title: A conditional maximized sequential probability ratio test for pharmacovigilance.
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.
authors: Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, 133 Brookline Ave., 6th floor, Boston, MA 02215, USA. lingling_li@post.harvard.edu
authors: Lingling
authors: L
authors: Li
authors: Martin
authors: M
authors: Kulldorff
mesh_terms: D000293:Adolescent; D000328:Adult; D016907:Adverse Drug Reaction Reporting Systems; D000465:Algorithms; D015982:Bias; D002648:Child; D003198:Computer Simulation; D016001:Confidence Intervals; D015986:Confounding Factors, Epidemiologic; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D015340:Epidemiologic Research Design; D006801:Humans; D006967:Hypersensitivity / Q000453:epidemiology / Q000276:immunology; D016013:Likelihood Functions; D015233:Models, Statistical; D009010:Monte Carlo Method; D030361:Papillomavirus Infections / Q000517:prevention & control; D053918:Papillomavirus Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use; D016012:Poisson Distribution; D011336:Probability; D011358:Product Surveillance, Postmarketing / Q000379:methods*; D012306:Risk; D014612:Vaccines / Q000009:adverse effects; D055815:Young Adult
chemical_list: D053918:Papillomavirus Vaccines; D014612:Vaccines