Clinical Trials

❘❙❚■ Chapter 28 | Repeated MeasurementsTable 1. Summary measures for repeated measurements, their applications and limitations.Summary measure Data type Application LimitationsMean No clear pattern Use to describe the central Sensitive to missing informationor trend level of an outcome variable Ignores within-subject variationwhen assessing drug efficacyMaximum Single peak Use to describe the maximum Sensitive to missing informationdrug concentration inSensitive to sampling time pointsa pharmacokinetic studyTime to maximum Single peak Use to describe the speed Sensitive to missing informationof drug absorption inSensitive to sampling time pointsa pharmacokinetic studyArea under the curve Peaked or no Assess an overall extent Ignores within-subject variationclear pattern of drug concentrationPercentage of time Multiple peaks Use when assessing the To get a stable estimate, manythe outcome variable or troughs fraction of time that the drug time points are neededis above or belowis effective for during thea certain valuestudy period, especially forpharmacodynamic studiesNumber of occasions Multiple peaks Use to assess the frequency of To get a stable estimate,on which the outcome or troughs fluctuations of pharmacodynamic many time points are neededvariable is above orparameters such as pH, bloodbelow a certain valuepressure, and heart rateRate of change Linear or Evaluate a rate of change in Coefficients are measurednon-linear trend an outcome variable by fitting with varying levels of precisiona linear or non-linear model depending on missing valuesoverall mean only describes the middle data point. In this case, the overall meanis not an ideal statistic to use to represent the SBP over the course of the study.This method is also susceptible to outliers in the data (ie, a measurement mightbe unusually high/low at one visit and consequently influence the overall mean).For example, if the measurement at week 4 for subject 10 had been 168.0 mm Hg,then the overall mean would have increased to 148.2 mm Hg. This would be higherthan the mean for subject 6, but would obviously not be representative of theentire profile for subject 10.MaximumAnother easily interpreted summary statistic is the maximum value of theresponse variable during the observation period. This can be used to assess themaximum effect of a study drug in a trial or the maximum drug concentration ina pharmacokinetic study.For example, in a study examining the immunological response to highly activeanti-retroviral therapy (HAART) in different age groups, the maximum CD4T-cell count over 31 months of follow-up was calculated for each subjectindividually, and then summarized and compared between age groups [8]. The322