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Carry-over effects in bioequivalence studies
G Dangelo1, D Potvin, J Turgeon
1Pharmacokinetics and Pharmacodynamics, MDS Pharma Services, Saint-Laurent, Montreal, Quebec, Canada.
Journal of Biopharmaceutical Statistics
|July 19, 2001
Summary
Carry-over effects are infrequent in bioequivalence studies. Analysis suggests adjusting for carry-over is often unnecessary, simplifying study design and analysis for pharmacokinetic variables like Cmax and AUC0-t.
Area of Science:
- Pharmacokinetics
- Clinical Trial Design
- Biostatistics
Background:
- Carry-over effects pose challenges in crossover study designs.
- The necessity of adjusting for carry-over in bioequivalence studies remains a key consideration.
Purpose of the Study:
- To investigate the frequency of carry-over effects in actual bioequivalence studies.
- To determine the impact of statistically significant carry-over effects on bioequivalence outcomes.
- To discuss the rationale for not adjusting for carry-over in bioequivalence study analyses.
Main Methods:
- Analysis of 96 three-period, three-treatment fed-fasted crossover studies for carry-over effects.
- Indirect assessment of carry-over effects in 324 two-period, two-treatment fasted studies via sequence effects.
- Modeling of log-transformed Cmax and AUC0-t pharmacokinetic variables using analysis of variance (ANOVA).
Main Results:
- Carry-over effects were observed with a certain frequency in the analyzed bioequivalence studies.
- Statistically significant carry-over effects can impact bioequivalence results.
- The study provides insights into the practical occurrence of carry-over effects.
Conclusions:
- The findings contribute to the understanding of carry-over effects in bioequivalence trials.
- The discussion addresses the justification for current practices regarding carry-over adjustment.
- This research informs decisions on managing carry-over effects in pharmacokinetic study designs.