Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘Table 1. Summary and analysis of the preeclampsia treatment described in Example 1 [3].Study groupsResultsNumbers Vitamins C and E Placebo Odds ratio (95% CI); P-valueWomen randomized 141 142Women who withdrew from the study 62 61Women developing preeclampsia 11 24Analysis. Percentage of women developing preeclampsia according to:Intention-to-treat analysis 8% (11/141) 17% (24/142) 0.42 (0.18, 0.93); P = 0.020Per-protocol analysis 8% (6/79) 26% (21/81) 0.23 (0.07, 0.66); P = 0.002identified 283 women as being at increased risk and randomly assigned them totreatment with either a combination of vitamin C (1,000 mg/day) and vitamin E(400 IU/day) or placebo during weeks 16–22 of gestation.Of the 141 women randomized to vitamins C and E, 62 women withdrew fromthe study, 79 completed it, and 11 (of whom six were fully compliant) developedpreeclampsia. Among the 142 women randomized to the placebo group, 61 withdrewfrom the study, 81 participated until delivery, and 24 women (of whom 21 were fullycompliant) developed preeclampsia (Figure 1).The results, as calculated by both methods of analysis, are presented inTable 1. In the ITT analysis, the risk of women developing preeclampsia differedsignificantly between groups, with 11 of 141 (8%) women in the vitamin groupdeveloping preeclampsia versus 24 of 142 (17%) women in the placebo group(odds ratio 0.42; 95% confidence interval [CI] 0.18, 0.93; P = 0.020). Using the PPmethod, which considers only the women who completed the entire study, thedifference in the frequency of preeclampsia was more pronounced, with 6 of 79(8%) women on vitamin therapy developing preeclampsia versus 21 of 81 (26%)women on placebo (odds ratio 0.23; 95% CI 0.07, 0.66; P = 0.002). The resultsfrom both the ITT and PP analyses suggest that supplementation with vitamins Cand E may be beneficial in the prevention of preeclampsia in women at increasedrisk of the disease, with vitamins shown to be more effective by the PP analysisthan the ITT analysis.What is the justification for an ITT analysis?It might initially appear from the example that the ITT method is not optimalsince it might not capture the full potential benefit of a therapy. However, an ITTanalysis actually has several specific advantages:257