title: Projecting adverse event incidence rates using empirical Bayes methodology.
abstract: Although there is considerable interest in adverse events observed in clinical trials, projecting adverse event incidence rates in an extended period can be of interest when the trial duration is limited compared to clinical practice. A naïve method for making projections might involve modeling the observed rates into the future for each adverse event. However, such an approach overlooks the information that can be borrowed across all the adverse event data. We propose a method that weights each projection using a shrinkage factor; the adverse event-specific shrinkage is a probability, based on empirical Bayes methodology, estimated from all the adverse event data, reflecting evidence in support of the null or non-null hypotheses. Also proposed is a technique to estimate the proportion of true nulls, called the common area under the density curves, which is a critical step in arriving at the shrinkage factor. The performance of the method is evaluated by projecting from interim data and then comparing the projected results with observed results. The method is illustrated on two data sets.
authors.affiliation: Gilead Sciences, 333 Lakeside Drive, Foster City, California, USA Julie.ma@gilead.com.
authors.forename: Guoguang Julie
authors.initials: GJ
authors.lastname: Ma
authors.affiliation: Gilead Sciences, 333 Lakeside Drive, Foster City, California, USA.
authors.forename: Jitendra
authors.initials: J
authors.lastname: Ganju
authors.affiliation: Amgen Inc., 1150 Veterans Blvd., South San Francisco, California, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D001499:Bayes Theorem; D019433:Chickenpox Vaccine / Q000009:adverse effects*; D017326:Clinical Trials, Phase III as Topic; D005544:Forecasting / Q000379:methods*; D006801:Humans; D015994:Incidence; D022542:Measles-Mumps-Rubella Vaccine / Q000009:adverse effects*; D009369:Neoplasms / Q000188:drug therapy; D017778:Vaccines, Combined / Q000009:adverse effects
chemical_list: D000970:Antineoplastic Agents; D019433:Chickenpox Vaccine; D022542:Measles-Mumps-Rubella Vaccine; D017778:Vaccines, Combined; C050102:measles, mumps, rubella, varicella vaccine
keywords: Projection; adverse events; empirical Bayes