The FDA outlook of events reporting after ticagrelor or clopidogrel in the PLATO trial: Impact of sponsor censoring dates, drug discontinuation, and withdrawal of consent

Victor L. Serebruany

Research output: Contribution to journalArticle

Abstract

Background: Censoring by the study sponsor of clinical endpoint events in indication-seeking randomized trials represents a controversial approach since the reported data may be biased in favor of experimental agents due to the obvious conflict of interest. The frequency of drug discontinuation and rates of consent withdrawal may also impact the trial outcomes. Purpose: To assess patterns of event reporting dependent on sponsor censoring dates, drug discontinuation and consent withdrawal in the PLATO trial. Methods: Analysis of theFood and Drug Administration Complete Response Review for ticagrelor. Results: Excluding adjudicated deaths, the distribution for clopidogrel appears more uniform while that for ticagrelor was skewed to the right, suggesting more events were reported after the sponsor censoring end date. PLATO investigators reported 16 unmatched primary endpoint events for ticagrelor immediately following the sponsor censoring date. Twenty-six out of 30 unreported events following early drug discontinuation occurred amongst patients using ticagrelor. More ticagrelor patients withdrew consent (Δ = 47), or were 'not willing' to complete the study (Δ = 87) when compared to clopidogrel. Conclusions: Site-reported primary endpoints were unequally distributed for clopidogrel and ticagrelor in the PLATO trial. This pattern suggests the importance of questioning the impact of sponsor-mediated censoring on event reporting by investigators in indication-seeking trials. In PLATO, this pattern seems to have favored the experimental drug and may require further assessment.

Original languageEnglish (US)
Pages (from-to)169-171
Number of pages3
JournalCardiology
Volume120
Issue number3
DOIs
StatePublished - Jan 2012

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clopidogrel
Pharmaceutical Preparations
Research Personnel
Conflict of Interest
Ticagrelor
(1,2-diamino-4-nitrobenzene)dichloroplatinum(II)

Keywords

  • Antiplatelet therapy
  • Clinical trials
  • Clopidogrel
  • Monitoring
  • Ticagrelor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Pharmacology (medical)

Cite this

@article{87a336ecf9c340148c870793e98e3316,
title = "The FDA outlook of events reporting after ticagrelor or clopidogrel in the PLATO trial: Impact of sponsor censoring dates, drug discontinuation, and withdrawal of consent",
abstract = "Background: Censoring by the study sponsor of clinical endpoint events in indication-seeking randomized trials represents a controversial approach since the reported data may be biased in favor of experimental agents due to the obvious conflict of interest. The frequency of drug discontinuation and rates of consent withdrawal may also impact the trial outcomes. Purpose: To assess patterns of event reporting dependent on sponsor censoring dates, drug discontinuation and consent withdrawal in the PLATO trial. Methods: Analysis of theFood and Drug Administration Complete Response Review for ticagrelor. Results: Excluding adjudicated deaths, the distribution for clopidogrel appears more uniform while that for ticagrelor was skewed to the right, suggesting more events were reported after the sponsor censoring end date. PLATO investigators reported 16 unmatched primary endpoint events for ticagrelor immediately following the sponsor censoring date. Twenty-six out of 30 unreported events following early drug discontinuation occurred amongst patients using ticagrelor. More ticagrelor patients withdrew consent (Δ = 47), or were 'not willing' to complete the study (Δ = 87) when compared to clopidogrel. Conclusions: Site-reported primary endpoints were unequally distributed for clopidogrel and ticagrelor in the PLATO trial. This pattern suggests the importance of questioning the impact of sponsor-mediated censoring on event reporting by investigators in indication-seeking trials. In PLATO, this pattern seems to have favored the experimental drug and may require further assessment.",
keywords = "Antiplatelet therapy, Clinical trials, Clopidogrel, Monitoring, Ticagrelor",
author = "Serebruany, {Victor L.}",
year = "2012",
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language = "English (US)",
volume = "120",
pages = "169--171",
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publisher = "Lippincott Williams and Wilkins Ltd.",
number = "3",

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T1 - The FDA outlook of events reporting after ticagrelor or clopidogrel in the PLATO trial

T2 - Impact of sponsor censoring dates, drug discontinuation, and withdrawal of consent

AU - Serebruany, Victor L.

PY - 2012/1

Y1 - 2012/1

N2 - Background: Censoring by the study sponsor of clinical endpoint events in indication-seeking randomized trials represents a controversial approach since the reported data may be biased in favor of experimental agents due to the obvious conflict of interest. The frequency of drug discontinuation and rates of consent withdrawal may also impact the trial outcomes. Purpose: To assess patterns of event reporting dependent on sponsor censoring dates, drug discontinuation and consent withdrawal in the PLATO trial. Methods: Analysis of theFood and Drug Administration Complete Response Review for ticagrelor. Results: Excluding adjudicated deaths, the distribution for clopidogrel appears more uniform while that for ticagrelor was skewed to the right, suggesting more events were reported after the sponsor censoring end date. PLATO investigators reported 16 unmatched primary endpoint events for ticagrelor immediately following the sponsor censoring date. Twenty-six out of 30 unreported events following early drug discontinuation occurred amongst patients using ticagrelor. More ticagrelor patients withdrew consent (Δ = 47), or were 'not willing' to complete the study (Δ = 87) when compared to clopidogrel. Conclusions: Site-reported primary endpoints were unequally distributed for clopidogrel and ticagrelor in the PLATO trial. This pattern suggests the importance of questioning the impact of sponsor-mediated censoring on event reporting by investigators in indication-seeking trials. In PLATO, this pattern seems to have favored the experimental drug and may require further assessment.

AB - Background: Censoring by the study sponsor of clinical endpoint events in indication-seeking randomized trials represents a controversial approach since the reported data may be biased in favor of experimental agents due to the obvious conflict of interest. The frequency of drug discontinuation and rates of consent withdrawal may also impact the trial outcomes. Purpose: To assess patterns of event reporting dependent on sponsor censoring dates, drug discontinuation and consent withdrawal in the PLATO trial. Methods: Analysis of theFood and Drug Administration Complete Response Review for ticagrelor. Results: Excluding adjudicated deaths, the distribution for clopidogrel appears more uniform while that for ticagrelor was skewed to the right, suggesting more events were reported after the sponsor censoring end date. PLATO investigators reported 16 unmatched primary endpoint events for ticagrelor immediately following the sponsor censoring date. Twenty-six out of 30 unreported events following early drug discontinuation occurred amongst patients using ticagrelor. More ticagrelor patients withdrew consent (Δ = 47), or were 'not willing' to complete the study (Δ = 87) when compared to clopidogrel. Conclusions: Site-reported primary endpoints were unequally distributed for clopidogrel and ticagrelor in the PLATO trial. This pattern suggests the importance of questioning the impact of sponsor-mediated censoring on event reporting by investigators in indication-seeking trials. In PLATO, this pattern seems to have favored the experimental drug and may require further assessment.

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