AIM: The investigations reported here aimed to evaluate the incremental benefit for dose finding by concentration-response analysis versus dose-response analysis. METHODS: Trials were simulated using an Emax model for a range of scenarios of drug properties, trial design options and target response levels. The simulated data were analysed by concentration-response and dose-response modelling; a dose was then chosen to target a specific response level in a confirmatory trial. The two approaches were compared in terms of the quality of model parameter estimation and the success rate for the confirmatory trial. RESULTS: While the accuracy for ED50 estimation was comparably good with both approaches, the precision was up to 90 % higher with concentration-response approach. The difference was most notable when clearance was highly variable between subjects and the top dose was relatively low. The higher precision by the concentration-response analysis lead to better dose selection and up to 20 % higher success rate for the subsequent confirmatory trial. The relatively small difference in success rate translated into a remarkable difference in sample size requirement. CONCLUSION: By customising these parameters, the approach and the findings can be applied to assessing the value of pharmacokinetic sampling in particular trial situations.
AIM: The investigations reported here aimed to evaluate the incremental benefit for dose finding by concentration-response analysis versus dose-response analysis. METHODS: Trials were simulated using an Emax model for a range of scenarios of drug properties, trial design options and target response levels. The simulated data were analysed by concentration-response and dose-response modelling; a dose was then chosen to target a specific response level in a confirmatory trial. The two approaches were compared in terms of the quality of model parameter estimation and the success rate for the confirmatory trial. RESULTS: While the accuracy for ED50 estimation was comparably good with both approaches, the precision was up to 90 % higher with concentration-response approach. The difference was most notable when clearance was highly variable between subjects and the top dose was relatively low. The higher precision by the concentration-response analysis lead to better dose selection and up to 20 % higher success rate for the subsequent confirmatory trial. The relatively small difference in success rate translated into a remarkable difference in sample size requirement. CONCLUSION: By customising these parameters, the approach and the findings can be applied to assessing the value of pharmacokinetic sampling in particular trial situations.
Authors: Nelson L Jumbe; Yan Xin; Douglas D Leipold; Lisa Crocker; Debra Dugger; Elaine Mai; Mark X Sliwkowski; Paul J Fielder; Jay Tibbitts Journal: J Pharmacokinet Pharmacodyn Date: 2010-04-28 Impact factor: 2.745
Authors: Monica Simeoni; Paolo Magni; Cristiano Cammia; Giuseppe De Nicolao; Valter Croci; Enrico Pesenti; Massimiliano Germani; Italo Poggesi; Maurizio Rocchetti Journal: Cancer Res Date: 2004-02-01 Impact factor: 12.701