Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘Table 7. Reduction in mean systolic blood pressure (SBP) by center in a hypothetical multicenter study.Center Number Mean SBP (mm Hg) Difference in SBP between Rank bynumber of patients Drug A Drug B drug B and drug A (mm Hg) difference1 100 –3.01 –1.42 1.59 32 100 –4.92 –5.78 –0.86 83 100 –3.39 1.36 4.75 14 100 –5.70 –6.75 –1.06 95 100 –4.88 –8.43 –3.55 106 100 –4.26 –4.19 0.07 77 100 –3.74 –3.16 0.58 58 100 –3.25 –0.25 3.01 29 100 –4.59 –4.31 0.29 610 100 –3.05 –2.31 0.74 4so the results from the main effect model should be reported. In reporting afactorial design trial, it should be clear that the potential interaction effectbetween treatments has been considered.Example 3: Treatment-by-center interaction in a multicenter trialThe above example demonstrates how to test for an interaction between twotreatments. However, in clinical trials it is sometimes necessary to check foran interaction between the treatment and other important prognostic factors.Of special importance is treatment-by-center interaction in multicenter studies.A multicenter study is a single study involving several study centers (sites orinvestigators) [5], which should permit an overall estimation of the treatmentdifference for the targeted patient population across different centers (seeChapter 16). When analyzing a multicenter study, it may be appropriate toexplore whether there is a treatment-by-center interaction.Consider a hypothetical multicenter trial for assessing the efficacy of two drugs(A and B) in reducing SBP among hypertensive subjects. The study is a randomized,multicenter trial that involves 1,000 patients in 10 centers (each center has100 patients). The mean changes in SBP from the baseline after 5 weeks of treatmentare given in Table 7, and the mean change in SBP against study centers is plottedin Figure 2. In this figure, the centers are ranked according to the magnitude ofthe difference in mean change in SBP between drugs A and B.As can be seen from Table 7, seven centers show a difference in the positivedirection, while three centers show a change in a negative direction. Regressionanalysis indicates that a significant qualitative interaction between treatment313