Use of ambulatory blood pressure monitoring in pharmacological trials.
Four factors govern precision in clinical trials with antihypertensive drugs: the magnitude of the differences in BP to be detected; uniformity in the responses to the antihypertensive agents; the accuracy of the diagnosis of hypertension; and the reproducibility of BP measurements. Ambulatory monitoring has an obvious bearing on all these points. Accuracy is needed for the diagnosis of hypertension. In a group of 255 subjects, 34% had 'false hypertension' on the basis of clinic BP measurements. Unless reproducibility of BP estimates is high, clinical trials must include large numbers of subjects if they are to detect modest differences in BP. With ambulatory monitoring the standard deviation of the difference between two BP readings is reduced by 50%. Changes in DBP of less than 5 mm Hg are not clinically relevant. A trial must be able to detect at least this order of difference. With ambulatory BP monitoring, this is achievable using a small number of subjects, whereas with clinic readings large-scale trials are required. Precision in clinical trials must be improved if antihypertensive drugs are to be introduced on the correct dose regimen. Uniformity in the response to antihypertensive agents has been little studied. Yet none of the agents in common use reduces DBP by more than 10 mm Hg in 50% of hypertensive subjects. Non-uniformity of response necessitates the use of crossover design and an accurate estimate of BP.