Statistical Evaluation of Bioequivalence Studies - BEBAC ...

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Sample Size: Planning• NfG on the Investigation of BA/BE• Problems/solutions• … as estimated from‣ a pilot experiment,‣ previous studies, or‣ published data,• The correct order should read:1. previous studies ⇒ 2. pilot study ⇒ 3. published data.‣ Only in the first case you ‘know’ all constraints resulting invariability.‣ Pilot studies are often too small to get reliable estimates ofvariability.‣ Advisable only if you have data from a couple of studies.Dissolution Testing, Bioavailability & Bioequivalence | Budapest, 24 May 2007 44
Sample Size: Planning• NfG on the Investigation of BA/BE• Problems/solutions• … the significance level desired …‣ Throughout the NfG the significance level (α, error type I:patient’s risk to be treated with a bioinequivalent drug) isfixed to 5 % (corresponding to a 90 % confidence interval).‣ You may desire a higher significance level, but such aprocedure is not considered acceptable.‣ In special cases (e.g., dose proportionality testing), acorrection for multiplicity may be necessary.‣ In some restrictive legislations (e.g., Brazil’s ANVISA),α must be tightened to 2.5 % for NTIDs (95 % confidenceinterval).Dissolution Testing, Bioavailability & Bioequivalence | Budapest, 24 May 2007 45
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 42 and 43: 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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