Clinical Trials

❘❙❚■ Chapter 19 | Comparison of MeansIntroductionIn the previous chapter, we described how to use the information from a sample(eg, sample size, mean, standard deviation) to make inferences about thecorresponding population parameters (eg, mean) by performing a hypothesis testand calculating a confidence interval (CI). We now extend the idea to situationswhere we want to compare the mean outcomes in two treatment groups.Example: Chronic airways limitation trialConsider 24 patients with chronic airways limitation (CAL) participating ina randomized placebo-controlled clinical trial to evaluate the efficacy ofa bronchodilator drug (denoted by treatment A) against placebo (denoted bytreatment B). The primary endpoint of this study is forced expiratory volumein 1 second (FEV 1) at 6 months. The secondary endpoint is the relative changein FEV 1from baseline (pretreatment) to 6 months (posttreatment). Table 1 liststhe raw data of FEV 1on these patients.Table 2 gives some summary statistics of the primary and secondary endpoints(FEV 1and percentage change in FEV 1, respectively) for these patients. Theseresults suggest a possible difference between active treatment and placebo interms of 6-month FEV 1values. However, the observed difference could be due tobias (systematic errors), confounding (differences in some predictors of FEV 1between treatments at baseline), or random (chance) variation (see Chapter 1) [1].In the absence of bias and confounding, we are able to assess whether chancevariation could reasonably explain the observed difference using significancetesting or the CI methods we illustrated in the previous chapter. Various questionscan be raised regarding the data in Table 2. Three frequently asked questions areas follows.Question 1At the start and end of the study, are the mean FEV 1values seen in both treatmentgroups as expected from the overall population of similar subjects?Question 2Is there any evidence of a significant change in mean FEV 1from baseline in eithertreatment group?Question 3Is the posttreatment mean FEV 1or mean FEV1 change within the activetreatment group significantly different from that in the control treatment?198