Comparison of the digoxin marker with capsule counting and compliance questionnaire methods for measuring compliance to medication in a clinical trial.

During the last quarter of the third year of follow-up in the Helsinki Heart Study, compliance to medication was measured in 1739 patients with digoxin used as a marker substance, capsule counting and a compliance questionnaire. The estimates for good and poor compliers were found to be highly dependent on the method and the cut-off points chosen for the compliance allocation. The methods studied here were more reliable for the detection of poor rather than good compliance. In the poor compliance group, defined with the use of the digoxin marker, there was 39% of subjects who returned less than 5% of their capsule dosage or reported a deviation less than 5%. In the good compliance group, defined by the digoxin marker, only 11.8% of patients either returned or reported a deviation of at least 25% of their dose. The compliance was better when measured by the questionnaire than by capsule counting. The size of the poor compliance group, defined by the use of the digoxin marker, was as large as a group who had returned at least 27% of their capsule dose and a group who had reported a deviation of 11% or more from their dosing schedule. The size of the group allocated to the good compliance category by the use of the digoxin marker was equivalent in size to a group of patients who had returned less than 15% of their prescribed dose or reported a deviation of less than 6% from their prescription. When the strictest criteria for the combination of all three methods were used, 57% of subjects were classified as good and 31% as poor compliers to medication in the third year of the primary prevention trial designed to reduce the incidence of coronary heart disease.