Ing. Helmut Schütz

Articles

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

The true Enlightenment thinker, the true rationalist,
never wants to talk anyone into anything.
No, he does not even want to convince;
all the time he is aware that he may be wrong.
– Karl R. Popper

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.

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Power Calculation and Sample Size Estimation

Equivalence

Parallel Design 246 KB (update 2021-08-08)
2×2×2 Design 217 KB (update 2021-10-24)
Higher-Order Crossover Designs 207 KB (update 2021-07-10)
Replicate Designs
- Average Bioequivalence 165 KB (update 2021-04-01)
- Scaled Average Bioequivalence
  - Highly Variable Drugs / Drug Products
    - RSABE (FDA, China’s CDE) 147 KB (update 2021-10-13)
    - ABEL (all others) 159 KB (update 2021-07-10)
  - Narrow Therapeutic Index Drugs (FDA) 🚧
  - Highly Variable Narrow Therapeutic Index Drugs (FDA) 🚧
- ABE, RSABE, ABEL: A Comparison 235 KB (update 2021-10-08)
Two-Stage Designs
- Group sequential (fixed sample design) 🚧
- Adaptive (sample size re-estimation) 🃏 🚧

Non-Inferiority, Non-Superiority

Non-Inferiority 🚧
Non-Superiority 🚧

Dose Proportionality 🚧

Prospective Power

Power Analysis 52 KB (update 2021-10-13)
Sensitivity Analysis 🚧

Noncompartmental Analysis

Trapezoidal Rules 139 KB (update 2021-10-08)
Estimation of λ_z 🚧
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 212 KB (update 2021-11-27) 🃏
Significant Treatment Effect 108 KB (update 2021-11-16) 🃏
Fixed or mixed effects? 🚧
Group ‘Effect’: To Pool or Not to Pool? 🃏 🚧
Post hoc Power 149 KB (update 2021-11-21) 🃏
‘Apparent’ Difference in t_max? 129 KB (update 2021-04-22)
Inflation of the Type I Error in SABE 🚧
Simulations 101 160 KB (update 2021-11-26)
A Rant About ‘Nice Numbers’ 78 KB (update 2021-06-24)
‘Precise’ Numbers in Reports 🚧
Subgroup Analyses 🚧
Adjusted Indirect Comparisons 🚧

Design Issues

Tricks and Traps of Washout Phases 🃏 🚧
SABE planned based on the CV_w from a 2×2×2 Crossover Design 🚧
Overall Power of Multiple Studies 🚧
Stratified Randomization. Why? 🚧

Software

The Wonderland of Representing Numbers in Computers 60 KB (update 2021-11-17)
🇷 on Windows 101 45 KB (update 2021-08-30)
Software Validation 🚧

Those people who think they know everything
are a great annoyance to those of us who do.
– Isaac Asimov

All articles are licensed under Creative Commons Attribution 4.0 Helmut Schütz 2021.

document date 2021-03-12 | last update 2021-11-24