Ing. Helmut Schütz

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.

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

Hypotheses – not only in Equivalence 62 KB (update 2023-05-10)
Parallel Design 308 KB (update 2023-05-31)
2×2×2 Design 421 KB (update 2023-06-01)
Higher-Order Crossover Designs 352 KB (update 2023-05-31)
Replicate Designs
- Average Bioequivalence 171 KB (update 2023-06-01)
- Scaled Average Bioequivalence
  - Highly Variable Drugs / Drug Products
    - RSABE (FDA, China’s CDE) 165 KB (update 2023-05-19)
    - ABEL (all others) 185 KB (update 2023-05-19)
  - NTIDs (FDA, China’s CDE) 161 KB (update 2023-05-19)
  - Highly Variable NTIDs (FDA, China’s CDE) 🚧
- ABE, RSABE, ABEL – A Comparison 281 KB (update 2023-05-18)
- 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 2023-06-01)

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 2023-05-31)
Estimation of λ_z 🚧
Extrapolation to Infinity – Observed or Predicted C_last? 108 KB (update 2023-03-24)
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 2023-05-05) 🃏
Significant Treatment Effect 134 KB (update 2022-10-19) 🃏
Fixed or mixed effects? 🚧
Group ‘Effect’ – To Pool or Not to Pool? 🃏 366 KB (update 2023-05-20)
Post hoc Power 182 KB (update 2022-10-19) 🃏
‘Apparent’ Difference in t_max? 375 KB (update 2023-01-28)
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? 146 KB (update 2022-10-19)
Stratified Randomization – Why? 🚧

Software

Representing Numbers in Computers – A Wonderland 111 KB (update 2022-10-19)
🇷 on Windows 101 63 KB (update 2023-04-24)
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 2023.

document date 2021-03-12 | last update 2022-11-02