Costs of medication nonadherence in patients with diabetes mellitus: a systematic review and critical analysis of the literature.

OBJECTIVES Information on the health care costs associated with nonadherence to treatments for diabetes is both limited and inconsistent. We reviewed and critically appraised the literature to identify the main methodological issues that might explain differences among reports in the relationship of nonadherence and costs in patients with diabetes. METHODS Two investigators reviewed Medline, EMBASE, Cochrane library and CINAHL and studies with information on costs by level of adherence in patients with diabetes published between January 1, 1997 and September 30th 2007 were included. RESULTS A total of 209 studies were identified and ten fulfilled the inclusion criteria. All included studies analyzed claims data and 70% were based on non-Medicaid and non-Medicare databases. Low medication possession ratios were associated with higher costs. Important differences were found in the ICD-9/ICD-9 CM codes used to identify patients and their diagnoses, data sources, analytic window period, definitions of adherence measures, skewness in cost data and associated statistical issues, adjustment of costs for inflation, adjustment for confounders, clinical outcomes and costs. CONCLUSIONS Important variation among cost estimates was evident, even within studies of the same population. Readers should be cautious when comparing estimated coefficients from various studies because methodological issues might explain differences in the results of costs of nonadherence in diabetes. This is particularly important when estimates are used as inputs to pharmacoeconomic models.