Abstract
Background: Across chronic diseases, suboptimal adherence to prescribed therapies compromises therapeutic benefits. In sickle cell disease (SCD), adherence to hydroxyurea (HU) in adolescents and young adults is often poor. Poor adherence may be either intentional or unintentional related to lack of capacity or resources. We used prescription refill data to examine barriers to adherence in two samples of 10-18 year old youth with SCD, known to be poorly adherent to HU, who participated in the multi-site "Hydroxyurea Adherence for Personal Best in SCD" (HABIT) feasibility and efficacy trials.
Methods: Parents provided written consent to contact their pharmacy(ies) for release of their child's HU prescription records for the year prior to study entry and duration of participation in the HABIT 6-month feasibility [2013-2015] (NCT02029742) and 12-month efficacy [2017-2021] (NCT03462511) trials. Refill data were retrieved by fax, email or in person. HU dose prescriptions were verified by electronic health record review at each study site. Data collected were pharmacy name, HU dispensation dates, formulation (capsule/tablet versus suspension), concentration (mg/capsule or tablet or mg/ml suspension), prescribed HU dose, number of capsules/tablets or volume of HU suspension dispensed, directions for use and number of days for which drug was dispensed, and number of times the HU prescription was filled. Data retrieval was considered complete if the interval for participants' HU dispensed reflected 80% or greater of the trial prescribing period (1.5 years feasibility; 2 years efficacy). Using the World Health Organization Multidimensional Adherence Model, we categorized factors as patient-related (prescription of HU suspension reflecting problems with swallowing capsules/tablets); treatment-related (complex HU regimen defined as different dosing patterns on different days of the week), and health care system related (prescription of HU capsule other than 500 mg reflecting potential need for prior authorization, use of more than one pharmacy, lack of dosing directions for HU dispensed; dispensing less than 30 days of HU during a dispensing period). Data were analyzed using descriptive statistics; sample barriers were compared using chi-square.
Results: Of 78 enrolled participants (28 feasibility trial, 50 efficacy trial), pharmacy data were available for 92.3% (27 feasibility trial, 45 efficacy trial; mean age 13.6±2.2 years, 72.2% Black, 30.6% Hispanic) (Table 1). On average, refill data collected spanned 81.9% of the trial period (74% feasibility trial; 86.7% efficacy trial). On average, HU prescriptions were filled 10.6±5.6 times within 18 months and 16.0±7.6 times within 24 months for feasibility and efficacy participants, respectively. The most frequently identified potential barriers to adherence in this sample were lack of dosing directions (66.7%), complex HU regimens (47.2%) and lack of direction specificity (i.e., the day(s) HU dose should be different) when complex regimens were prescribed (47.1%) (Table 2). Over 20% of youth were prescribed liquid HU formulation, while HU capsules/tabs other than 500 mg/capsule were infrequently prescribed (27.8%). No significant differences in barriers were seen between the two trials reflecting a period of 8 years.
Discussion: Use of individual patient prescription refill data provides insight into multi-level barriers at the patient-, treatment- and health system-related levels, each of which is likely unintentional. Despite recent availability of HU capsules/tablets in varying concentrations, complex HU regimens, often lacking specific dosing directions, were common in this socially vulnerable multi-site sample. These findings suggest that barriers to adherence occur at all levels and did not change across the two trial periods. Reducing adherence barriers likely require development and testing of multi-level interventions which simplify medication schedules, incorporate more recent dose formulations of HU capsules/tablets when needed, provide explicit dosing directions on bottle labels and facilitate convenient HU access including dispensing greater than 30 day quantity of HU via pharmacy or mail order.
Disclosures
Manwani:Global Blood Therapeutics: Consultancy; Novartis: Consultancy; Pfizer: Consultancy. Aygun:National Heart, Lung, Blood Institute: Research Funding; National Institute of Nursing Research: Research Funding; Patient Centered Outcomes Research Institute: Research Funding; bluebird bio, Inc.: Membership on an entity's Board of Directors or advisory committees, Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees. Appiah-Kubi:Global Blood Therapeutics: Other: Commercial Advisory Board. Smith-Whitley:Global Blood Therapeutics: Current Employment, Current holder of stock options in a privately-held company.
