Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘Relationship between significant testing and CIsWhen comparing, for example, two treatments, the purpose of significance testingis to assess the evidence for a difference in some outcome between the two groups,while the CI provides a range of values around the estimated treatment effectwithin which the unknown population parameter is expected to be with a givenlevel of confidence.There is a close relationship between the results of significance testing and CIs.This can be illustrated using the previously described Z-test for the SBP dataanalysis. If H 0: μ = μ 0is rejected at the α% significance level, the corresponding(1 – α)% CI will not include μ 0. On the other hand, if H 0: μ = μ 0is not rejected atthe α% significance level, then (1 – α)% CI will include μ 0.For the SBP data of adult males, the significance test shows that μ issignificantly different from μ 0(= 129 mm Hg) at the 5% level, and the 95%CI (= 129.1 to 130.9 mm Hg) did not include 129 mm Hg. On the other hand,the difference between μ and μ 0is not significant at the 1% level; the 99%CI (129 ± [2.58 × 10] / √500 = 128.8 to 131.2 mm Hg) for μ does indeed containμ 0. Further information about the proper use of the above two statistical methodscan be found in [6].Further examplesLet us assume that four randomized, double-blind, placebo-controlled trials areconducted to establish the efficacy of two weight-loss drugs (A and B) againstplacebo, with all subjects, whether on a drug or placebo, receiving similarinstructions as to diet, exercise, behavior modification, and other lifestyle changes.The primary endpoint is the weight change (kg) at 2 months from baseline. Thedifference in the mean weight change between active drug and placebo groups canbe considered as weight reduction for the active drug against placebo. Table 3presents the results of hypothesis tests and CIs for the four hypothetical trials. Thenull hypothesis for each trial is that there is no difference between the active drugtreatment and placebo in mean weight change.In trial 1 of drug A, the reduction of drug A over placebo was 6 kg, with only40 subjects in each group. The P-value of 0.074 suggests that there is no evidenceagainst the null hypothesis of no effect of drug A at the 5% significance level.The 95% CI shows that the results of the trial are consistent with a differenceranging from a large reduction of 12.6 kg in favor of drug A to a reduction of0.6 kg in favor of placebo.193