Summarizing EC50 estimates from multiple dose-response experiments: a comparison of a meta-analysis strategy to a mixed-effects model approach.
Dose-response studies are performed to investigate the potency of a compound. EC50 is the concentration of the compound that gives half-maximal response. Dose-response data are typically evaluated by using a log-logistic model that includes EC50 as one of the model parameters. Often, more than one experiment is carried out to determine the EC50 value for a compound, requiring summarization of EC50 estimates from a series of experiments. In this context, mixed-effects models are designed to estimate the average behavior of EC50 values over all experiments by considering the variabilities within and among experiments simultaneously. However, fitting nonlinear mixed-effects models is more complicated than in a linear situation, and convergence problems are often encountered. An alternative strategy is the application of a meta-analysis approach, which combines EC50 estimates obtained from separate log-logistic model fitting. These two proposed strategies to summarize EC50 estimates from multiple experiments are compared in a simulation study and real data example. We conclude that the meta-analysis strategy is a simple and robust method to summarize EC50 estimates from multiple experiments, especially suited in the case of a small number of experiments.
Division of Biostatistics, German Cancer Research Center, Im Neuenheimer Feld, 280, 69120 Heidelberg, Germany.
Xiaoqi
X
Jiang
Annette
A
Kopp-Schneider
D016475:3T3 Cells; D000818:Animals; D001699:Biometry / Q000379:methods*; D004305:Dose-Response Relationship, Drug; D007928:Lethal Dose 50; D015201:Meta-Analysis as Topic; D051379:Mice; D015233:Models, Statistical; D012967:Sodium Dodecyl Sulfate / Q000633:toxicity; D018675:Toxicity Tests
D012967:Sodium Dodecyl Sulfate
Dose-response analysis; EC50 estimate; Log-logistic model; Meta-analysis; Nonlinear mixed-effects model