Will the Cong Oversight / Investigations Committee Ask FDA the Tough Questions?

Will the Cong Oversight / Investigations Committee Ask FDA the Tough Questions?

Wed, 22 Sep 2004

FDA’s complicity in concealing vital drug safety information that might have saved lives, is the subject of tomorrow’s hearing by the House subcommittee on Oversight and Investigations. Rayburn Office Bldg, room 2123 at 11:00.

Below are 13 suggested questions that were submitted earlier to the Congressional staff, to help them prepare for the hearing at which senior FDA officials–Drs. Temple / Laughren / Katz–will be asked about the suppression of clinical trial evidence from the public, and the suppression of Dr. Andrew Mosholder’s February 2004 report.

For those unfamiliar with FDA’s legal responsibility: The Code of Federal Regulations spells out FDA’s responsibility regarding drug labeling: “The labeling shall be revised to a include a warning as soon as there is reasonable evidence of an association of a serious hazard with a drug; a causal relationship need not have been proved.” 21 C.F.R. § 201.57(e)

Reasonable evidence of a suicide-risk linked to SSRI antidepressants existed since 1990–but the FDA has failed to implement that regulatory requirement.

A causal relationship has now been established between suicidal behavior in children and adolescents and antidepressants. FDA’s advisory panel recommended black box warnings on ALL antidepressants – including SSRIs, SNRIs, and the older tricyclics.

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1. The FDA has known since the 1990s that there was reasonable evidence from clinical trial data–Lilly, Pfizer, GlaxoSmithKline–showing higher rates of suicidal acts with Prozac, Zoloft, Paxil, than with placebo. There were also case reports of suicidality – in depressed and non-depressed patients–including challenge-re-challenge cases. In light of 1990s reports, did the FDA analyze the SSRI-SNRI pediatric data prior to 2004? If not, why not?

2. If yes, what were the findings – and why were they not shared with the public?

3. Do senior FDA officials pay attention to the agency’s own reviewers’ warning about safety hazards of drugs–only when their actions are being investigated by a congressional committee?

4. If manufacturers failed to submit clinical trial data – as was revealed in a 1998 GlaxoSmithKline memo*–why has the FDA failed to prosecute a single antidepressant manufacturer for concealing data?
*See: http://www.ahrp.org/risks/SSRI0204/GSKpaxil/index.php

5. Why did the FDA fail to use its authority to accomplish what New York State Attorney General, Eliot Spitzer, accomplished in less than 3 months by obtaining a court ordered mandate requiring GlaxoSmithKline to disclose fully all clinical trial data?

The value of a full disclosure mandate is that we now learn from GSK’s posted data (Table 5) that there was a striking increased incidence rate of suicide-related behavior in depressed and non-depressed children on Paxil compared to those on placebo, for who the risk was low and remained stable. The increased risk worsened from withdrawal symptoms when they stopped taking the drug:

During acute treatment phase:
Paxil:     18 became suicidal out of 738 (2.4%)
Placebo: 7 became suicidal out of 647 (1.1%)

During treatment + 30 day follow-up, the number of children who became suicidal reached:
25 out of 738 on Paxil      (3.4%)
  8 out of 647 on placebo (1.2%)

See: Table 5. Incidence of Events Possibly Related to Suicidal Behavior in Controlled Pediatric Studies at: http://www.gsk.com/media/paroxetine.htm

6. Has the FDA investigated all the duloxetine trial data–including the suicide of Traci Johnson, a 19 year old student, who was a healthy volunteer, and the suicides of the other four subjects in that trial?

7. Inasmuch as there were 5 suicides in recent duloxetine trials, why was the duloxetine data excluded from the reviews by Dr. Mosholder and Dr. Hammad?

8. What does the safety and efficacy data from all the duloxetine trials show–and is that data publicly accessible?

9. Given that a causal relationship has been established between antidepressants and suicidal behavior, and given that Traci Johnson was a non-depressed, healthy volunteer–according to Eli Lilly–how does the FDA explain its determination ruling out the possibility that duloxetine – an SNRI–played a role in her suicide?

See: Aug 12, 2004, The Indianapolis Star reported that the FDA exonerated duloxetine, and that an FDA investigation “found (the drug) couldn’t be linked to her death,” an FDA spokesperson said Wednesday. *Of note: FDA’s own analysis demonstrated that SNRIs have an even higher risk than the SSRIs.

10. Why did the FDA approve duloxetine with mislabeled information – denying a drug-induced risk – even after the agency’s own reviews had demonstrated a causal relationship between SNRIs and suicide risk?

11. In light of the scientifically established causal relationship between SSRI and SNRI antidepressants and a suicidal risk, will the FDA change its ruling about the role duloxetine played in Traci Johnson’s death?

12. In light of the established evidence of a causal relationship between all SSRI and SNRI antidepressants and a suicidal risk, will the FDA retract the false statements FDA officials made in briefs submitted in court cases in which the agency falsely claimed that evidence is lacking to demonstrate causal relationship between antidepressants and a suicide risk?

13. Why has the FDA waited for 20 years to analyze the adult SSRI-SNRI data–from controlled trials and MedWatch reports?

Contact: Vera Hassner Sharav
Tel: 212-595-8974