anastrozole). Can Seroquel be far behind?
- I also give Dr. Rost credit for applying for positions in the drug industry. Read his hilarious (and accurate) cover letter.
- Philip Dawdy notes that yet another class action lawsuit has been filed against Lilly for its heavy pimping of Zyprexa.
- Seroxat Secrets points out another example of patient advocacy groups carrying Big Pharma's water. In this case, it appears that the Depression Alliance is participating in the marketing of Cymbalta. The Cymbalta Pimp-A-Thon continues.
Wednesday, April 11, 2007
When 6-year-old Desre’e Watson threw a tantrum in her kindergarten class a couple of weeks ago she could not have known that the full force of the law would be brought down on her and that she would be carted off by the police as a felon.Read the whole story at Welcome to Pottersville. Sheesh.
But that’s what happened in this small, backward city in central Florida. According to the authorities, there were no other options.
“The student became violent,” said Frank Mercurio, the no-nonsense chief of the Avon Park police. “She was yelling, screaming — just being uncontrollable. Defiant.”
“But she was 6,” I said.
The chief’s reply came faster than a speeding bullet: “Do you think this is the first 6-year-old we’ve arrested?”
The child’s tantrum occurred on the morning of March 28 at the Avon Elementary School. According to the police report, “Watson was upset and crying and wailing and would not leave the classroom to let them study, causing a disruption of the normal class activities.”
After a few minutes, Desre’e was, in fact, taken to another room. She was “isolated,” the chief said. But she would not calm down. She flailed away at the teachers who tried to control her. She pulled one woman’s hair. She was kicking.
I asked the chief if anyone had been hurt. “Yes,” he said. At least one woman reported “some redness.”
Well, Portland, Maine has a program going that claims it takes people at risk for psychosis, provides intervention (including low-dose antipsychotics) and BAM they DON'T develop psychosis. The details are cloudy at this point. They certainly have an attractive website and they stick with the time honored brain disease model of mental illness to a point that is often well beyond the science.
I've not the time to look at this in more depth today, but fortunately Furious Seasons has given this a good look and I strongly encourage everyone to read about it on his site.
This does have shadows of the eerily awful study that provided "at risk" individuals with Zyprexa to help them not develop schizophrenia or to help them develop diabetes, depending on how you look at it.
But without academics pushing SSRIs, their use will wane--and, importantly, so will their support of the diagnosis "Major Depression." This is going to sound controversial, inane, but it will happen.
Look for upcoming articles finding that "Depression" is overdiagnosed, that it is really just-- life. Look for articles that now find SSRIs aren't that effective after all, that the old "10% better than placebo" is a statistical trick with little clinical utility. That they are way overused in kids.Nice to see a great post by another person who has noticed the sea change toward antipsychotics, er, "broad spectrum psychotropics." And bipolar disorder -- Oh yes, some academics have been saying for years that many cases of depression were bipolar in disguise, and now we're finding that more and more folks are jumping on that bandwagon. How convenient.
You might say, wait, isn't the decline of polypharmacy a good thing; that SSRIs are overused in kids; that they aren't that great; and that depression is overdiagnosed? All of this is true, but this isn't psychiatry finally coming to its senses; this is psychiatry entering the manic phase. Sure, it's less SSRIs for kids; but it's more antipsychotics.
Because simultaneously there will be articles pushing the idea that recurrent unipolar depression is really bipolar depression; that there are common genetic or heritability patterns; that the epidemiology and course is similar, etc. The move will be to squeeze out MDD into "life" and bipolar. This done, antipsychotics become first line agents. Oh, and look for antipsychotics to get FDA approvals for kids.
And polypharmacy will only be reincarnated-- in the form of multiple simultaneous antipsychotics (Abiliquel, anyone?), with preposterous pharmacologic justifications ("this one acts on serotonin, so it's the antidepressant, and this one on dopamine, so it's the antimanic.") If anyone says that to you, stab them.
Brief History of Diagnostic Trends: When benzos were the big drugs, everyone had anxiety. When the SSRI era was born, depression was the disease of the day. When depression was saturated, the move was on to raise awareness about social anxiety, generalized anxiety, PTSD, etc, as the SSRIs still had patent life to spare, and hence markets to conquer. The new frontiers are depression with pain, for which Cymbalta is allegedly the drug of choice (despite rather meager supportive evidence), and bipolar, for which Seroquel, Abilify, Zyprexa, and Risperdal/Invega have already made significant inroads. Lilly cleverly tried to expand the bipolar market with the Viva Zyprexa and Zyprexa Limitless campaigns, but it was just the first step in a much larger campaign.
Again, here's the link to the Last Psychiatrist's post.
Tuesday, April 10, 2007
Depression Diagnosis is Arbitrary: As an astute reader (Dr. BK) pointed out, there is no doubt that having to meet a selected number of symptoms to qualify for a diagnosis will always leave some room for error. In the case of depression, it’s a lot of error, as someone could have only three symptoms of depression and not qualify for a depression diagnosis. If these are really nasty symptoms (say, extreme sadness and guilt along with suicidal ideation), then it’s a little odd to say the person is not depressed.
But let’s not get all tied up in the DSM definition of depression – I could go on regarding this topic for days.
I have two more main concerns.
1. Expanding the boundaries of depression and anxiety to indicate that less severity = you still need treatment.
2. If someone is experiencing depression/anxiety as a normal reaction to some sort of loss, is treatment a good idea?
Expanding the Boundaries. It seems that expanding the boundaries of depression and anxiety, meaning stating that more people with less severe manifestations of these conditions require treatment, is based on a very shoddy foundation. It’s somewhat like lowering the threshold for what constitutes high blood pressure or high cholesterol. Treatment may help some of these people who did not “need” intervention until recently, but the great majority of them will see no benefit. Likewise, if we move the bar from, say, more depressed than 85% of the population to more depressed than 60% of the population, is there any long-term (or even short-term) benefit from treatment? Are we really reducing the risk that these folks will become more depressed and more anxious later in life? Are we improving their quality of life?
And let’s face it – these people, the “worried well,” are in large part not receiving psychotherapy. And there is not much data to say that if they did receive therapy, they’d be any better off. We know that psychotherapy works fairly well with folks who have various DSM conditions, but for these lower grade problems, I don’t think there is much supportive evidence. I believe that psychotherapy may indeed help some of them, but like I said, the point is relatively moot, as expanding diagnostic boundaries leads to more people receiving meds, with a somewhat negligible effect on those receiving psychological intervention.
To my knowledge, no drug has any consistent data to support its use in this group of “patients,” and this is certainly true for long-term outcomes. So, if we’re going to treat people who have mild anxiety and/or depression, keep in mind that it is based on hope (for profits and/or people’s well-being), not science. If the drugs (namely, SSRIs) relate to increased suicidality and sexual side effects, then is that the price we’re willing to pay? What if people frequently have difficulty discontinuing the medication due to withdrawal effects?
“Normal” Depression and Anxiety: If you are having significant problems with your family members, friends, spouse, boyfriend/girlfriend, coworkers, boss, etc., and you are experiencing depression/anxiety as a result, do you need treatment? It would seem somewhat normal to struggle to a degree when dealing with the aforementioned life circumstances.
I’m advocating that in some cases we may want to take a [gasp] minimal intervention approach. Suppose someone rolls up to your office and she is pretty bummed out after losing a job and is having a tough time in a relationship. Before whipping out the prescription pad, maybe provide some brief counseling. Have the person follow up in a couple weeks and see if she is improving on her own. People are generally pretty resilient. With some time, many folks will bounce back on their own or with a little bit of help. Though the analogy is not exact, we know that chasing after victims of hurricanes and other disasters and insisting that they all receive some sort of counseling does not seem to help their psychological state. So, we shouldn’t be so sure that we can just intervene with everyone who is undergoing some type of hardship and expect positive results. One could argue that the people seeking treatment are the ones who are not very resilient, and that’s a discussion to be had at another time.
To be clear, if someone is falling apart, then by all means offer serious treatment. If someone is mildly anxious/depressed, then it would seem that a more mild intervention (like brief counseling with some follow-up) is in order. Have I gone out of my mind? Does this seem unreasonable?
Maybe this is all pie in the sky hypothetical crap anyway. Most of the people who have some sort of problem adjusting to life’s many problems are likely heading to their primary care physician, who is likely not all that well-trained in mental health, who very well may have the belief that SSRIs are harmless and should be prescribed for whatever mental ailment, short-term or long-term, mild or debilitating, that you have. And how can we blame the doctor – he/she has little training in mental health, has been encouraged to treat mental health cases rather than refer them, and is likely unable to understand the limitations of the research regarding the treatments he/she prescribes because that sort of information was not covered in medical school or in the continuing “medical education” classes he/she has taken for the past ten years since leaving med school.
Other posts surrounding patient advocacy groups and conflicts of interest can be seen here and here.
Monday, April 09, 2007
Above are some pictures of a Swiss Army Knife and a tape measure, both adorned with the Zyprexa name, which can be purchased on Ebay. The Swiss Army Knife was apparently used in the Zyprexa Primary Care marketing campaign as a gift to doctors (see the documentation here). Not sure where the tape measure came from, but I'd bet it was also some sort of marketing tool.
More on the Zyprexa marketing story can be seen here, here, here, and here.
Friday, April 06, 2007
Thursday, April 05, 2007
- Conflicts of Interest, What Conflicts of Interest? Well, Seroxat Secrets can help to answer that question. Seems like I also had a post on a similar topic. Yep, here it is.
- Furious Seasons provides an update on the Zyprexa legal debacle. Make that two updates.
- Pfizer Legal = Retaliation 101? Find out here. While you're at Rost's blog, check out the story on Corporate Spies.
- Pharmalot points out that working as an AstraZeneca sales rep apparently ain't all that much fun. Incidentally, if you're not reading Pharmalot on a daily basis, you need to change your reading habits. Pronto.
- Pharma Giles is (again) brilliant in his parody of both a fictional (?) pharma CEO and how big Pharma might not like blogs such as his.
- Many great posts on the Genotropin/Pfizer story this week, and I am particularly fond of Health Care Renewal's fine take on the issue.
- Last, but certainly not least, Brandweek NRX discusses the issue of celebrity endorsements of drugs (legal dugs, for your Scott Weiland fans). Note that celebrities apparently love antidepressants.
Corcept Therapeutics Incorporated (NASDAQ: CORT) today announced the completion of a private placement of 9,000,000 shares of its common stock at a price of $1.00 per share, pursuant to a definitive agreement entered into today with accredited investors. The investors are led by Paperboy Ventures LLC, who is currently a significant shareholder of Corcept. Sutter Hill Ventures, Alta Partners, LLP, venture capital firms that are currently significant shareholders in Corcept, and members of the Corcept Board of Directors, Joseph C. Cook, Jr., James A. Harper, David L. Mahoney, Alan F Schatzberg, M.D. and James N. Wilson, are also investors. In addition, investors in this financing round included Black Point Group, LLP, Vaughn Bryson and Daniel Bradbury.Already a good short-term investment, as the stock is now at $1.21 a share. If you've read my prior writings about Corcept, you can see that I'm highly skeptical about it's main product, Corlux (mifepristone/RU-486), which is aiming to treat psychotic depression. Although the company has tried to spin negative findings as actually being positive, it's hard to see how a series of studies showing poor efficacy will lead to helping patients in any meaningful fashion. Might the latest influx of cash help out the Corcept insiders who hold a major stake in the company? Sure.
Conflicts of Interest: It appears that Dr. Alan Schatzberg bought 50,000 shares in the latest round of funding. It has been reported previously that Schatzberg has written quite positive comments about Corlux in journals and some have questioned whether his financial stake in the company has skewed his judgment on the topic. I want everyone to consider the following conundrum...
Schatzberg holds about 4.83 million shares of Corcept currently. So, if Corlux bombs a clinical trial, is he going to:
A. Immediately report the negative results in a press release
B. Move publishing the negative results in a scientific journal to the top of his to-do list
C. Spin the results in a very favorable fashion (or make sure that someone who writes the press release and/or scientific paper does so)
D. Just bury it entirely (probably not an option with such a small company that likely announces most if not all of its trials beforehand)
If I was in a position where I had such a large financial stake, I'd have a hell of a time doing A. or B. When large dollar amounts are at stake, it's not easy to say, "Hey, this product doesn't seem to work" and watch your stock holdings evaporate. This is why conflicts of interest are a problem.
Some academic researchers really are just in it for the money. I think they are a very small minority. I bet that most researchers who end up with big-time conflicts of interest start off thinking, "Hey, this could be a great new form of treatment for condition X." Then, hey, why not make some money while you're doing God's work, helping to heal people. We're an entrepreneurial society, so we tend to believe that people should be rewarded for having an enterprising spirit. Now, if the product turns out to not be so effective and/or to have some unpleasant side effects, then look at the predicament... Here's the conflict -- help people with condition X or help my own cash flow?
Or say I'm a doctor who makes some good money on the side giving "educational" speeches to fellow physicians about a drug, say, Zyprexa. When I find out that said drug is linked to numerous health problems, do I bring that up in my speeches, knowing fully that such discussion is likely going to get me canned from the speaking circuit?
The list of potential examples could go on for days.
The current diagnostic system does not weed out these people as not having depression. In fact, the only thing that counts as an "excuse" to have a significant number of depressive symptoms is bereavement (having a loved one die). So if you lose a job, get divorced, lose a pet, have a falling out in a relationship with a friend or family member, etc... the current system says if you have significant symptoms of depression for two weeks or more, then BAM, you're depressed.
And we all know that "depression" is predominantly treated with medications. Sure, you might get psychotherapy but the odds of receiving medication are certainly greater than getting psychotherapy. The "epidemic" of depression has been very sweet to those who sell SSRIs.
So, to summarize, tens of thousands of people who have been experiencing difficulties as a result of a loss of some sort have likely been mislabeled as depressed, likely leading to unnecessary treatment. Should real depression be treated? Yep. Should people receive "therapy" of some sort because their boyfriend/girlfriend kicked them to the curb and that's led to a rough month in their life? Hmmm...
Hat Tip: Furious Seasons. BTW, I'd like to write something waaaaaaay more insightful here, but there's only 24 hours in a day, so maybe next week??
Update: Read the comments! Excellent points made by three individuals so far. Feel free to join the conversation...
Wednesday, April 04, 2007
Has anyone else wondered if the prevalence of ADHD doesn't parallel caffeine use and sleep deprivation, especially in kids (kids don't take naps anymore)? And that the main treatments are-- stimulants?Interesting...
Tuesday, April 03, 2007
GSK -- More Documents. Oh boy. The good folks at Healthy Skepticism have posted a slew of documents pertaining to the infamous GSK Study 329, in which Paxil was described in a 2001 journal article as safe and effective, yet the data showed some rather heinous side effects occurring much more frequently in the Paxil group (such as significant aggression and suicidal behavior) than in the placebo group. The data also showed, at best, a small advantage for Paxil over placebo, an advantage that was more than outweighed by the significant incidence of serious side effects.
I've looked at a few of the newly posted documents and hope to post my take on them in the near future. In the meantime, I refer you to the documents on Healthy Skepticism's excellent website.
Hat tip to Philip Dawdy at Furious Seasons for beating me to the punch and linking to the above documents. Also beating me to the story, he mentioned that in the latest American Journal of Psychiatry, there is an editorial on adolescent bipolar disorder written by Boris Birmaher, one of the articles on the now discredited GSK 329 study. Birmaher states that it is quite important for bipolar disorder to be increasingly recognized and treated in youth.
Dawdy essentially asks why we should trust Birmaher given his involvement in the scandalous GSK Study 329 (please read this link for background info). Despite several years passing since the publication of the study's results, not a single one of the "independent" academic authors have apologized or spoken out against the way the data were manipulated and misinterpreted.
Key Opinion Leaders or Used Car Salespeople? If academic psychiatry wants some credibility, then it is high time for the so-called opinion leaders to issue a mea culpa -- it's time to admit some fault. Here's my message to the the big-name academics in psychiatry, which likely applies to the academic bigwigs in many other branches of medicine as well: Rather than pimping drugs in corporate press releases, taking cushy consulting gigs, and rubber stamping your name on ghostwritten articles (based on data you have never actually seen) and infomercials labeled as "medical education," turn over a new leaf. Have you been used? Are you really performing science or are you just a tool of a marketing division? What good is your research actually doing for patients? Does selectively reporting only positive data and burying the negative data really help people struggling with mental anguish?
How is it different to hide the faulty mechanics on a 1986 Ford Tempo as a car salesperson versus, as a researcher, to hide safety and efficacy data on a medication? The same rule is applying -- Tell to Sell. In other words, if it ain't going to help sell (the car or the drug), then keep your mouth shut.
Must...take..."broad spectrum psychotropic agent"...too outraged to function...
Sunday, April 01, 2007
Sheesh, I wonder what I gotta do to pick up a little respect over at John Mack's Pharma Blogsophere. It ain't enough that this site apparently ranked highly on Mack's own survey -- I'm still only getting second-tier billing over at his site. Where's the love, John? This kind of treatment might give me generalized anxiety disorder!