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Improvement of Parameter Estimations in Tumor Growth Inhibition Models on Xenografted Animals: Handling Sacrifice Censoring and Error Caused by Experimental Measurement on Larger Tumor Sizes
- Source :
- The AAPS journal. 18(5)
- Publication Year :
- 2016
-
Abstract
- The purpose of this study was to explore the impact of censoring due to animal sacrifice on parameter estimates and tumor volume calculated from two diameters in larger tumors during tumor growth experiments in preclinical studies. The type of measurement error that can be expected was also investigated. Different scenarios were challenged using the stochastic simulation and estimation process. One thousand datasets were simulated under the design of a typical tumor growth study in xenografted mice, and then, eight approaches were used for parameter estimation with the simulated datasets. The distribution of estimates and simulation-based diagnostics were computed for comparison. The different approaches were robust regarding the choice of residual error and gave equivalent results. However, by not considering missing data induced by sacrificing the animal, parameter estimates were biased and led to false inferences in terms of compound potency; the threshold concentration for tumor eradication when ignoring censoring was 581 ng.ml(-1), but the true value was 240 ng.ml(-1).
- Subjects :
- Observational error
Estimation theory
Pharmaceutical Science
Models, Theoretical
Missing data
Residual
030226 pharmacology & pharmacy
Xenograft Model Antitumor Assays
03 medical and health sciences
0302 clinical medicine
Euthanasia, Animal
030220 oncology & carcinogenesis
Censoring (clinical trials)
Animals, Laboratory
Stochastic simulation
Statistics
Tumor growth inhibition
Animals
Tumor growth
Computer Simulation
Mathematics
Subjects
Details
- ISSN :
- 15507416
- Volume :
- 18
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- The AAPS journal
- Accession number :
- edsair.doi.dedup.....f3417eccbcdf426d78283ea844064807