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Average Bioequivalence

This calculator uses the 2 x 2 crossover design recommended by FDA guidelines. The test of average bioequivalence is a the same as testing the equivalence for means. If another design is used, the two sample crossover calculator for hypotheses on means can be used.

Letting \(y_{ijk}\) be the PK response of interest (in log transfored or in original units) of the \(i^{th}\) subject in the \(k^{th}\) sequence in the \(j^{th}\) dosing period, the model used to test average bioequivalence is given by:

\[ y_{ijk} = \mu + F_l + P_j + Q_k + S_{ikl} + \epsilon_{ijk} \]

where \(\mu\) is the overall mean, \(P_j\) is the fixed period effect, \(Q_k\) is the fixed sequence effect, \(F_l\) is the fixed effect of the \(l^{th}\) formulation (\(l = T, R\)), and \(S_{ikl}\) is the random effect of the \(i^{th}\) subject in the \(k^{th}\) sequence using the \(l^{th}\) formulation (see Chow et at. and the FDA guidance for a more detailed specification of the model).

To test average bioequivalence, we test the hypothesis:

\[ H_0: \delta \le \delta_L \text{ or } \delta \ge \delta_U \text{ versus } H_1: \delta_L \lt \delta \lt \delta_U \]

where \(\delta = F_{T} - F_{R}\) and \(\delta_L\) and \(\delta_U\) are bioequivalence limits.

To perform this calculation, we need to estimate the standard deviation of the intersubject comparison: \(\sigma_{1,1}\). The value can be estimated by:

\[ \hat{\sigma}_{1,1} = \frac{1}{2(n - 1)} \sum^2_{k=1} \sum^n_i=1 (y_{i1k} - y_{i2k} - \bar{y}_{\cdot1k} + \bar{y}_{\cdot2k})^2 \]

Power Calculation Parameters

To input multiple values, seperate them by a comma.

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Power Calculation Explanation

Solve For
The unknown you are interested in solving for.
N
The sample size used to test the hypothesis.
Alpha
The \(\alpha\) (Type I error rate) level of the hypothesis test.
Power
The power (1 - Type II error rate) of the hypothesis test.
\(\delta\)
The difference of the fixed effects.
Standard Deviation (\(\sigma_{1,1}\))
The standard deviation for the inter-subject comparison.
Bioequivalence Margin
The difference between the upper (lower) bioequivalence limit and \(\delta\) (i.e. \(\delta_U - \delta\)). Note: for this calculator, we assume \(\delta_U - \delta = \delta - \delta_L\)
Known Standard Deviation
If the standard deviation is known or estimated (usually it is estimated).

Calculation Results

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Known Standard Deviation

Unknown Standard Deviation

N Alpha Power \(\delta\) Standard Deviation Margin
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References