In response to the recently published paper by Liuet al,1 we wish to initiate further discussion regarding the proposed area under the curve (AUC) summary measure and comment on some inherent difficulties with this method.

In the paper, Liu et al note that when constructing the summary AUC, the “essential components are the sets of serial impairment or disability data, preferably with frequent sampling points for each patient...” This is in fact a crucial point and depending on the schedule of observations, the observed plot of the expanded disability status scale (EDSS) over time can look quite different from the true curve. For example, consider figure D that has been reproduced below from the paper (figure A). This plot of EDSS over time represents a continuum, which in reality is unlikely to be fully observed as patients are not seen on a daily or weekly basis throughout a study because it is not practical to do so. Instead, patients are scheduled to return for assessment at certain times during the study. If, hypothetically, this patient was seen every 3 months by the study investigator, the observed plot of EDSS over time would appear as figure B. However, if this patient was seen every 6 months during the study instead, the observed plot of EDSS over time would appear as figure C. These two “observed” EDSS curves look different, even though they represent the same underlying curve. It is obvious that the resulting AUC for each plot would also differ in magnitude. If patients could be measured daily to create a smooth, accurate curve, this would not be an issue. In practice, the resulting EDSS curve over time is spiky and uneven and so the AUC measurement …