A Systematic Literature Review Assessing the Directional Impact of Managed Care Formulary Restrictions on Medication Adherence, Clinical Outcomes, Economic Outcomes, and Health Care Resource Utilization

BACKGROUND: There is extensive literature demonstrating that formulary restrictions reduce the pharmacy costs and utilization of restricted drugs. However, some research suggests that there may be unintended consequences of formulary restrictions on other patient outcomes. While several literature reviews have assessed the relationship between formulary restrictions and medication adherence, clinical outcomes, economic outcomes, or health care resource utilization, these reviews were either not systematic, were conducted more than 5 years ago, or did not assess the aggregate directional impact of the relationships. OBJECTIVES: To conduct a systematic literature review assessing the direction (positive, negative, or neutral) of the relationship between managed care formulary restrictions (including step therapy, cost sharing, prior authorization, preferred drug lists, and quantity limits) on medication adherence, clinical outcomes, economic outcomes, and health care resource utilization. METHODS: Articles published in 1993 or later were identified from PubMed using 2 lists of search terms. List A included 12 formulary restriction terms and List B included 12 patient outcomes terms, resulting in 144 unique search term combinations. Each article was evaluated by 2 investigators against the following exclusion criteria using a stepwise approach: (a) the article was a commentary or review article; (b) the article did not assess the impact of managed care formulary restrictions on outcomes; and (c) the study was conducted outside the United States. The total number of studies was reported by formulary restriction type. Next, the total number of outcomes reported in each study was summed to conduct an outcomes-level analysis. The outcomes were categorized by type of outcome (medication adherence, clinical, economic, or health care resource utilization) and direction of association (positive, negative, or neutral/not significant) based on the relationship reported in each study. The frequencies of each type of outcome were stratified by direction of association. RESULTS: A total of 93 studies were included from 811 reviewed articles. Cost sharing was the most commonly assessed type of formulary restriction (60.2% of included articles), followed by prior authorization (21.5%). Of the 262 patient outcomes assessed, medication adherence was the most common (120 outcomes, 45.8%). Overall, formulary restrictions were most frequently negatively correlated with outcomes (130 outcomes, 49.6%). When outcome type was stratified by direction of association, 68.3% (82/120) of medication adherence outcomes were negative. The direction of association of economic outcomes (n = 59) with formulary restrictions was split between neutral (37.3%), positive (33.9%), and negative (28.8%). Health care resource utilization outcomes (n = 72) had no association with formulary restrictions in 50.0% of the outcomes assessed. There were 11 clinical outcomes identified in the literature review. CONCLUSIONS: There is a strong evidence base demonstrating a negative correlation between formulary restrictions on medication adherence outcomes. Additional research on commonly used formulary restrictions, specifically prior authorization and step therapy, as well as on the association between formulary restrictions and clinical outcomes, is warranted.