Compliance-guided therapy - A new insight into the potential role of clinical pharmacologists

Background and objective: In the field of drug noncompliance, we investigated an original approach that could give the prescribing physician, in collaboration with a clinical pharmacologist, an active role. The aim here is for the prescribing physician to take compliance into account so as to provide an optimised prescription (choice of molecule prescribed and its rhythm of administration) adapted to each patient. The example considered is that of oral anticoagulant treatment prescribed long-term. Methods: In order to investigate the choice of the best molecule and treatment regimen for a given noncompliance pattern, we performed an in silico study with two oral anticoagulant agents, warfarin and acenocoumarol, each taken in one or two daily doses. Three linked models were used: the first model generated specific noncompliance patterns, the second model described the pharmacokinetics of oral anticoagulant agents and the third model summarised the pharmacokinetic-pharmacodynamic relations. Results: Considering different patterns of noncompliance (including timing errors in drug intake and the phenomenon of drug holidays) and comparing warfarin with acenocoumarol, we identified different situations in which one agent (prescribed once or twice daily) could clearly minimise both the thromboembolic and haemorrhagic risks. However, for some specific noncompliance patterns, the choice of the optimal therapy should also be guided by the basal individual thromboembolic and haemorrhagic risks. Conclusion: Individualisation of drug therapy involves both drug dose and drug choice. In addition to the classical approach (i.e. drug level measurements, enzyme assays and even genetic sequence data), our study suggests that compliance-guided therapy may represent a potential, evolving way for the individualisation of prescriptions.