May 12,2004

Grassley Continues Review of FDA's Handling of Research on Antidepressants, Child Suicide

WASHINGTON — Sen. Chuck Grassley has asked the Food and Drug Administrationand the Department of Health and Human Services for detailed information about an FDAcontract with Columbia University as part of his larger review of allegations that the governmentinitially withheld information from the public about risks for children given antidepressants.

Grassley said he wants to make sure that the Food and Drug Administration is notattempting through an outside evaluation underway by Columbia University to undermine thefindings of the scientist who identified a possible link between child suicide and antidepressants.The text of Grassley's letter to the FDA and the Department of Health and HumanServices follows here.

May 11, 2004

The Honorable Tommy G. Thompson
Department of Health and Human Services
200 Independence Avenue, SW
Washington, D.C. 20201

Mr. Lester M. Crawford, D.V.M., Ph.D.
Acting Commissioner
U.S. Food and Drug Administration
5600 Fishers Lane
Rockville, MD 20857

Dear Secretary Thompson and Mr. Crawford:

On March 25, 2004, I requested that the Food and Drug Administration (FDA) answer aseries of questions related to its March 22, 2004 Public Health Advisory on “Cautions for Use of Antidepressants in Adults and Children.” As you know, my inquiry is in response to allegations that the FDA has withheld very important information from the public regarding the risks associated with children and their use of antidepressants. In the FDA’s April 14, 2004 response, it states “Agency staff determined that an independent panel of experts in suicidology should be convened to carefully evaluate and reclassify the reported adverse events. DNDP (Division ofNeuropharmacological Products) arranged for this work to be performed under a contract withColumbia University and this review is ongoing.”

In light of my concerns, I request that the FDA provide detailed responses to thefollowing questions:

1. On what date was it decided that these data needed to be analyzed by non-FDAreviewers?

2. Who decided to have these data analyzed by a third party? Please provide the name ofeach individual who engaged either directly or indirectly in this decision, including theirtitle and division assignment.

3. Describe in detail the rationale behind the decision to have non-FDA reviewers analyzethese data?

4. How was Columbia University selected as the non-FDA reviewer of these data?

5. What is the dollar amount of the contract awarded to Columbia University?

6. Provide a list of all similar instances in the past five years where the Division ofNeuropharmacologic and Psychiatric Drug Products contracted with non-governmentparties with the expressed purpose of having safety data from new drug application(NDA) clinical trials reviewed and analyzed using patient-level data from these studies.Provide a similar list of all such instances within the Center for Drug Evaluation andResearch (CDER). This request is specific to the analysis of NDA clinical trial safety dataand excludes any instances of analysis of safety data from observational, phase 4, or othernon-pre-approval studies.

7. Provide the names, qualifications and curricula vitae of all personnel from ColumbiaUniversity who will be participating in the analysis of SSRI data under contract to theFDA. Provide all documents related to FDA’s evaluation of Columbia Universitypersonnel for potential conflicts of interest.

8. Provide the names, qualifications and curricula vitae of all personnel working on thisanalysis that are not affiliated with Columbia University.

9. For each member of the Columbia University group that will be participating in the SSRIanalysis, provide a list of all work done with the pharmaceutical industry either directly orindirectly or its representatives covering the past five years. This list should include thenature of the work, the company for which it was performed and the amount of moneyreceived. This includes all consultative work, speaking engagements and any other typeof arrangement with the pharmaceutical industry, as well as, stock holdings or otherinvestments.

I understand further that the FDA referred the “details” (narrative summaries) of suicidesfrom SSRI clinical trials in minors to Columbia University for review. The following series ofquestions relate to these “details.”

1. What data is included in these “details”? Please be specific.

2. Who developed the data included in the “details” provided to Columbia University?Please provide a copy of their respective CVs.

3. Please describe the methodology used to determine the date included in these “details”?Please identify whom developed the methodology and what the rationale was behind themethods used.

4. Please describe in detail, the process used to develop the narrative “details.” Among otherthings, address the following for each “detail” prepared and proved to ColumbiaUniversity:

a. whether or not the subject was interviewed;

b. whether or not the subject’s parent(s)/guardian(s) were interviewed;

c. whether or not the subject’s treating physician was interviewed; and

d. whether or not those subjects who left the trial were included in the details.

5. How much time lapsed between an adverse event and each “detail” written and providedto Columbia University for the study?

When preparing responses to the questions identified above please be sure to re-state thequestion and provide a detailed response. In the event that documents or other materials arerequested, please be sure to mark them accordingly.

In closing, I look forward to hearing from you no later than June 7, 2004 regarding myrequests and concerns set forth in this letter. Thank you for your attention to this importantmatter.


Charles E. Grassley