Computation of model-dependent tolerance bands for ambulatorily monitored blood pressure

The construction of time-specified reference limits requires systematic sam pling in clinical health, particularly for those variables characterized by a circadian rhythm of large amplitude, as it is the case for blood pressur e (BP). For the detection of false negatives, tolerance intervals (limits t hat will include at least a specified proportion of the population with a s tated confidence) are important and should substitute when possible for pre diction limits. We have previously described a nonparametric method for the computation of model-independent tolerance intervals that are constructed by first dividing the sampling range in several time spans in which no appr eciable changes in population characteristics (namely, mean and variance) t ake place. The tolerance interval is then computed for each of the time spa ns. The limits thus computed, as well as results of any comparison of a giv en individual's profile against such tolerance intervals, are highly depend ent on the sampling scheme of both the reference individuals and the test s ubject. To avoid this problem, we have developed an alternative method that allows the computation of model-dependent tolerance bands for hybrid time series. Assuming that a set X of longitudinal series monitored from a given group of reference individuals can be fitted with the same individual mode l, a population model C(X,t) can be also determined, as well as the deviati on S(X,t) of each individual curve from the population model. The tolerance band will then have the form C(X,t) +/- kS(X,t), where k is here estimated following a nonparametric approach based on bootstrap techniques. Alternat ively, two different values of k can be estimated (for the lower and upper limits of the tolerance interval, respectively) in cases for which we canno t assume symmetry. The method is generally applicable for any population mo del describing the reference population (including the fit of multiple sign ificant components, nonsinusoidal waveforms, and/or trends). The method was used to establish time-specified tolerance bands for time series of blood pressure monitored automatically in healthy individuals of both genders. Mo del-dependent intervals are preferred to the model-independent limits when reliance on a specified sampling rate needs to be avoided. These limits may serve for an objective and positive definition of health, for the screenin g and diagnosis of disease, and for gauging the subject's response to treat ment.