The FDA’s Flawed System of How Antidepressants Get Approved; Negative Trials Ignored
Sunday, August 14, 2016 10:38 am Email this article
Irving Kirsch, PhD from Harvard Medical School tells how antidepressants get approved by the FDA and why it is a flawed system.
Only Two Positive Drugs Studies Needed for Approval, While Negative Trials Ignored
He notes that drug companies only have to provide two studies showing positive results to get a drug approved regardless of how many trials failed to show any benefit.
“The FDA requires two adequately conducted clinical trials showing a significant difference between drug and placebo,” Kirsch writes.
“But there is a loophole: There is no limit to the number of trials that can be conducted in search of these two significant trials.
“Trials showing negative results simply do not count.
“Furthermore, the clinical significance of the findings is not considered.
“All that matters is that the results are statistically significant.”
Example of Something that Might Be Statistically Significant, but Clinically Meaningless
Kirsch gives an example of something that might be statistically significant, but not clinically significant, saying that if they studied a large group of people and found that smiling increases life expectancy by 5 minutes, this might be statistically significant, but clinically meaningless.
Approval of Vilazodone (Viibryd®)
“The most egregious example of the implementation of this criterion is provided by the FDA’s approval of vilazodone [Viibryd®] in 2011,” Kirsch continues.
“Seven controlled efficacy trials were conducted.
“The first five failed to show any significant differences on any measure of depression, and the mean drug-placebo difference in these studies was less than 1/2 point on the [Hamilton Depression Scale], and in two of the three trials, the direction of the difference actually favored the placebo.
“The company ran two more studies and managed to obtain small but significant drug-placebo differences (1.70 points).
“The mean drug-placebo difference across the seven studies was 1.01 [Hamilton Depression Scale] points.
“No mention is made of the five failed trials that preceded the two successful ones.
“The failure to mention the unsuccessful trials was not merely an oversight; it reflects a carefully decided FDA policy dating back for decades.
FDA Director Thinks Excluding Info About Negative Drug Trials is Potentially ‘False and Misleading’
Kirsch continues by saying,
“To my knowledge, there is only one antidepressant in which the FDA included information on the existence of negative trials.
“The exception is citalopram [Celexa], and the inclusion of the information followed an objection raised by Paul Leber, who was at the time the director of the FDA Division of Neuropharmacological Drug Products.
“In an internal memo dated May 4, 1998, Leber wrote:
“One aspect of the labeling deserves special mention.
“The [report] not only describes the clinical trials providing evidence of citalopram’s antidepressant effects, but make mention of adequate and well-controlled clinical studies that failed to do so…
“The Office Director is inclined toward the view that the provision of such information is of no practical value to either the patient or prescriber.
“I believe it is useful for the prescriber, patient, and 3rd-party payer to know, without having to gain access to official FDA review documents, that citalopram’s antidepressants effects were not detected in every controlled clinical trial intended to demonstrate those effects.
“I am aware that clinical studies often fail to document the efficacy of effective drugs, but I doubt that the public, or even the majority of the medical community, is aware of this fact.
“I am persuaded that they not only have a right to know but that they should know.
“Moreover, I believe that labeling that selectively describes positive studies and excludes mention of negative ones can be viewed as potentially ‘‘false and misleading.”
(Leber, May 4, 1998).
Irving Kirsh’s book The Emperor’s New Drugs: Exploding the Antidepressant Myth
Irving Kirsch, PhD
Beth Israel Deaconess Medical Center Gen. Med. Pricare
330 Brookline Avenue
Boston, MA 02215 USA
Tel. +1 617 945-7827
Other Articles About Antidepressants
Here are links to other articles about antidepressants.