Statistical Evaluation of Bioequivalence Studies - BEBAC ...

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Sample Size: Planning• NfG on the Investigation of BA/BE• The number of subjects required is determined by• the error variance associated with the primary characteristicto be studied as estimated from‣ a pilot experiment,‣ previous studies, or‣ published data,• the significance level desired,• the expected deviation (∆) from the reference productcompatible with BE and,• the required power.Dissolution Testing, Bioavailability & Bioequivalence | Budapest, 24 May 2007 42
Sample Size: Planning• NfG on the Investigation of BA/BE• Problems/solutions• … the error variance associated with the primarycharacteristic to be studied …‣ Since BE must be shown both for AUC and C max, and,‣ if you plan your sample size only for the ‘primary characteristic’(e.g., AUC), in many cases you will fail for thesecondary parameter (e.g., C max), which most likely showshigher variability – your study will be underpowered.‣ Based on the assumption, that CV is identical for test andreference (what if only the reference formulation has highvariability, e.g., *prazoles?).Dissolution Testing, Bioavailability & Bioequivalence | Budapest, 24 May 2007 43
Page 1: Statistical Evaluation ofBioequival
Page 7: Assumptions: StatisticsMultiplicati
Page 12: Nonparametrics5. In which cases may
Page 16 and 17: Acceptance range for C max2. Assess
Page 18 and 19: Outliers• Problems• Parametric
Page 20 and 21: Outliers• Solution II• Stay wit
Page 22 and 23: Re-testing of subjectsn=24: 83.3%-1
Page 24 and 25: Add-on Design• Reasonable,• if
Page 26 and 27: Group Sequential Design± EU• Per
Page 29 and 30: Studiesof >2 formulations• Disadv
Page 31 and 32: Studiesof >2 formulations• Often
Page 33: Parallel Groups• Design Issues•
Page 36 and 37: Parallel Groups: Example• Evaluat
Page 38 and 39: Parallel Groups: Example• Evaluat
Page 40 and 41: Sample Size• Minimum Number of Su
Page 44 and 45: Sample Size: Planning• NfG on the
Page 46 and 47: Sample Size: Planning• NfG on the
Page 48 and 49: Sample Size: PlanningDoxicycline (3
Page 50 and 51: Sample Size: PowerPower to show BEw
Page 53: Sample Size: Sensitivity Analysis
Page 58: Low Variability• Drugs / Drug Pro
Page 63 and 64: Nuisance: sequence effect• In a
Page 65 and 66: Nuisance: sequence effect• In a l
Page 67 and 68: Nuisance: sequence effect• Conclu
Page 69 and 70: Are we making progress?• About 3
Page 71 and 72: ...to be rememberedWhenever a theor
Page 73 and 74: Statistical Evaluation ofBioequival

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