Clinical Trials

Clinical Trials: A Practical Guide ■❚❙❘Key considerations when dealing with repeatedmeasurement dataThere are two key considerations when dealing with repeated measurement data.The first consideration is how to deal with the correlation between the repeatedmeasurements for an individual (known as the correlation structure). This is theprincipal distinction between the different methods of analysis [1–3]. To drawvalid scientific inferences, the correlation structure must be taken into account.Failure to control for such correlation effects can lead to biased results: thestatistical significance of the observed treatment effects may be over estimatedand spuriously significant conclusions could be drawn [1,2].Secondly, not all repeated measurement data are complete – individuals might belost to follow-up, withdraw consent, or die during the study – consequently, somemeasurements might be missing [4]. In Figure 1, data on SBP are missing forsubjects 2 and 10 at 8 weeks.What strategies are used to analyze repeatedmeasurement data?Four main strategies for handling repeated measurement data have been used inclinical research [3,5,6]. They are:• analysis at a predefined time point• time-by-time analysis• use of statistical models• use of summary measuresAnalysis at a predefined time pointThe first strategy is to analyze the response outcome at a predefined time point[5]. This approach is most suitable when the response to the treatment at aparticular time point is of clinical interest. The change in response from baselinecan also be measured to control for individual variations in baseline values.However, the strategy does not utilize information from other time points, thuswasting potentially valuable information. To address this problem, a time-by-timeanalysis is sometimes performed [5].Time-by-time analysisAn alternative to analysis at a predefined time point is time-by-time analysis.A group mean (the mean of all the patients’ data) can be calculated at eachseparate time point and a statistical analysis carried out – a time-by-time analysis.319