The Pfizer Geodon Trial And Physician Mishaps
17 CommentsBy Ed Silverman // April 28th, 2010 // 8:58 am
Earlier this month, the FDA sent Pfizer a warning letter for failing to properly monitor pediatric clinical trials in which at least 13 children with bipolar disorder experienced overdosing that led to restless legs, tremors, involuntary facial movements and a serious skin disorder.
This is a big problem for the drugmaker, since Pfizer hopes to receive an extra six months of marketing exclusivity in return for having conducted the pediatric trials. But the dosing scandal could prompt the FDA to request further trials, which would require so much additional time that exclusivity would likely be lost, since the basic Geodon patent expires in 2012. This would also delay pediatric approval, which would expand the possibilities for a drug that generated $1.1 billion in sales last year.
But who were some of the doctors involved? A Pfizer spokeswoman declined comment, but as it turns out, the FDA issued warning letters to at least three physicians who were involved in the Geodon pediatric trial. One was Timothy Summers (warning letter), who was cited for such things as giving the drug to kids without bipolar disorder; failing to maintain case histories; failing to obtain informed consent and making changes to his research without approval of the Institutional Review Board, or IRB. In a May 2009 memo prepared for an FDA panel set to review safety and efficacy issues for antipsychotics in children, Summers was described has having committed ‘widespread’ good clinical practice violations (see page 149). Summers didn’t respond to messages.
Then there was Sohail Punjwani, who was cited for numerous instances in which the wrong dosage was given children. Punjwani ran one of three sites that were responsible for 40 patients receiving incorrect doses, or 16 percent of the kids involved, and half of them were given more than the maximum tolerated dose for the trial (see the chart and footnote on page 159 of the May 2009 FDA document noted above). You can read more about the overdosing in the FDA warning letter sent to Punjwani here.
Punjwani has made headlines in Florida, where he is based, for treating 7-year-old Gabriel Myers, who hanged himself with a shower cord in a foster home. The boy’s death prompted a probe by a Department of Children & Families task force and proposed legislation before the Florida Senate (background here). He did not respond to messages.
And there was also Thomas Gazda. As with Punjwani, the FDA issued him a warning letter and a 483 inspection letter due to problems with their participation in the trial, such as failing to follow protocols, including daily follow-up with parents or guardians, and maintaining case histories. He recently told The New Scientist that “one learns from one’s mistakes.” The Scottsdale, Arizona, physician, by the way, received more than $12,000 from Pfizer last year for other activities, such as speaking (look here).
As a result of the various problems, data from Punjwani and Gazda were not considered valid to
support Pfizer’s submission to the FDA in advance of the June 2009 meeting of the agency’s Psychopharmacologic Drugs Advisory Committee. As a result, Laughren wrote that he wanted Pfizer to reanalyze the primary efficacy and key secondary efficacy data - excluding all data obtained from those two docs - as well as from Summers, whose data was already excluded by Pfizer.
As we have pointed out before, this is the sort of episode that bolsters criticism of the deal in which drugmakers were awarded patent extensions for agreeing to run pediatric trials. Moreover, this is also the same drugmaker that was fined $301 million for improperly marketing Geodon for unapproved uses; unapproved patients, including children, and for higher doses than approved by the FDA (see here). The unfortunate take-away message suggests a disregard for children, although Pfizer maintains it takes the situation seriously and maintains it has instituted new procedures to prevent a recurrence.
patrons99
In my experience, these kinds of ethical lapses are VERY common in clinical research. FDA has let this kind of crap happen for a VERY long time. They rarely do anything about it. The more NDAs, sNDAs, and pharma research sponsors involved, the less likely FDA is to take any action at all. It gets ignored and “swept under the carpet”. When, and if, FDA finally does act, its only for damage control…at that point, they have no real choice but to act. I can cite MANY examples.
Evelyn Pringle
Great article ED! I find it maddening that the FDA makes it almost impossible to decode the warning letters so the public won’t figure out who is involved in these cases.
Great job!
Lisa Van Syckel
I had testified before Congress in 2007, I had asked Congressman Pallone, who is the Chairman, Subcommitte on Health to investigate this issue, unfortunately nothing came of it. Its a shame that so many children have been harmed. We need campaign finance reform!
patrons99
Whoa. Hold everything. We may have several new candidates here for the Hall of Shame.
It would be an instructive to make a tally of the number of violations of the Nuremberg Code and Declaration of Helinski we find here.
With this kind of regulatory oversight, why would anyone be brave enough to enter a clinical “research” trial, much less believe in the results of the ghostwritten study findings?
Why would anyone be in a hurry to try out any newly “approved” drug, with this kind of “research” underlying the approval?
anon
fda policy- remove offending data such as data for overdosed children with terrible side effects.
discarding the annoying data,is easier for the FDA than dealing with the crime, off-label promotion and overdosing kids.
Oh a FDA warning letter. pfizer must be scared.
ATG
Found this on the web: http://i37.photobucket.com/albums/e84/Virus9484/EatBabies.jpg
I thought it about sums it up. What’s the difference? Except after all the toxic crap these poor kids are being made to ingest, I don’t think they’ll be very edible. Good enough for dingos though.
Arnie
Man oh man - who is in charge of Punjwani’s PR department? Fire him Punjwani! And then find yourself another profession.
patrons99
@ ATG -
Let’s try to put a positive spin on all of these horrors. At least we’ll never seriously be considered as a source of food in the future, e.g. Soylent Green. We’re much too “toxic”! Too many heavy metals, e.g. aluminum adjuvants (neurotoxins), mercury (in our dental fillings), fluoride (toothpaste and the public water supply). Too much non-human viral DNA, e.g. SV-40, avian retrovirus, reverse transcriptase, and various assorted “degradation products”, from our cradle-to-grave vaccination schedules, and government-mandated “jabs”.
M Helm, MD
Oh, there are so many problems here…
How do you suppose a valid diagnosis of “bipolar disorder” was supported in these children? There are not validated approaches to this alleged condition. see: http://www.dsm5.org/research/pages/externalizingdisordersofchildhood(attention-deficithyperactivitydisorder,conductdisorder,oppositional-defiantdisorder,juven.aspx
P99’s comments about the fundamental tenets of human research are spot on. However, in my experience, off-label/experimental use of potent psychotropic medications in children without regard to: dosing, therapeutic duplication, interaction/interference with other meds (such as stimulants), monitoring of side effects, informed consent for treatment with specific medicaitons (which might include a list of specific known or suspected side effects), accurate diagnosis, use of a standardized tool to evaluate treatment response, and other lapses of “good clinical practice” are common-place. This is especially true in populations of foster children and Medicaid recipients.
Since the data has been collected on children who were exposed to the wrong dose or wrong medicine for a condition, would it not be instructive for those data to be published. This might help clinicians to recognize when they are out of bounds. Otherwise, it will be only Dr. Punjwani learning from his mistakes, and there will be no benefit to others.
I’m thinking that if this is Dr. Punjwani’s learning style, a) he probably knows a great many things from personal experience that I will never permit myself to learn (having a preference to first study all I can, and always try hard not to make a mistake with another person’s life and health), and b) he should probably warn his patients that his practice philosophy is so very cavalier.
I’m still an advocate for a nation-wide registry of all children with supposed mood and behavior disorders treated with antipsychotics and/or anticonvulsants. Enrollment in such a registry (with a comprehensive monitoring program) should be a prerequisite for having any of these medications covered through Medicaid/CHIP program funds. Funding could come from the fines levied for off-label promotion - wouldn’t even need to tap the “comparative effectiveness” stimulus money.
patrons99
Doc Helm -
I agree that the appropriate uses of clinical databases have immense potential. But, clearly, “appropriate” [uses] is the operative word here. Perhaps equally important, control of access to the database, control of data entry into the database, integrity of the data entered into the database, and freedom from bias in the analysis of such data is of immense importance.
The potential for “inappropriate” uses of such data are legion. There are also certain patient confidentially issues, which would have to be defined prospectively, and cannot be violated.
patrons99
Clinical databases and outcomes research seem to go hand in hand. Imagine a perfectly level playing-field, with no bias. Imagine some of the wonderful, prospective, head to head active comparator studies that could be designed and conducted. I’d love to be involved in such research. I’d be willing to give up my daytime job to do it…seriously. But, maybe I’m too old. Oh well…reality check.
M. Black
ATG - that image was just incredibly disturbing.
And thus, effective. Nice work!
This issue may have too many conflicting facets to really hash out. I’m certainly not a naysayer, as shown by the callous the size of a softball on
my forehead in my attempts to bust through some real roughies in the trenches.
MB
Ellie B.
I think it is terribly important for your readers to know what is happening in this arena of the psychotropic drugging of children, many of whom are Medicaid children.
So thanks for the article.
I personally am very interested to know all the facts on some of these matters. For example, how could “Doctor” Punjwani and “Doctor” Summers still be practising and have only received a warning from the FDA? Punjwani and his fellow psychiatrists should have their licences taken away. Others would be hauled off to jail for what they do.
Proof from Pfizer should be insisted upon to show they really have done something to prevent reoccurrences of high dosages of these drugs to kids.
Thank you for your article.
Sincerely, Ellie
Alma Pendergrass
Thanks for the good data. Horrifying to think that after all foster kids and “poor” kids go through, they should be exterminated by big business. The dollar has soylent green all over it.
Carolyn Meece
As a survivor of “Soviet-style Psychiatric Terrorism”, Trauma-based Mind Control, Suicidal Ideology we can see the Nuremberg Code violations involving a number of psychiatrists. We can see the drugs are used for control and non-mental health issues. A great number of psychiatrists need to be put on trial for their “Unspeakable Crimes Against Humanity” and their illegal forced drugging. I do not find a number of psychiatrists healthy in mind or soul. They knowingly break the laws, lie, and over-doze with the psychiatric drugs that people do not even need. They are known to destroy the lives and and health and determinded try to destory minds in order to cover up the crimes that have committed. Tens of thousands of dollars from health insurance are thrown in cesspools.
HiGround
There’s a new iPhone app that addresses this. It’s called “Drug Alert” and gives you drug warnings in plain, understandable English. (It even connects you to the FDA when you want to report a drug reaction.) It’s probably at the iPhone app Web site.
David G
Thanks for this explaining article, Ed. It makes me quite cynical to see such lapses of ethics and judgment almost as the industry practice.