Psychiatric medications, science, marketing, psychiatry in general, and occasionally clinical psychology. Questioning the role of key opinion leaders and the use of "science" to promote commercial ends rather than the needs of people with mental health concerns.
Friday, May 30, 2008
BOLDER Update: Lilly Started It
Lilly Started It: It just so happens that Philip Dawdy (who has apparently been christened as Dr. Dawdy) at Furious Seasons recently had a letter published in the Journal of Clinical Psychopharmacology on this issue of statistics. Dawdy noted that the authors' use of a statistical method known as mixed models repeated measures (MMRM) rather than the more conventional last observation carried forward (LOCF) resulted in a major inflation in effect size. As I mentioned earlier, the choice of methods to calculate the effect size (the magnitude of difference between drug and placebo) had a big impact. Dawdy aptly noted that the authors should have reported the effect sizes calculated by both methods so that readers could note how one method made Seroquel look better than did the other method. To quote Dawdy, "...the authors should also have reported the LOCF effect sizes so that the readers would have been aware of how the method impacted the findings." I was flattered to see that my blog was cited in Dawdy's letter. I heard through the grapevine that another author attempted to cite my blog in a letter to the editor, but that the journal struck the citation to my site in the final version of the published letter. If some of y'all researchers who read this blog wanna cite my site, go ahead.
I'm not saying that Seroquel was a dud, but that it did get a boost from the analysis used in the study. When the authors are playing by a new rule when it comes to calculating the differences between drug and placebo, it would make sense to report the results using both the old rules and new rules. In his response, Michael Thase of the BOLDER team responded that "It is my understanding that mixed model repeated measurement (MMRM) analysis was chosen to compute effect sizes in the BOLDER studies because it would permit direct comparison with the results of the study of the only other treatment approved for bipolar depression, the combination of olanzapine and fluoxetine (OFC). Thus, in plain and simple terms, we were attempting to facilitate an apples to apples comparison between quetiapine monotherapy and OFC." So because Lilly did it, we did it. Um, OK. But is there some kind of law against reporting the results from both the newfangled MMRM analysis and the old-fashioned LOCF analysis? Just wondering. And if Lilly started saying it was okay to market Zyprexa off-label for various conditions, would that mean all antipsychotics could be marketed off-label for all sorts of issues? (Hypothetically speaking, of course.)
Stats: Thase goes on to note that there is some research suggesting that MMRM does not overinflate effect sizes; rather, LOCF underestimates them. I know a bit about stats, but I'm not a statistician. Basically, the differences between the methods boil down to how data is handled for persons who dropped out of a study. The best solution is to try to track down study dropouts and assess how they are functioning, rather than having a statistical model guess at their sense of mental well-being, but this requires extra effort and time, and is sometimes not possible. Basically, the LOCF model makes some assumptions that are quirky at best, while MMRM seems to handle missing data better in many situations. All that being said, in many trials where a drug beats placebo, MMRM appears to generate effect sizes that are higher than LOCF, which then leads us to a question "Geez, have we been underestimating the effects of drugs by 50%?" -- um, that seems a little hard to swallow. I'm not quite ready to buy into that.
Friday, May 23, 2008
Smoke and SHHHHHHHHHHHH!
“There is restrictive language in here,” said Francis L. Macrina, Virginia Commonwealth’s vice president for research, who acknowledged that many of the provisions violated the university’s guidelines for industry-sponsored research. “In the end, it was language we thought we could agree to. It’s a balancing act.”Oh, that's okay then. Just because you are Philip Morris's hush-hush scientific whore, it's not a big deal. It's a "balancing act," which roughly translates to "We'll do anything for a buck."
Rick Solana, the senior vice president for research and technology, said university scientists were studying how to identify early warning signs of pulmonary disease, and how to reduce nitrogen and phosphorus drained into rivers from processing tobacco leaves. Dr. Solana also said the contract represented a new focus on developing tobacco products with reduced risks, a shift in strategy in underwriting university research that requires more confidentiality to protect the corporation’s intellectual property rights. And he said Philip Morris had similar arrangements with other universities — although he declined to say how many or which ones.
Imagine that, other universities taking money from tobacco. All in the name of good science, naturally. The contract forbids faculty from publishing results without PM's permission, which is a direct violation of VCU's guidelines for industry-faculty collaboration. But, again, when taking in buckets o' money, all is fair game. Hey, keep cutting public funding for universities and see if we can make researchers yet more dependent on pharma, tobacco, and whomever else waves the dolla dolla bill.
Much more analysis available here.
Tuesday, May 20, 2008
The Bipolar Child Strikes Again
1. Max's problems are described by the journalist as "incurable" and as "a life sentence." It is true that the kid is likely in for a life of trouble. But stating that such difficulties are a certainty for the rest of his life? That's a little too certain and it's not based on any evidence. Show me one study that indicates that 100% of children like Max will always have a high level of psychological difficulties and essentially be unable to function independently.
2. The biology of child bipolar disorder is discussed as if we have a very firm grasp on the concept, then one major limitation is noted quite briefly.
So dedicate space to how far science has progressed then quickly note that, by the way, these biological findings are useless in making a diagnosis. That's a rather important limitation.Scientists now know that bipolar children have too much activity in a part of the brain called the amygdala, which regulates emotions, and not enough in the prefrontal cortex, the seat of rational thought. "They get so emotional that they can't think," says Mani Pavuluri, a child psychiatrist at the University of Illinois at Chicago. More than the rest of us, a bipolar child perceives the world as a dramatic and dangerous place. If he is shown a picture of a neutral face, he may see it as angry. Show him one that really is angry, and his prefrontal cortex will shut down while his amygdala lights up like a firecracker. The typical result: a fury that feeds on itself. Neurological research has its limits, though, and bipolar disorder still cannot be identified based on brain scans.
3. How are all of the medications working out for Max?
By 7½, Max was on so many different drugs that Frazier and his parents could no longer tell if they were helping or hurting him. He was suffering from tics, blinking his eyes, clearing his throat and "pulling his clothes like he wanted to get out of his skin," says Richie. In February 2005, under Frazier's supervision, the Blakes took Max off all his meds. With the chemicals out of his system, Max was not the same child he had been at 2. He was worse. Bipolar disorder often gets more serious with age. The brain also reacts to some drugs by remodeling itself, and its dopamine receptors end up naked and sensitive. When the drugs are removed, it's a shock. Off his meds, Max became delusional and paranoid. He imagined Amy was poisoning him and refused to eat anything she cooked. He talked about death constantly and slept little more than two hours a night. Within a month Frazier had put him back on medication, but with a caveat: she wanted to place him in a short-term bed in a child psych ward.
But wait, there's more...
At 10, he has been on 38 different psychoactive drugs. The meds have serious side effects. They have made Max gain weight, and because he's still growing, they frequently need to be changed. The Blakes are aware that many people think their child—any child—should not be on so many drugs. They aren't always happy about it either. But to some degree, they have made their peace with medication.
Yes, you read that correctly -- he's been on thirty-eight psychiatric meds and he's 10 years old. Gee, I wonder if such a heavy regimen of medication is healthy for the developing brain?
4. More on "the bipolar brain"
Um, okay. The bipolar brain "ropes in" other, unspecified brain areas to help the weakling prefrontal cortex and then these areas become dysfunctional too. I'm not a neuroscientist, but I think this explanation is strange at best.The bipolar brain tries to compensate for its weak prefrontal cortex by roping in other areas to help; these areas may now become dysfunctional, too. Child psychiatrists thus face an enormous practical challenge: they often can't treat one disorder without affecting another one. "It's like a balloon where you push on one side and the other side pops out," says Wozniak, the MGH psychiatrist who helped define childhood bipolar disorder. With kids like Max, she adds, parents often have to settle for "just having one part of the symptoms reduced."
5. Get ready for MANIA
Laughing, yelling, rolling on the floor -- it's definitely a manic episode. They probably should have given him a fat injection of Risperdal Consta to calm him down. Oh, and smiling is a symptom of mania as well. Gosh, I am learning sooooooooooo much about bipolar disorder from this article. I can't wait until the DSM-V comes out, at which point we'll discover that we're all bipolar.During a recent appointment at Frazier's office, he went into full-fledged mania. Laughing wildly, he rolled on the floor, then crawled over to his parents and grabbed an empty medication bottle, yelling, "Drugs! I've got drugs! It's child safety!" Richie grabbed it back, Max screamed, Richie threw the bottle across the room, as if playing fetch. Max squealed and dove for it, then began to sing into the neck of the bottle: "Booorn to be wiiiiild …" Amy rolled her eyes: "Two kids." And then: "It's hard not to laugh."
It was. And it was hard to look at Max, who has borne so much, and remember that the grin on his face was not a sign of childish goofiness but a symptom of an illness.
Sarcasm aside for a moment, I am not making light of the situation faced by Max and his family. I can understand the sense of desperation felt by the parents and, to some extent, by the treating physicians. The story just rubbed me the wrong way a few times. The story's author was able to find some psychiatrists who were on the bipolar bandwagon, but she was somehow just not quite able to track down the unnamed critics of the bipolar child paradigm that she briefly mentioned in her story. So the bipolar advocates are given names and are quoted, while the nameless critics are essentially a footnote in her story.
I've also written previously about the tangled web of child bipolar disorder.
Hat Tip: Furious Seasons.
Wednesday, May 14, 2008
Sexual Side Effects of SSRI's: Is the Blindfold Coming Off?
Don't Ask, Don't Tell. Because they were often not assessed in clinical trials, sexual side effects were reported to be relatively rare occurrences. If you've followed this story much at all, this is not necessarily news, but it is certainly worth mentioning anyway.
Post market research has clearly established that the SSRIs and SNRIs can affect most every aspect of sexual functioning at rates significantly higher than the 2-16% rates reported in pre-market trials and currently listed in the drug insert literature. Large prospective studies in which baseline assessment excludes participants with pre-existing sexual dysfunction have found rates of treatment-emergent sexual dysfunctions such as decreased libido, delayed orgasm, anorgasmia, erectile dysfunction, and difficulties with arousal, of between 36 and 70%."Evidence-Based" Guidelines. Bahrick notes that the literature contains advice that sexual side effects are "medically benign" and "all data suggest return of sexual functioning to baseline once the medication is stopped." Which would be fine if such statements weren't wrong. A lot wrong. Bahrick cites research indicating that:
An estimated 5 to 10% of individuals may experience a diminution of the SSRI or SNRI emergent sexual side effects over time as they remain on the medication, but for the vast majority, the sexual side effects are intractable and will continue for at least as long as they take the medication.
Numb Genitals, Anyone? A variety of SSRI-induced sexual side effects have been reported. Bahrick goes into depth about some of those that are less commonly reported in the literature (maybe because nobody bothers to ask about such effects).
There are indications that some SSRI/SNRI sexual side effects thought to be rare are actually common. The most frequently documented sexual side effects are diminished libido, unspecified problems with arousal, and delayed orgasm or anorgasmia. Delayed ejaculation or orgasm, and anorgasmia have been those symptoms that the literature links most clearly and most frequently to SSRI treatment, vs. to depression itself. However the symptoms of genital anesthesia and pleasureless orgasm, outside the range of common experience and appearing to often occur together, are frequently reported among men and women in Internet communities, in an accumulating case reports literature, and in one research investigation.Sounds like fun, no? Bahrick then briefly describes the cases of one man and one woman who clearly experienced treatment-induced genital anesthesia. Even after researchers belatedly began to examine the sexual side effects of SSRIs, their measures do not assess for the presence of genital anesthesia. Again, don't ask, don't tell. Only one measure (Rush Sexual Inventory) was reported to assess genital anesthesia, and here's what research found using this measure:
Ferguson did not report specific symptom results, and Zajecka et al. reported only partial results. Zajecka et al. found that among 42 depressed patients taking a variety of SSRIs, 28% of women reported treatment-emergent decreased genital sensitivity and 25% of men reported treatment-emergent decreased intensity of orgasm, suggesting the symptoms are not uncommon.Zajecka et al. was a small study, to be sure, but this clearly indicates that more research needs to be done on the topic.
In the Long Term. Bahrick also went over some of the evidence she presented in an earlier paper, which I discussed months ago as follows...
According to Bahrick, there is only one study (Montejo et al., 1999) that has examined the emergence of sexual side effects after cessation of SSRI medication. In this study, patients who had experienced significant reductions in depressive symptoms in response to an SSRI were switched to amineptine (which impacts the dopaminergic system and noradrenergic systems to a much greater extent than it impacts serotonin) or to Paxil. A third group received amineptine only (they were not switched from an SSRI). Amineptine-only treatment resulted in 4% incidence of sexual dysfunction, whereas the switched-to-Paxil group had an 89% incidence of sexual dysfunction, and the switched-to-amineptine group decreased from a 100% to a 55% incidence of sexual side effects. Mind you, these treatments lasted for six months, so those who switched to amineptine, a drug that rarely induces sexual side effects, still had a high rate of sexual side effects six months after SSRI treatment discontinuation.Bahrick also noted that there is quite credible evidence from two trials that SSRIs can prolong ejaculatory latency after the discontinuation of treatment. For some individuals, this is a desired effect. For others, not so much. Likely because they are perceived as so benign, it was also noted that, among urologists, SSRIs are the most widely used treatment for premature ejaculation.
The Internet. Over 1500 individuals belong to one internet-based group whose main focus is the discussion of SSRI-related sexual side effects. Bahrick's review of their discussion indicated:
Sexual side effects are reported also to sometimes change over time: for example, there are indications that what was initially experienced as a positive ejaculation delay evolved over time into persistent post-medication low libido, impotence, leaking semen, and a precipitous decline in quality of orgasm and genital sensation.Again, sounds like fun, right? Some naysayers may say that this is just a bunch of internet crazies who bonded together based on some bogus perceptions, who blamed treatment for their psychological problems. Alternatively, one might note that the small body of available evidence all converges on SSRIs causing sexual dysfunction in a relatively high percentage of people, so the concerns of this internet group are likely well-founded in reality.
And More. Bahrick also notes that there are four published case reports, totaling eight cases, where the symptoms described in the article have occurred in patients who had no history of sexual difficulties prior to starting SSRIs. On top of that, another report recently appeared in Primary Psychiatry, which noted, among other items...
Sexual side effects manifest in a variety of presentations and severities, but sexual functioning is assumed to return to normal once antidepressants are discontinued. In the recent peer-reviewed literature, three separate case reports have detailed sustained persistence of sexual dysfunction and genital anesthesia well after termination of SSRIs in the absence of residual psychopathology or another identifiable disorder. In each report, the annoying symptoms were absent prior to antidepressant therapy. Oddly, these case reports have not appeared in the psychiatric or psychopharmacology literature, but rather, two have been published in psychology journals and the third in a gynecology/women’s health journal.Starting a Movement. I often get hits to my site based on Google searches for genital anesthesia combined with various SSRI drugs. These hits have come from across the world. There appears to be a real problem with long-lasting sexual side effects from SSRIs, but the "key opinion leaders" in psychiatry seem much more interested in lining their pockets with drug company money, badly misinterpreting research findings, and looking the other way. And this is what passes for evidence-based medicine?
Read Bahrick's article regarding long-term sexual side effects of SSRIs and ask your doctor about these effects. You are certain to receive an awkward glance. When that happens, feel free to pass along a copy of the article to your physician. If continuing medical education and drug reps aren't going to educate doctors on this issue, I suppose a grassroots effort is in order. Let me know how it goes.
Update. Thanks to an alert commenter for noting that the link to the article does not work. A less direct way to access the article is to follow this link then look for the article in Volume 1. The journal publisher has not yet mastered decent web design. The point of an open access journal is to allow easy access!
Monday, May 12, 2008
Bipolar Overawareness Week Starts With a Bang
Wednesday, May 07, 2008
Bipolar Overawareness Week Starts on Monday
It appears that the massive bipolar awareness campaigns from NAMI and various drug companies have paid off big time. The conclusions of a new study by Mark Zimmerman and colleagues in the Journal of Clinical Psychiatry state, in part:
However, our results suggest that overdiagnosis of bipolar disorder is as much, if not more, of a problem than underdiagnosis.Say what? Well, if you've been following the mental health world, you may have noted that bipolar disorder is the new plague -- it is apparently spreading like wildfire. David Healy wrote an excellent article in PLoS Medicine in 2006 which has been validated by Zimmerman et al.'s latest study. Healy wrote in part:
One of the most famous direct-to-consumer television adverts for a drug begins with a vibrant woman dancing late into the night. A background voice says, “Your doctor probably never sees you when you feel like this.” The advert cuts to a shrunken and glum figure, and the voiceover now says, “This is who your doctor usually sees.” Cutting again to the woman, in active shopping mode, clutching bags with the latest brand names, we hear: “That's why so many people with bipolar disorder are being treated for depression and not getting any better—because depression is only half the story.” We see the woman again depressed, looking at bills that have arrived in the post before switching to seeing her again energetically painting her apartment. “That fast- talking, energetic, quick tempered, overdoing it, up-all-night you,” says the voiceover, “probably never shows up at the doctor's office, right?”Here's part of an Abilify for bipolar ad...
No drugs are mentioned. But viewers are encouraged to log onto www.bipolarawareness.com, which takes them to a Web site called “Bipolar Help Center,” sponsored by Lilly Pharmaceuticals, the makers of olanzapine (Zyprexa). The Web site contains a “mood disorder questionnaire” (http://www.bipolarhelpcenter.com/resources/mdq.jsp). In the television advert, we see our heroine logging onto www.bipolarawareness.com and finding this questionnaire. The voice encourages the viewer to follow her example: “Take the test you can take to your doctor, it can change your life….getting a correct diagnosis is the first step in treating bipolar disorder. Help your doctor to help you.”
This advert markets bipolar disorder. The advert can be read as a genuine attempt to alert people who may be suffering from one of the most debilitating and serious psychiatric diseases—manic-depressive illness. Alternatively, the advert can be read as an example of what has been termed disease mongering. Whichever it is, it will reach beyond those suffering from a mood disorder to others who will as a consequence be more likely to see aspects of their personal experiences in a new way that will lead to medical consultations and in a way that will shape the outcome of those consultations. Adverts that encourage “mood watching” risk transforming variations from an emotional even keel into potential indicators of latent or actual bipolar disorder. This advert appeared in 2002 shortly after Lilly's antipsychotic olanzapine had received a license for treating mania. The company was also running trials aimed at establishing olanzapine as a “mood stabilizer,” one of which was recently published.
Back to the Zimmerman study. The researchers interviewed 700 patients with the Structured Clinical Interview for DSM-IV (SCID). Keep in mind that the SCID is not a conservative measure. When patients receive an unstructured interview, they tend to receive fewer diagnoses than when they are interviewed with the SCID, which makes sense because the SCID sticks to asking detailed questions about DSM-IV symptoms, whereas most interviews ask questions about a variety of topics, and don't go into nearly as much depth regarding one's DSM-specific symptoms.
These 700 patients were also asked if they had been diagnosed as bipolar by a healthcare professional. 145 of the 700 patients included in the study indicated they had been diagnosed as bipolar. Then it gets interesting...
Of the 145 patients diagnosed as bipolar prior to being interviewed for the present study, only 63 (43.4%) were labeled as having bipolar disorder according to the SCID. Remember, the SCID tends to generate more diagnoses than a typical clinical interview, so it's not like the SCID is generally insensitive to picking up on DSM-IV disorders. The researchers even took the liberty of diagnosing many patients who did not officially meet bipolar I or bipolar II diagnostic standards as having bipolar NOS (not otherwise specified); about 25% of those diagnosed with bipolar according to the SCID were labeled as having bipolar NOS. In other words, the authors of the study went out of their way to be quite inclusive, to label some cases that did not quite meet DSM-IV criteria for bipolar as bipolar NOS. So one cannot reasonably state that they were being too restrictive with how they made their bipolar diagnoses.
To put it straight: Over half of the patients coming into the study with a bipolar diagnosis were not labeled as bipolar in the present study when given a thorough diagnostic interview.
Naysayers. Of course, the "bipolar spectrum" club will unite to say that this article is junky. I read an email from a psychiatrist who stated that the study was flawed because the DSM-IV model of diagnosing bipolar is wrong; it is too restrictive. But since the current researchers went past official DSM-IV criteria to make some of their bipolar diagnoses, I'm not sure that is a very valid concern. But similar points will be raised over and over again. Those in favor of expanding the boundaries of bipolar disorder will insist that all this study showed was that the DSM needs change; it needs to broaden its definition of bipolar disorder. Those who were diagnosed as having bipolar disorder but were not labeled as such according to a thorough interview based on the DSM -- those people had "subthreshold" bipolar disorder, which will be labeled as an "underdiagnosed and undertreated" condition that needs to be remedied through more Awareness Days and the like. Doubt me? A group of researchers recently stated that "subthreshold bipolar disorder" was not receiving the treatment it needed, a claim they later retracted when it was pointed out that there was not a single shred of evidence to suggest that such a "condition" received any benefit from treatment with mood stabilizers or antipsychotics.
Why did bipolar become so hip? Mark Zimmerman, lead author of the present study is no pharma hater. By that, I'm not suggesting that he's in bed with pharma either; I'm just saying that he has no axe to grind. So how did he interpret his team's findings?
The impact of marketing efforts and publicity probably also plays a role. Direct-to-consumer advertisements that refer individuals to screening questionnaires can result in patients suggesting to their treaters that they have bipolar disorder. We have seen evidence of this in our practice...News flash, folks. Remember, documents seem to indicate that Lilly was pushing Zyprexa in primary care to treat watered down cases of... bipolar disorder. Cases that would not pass DSM-IV muster, but, if you stretched the diagnostic boundaries quite a bit, BAM, you've got bipolar disorder.
We hypothesize that the increased availability of medications that have been approved for the treatment of bipolar disorder might be influencing clinicians who are unsure whether or not a patient has bipolar disorder or borderline personality disorder to err on the side of diagnosing the disorder that is medication responsive. The bias is reinforced by the marketing message of pharmaceutical companies to physicians that has emphasized the literature on the delayed recognition and underrecognition of bipolar disorder, and may be sensitizing clinicians to avoid missing the diagnosis of bipolar disorder. The campaign against underrecognition, which is also illustrated in the titles of published articles in peer-reviewed journals, has probably resulted in some anxious, agitated, and/or irritable depressed patients who complain of insomnia and "racing thoughts" being misdiagnosed with bipolar disorder.
The Last Psychiatrist has also been duly keeping tabs on the bipolar epidemic (1, 2, 3) and I recommend reading his posts on the topic. To quote from one of them:
Yes, but even though the world agrees the symptoms are the same, the consequences of each label is very different, right? The epidemiology, the prognosis-- the meds?Right. We relabel conditions and act as if we just figured out the laws of relativity. It's not ADHD or conduct disorder or borderline personality or anger management issues or just, life sucks for you right now and you're having a difficult time adjusting to life's difficulties -- it's... bipolar disorder! Look at the progress we've made! But where is the data showing that these people who are being newly christened as bipolar are actually doing any better due to their new label and their new course of treatment? Doesn't giving someone a bipolar label impact that person? I'd probably feel differently about life if a medical authority labeled me as bipolar.
But the real difference is the societal implications. Getting a diagnosis changes the way you relate to the world, and the world relates to you. The label changes your identity and how you think.
Don't agree? Try killing someone and using "pervasive ADHD" as a defense. Get it?
We pretend that psychiatry is an emerging science, and hide behind a feigned ignorance ("we don't know everything, but we're making progress!") And so no one has to take responsibility, or even admit, that psychiatry is changing the evolution of humanity, right in front of our eyes, with nothing more than words.
So I propose that we start a Bipolar Overawareness Week, complete with a website linking to a questionnaire that makes statements like:
- Do you know that your symptoms are probably not indicative of bipolar disorder?
- Ask your doctor if you've been misdiagnosed with bipolar.
- Find out if you are unnecessarily taking Zyprexa today.
Hat Tip: Furious Seasons.
Tuesday, May 06, 2008
Furious Seasons is On Fire
Furious Seasons suffers from a chronic case of excellence, but standing out even more than usual were a quartet of posts today that should be read by all:
- DSM-V Authors Tied to Pharma (hardly surprising, but interesting)
- Beatdowns in Texas Mental Hospitals. In the land of TMAP, disgusting behavior is apparently quite widespread.
- Is Bipolar Disorder Overdiagnosed? Nah, of course not.
- Seroquel for Depression -- Start the Countdown. Another chapter in the Seroquel for Everything saga about to be put into print. Lock up the women and children, since they'll be the first to be 'Quelled.
Monday, May 05, 2008
In the Name of Science and Charity
- The American Psychiatric Association
- Massachusetts General Hospital's Psychiatry Department
- National Alliance for the Mentally Ill
- Medscape
- American Academy of Child and Adolescent Psychiatry
- Center for Medical Knowledge
- Continuing Medical Education, LLC
- Institute for Continuing Healthcare Education
- Johns Hopkins University School of Medicine
- Postgraduate Institute for Medicine
- University of California -- Irvine
Read some of the details at Furious Seasons and read Lilly's report as well. To Lilly's credit, at least they are making an attempt at disclosure; their industry colleagues are more than welcome to follow suit. Remember that the figures from Lilly's report are from the first quarter of 2008 only.