The rationale for this trial rested on unreplicated early data and suspect post hoc assumptions: An initial report from transgenic mice showing that tarenflurbil lowered Aβ42 in brain by targeting γ-secretase (43, 44) could not be confirmed by others (45). In the phase 2 trial that formed the basis of the phase 3 trial, the results were analyzed by using post hoc criteria after an initial analysis of data (46). Specifically, dose-related effects of the drug on activities of daily living and global function ratings were used to draw conclusions, even though the patients in the phase 2 trial did not exhibit the cognitive changes required by the statistical analysis plan (6). With these post facto choices, the investigators accepted the following risky (statistically speaking) scenario strategy for developing the phase 3 trial: Because patients treated under the protocol conditions for the phase 2 trial failed to benefit from the drug, the investigators selected alternative outcomes (activities of daily living and global function ratings) that favored further tarenflurbil development. Drawing in this way on multiple comparisons (as a result of
