Kid Overdoses in Antipsychotic Trial Caps a History of Screwups at Pfizer
The FDA's letter to Pfizer (PFE) describing overdoses of the antipsychotic Geodon given to 13 children in clinical trials is merely the latest in a long history of controversies that have dogged the drug at virtually every stage of its existence. Among those controversies: Discredited doctors allegedly prepared research on Geodon for the FDA; Pfizer allegedly promoted the drug for unapproved uses in kids; and the company allegedly paid a non-profit mental health advocacy group to promote Geodon for kids.
Taken together, the string of incidents suggests a lack of management accountability. Like many large companies, Pfizer operates as a series of silos or divisions, with different managers for sales, marketing, R&D, and regulatory compliance. The fact that screwups have occurred across all these divisions illustrates the value of having one manager, or management team, with accountability for the entire product, from soup to nuts.
The FDA warned Pfizer that its trials of Geodon in children were improperly monitored, and that children got too much drug by mistake:
... dosing errors occurred and overdosing extended over several days for all seven pediatric subjects; in one case for as long as 22 days.
...a Pfizer internal document dated October 3, 2007 and entitled "Safety Information on Affected Subjects" refers to the overdosing of an additional six pediatric subjects in study (b)(4) at two different sites...The kids suffered from nervous tics and a loss of control of their limbs, among other symptoms. Pfizer said it conducts tests globally according to the highest ethical and scientific standards:
Pfizer recognizes the seriousness of the issues cited by the FDA and is committed to fully addressing FDA's concerns. Many of the items cited by the FDA were first uncovered and reported to the FDA by Pfizer as far back as four years ago as part of our ongoing clinical trial monitoring and quality assurance processes. Since that time, Pfizer has instituted several new measures designed to improve monitoring and execution of clinical trials, including our oversight of clinical investigators.The tests took place between 2005 and 2007. At least some of those tests were done by Dr. Joseph Biederman, the controversial Harvard physician who said he was not God because he was one pay-scale below God in Harvard's staff rankings.Pfizer has communicated with the FDA about our conduct of clinical trials and, over the next two weeks, will provide an outline of new and existing processes for preventing similar issues with Pfizer clinical trials in the future.
An FDA panel said in 2008 that it believed antipsychotics, including Geodon, are overused in kids, after prescription rates for children increased more than fivefold in the previous decade and a half. Doctors use the drugs to settle outbursts and aggression.
When Pfizer submitted its application to sell Geodon to the FDA, it allegedly used three physicians who were later accused of misconduct to prepare submission, according to a whistleblower lawsuit brought by a Harrisburg, Pa., doctor. Two of them later ended up in prison for research misconduct. The doctor who made the allegations called the Geodon application "intentionally misleading" regarding its cardiovascular effects. Pfizer denied the allegations but settled the case.
After the drug was approved in 2000, Pfizer was accused by the Department of Justice of promoting the drug for unapproved, "off-label" uses. The DOJ said in a 2009 statement:
The government alleges that Pfizer also promoted Geodon for use by unapproved patients, including pediatric and adolescent patients, and promoted Geodon for higher dosages than were approved by the FDA. This conduct included direct promotion by Pfizer sales representatives and promotion through the hiring of physicians, or "key opinion leaders", to give promotional talks to other physicians about unapproved uses and dosages of Geodon. Specifically, these talks included encouraging doctors to prescribe the drug for children, and to prescribe the drug at substantially higher than approved dosages.One doctor was paid $4,000 a day to fly his private helicopter to meetings where he promoted Geodon off-label, according to a separate whistleblower suit, which Pfizer also settled.
And Pfizer allegedly gave more than $1.3 million in funds to the National Alliance for the Mentally Ill, a non-profit advocacy group, and hired the president of the organization as a paid speaker, according to another whistleblower suit. In an amazing coincidence, NAMI published a web page which advocated off-label use of Geodon in children.
The number of antipsychotic scripts written for children doubled to 4.4 million between 2003 and 2006, the Pfizer sales rep who made the NAMI allegations claimed. His case was also settled.
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