Clinical Trials

❘❙❚■ Chapter 19 | Comparison of MeansTable 4. The results from t-testing the H 0: μ = 2000 together with 95% CIs for FEV 1at pre-and posttreatment.Treatment Time Point estimate t-value P-value 95% CIA Pretreatment 2010.6 0.14 0.891 1845.1 2176.0Posttreatment 2482.8 3.83 0.003 2205.1 2760.6B Pretreatment 1992.3 –0.09 0.927 1813.4 2171.3Posttreatment 2085.2 0.65 0.531 1795.1 2375.2These results imply that the posttreatment mean FEV 1in the population ontreatment A is significantly different from the reference value of 2000 mL, butbaseline measurements and the posttreatment mean in the placebo group are not.The interpretation of this finding depends on what the value of 2000 mLrepresents; if it is the mean FEV 1expected of a ‘typical’ group of patients sufferingfrom severe CAL, we could conclude that there is evidence to suggest thatpatients who had taken drug A were significantly improved compared to the‘typical’ group following standard treatment.By implication, the one-sample t-test is based on the assumption that the outcomevariable is normally distributed, and it is the mean of a normal distribution that istested. We can check for this assumption using an inverse normal plot (Q-Q plot)(see Chapter 17) [6]. Figure 2 shows the inverse normal plots for the four outcomevariables displayed in Table 1. As these plots are close to linear patterns, theimplication is that these samples are approximately normally distributed [6].Paired t-testFor some uncontrolled open-label clinical trials, the main objective is to evaluatethe drug effect before and after the treatment based on changes from baseline.This generates ‘paired’ data. The key feature of paired data is that the two samplesto be compared are not independent. Alternatively, there might be two separatesamples that have been selected in pairs to resemble each other. Statisticalanalysis assesses whether the data provide evidence that there is a statisticallysignificant difference in the outcome variable before and after treatment within atreatment group, in this case group A (Question 2). We can now address thisquestion by performing a paired t-test.The null hypothesis can be expressed as:H 0: μ d= μ pre– μ post= 0204