A conditional maximized sequential probability ratio test for pharmacovigilance

Statistics in Medicine
Lingling Li, Martin Kulldorff

Abstract

The importance of post-marketing surveillance for drug and vaccine safety is well recognized as rare but serious adverse events may not be detected in pre-approval clinical trials. In such surveillance, a sequential test is preferable, in order to detect potential problems as soon as possible. Various sequential probability ratio tests (SPRT) have been applied in near real-time vaccine and drug safety surveillance, including Wald's classical SPRT with a single alternative and the Poisson-based maximized SPRT (MaxSPRT) with a composite alternative. These methods require that the expected number of events under the null hypothesis is known as a function of time t. In practice, the expected counts are usually estimated from historical data. When a large sample size from the historical data is lacking, the SPRTs are biased due to the variance in the estimate of the expected number of events. We present a conditional maximized sequential probability ratio test (CMaxSPRT), which adjusts for the uncertainty in the expected counts. Our test incorporates the randomness and variability from both the historical data and the surveillance population. Evaluations of the statistical power for CMaxSPRT are presented under different scenarios.

References

Jan 1, 1983·Thrombosis Research. Supplement·D W TaylorD L Sackett
Mar 1, 1984·Controlled Clinical Trials·C Jennison, B W Turnbull
Feb 24, 2001·Statistical Methods in Medical Research·B SpiessensD L DeMets
Jan 23, 2002·Pharmacoepidemiology and Drug Safety·F DeStefano, UNKNOWN Vaccine Safety Datalink Research Group
Jun 20, 2002·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Ana SzarfmanRobert T O'Neill
Oct 25, 2007·Medical Care·Tracy A LieuUNKNOWN Vaccine Safety Datalink Rapid Cycle Analysis Team
Nov 29, 2007·Clinical Trials : Journal of the Society for Clinical Trials·Michael P FayNana A Y Twum-Danso

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Citations

Apr 3, 2014·Statistics in Medicine·Rongxia LiMichael M McNeil
Dec 9, 2015·Pharmaceutical Statistics·Jianing DiMichael Krams
Jan 29, 2019·Statistics in Medicine·Ivair R SilvaW Katherine Yih
Oct 20, 2010·International Journal of Cancer. Journal International Du Cancer·M Rami BailonyJess Ghannam
May 4, 2011·Pharmacoepidemiology and Drug Safety·Sharon K GreeneGrace M Lee
Nov 18, 2015·Pharmacoepidemiology and Drug Safety·Weiling Katherine YihGrace M Lee
Oct 28, 2016·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Hélène ThéophileAntoine Pariente
May 2, 2018·Therapeutic Innovation & Regulatory Science·Rima IzemYueqin Zhao
Jan 15, 2020·Pharmaceutical Medicine·Torbjörn CallréusMorten Andersen
Jan 1, 2019·Sequential Analysis·Ivair R SilvaMartin Kulldorff
Jan 1, 2020·Statistics in Biopharmaceutical Research·Lili ZhaoGary Freed
Dec 6, 2011·Statistical Methods in Medical Research·Jennifer C NelsonBruce M Psaty
May 11, 2021·Statistics in Medicine·Shuoran Li, Lili Zhao
Jul 20, 2011·American Journal of Preventive Medicine·Grace M LeeUNKNOWN Vaccine Safety Datalink Project
Apr 12, 2012·Drug Safety : an International Journal of Medical Toxicology and Drug Experience·Peter M WahlRhonda L Bohn
Jan 1, 2012·Pharmaceutics·Marc Suling, Iris Pigeot

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