Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘The summary measure needs to be chosen prior to the analysis of the dataand it should be representative of some relevant aspect of the subject’s responseprofile. In some situations, more than one summary measure is needed. Thisis the main statistical method that is used in the analysis of pharmacokinetic andpharmacodynamic data. As the most straightforward method of analysis, the useof a summary statistic is the focus of this article and will be discussed in greaterdetail below.The summary measure approachThe use of the summary measurement approach has two main advantages. Firstly,the analysis is easily interpreted because it is based on summary statistics thathave been chosen because of their clinical relevance to the study objective [6].Secondly, the analysis avoids the problem of correlation structure [5,6]. Once asummary measure is constructed, the number of repeated measurements isreduced to a single quantity for each subject. Therefore, values for differentsubjects can be thought of as independent – a key requirement of most standardstatistical methods.Most importantly, the trial designer needs to think carefully about the questionsto be addressed to determine the best summary measure to use. Making theright decision before data are collected can lead to improvements in the design ofthe trial.Commonly used summary statisticsSome commonly used summary measures are summarized in Table 1. Theirapplications and limitations are explained in the following sections.MeanThe simplest and most commonly used summary measure is the mean of theresponse over time, since many clinical trials are most concerned with differencesin the overall treatment effect rather than more subtle effects. The mean isparticularly useful if the individual profiles show no clear pattern or trend withtime (see Figure 2 for a SBP profile). For the data in Figure 1, the mean SBP overfive visits for subject 6 is 143.2 mm Hg, whereas the mean SBP over four visits forsubject 10 is 137.0 mm Hg.Obviously, this method has a serious drawback: it does not take into account thevariability in response variable with time. For example, in Figure 1, there is a cleardownward trend in SBP for subjects 6 and 10 after drug administration, but the321