tetano
Editor, Senior Moderator
Pharmacoepidemiol Drug Saf. 2014 Jun 19. doi: 10.1002/pds.3669. [Epub ahead of print]
Signal detection based on time-to-onset: extending a new method from spontaneous reports to observational studies.
Van Holle L1, Tavares Da Silva F, Bauchau V.
Author information
Abstract
PURPOSE:
A proof-of-concept study has previously highlighted the added value of a method using time-to-onset (TTO) for quantitative and non-parametric signal detection on spontaneous report data. The aim of this study was to assess the added value of this new TTO signal detection method adapted to observational studies.
METHODS:
For each adverse event collected during the conduct of an observational study of H1N1 pandemic influenza vaccine, the TTO distribution was tested against the 'follow-up distribution' from vaccination to 'lost to follow-up' by a Kolmogorov-Smirnov test. Events rejecting the null hypothesis of similar distribution were flagged as signals, and a safety physician evaluated their relevance for further medical assessment. We simulated ongoing surveillance by performing retrospective weekly signal detection based on TTO.
RESULTS:
The TTO method detected 21, 15 and 4 signals within a 30-day period post-dose 1 with confidence levels set at 90%, 95% and 99%, respectively. Of these signals, 14 (67%), 10 (67%) and 2 (50%) were considered as relevant. Among the 14, six had not been identified by previous signal detection activities. When performed weekly, the Kolmogorov-Smirnov test detected 26 events as signals (alpha = 0.05). Three weeks after first participant first dose, one of the six new signals could theoretically have been detected.
CONCLUSIONS:
This study provided evidence that the Kolmogorov-Smirnov method can screen all TTO distributions and objectively flag the unexpected, leading to earlier detection of signals, and thus potential safety issues. ? 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.
? 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.
KEYWORDS:
Kolmogorov-Smirnov; observational study; pharmacoepidemiology; pharmacovigilance; signal detection; time-to-onset; vaccine safety
PMID:
24946233
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24946233
Signal detection based on time-to-onset: extending a new method from spontaneous reports to observational studies.
Van Holle L1, Tavares Da Silva F, Bauchau V.
Author information
Abstract
PURPOSE:
A proof-of-concept study has previously highlighted the added value of a method using time-to-onset (TTO) for quantitative and non-parametric signal detection on spontaneous report data. The aim of this study was to assess the added value of this new TTO signal detection method adapted to observational studies.
METHODS:
For each adverse event collected during the conduct of an observational study of H1N1 pandemic influenza vaccine, the TTO distribution was tested against the 'follow-up distribution' from vaccination to 'lost to follow-up' by a Kolmogorov-Smirnov test. Events rejecting the null hypothesis of similar distribution were flagged as signals, and a safety physician evaluated their relevance for further medical assessment. We simulated ongoing surveillance by performing retrospective weekly signal detection based on TTO.
RESULTS:
The TTO method detected 21, 15 and 4 signals within a 30-day period post-dose 1 with confidence levels set at 90%, 95% and 99%, respectively. Of these signals, 14 (67%), 10 (67%) and 2 (50%) were considered as relevant. Among the 14, six had not been identified by previous signal detection activities. When performed weekly, the Kolmogorov-Smirnov test detected 26 events as signals (alpha = 0.05). Three weeks after first participant first dose, one of the six new signals could theoretically have been detected.
CONCLUSIONS:
This study provided evidence that the Kolmogorov-Smirnov method can screen all TTO distributions and objectively flag the unexpected, leading to earlier detection of signals, and thus potential safety issues. ? 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.
? 2014 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons, Ltd.
KEYWORDS:
Kolmogorov-Smirnov; observational study; pharmacoepidemiology; pharmacovigilance; signal detection; time-to-onset; vaccine safety
PMID:
24946233
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/24946233