An Ana的lytic Road Map for Incomplete Longitudinal Clinical Trial Data.pptVIP

An Analytic Road Map for Incomplete Longitudinal Clinical Trial Data Craig Mallinckrodt Graybill Conference June 12, 2008Fort Collins, CO Acknowledgements PhRMA Expert Team on Missing Data Peter Lane GSK Craig Mallinckrodt Lilly James Mancuso Pfizer Yahong Peng Merck Dan Schnell PG Geert Molenberghs Ray Carroll Many Lilly colleagues Outline Why do we care What do we know Theory Application What we should do Need for More Effective Medicines Therapeutic Area Efficacy rate(%) Alzheimer’s 30 Analgesic’s (Cox-2) 80 Asthma 60 Cardiac Arrhythmias 60 Depression (SSRI) 62 Diabetes 57 HCV 47 Incontinence 40 Migraine (acute) 52 Migraine (prophylaxis) 50 Oncology 25 Osteoporosis 48 Rheumatoid arthritis 50 Schizophrenia 60 RD Productivity Decreasing Outline Why do we care What do we know Theory Application What we should do Starting Point No universally best method for analyzing longitudinal data Analysis must be tailored to the specific situation at hand Consider the hypothesis to be tested, desired attributes of the analysis, and the characteristics of the data Missing Data Mechanisms MCAR - missing completely at random Conditional on the independent variables in the model, neither observed or unobserved outcomes of the dependent variable explain dropout MAR - missing at random Conditional on the independent variables in the model, observed outcomes of the dependent variable explain dropout, but unobserved outcomes do not Missing Data Mechanisms MNAR - missing not at random Conditional on the independent variables in the model and the observed outcomes of the dependent variable, the unobserved outcomes of the dependent variable explain dropout Consequences Missing data mechanism is a characteristic  of the data AND the model Differential dropout by treatment indicates covariate dependence, not mechanism Mechanism can vary from one outcome to  another in the same dataset Research Showing MAR Is Useful And