Bioequivalence and Bioavailability Forum

Hi (especially biostatisticians),

Does anyone have experience dealing with stat analysis for multi-factor, full-design stability studies? The part I am not sure about is "Testing for poolability of all factors and factor combinations" which involves using analysis of covariance. Helmut is probably gonna kill me for including a long quote below from FDA guidance:

Analysis of covariance can be employed to test the difference in slopes and intercepts of the regression lines among factors and factor combinations (Chen et al. 1997; Fairweather et al. 1995). The purpose of the procedure is to determine whether data from multiple factor combinations can be combined for the estimation of a single shelf life.
The full statistical model should include the intercept and slope terms of all main effects and interaction effects and a term reflecting the random error of measurement. If it can be justified that the higher order interactions are very small, there is generally no need to include these terms in the model. In cases where the analytical results at the initial time point are obtained from the finished dosage form prior to its packaging, the container intercept term can be excluded from the full model because the results are common among the different container sizes and/or fills.
The tests for poolability should be specified to determine whether there are statistically significant differences among factors and factor combinations. Generally, the pooling tests should be performed in a proper order such that the slope terms are tested before the intercept terms and the interaction effects are tested before the main effects. For example, the tests can start with the slope and then the intercept terms of the highest order interaction, and proceed to the slope and then the intercept terms of the simple main effects. The most reduced model, obtained when all remaining terms are found to be statistically significant, can be used to estimate the shelf lives.


Thanks
John