A framework for quantifying the influence of adherence and dose individualization.

A failure to accommodate for a patient's imperfect adherence may result in therapeutic failure. Similarly, failure to accommodate a patient's individual needs via dose individualization may also result in poor patient outcomes. The property of a drug that signifies the likelihood of therapeutic success to imperfect adherence is termed "forgiveness." We introduce an extension to this concept as: (1) a priori forgiveness (forgiveness when dose individualization is not considered) and (2) a posteriori forgiveness (forgiveness when considering dose individualization). We illustrate cases when adherence is of primary importance and in which dose individualization is of primary importance. The concept of a priori forgiveness and a posteriori forgiveness provides a quantitative measure that allows the influence of adherence to be disentangled from dose individualization and could be used to provide clear guidelines about the relative importance of each in clinical practice.

Quantification of the Forgiveness of Drugs to Imperfect Adherence.

The circumstance of how sensitive therapeutic success is under imperfect adherence is driven by the property known as forgiveness. To date, no studies have considered variability in the pharmacokinetic-pharmacodynamic process in conjunction with imperfect adherence patterns in order to develop a comparative criterion to determine the forgiveness of a drug. In this study, we have proposed a criterion to quantify forgiveness; illustrated the criterion for a theoretical example and evaluated the forgiveness of a motivating example, namely warfarin. A forgiveness criterion, relative forgiveness, is defined as the number of times more likely that a target is successfully attained under perfect adherence compared to imperfect adherence; or when comparing two drugs under a standard setting of imperfect adherence. The relative forgiveness criterion may have important implications for both drug development and clinical practice since the choice of drug can account for the likely influence of its forgiveness.

A model-based meta-analysis of the influence of factors that impact adherence to medications.

WHAT IS KNOWN AND OBJECTIVE: Several studies have investigated factors that may influence adherence for a given disease. The influence of disease on adherence has received limited attention. Less work has been conducted to investigate the influence of other factors in conjunction with disease on adherence. The aim of this study was to determine the independent influence of disease and other factors on adherence. METHODS: A literature search was conducted to retrieve adherence studies using medication event monitoring system devices. Studies were categorized into different therapeutic areas. Only the two most commonly studied therapeutic areas were selected. Pseudopatient-level data were extracted from each study. The extracted data were analysed using a model-based meta-analysis technique. Univariate and multivariate models were developed. Model selection was based on a likelihood ratio test and visual plots. RESULTS: The most commonly studied therapeutic areas were HIV and hypertension. The most commonly recorded adherence criterion was percentage of prescribed doses taken per day. Based on this adherence criterion, ultimately, 24 HIV papers and 12 hypertension papers were included for data extraction. The statistically significant factors were disease, age and dosing regimen. The independent influences of each factor on adherence were as follows: an increase in adherence of approximately 8% per 10-year increase of age, a 15-19% reduction from once to thrice daily dosing and that patients with HIV were 5% more adherent than those with hypertension. WHAT IS NEW AND CONCLUSION: Although the influence of disease on adherence was significant, it was of limited clinical significance in the diseases studied here. Adherence appears to improve with age and decline with more frequent dosing. Additionally, the influence of dosing regimen wanes with increasing age. These results should be treated as exploratory and require prospective assessment.