Clinical Trials

❘❙❚■ Chapter 27 | InteractionTable 5. Rate of primary endpoint (number of primary endpoint) by treatment in the GISSI-Prevenzione trial [4].n-3 polyunsaturated fatty Vitamin E supplementation Totalacids supplementationPlaceboActivePlacebo 14.64% (414) 13.11% (371) 13.87% (785)Active 12.55% (356) 12.69% (359) 12.62% (715)Total 13.59% (770) 12.90% (730)Table 6. Use of a logistic regression model to evaluate the interaction effect between n-3 polyunsaturated fattyacids (PUFA) and vitamin E supplementation in the GISSI-Prevenzione trial [4].Regression Variable Regression P-value 95% CIanalysis modelcoefficientMain effect model n-3 PUFA 0.90 0.05 0.80 1.00Vitamin E 0.94 0.27 0.84 1.04Main and interaction n-3 PUFA 0.84 0.02 0.72 0.97effect modelVitamin E 0.88 0.10 0.76 1.02(n-3 PUFA) (vitamin E) 1.15 0.21 0.93 1.43The number of patients randomized to each arm of the trial is summarized inTable 4. In Table 5 the event rates for each of the four arms are given, as wellas the total event rates for the n-3 PUFA and vitamin E arms. The differencein the event rate between subjects receiving placebo and active n-3 PUFA is0.42% (= 13.11% – 12.69%) for subjects receiving active vitamin E, and 2.09%(= 14.64% – 12.55%) for subjects receiving placebo (instead of active vitamin E).Similarly, the difference in the event rate between those receiving placebo andactive vitamin E is –0.14% (= 12.55% – 12.69%) for subjects receiving activen-3 PUFA, and 1.53% (= 14.64% – 13.11%) for subjects receiving placebo(instead of active n-3 PUFA).These descriptive statistics suggest that the difference in the event rate forone treatment may depend on the level of the other treatment, or, in other words,that there is a possible interaction effect between two treatments. To explore thisformally, two logistic regression models were fitted (a main effect model and aninteraction effect model), where the outcome variable was the occurrence of theprimary endpoint. The results are displayed in Table 6.The results from the main and interaction effect logistic regression model inTable 6 suggest that there is no evidence of an interaction effect between the twotreatments (for the interaction term, P = 0.21). In other words, the observedtreatment effects were the result of chance. Therefore, the reduction in the primaryendpoint event rate attributed to n-3 PUFA is not affected by taking vitamin E,312