Meta- Analysis of Retention Rates of Post-Marketing Trials to Compare Effectiveness of Second Generation Antiepileptic Drugs
Eugène Cox (1), D. Russell Wada (1), Nancy Zhang (1) & Frank Wiegand (2)
(1) Quantitative Solutions, Menlo Park, CA, USA & Breda, The Netherlands ; (2) Johnson & Johnson Pharmaceutical Services, L.L.C., Raritan, NJ, USA
Objectives: Retention is the duration of time a patient stays on treatment. It reflects the overall patient experience with the efficacy and tolerability of a drug. The current meta-analysis develops a methodology to analyze the time-course of retention from post-marketing clinical trial publications on second generation antiepileptic drugs (AEDs) in patients with partial onset seizures (POS).
Methods: From a comprehensive literature search 34 post marketing studies for five AEDs used as adjunctive therapy in patients with POS were selected (topiramate, 11; levetiracetam, 13; lamotrigine, 9, gabapentin, 7, and tiagabine, 5). Longitudinal retention data was extracted along with other relevant trial data. A constant hazard model that accounts for long term-steady state retention was used. Various drug and covariate effects were evaluated, and random study-effect was included in the model. Parameters were estimated using nonlinear mixed-effects regression using the nlme function in S-plus 6.1. Model quality was evaluated by considering the effect of trial size and publication date on the magnitude of effect.
Results: This methodology resulted in good model fit of the retention profiles over time for each of the five drugs. Each AED appears to have a unique and consistent retention profile across trials, with the following rank order in retention rates (1 year rate, 95% CI): lamotrigine (74%, 68%-80%) >levetiracetam (71%, 64%-77%) >topiramate (64%, 56%-71%) >gabapentin (49%, 40%-59%) ~tiagabine (48%, 36%-64%). The covariate analysis indicated baseline AEDs and year of publication, but not sample size, are correlated to retention.
Conclusions: The presented hazard model worked well in describing the time-course of retention for five second generation AEDs. The analysis suggests that each drug demonstrates a distinct retention profile.
