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 63 KB (update 2023-09-19)
• Parallel Design 317 KB (update 2023-10-01)
• 2×2×2 Design 421 KB (update 2023-09-29)
• Higher-Order Crossover Designs 355 KB (update 2023-10-01)
• Replicate Designs
  • Average Bioequivalence 171 KB (update 2023-06-21)
  • Scaled Average Bioequivalence
    • Highly Variable Drugs / Drug Products
      • RSABE (FDA, China’s CDE) 165 KB (update 2023-06-21)
      • ABEL (all others) 185 KB (update 2023-06-21)
    • NTIDs (FDA, China’s CDE) 163 KB (update 2023-06-21)
    • Highly Variable NTIDs (FDA, China’s CDE) 🚧
  • ABE, RSABE, ABEL – A Comparison 282 KB (update 2023-06-15)
  • Inflation of the Type I Error in SABE 317 KB (update 2022-12-11)
• Two-Stage Designs
  • Group sequential (fixed sample design) 🚧
  • Adaptive (sample size re-estimation) 🃏 🚧

Non-Inferiority/Superiority, Non-Superiority 120 KB (update 2023-06-21)

Dose Proportionality 🚧

Prospective Power

• Power Analysis 55 KB (update 2022-10-19)
• Power Table 190 KB (update 2022-10-28)
• Sensitivity Analysis 240 KB (update 2022-10-19)

Noncompartmental Analysis

• Trapezoidal Rules 258 KB (update 2023-06-16)
• Estimation of λ_z 🚧
• Extrapolation to Infinity – Observed or Predicted C_last? 108 KB (update 2023-06-15)
• Demonstration of Steady State Achievement? 167 KB (update 2023-05-17)
• 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 270 KB (update 2023-07-06) 🃏
• Significant Treatment Effect 134 KB (update 2022-10-19) 🃏
• Fixed or mixed effects? 🚧
• Group ‘Effect’ – To Pool or Not to Pool? 🃏 370 KB (update 2023-09-18)
• Post hoc Power 182 KB (update 2022-10-19) 🃏
• ‘Apparent’ Difference in t_max? 372 KB (update 2023-06-13)
• Simulations 101 235 KB (update 2023-05-30)
• ‘Nice Numbers’ – A Rant 150 KB (update 2023-05-18)
• ‘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 2022-10-19)
• Limited Capacity of a Clinical Site – Groups or Replicates? 149 KB (update 2023-06-07)
• Stratified Randomization – Why? 🚧

Software

• Representing Numbers in Computers – A Wonderland 111 KB (update 2022-10-19)
• 🇷 on Windows 101 64 KB (update 2023-06-16)
• Software Validation 🚧

All articles are licensed under Creative Commons Attribution 4.0 Helmut Schütz 2023.