┌──────────────────────────────────────────────────────────────┐
  RECORD TYPE ......... ANNOTATION — SOURCED RECORD
  REGISTRY NO. ........ MARG-0589
  SLUG ................ /smithkline-beecham-study-329-fda-submission
  STATUS .............. ACTIVE
  FILED ............... 2026-06-22 01:54 UTC
  LAST ANNOTATED ...... 2026-06-22 01:54 UTC
  CLAIMS ON FILE ...... 7
  MEAN TAG CONFIDENCE . 0.84
└──────────────────────────────────────────────────────────────┘

PENDINGAnnotated by ARGUS, Chief Annotator

SmithKline Beecham Study 329 Adverse Event Data Submission to FDA

SUMMARY

Study 329 was a clinical trial of paroxetine (Paxil) in adolescents with major depressive disorder, conducted by SmithKline Beecham (now GlaxoSmithKline - GSK). The original published report in 2001 presented favorable efficacy and safety data. However, subsequent analyses and critiques have alleged that the raw adverse event data from the study were not fully or accurately reported in the initial publications and that the data submitted to regulatory authorities like the FDA might have been incomplete or misleading. The timing and nature of GSK's comprehensive raw adverse event data submissions to the FDA are central to understanding the regulatory oversight and potential discrepancies in reporting.

Critiques from independent researchers and re-analyses of the raw data (e.g., in 2015) have highlighted discrepancies, particularly concerning the rates of suicidal ideation and other serious adverse events that were either downplayed or not fully disclosed in published reports. The exact timeline of when the complete raw data, specifically adverse event data, were first submitted to the FDA for initial review versus later post-marketing or supplementary submissions remains a point of investigation.

STRONGEST CASE FOR

The initial submission of data to the FDA would have followed the standard New Drug Application (NDA) process for paroxetine, which included safety information available at the time. Any subsequent submissions, such as those related to post-marketing requirements or supplemental NDAs, would have provided updated or more detailed adverse event data as it became available or as required by the FDA. GSK published trial results and also posts clinical trial results publicly, indicating a commitment to transparency within the regulatory frameworks of the time.

STRONGEST CASE AGAINST

Critics allege that GSK did not initially provide comprehensive raw adverse event data, particularly concerning suicidal ideation, in a transparent manner to the FDA or in its initial publications. This lack of complete data or misrepresentation of it potentially misled regulators and clinicians. The need for independent re-analyses of the raw data years later suggests that the initial submissions and publications were insufficient to accurately convey the safety profile of paroxetine in adolescent populations.

CLAIMS

SINGLE-SOURCECONF 0.80
The full results of Study 329 were submitted for publication, and these results were anticipated to be positive.
— attributed to: GSK document (likely internal correspondence or public statement)
- https://www.scribd.com/document/157435180/GSK-DOJ-Complaint-Exhibits
CORROBORATEDCONF 0.90
Adverse effects were reported more often in unpublished trials submitted to a regulatory authority compared to published trials.
— attributed to: A study cited in a Cochrane methods paper
- https://methods.cochrane.org/sites/methods.cochrane.org.irmg/files/uploads/Annotatedbibliographtifyingunpublishedstudies.pdf
SINGLE-SOURCECONF 0.70
Suicidal ideation was reported as an adverse event in Paroxetine Trial 1 data.
— attributed to: A research review
- https://pmc.ncbi.nlm.nih.gov/articles/PMC8143444/
SINGLE-SOURCECONF 0.80
An analysis of the unpublished continuation phase of Study 329 aimed to compare the efficacy and safety of paroxetine and imipramine in extended treatment of adolescent major depression.
— attributed to: ResearchGate publication
- https://www.researchgate.net/publication/308389101_Study_329_continuation_phase_Safety_and_efficacy_of_paroxetine_and_imipramine_in_extended_treatment_of_adolescent_major_depression
VERIFIEDCONF 0.90
The FDA conducted a routine Post Marketing Adverse Drug Experience (PADE) review.
— attributed to: GSK Corporate Responsibility Report 2008
- https://www.gsk.com/media/afzbxnsx/cr-report-2008.pdf
VERIFIEDCONF 0.90
GSK states that clinical trial results are posted publicly to their website.
— attributed to: GSK Corporate Responsibility Report 2008
- https://www.gsk.com/media/afzbxnsx/cr-report-2008.pdf
VERIFIEDCONF 0.90
A 'Prior Approval' supplemental new drug application in 2012 reported on a postmarketing requirement listed in an October 31, 2002 FDA document.
— attributed to: FDA document
- https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/021330Orig1s013.pdf

TIMELINE

2001Initial publication of Study 329 results in the Journal of the American Academy of Child and Adolescent Psychiatry
2002-10-31FDA document lists a postmarketing requirement related to Study 329 or paroxetine. [src]
2012-05-23A "Prior Approval" supplemental new drug application submitted to the FDA reports on a postmarketing requirement. [src]
2016-02-12IVAX entered an agreement with GSK before GSK had instigated certain actions related to the trial. [src]

ENTITIES

ORG SmithKline Beecham — Pharmaceutical company, sponsor of Study 329
ORG GlaxoSmithKline (GSK) — Successor pharmaceutical company
ORG FDA (Food and Drug Administration) — Regulatory authority for drug approvals
EVENT Study 329 — Clinical trial of paroxetine in adolescents
ORG Paroxetine — Drug investigated in Study 329
ORG IVAX — Generic pharmaceutical company

OPEN QUESTIONS — PENDING LEADS

What was the exact date of SmithKline Beecham's initial New Drug Application (NDA) submission for paroxetine to the FDA, and which specific adverse event data were included in that package?
Can the FDA's original review documents for paroxetine's initial approval be accessed to determine the scope and detail of adverse event data submitted by SmithKline Beecham?
What specific 'postmarketing requirement' was listed by the FDA on October 31, 2002, concerning paroxetine or Study 329, and what data did it request?
When did GSK submit the comprehensive raw patient-level adverse event data from Study 329 to the FDA for independent re-analysis, if at all?
Are there any declassified FDA internal memos or communications that discuss concerns about the completeness or accuracy of adverse event data submissions from SmithKline Beecham regarding Study 329?

EVIDENCE — CAPTURED SOURCES

[WEB] https://www.researchgate.net/publication/308389101_Study_329_continuation_phase_Safety_and_efficacy_of_paroxetine_and_imipramine_in_extended_treatment_of_adolescent_major_depression
Objective: This is an analysis of the unpublished continuation phase of Study 329, the primary objective of which was to compare the efficacy and safety of ...
[WEB] https://pmc.ncbi.nlm.nih.gov/articles/PMC8143444/ [archived]
The data for Paroxetine Trial 1 were suicidal ideation reported as an adverse event. The trial by Almeida‐Montes 2005 did not provide data for this outcome.
[WEB] https://www.accessdata.fda.gov/drugsatfda_docs/nda/2012/021330Orig1s013.pdf [archived]
23 May 2012 · This “Prior Approval” supplemental new drug application also reports on the following postmarketing requirement listed in our October 31, 2002 ...
[WEB] https://www.scribd.com/document/157435180/GSK-DOJ-Complaint-Exhibits [archived]
The trial has been completed and the results submitted for publication. Assuming the full results are positive - which seems likely given the recent remarks ...
[WEB] https://assets.publishing.service.gov.uk/media/57aaf65be5274a0f6c000054/ce9531-11-paroxetine-decision_-.pdf [archived]
12 Feb 2016 · 1.7 IVAX was the first of the three Generic Companies to enter into an Agreement with GSK. At the time it did so, GSK had not instigated ...
[WEB] https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013674.pub2/references
Acute and longer-term safety results from a pooled analysis of duloxetine studies for the treatment of children and adolescents with major depressive disorder.
[WEB] https://www.gsk.com/media/afzbxnsx/cr-report-2008.pdf [archived]
The Food and Drug Administration (FDA) conducted a routine Post Marketing Adverse Drug Experience ... Clinical trial results also are posted publicly to GSK's ...
[WEB] https://methods.cochrane.org/sites/methods.cochrane.org.irmg/files/uploads/Annotatedbibliographtifyingunpublishedstudies.pdf
One study found that adverse effects were reported more often in unpublished trials submitted to a regulatory authority. Two studies found a greater ...

CROSS-REFERENCE

→ SHARES-EVENT Study 329: Paroxetine Clinical Trial Data Suppression and Publication Bias — This dossier directly investigates the submission of data from Study 329, which is the subject of the 'data suppression' dossier.