title: Likelihood ratio based tests for longitudinal drug safety data.
abstract: This article presents longitudinal likelihood ratio test (LongLRT) methods for large databases with exposure information. These methods are applied to a pooled large longitudinal clinical trial dataset for drugs treating osteoporosis with concomitant use of proton pump inhibitors (PPIs). When the interest is in the evaluation of a signal of an adverse event for a particular drug compared with placebo or a comparator, the special case of the LongLRT, referred to as sequential LRT (SeqLRT), is also presented. The results show that there is some possible evidence of concomitant use of PPIs leading to more adverse events associated with osteoporosis. The performance of the proposed LongLRT and SeqLRT methods is evaluated using simulated datasets and shown to be good in terms of (conditional) power and control of type I error over time. The proposed methods can also be applied to large observational databases with exposure information under the US Food and Drug Administration Sentinel Initiative for active surveillance. Published 2014. This article is a US Government work and is in the public domain in the USA.
authors.affiliation: Division of Biometrics V, Office of Biostatistics, OTS, CDER, FDA, Silver Spring, MD 20993, U.S.A.
authors.forename: Lan
authors.initials: L
authors.lastname: Huang
authors.forename: Jyoti
authors.initials: J
authors.lastname: Zalkikar
authors.forename: Ram
authors.initials: R
authors.lastname: Tiwari
mesh_terms: D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D003198:Computer Simulation; D003627:Data Interpretation, Statistical; D004359:Drug Therapy, Combination / Q000009:adverse effects; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D016013:Likelihood Functions; D008137:Longitudinal Studies; D010024:Osteoporosis / Q000188:drug therapy; D004364:Pharmaceutical Preparations / Q000592:standards*; D054328:Proton Pump Inhibitors / Q000627:therapeutic use
chemical_list: D050071:Bone Density Conservation Agents; D004364:Pharmaceutical Preparations; D054328:Proton Pump Inhibitors
keywords: active surveillance; drug exposure; longitudinal method; safety surveillance; sequential method