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Figure 4 Putative placebo analysis for Stroke Prevention Using Oral Thrombin Inhibitor in Atrial Fibrillation (SPORTIF) trials. Imputed comparisons of ximelagatran versus "putative" placebo from data derived from SPORTIF III, SPORTIF V, and combined SPORTIF III+V trials are shown. The putative placebo approach is illustrated where the estimate of risk ratio of ximelagatran relative to placebo (derived risk ratio) is obtained by multiplying the risk ratio of ximelagatran relative to warfarin (observed risk ratio), from the current trial, by the historical warfarin versus placebo risk ratio (historical risk ratio). Historical risk ratio is obtained from a random-effect meta-analysis of five primary prevention trials and is 0.37 (0.28 to 0.50). Derived risk ratios are 0.27 (0.16 to 0.44) for SPORTIF III, 0.52 (0.31 to 0.86) for SPORTIF V, and 0.37 (0.24 to 0.55) for SPORTIF III+V. Superiority over putative placebo is established if the derived risk ratio is <1.0. Non-inferiority is established if the worst (upper) limit of the "derived risk ratio" does not exceed the fractional threshold estimated as a fraction (arbitrarily 50%) of the "historical risk ratio." In SPORTIF trials, this estimate is obtained mathematically as the square root of the "historical risk ratio" and is equivalent to 0.61 (0.53 to 0.71). The lower bound (LB) of this interval (0.71) represents a liberal fractional threshold for non-inferiority. In contrast, the upper bound (UB) of this interval (0.53) constitutes a conservative fractional threshold (15).
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