Properties of the estimated variance component for subject-by-formulation interaction in studies of individual bioequivalence
✍ Scribed by Laszlo Endrenyi; Nathan Taback; Laszlo Tothfalusi
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 116 KB
- Volume
- 19
- Category
- Article
- ISSN
- 0277-6715
No coin nor oath required. For personal study only.
✦ Synopsis
Characteristics of the variance component for the subject-by-formulation interaction ( 2 D ), estimated in simulated studies of individual bioequivalence and in three-and four-period cross-over trials reported by the FDA, were compared. 2 D was estimated by (i) restricted maximum likelihood (REML) and (ii) the method of moments (MM). Variation of the variance component, estimated by both procedures (s 2 D ) and for both the simulated and FDA data, increased with rising intra-individual variation. Consequently, a constant level of s 2 D (such as 0.0225 suggested by the FDA) may not be regarded as a basis for demonstrating substantial interactions. Features of the FDA and simulated parameters were similar. The results suggested that the FDA data were compatible with assuming D = 0:05 or perhaps 0.00. Therefore, there is no foundation for concerns about public health. Both simulations and calculations demonstrated that s 2 D estimated by MM was unbiased and its variance was proportional to 4 WF when 2 D = 0.