Parameter estimation of Weibull distribution for the number of days between drug administration and early onset adverse event

• Published in: Journal of biopharmaceutical statistics Vol. 33; no. 3; pp. 386 - 399
• Main Authors: Ogura, Toru, Shiraishi, Chihiro
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 04.05.2023; Taylor & Francis Ltd
• Subjects: Adverse Drug Reaction Reporting Systems; Adverse event; discrete data; Drug-Related Side Effects and Adverse Reactions - diagnosis; Drug-Related Side Effects and Adverse Reactions - epidemiology; FAERS data; Humans; Parameter estimation; Software; Statistical Distributions; two-sample Kolmogorov-Smirnov test; United States; United States Food and Drug Administration; Weibull distribution; United States; Adverse event; two-sample Kolmogorov–Smirnov test; Weibull distribution; discrete data; FAERS data
• ISSN: 1054-3406; 1520-5711
• DOI: 10.1080/10543406.2022.2154940

The Weibull distribution is applied to the number of days between the start date of drug administration and the date of occurrence of an adverse event. The tendency of occurrence of adverse events can be clarified by estimating the two- or three-parameter Weibull distribution, using the data regarding the number of days. Our purpose is to estimate the parameters of the Weibull distribution with high accuracy, even in low-reported adverse events, such as new drugs, polypharmacy and small clinical trials. Furthermore, the two-sample Kolmogorov - Smirnov test (two-sided) is used to examine whether the tendency of occurrence of adverse events is different for two Weibull distributions estimated from two drugs with similar efficacy. We used discrete data derived from FDA Adverse Event Reporting System (FAERS), as the FAERS data are presented in years, months and days without hours and minutes. Because this study focuses on early onset adverse events, data may be contained 0 days. The discreteness of the data and the fact that it may include zero make this distribution different from the general Weibull distribution, which is defined for continuous data greater than zero. We search for the optimal parameter estimation method for the Weibull distribution under these two conditions, and verify its effectiveness using Monte Carlo simulations and FAERS data. Because the results obtained from FAERS data may differ depending on data handling, we describe the of data handling technique and the sample code that can reproduce the results.