Statistical Evaluation of Bioequivalence Studies - BEBAC ...

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Sample Size: Planning• NfG on the Investigation of BA/BE• Problems/solutions• … the expected deviation (∆) from the reference …‣ Reliable estimate only from a previous full-sized study.‣ If you are using data from a pilot study, allow for a safetymargin.‣ If no data are available, commonly a GMR (geometrictest/reference-ratio) of 0.95 (∆ = 5 %) is used.‣ If more than ∆ = 10 % is expected, questions from theethics committee are likely.Dissolution Testing, Bioavailability & Bioequivalence | Budapest, 24 May 2007 46
Sample Size: Planning• NfG on the Investigation of BA/BE• Problems/solutions• … the required power.‣ Generally the power is set to at least 80 % (β, error type II:producers’s risk to get no approval for a bioequivalentdrug; power = 1 – β).Remember: 1 out of 5 studies will fail just by chance!‣ If you plan for power of less than 70 %, problems with theethics committee are likely.‣ If you plan for power of more than 90 % (especially withlow variability drugs), problems with the regulator arepossible (‘forced bioequivalence’).‣ Add subjects according to the expected drop-out rate!Dissolution Testing, Bioavailability & Bioequivalence | Budapest, 24 May 2007 47
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 44 and 45: 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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