FDA and the Life-Sciences Industry: Business as Usual?
Koski, Greg, The Hastings Center Report
On April 15, while most Americans were signing and mailing their 1040s, Rep. Joe Barton (R-TX.), chair of the House Energy and Commerce Committee, issued a press release in which the Food and Drug Administration admitted, for the first time, that an important report regarding concerns for the safety of children taking prescription antidepressants had not been released to the public. As the complex story of the FDA's oversight on antidepressants unfolded, it fueled mounting concerns about the extent to which the pharmaceutical industry has permeated the agency and how it may be influencing the agency's policies, practices and regulatory actions.
The FDA'S admission was contained in a response to an inquiry from Barton and Rep, James Greenwood (R-PA), both of whom served on the Energy and Commerce Committee's Oversight and Investigations Subcommittee. The FDA acknowledged that an internal consultant had concluded that data supported an association between the use of antidepressants and suicidality in children. The internal consultant was Andrew Mosholder, a member of the agency's Office of Drag Safety and a former reviewer for the Division of Neuropharmacological Products of the FDA's Center for Drug Evaluation and Review (CDER). After conducting a seven-month review, Mosholder recommended that the FDA take additional regulatory action. (1)
Not all of the CDER staff had agreed with Mosholder's recommendations. CDER staff decided that, while the tiara from which Mosholder had reached his conclusions should be presented at an upcoming meeting of the FDA's Advisory Committee, having Mosholder do so "would be potentially harmful to public health as it might lead patients who were actually benefiting from the use of these drugs to quit taking them." Instead, Thomas Laughren, also from the Division of Neuropharmacological Products, "presented the same data from which Dr. Mosholder had reached his conclusions," as well as the data from which the Medicines and Healthcare Products Regulatory Agency (the United Kingdom's equivalent of the FDA) had already reached a conclusion essentially identical to Mosholder's--namely, that the association between antidepressant use and suicide in children was substantiated by the evidence. Laughren also described the FDA's plans for further analyzing the data and conducting a more definitive review after that analysis was complete. That analysis, later conducted by independent scientists at Columbia University and released in August (as this essay is being written), fully supported Mosholder's original analysis. (2) Still, the FDA has been slow to take the regulatory action Mosholder recommended.
The events surrounding the Mosholder report and the February 2004 Advisory Committee meeting are now the subject of an ongoing Congressional investigation. (3) One very troubling question is whether Mosholder's conclusions had been inappropriately suppressed, but other, broader concerns may ultimately be even more significant.
The initial inquiry from Representatives Barton and Greenwood noted that concerns about an association between antidepressants and suicide are hardly new. (4) In fact, they date back over twelve years, to when an earlier FDA advisory committee concluded that no association existed. Further, the FDA continued to monitor the situation for more than a decade following its initial determination, during which time several companies submitted data from new clinical trials seeking approval of a pediatric labeling indication for certain antidepressants already approved for use in adults. Barton and Greenwood also called attention to a January 2004 FDA memorandum in which Laughren revealed that twelve of fifteen studies in children with major depressive disorder showed no efficacy compared with placebo--worse yet, possible indicators of increased suicidal risk were apparently found in five of seven pediatric antidepressant trials, according to the congressional letter of inquiry. …