Ing. Helmut Schütz

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Articles

This series of articles was inspired by recurrent discussions at the Bio­equi­va­lence and Bio­avail­ability Forum and questions I received from my clients or regulatory assessors.

The content expressed in the articles presents my sole personal opinion. Although regulatory requirements are incorporated to a high degree, some strong views are strictly scientifically based on my 40 years of experience in the field and do not represent any type of “cookbook approach” which should be followed unreflecting.
I do not make any representations or warranties regarding the accuracy of such content.

To the right articles are listed in chronological order. Below are articles arranged by topic.

• 🃏 Related to questions commonly asked by regulatory assessors.
• 🆕 Published within the last two weeks.
• 🚧 Article under construction.

To reproduce the articles’ examples is required.

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Power Calculation and Sample Size Estimation

Equivalence

• Hypotheses – not only in Equivalence 56 KB (update 2022-08-06)
• Parallel Design 288 KB (update 2022-09-10)
• 2×2×2 Design 424 KB (update 2022-09-10)
• Higher-Order Crossover Designs 342 KB (update 2022-09-08)
• Replicate Designs
  • Average Bioequivalence 160 KB (update 2022-06-16)
  • Scaled Average Bioequivalence
    • Highly Variable Drugs / Drug Products
      • RSABE (FDA, China’s CDE) 162 KB (update 2022-04-04)
      • ABEL (all others) 171 KB (update 2022-04-28)
    • NTIDs (FDA, China’s CDE) 149 KB (update 2022-05-05)
    • Highly Variable NTIDs (FDA, China’s CDE) 🚧
  • ABE, RSABE, ABEL – A Comparison 279 KB (update 2022-07-12)
  • Inflation of the Type I Error in SABE 316 KB (update 2022-09-20)
• Two-Stage Designs
  • Group sequential (fixed sample design) 🚧
  • Adaptive (sample size re-estimation) 🃏 🚧

Non-Inferiority/Superiority, Non-Superiority 115 KB (update 2022-09-10)

Dose Proportionality 🚧

Prospective Power

• Power Analysis 55 KB (update 2022-06-21)
• Sensitivity Analysis 240 KB (update 2022-07-02)

Noncompartmental Analysis

• Trapezoidal Rules 234 KB (update 2022-06-20)
• Estimation of λ_z 🚧
• Extrapolation to Infinity – Observed or Predicted C_last? 107 KB (update 2022-09-12)
• Demonstration of Steady State Achievement? 165 KB (update 2022-09-12)
• Partial AUC 🚧
• Cut-off Times for Biphasic Release Products 🚧
• C_min and C_τ 🚧

Miscellaneous

Statistics

• A Short History of Bioequivalence 🚧
• Carryover – A Never Ending Story 271 KB (update 2022-08-06) 🃏
• Significant Treatment Effect 134 KB (update 2022-06-27) 🃏
• Fixed or mixed effects? 🚧
• Group ‘Effect’ – To Pool or Not to Pool? 🃏 334 KB (update 2022-09-13)
• Post hoc Power 182 KB (update 2022-07-26) 🃏
• ‘Apparent’ Difference in t_max? 371 KB (update 2022-07-29)
• Simulations 101 224 KB (update 2022-07-06)
• ‘Nice Numbers’ – A Rant 148 KB (update 2022-08-06)
• ‘Precise’ Numbers in Reports 🚧
• Subgroup Analyses 🚧
• Adjusted Indirect Comparisons 🚧
• Detecting Data Manipulation / Fraud 🚧

Design Issues

• Washout Phase – Tricks and Traps 🃏 🚧
• Pilot → Pivotal Studies 🚧
• SABE planned based on the CV_w of a Crossover Design 51 KB (update 2022-06-21)
• Limited Capacity of a Clinical Site – Groups or Replicates? 146 KB (update 2022-08-19)
• Stratified Randomization – Why? 🚧

Software

• Representing Numbers in Computers – A Wonderland 111 KB (update 2022-06-18)
• 🇷 on Windows 101 63 KB (update 2022-08-26)
• Software Validation 🚧

All articles are licensed under Creative Commons Attribution 4.0 Helmut Schütz 2022.