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Alliance for Human Research Protection

AHRP is a national network of lay people and professionals dedicated to advancing responsible and ethical medical research practices, to ensure that the human rights, dignity and welfare of human subjects are protected, and to minimize the risks associated with such endeavors.

Evidence of Antidepressant Harm that the FDA Sought to Suppress from FDA's Public Advisory Committee Meeting on February 2

Evidence will be presented on February 2 at AHRP's press briefing by the following scientists:

AHRP's written testimony: Where is the Scientific Evidence to Justify Exposing Children to the Risks of Antidepressant Drugs?

AHRP correspondence with FDA demonstrating that the FDA would not permit this evidence to be presented at the public hearing:

ALLIANCE FOR HUMAN RESEARCH PROTECTION   (AHRP)
142 West End Ave, Suite 28P
New York, NY 10023
http://www.ahrp.org
Tel: 212-595-8974
e-mail:

October 29, 2003
To:   Thomas Laughren, MD
         Team Leader, Psychiatric Drug Products Group
         Division of Neuropharmacological Drug Products

CC: Robert Temple, MD
        Janet Woodcock, MD
        CENTER FOR DRUG EVALUATION & RESEARCH
        FOOD AND DRUG ADMINISTRATION  

RE:  FDA Advisory Committee Meeting, Feb 2, 2004 Invitation for expert testimony to shed light about Antidepressant Reports Of Suicidality In Children

Dear Dr. Laughren:

In light of the criticism leveled at the FDA for its mishandling of the 1991 advisory committee meeting, to which knowledgeable independent experts were not invited to speak, it is important for the FDA to ensure that a meaningful exchange of information among analysts who have examined the primary data takes place at the upcoming February 2, 2004 Advisory Committee meeting.

For this reason, the Alliance for Human Research Protection (AHRP) requests that the FDA extend an invitation to David Healy, MD, FRCPsych, an internationally renowned psychiatrist who has examined some of the primary data. As you are undoubtedly aware, Dr. Healy triggered the British Medicines Healthcare Products Regulatory Agency (MHRA) to review the SSRI safety issues for children that led to the subsequent decision by that agency to initiate strong measures to protect children from harmful exposure to these drugs. (See Dr. Healy's curriculum vitae forwarded by e-mail.)

Dr. Healy can provide evidence relevant to the issues to be discussed at the upcoming FDA meeting in February, 2004, bearing on the safety of prescribing SSRIs for children. His credentials include:

  • Former Secretary of the British Association for Psychopharmacology (BAP)
  • Author of BAP consensus statement on use of psychotropic drugs for children.
  • Invited to present to the British Medicines Healthcare products Regulatory Agency (MHRA) twice on these issues.
  • Has reviewed a large amount of the raw data used in published articles.
  • Has written the leading history of the antidepressants, entitled The Antidepressant Era, published in 1997 by Harvard University Press.
  • Consultant, clinical trialist, or speaker for all the major psychotropic drug-producing companies.
  • Has rendered numerous medical opinions as expert witness in SSRI legal cases, most of which discounted the role of medication in the claimed adverse effects. In a small series of cases, however, his opinions were offered for the claimants/defendants.
  • Conflict of Interest Declaration will be submitted if invited to speak.

Should you need any additional information about Dr. Healey, I shall be happy to assist.

Sincerely,

Vera Hassner Sharav
President
Alliance for Human Research Protection
CC: Marc McLellan, MD, Commissioner, FDA
         Warren Rumble, Ombudsman, FDA


-----Original Message-----

From: VERACARE
Sent: Friday, December 19, 2003 11:38 AM
To: Robert Temple MD; Russell Katz MD
Cc: Warren Rumble; Mark McClellan MD; Anuja Patel
Subject: Dr. David Healy's request permission to present data analysis at advisory meeting Feb 2

ALLIANCE FOR HUMAN RESEARCH PROTECTION (AHRP)
http://www.ahrp.org
Contact: Vera Hassner Sharav
Tel: 212-595-8974
e-mail:

Dear Drs. Temple and Katz,

Attached is Dr. David Healy's December 12th letter in which he requests permission to present his original analysis of suicidal behavior in pediatric trials before the advisory committee on Feb 2.

It will be difficult for the FDA to explain why an invitation has not been extended to Dr. Healy indeed why there has been no response to his request for reasonable time (about 20 minutes). Dr. Healy offers to present an original analysis of suicidal episodes in over 2,700 patients taken exclusively from placebo-controlled randomized pediatric trials, across a range of depressive and non-depressive indications.

Since the phenomenon of drug-induced suicidal effects is the focus of the Feb. 2 meeting, how will FDA officials explain such apparent disinterest?

Additionally, the Alliance for Human Research Protection has not received a response to our December 1 letter of concerns (attached). That letter deals with procedural aspects the meeting to ensure that this meeting is not marred by bias and conflicts of interest as was the previous meeting dealing with this controversial issue.

Thank you,

Vera Sharav
President, Alliance for Human Research Protection


North Wales Dept of Psychological Medicine
Bangor
Wales LL57 2PW
United Kingdom
Fax 44-1248-371397  

December 12th 2003  

FDA Review of the Effectiveness and Safety of Antidepressant Treatment in Pediatric Major Depression

February 2nd 2004

To: Robert J. Temple MD
Associate Director for Medical Policy
Center for Drug Evaluation and Research
Food and Drug Administration
HFD-40
Rockville Md 20852
Fax: 301-594-5298

Russell G. Katz MD
Director Division of Neuropharmacological Drug Products
Center for Drug Evaluation and Research
Food and Drug Administration
HFD-120
Rockville MD 20852
Fax: 301-594-2859

Anuja Patel,
Advisors and Consultants Staff
Office of Executive Programs
Center for Drug Evaluation and Research, FDA
5630 Fishers Lane, HFD-21, Room 1093
Rockville, MD 20857
Fax: 301 827 6776

Dear Dr Temple,

I am writing to request permission to present at the forthcoming advisory panel on pediatric SSRI use. As a former Secretary for the British Association of Psychopharmacology, who convened a consensus conference in 1996 on the use of psychotropic drugs for children, the proceedings of which endorsed the use of SSRIs for a range of pediatric disorders, the issues under discussion on February 2nd have long been of interest to me. The 1996 BAP conference had significant input from Dr Paul Leber, then Director of the CNS division within FDA, who was one of my invited discussants at this meeting.

There appear to be two interlinked issues for consideration in February. One is how best to ensure the safe use of SSRI agents for children and a second has to do with perceptions of FDA credibility.

On the issue of the safety and efficacy of the SSRIs, I have been able to review in GlaxoSmithKline's archives the studies of Paxil in children, which triggered off current clinical and regulatory concerns. I have also had access to unpublished expert and company reports from Pfizer's pediatric trials of sertraline. In a majority of cases of suicidality, I have been able to review the kinds of clinical features you would expect someone conversant with clinical trials to be interested in such as the narrative summaries of events, the time to dose escalation or de-escalation, clinical judgments concerning relatedness to treatment, and adequacy of follow-up among other factors.

I can bring to the meeting an analysis of public domain suicidal episodes in over 2,700 patients taken exclusively from placebo-controlled randomized pediatric trials, across a range of depressive and non-depressive indications.

I have not hitherto presented this analysis nor asked the kind of questions based on archive access that could be asked in any forum. In other words this material played no part in the recent decisions made by British regulators.

On the matter of FDA's credibility I am in possession of documents, which indicate that one of the SSRI companies did not intend to make their clinical trial data available to FDA for reasons that will be likely to alarm most regulators. This apparent intention clearly stands at odds with FDA requests to SSRI companies as of 1991 to undertake studies of these agents in children to establish the safety profile of treatment.

Aside from such documents senior FDA figures have been widely cited or, given the complexity of the issues at stake, perhaps misreported in the press recently. Among the statements inferred or impressions taken by journalists have that given that there were no suicides in the pediatric trials, that FDA were not clear that there is a serious problem at stake. However, as FDA have granted a license to Novartis for suicide prevention in schizophrenia on the basis of a lower frequency of suicidal episodes on clozapine, even though clozapine was associated with more suicides than olanzapine in the recent InterSePT trial, this impression must necessarily be misleading.

A second idea circulating widely at present is the notion that FDA has been frustrated by the high rate of placebo responders in SSRI pediatric trials, and has been considering making judgments of efficacy on the basis of worsening mental states following discontinuation of treatment. Given that Paxil has been linked to a greater frequency of adverse event reporting for withdrawal reactions than any other psychotropic drug in history, this proposed method of demonstrating efficacy, which current data suggest would be unquestionably effective in the short run, might do FDA and medicine in general a great deal of harm in the longer run.

There seems to be a wider crisis also, in that arguably there is no greater divide anywhere in therapeutics between the evidence base and its representation than there is between the representations of the adverse effects of SSRIs in pediatric populations in the scientific literature and the evidence from the raw data taken from clinical trials as to what the true frequency of those adverse effects actually was. This makes it difficult for FDA to rely on input from academic clinicians.

These issues need careful consideration given the very real indicators from the clinical trial database that SSRIs may be effective for some children with nervous disorders. It will take me about 20 minutes to present the material for consideration that I believe would be most constructive for the purposes of your review.

David Healy MD


FDA response to AHRP procedural questions (FDA sham conflicts of interest policy)