Impact of Dosing Frequency of Oral Oncolytics on Refill Adherence Among Patients with Hematological Malignancies

Background : With advances in oral oncolytics for hematologic malignancies, it is important to consider dosing frequency and treatment (tx) adherence, as prior data have shown poor adherence to oral cancer medications may result in inferior tx outcomes (Huang WC, Expert Rev Anticancer Ther, 2016; Muluneh B, J Oncol Pract, 2018). There is limited evidence regarding the impact of dosing frequency on tx adherence among patients with hematological malignancies treated with oral oncolytics. The objective of this study was to characterize real-world demographic and clinical characteristics, and compare refill adherence, among patients with hematological malignancies receiving once-daily (QD) versus twice-daily (BID) oral oncolytics. Methods : This retrospective cohort study used multi-year (2012-2020) commercial claims data from Optum's de-identified Clinformatics ® Data Mart Database and included adults (≥18 yr) with a diagnosis of a hematological malignancy identified using ICD-9-CM and ICD-10-CM codes. The exposure of interest was receipt of an oral oncolytic, and the date of the first observed oral oncolytic (QD or BID) was considered the index date. All patients were required to have continuous health plan enrollment for ≥6 mo prior and ≥6 mo after the index date. The 6-mo period prior to the index date was considered the baseline period for determining patient demographics, clinical characteristics, and prior medication use. To minimize the effect of the differences in observable baseline patient characteristics between the QD and BID groups on refill adherence, 1:1 propensity score (PS) matching was used. Tx refill adherence to QD and BID oral oncolytics was measured using two established metrics: proportion of days covered (PDC) and medication possession ratio (MPR). PDC, a conservative measure of refill adherence, was considered for primary analysis as it measures total days of drug coverage within a pre-specified follow-up period; whereas MPR which was included for sensitivity analysis, measures total drug supplied within the pre-specified follow-up period. PDC and MPR were measured at pre-defined time periods of 3 and 6 mo, and from the index date until the end of the follow-up period (variable-length follow-up). Patients with drug coverage for ≥80% (PDC or MPR ≥0.8) of pre-defined time periods were considered tx refill adherent. Results: The study identified 5,874 adults with hematological malignancies, of whom 4,938 (84.1%) received QD oral oncolytics and 936 (15.9%) received BID oral oncolytics. Before 1:1 PS matching, there were significant differences between the two groups in terms of mean age (67.5 yr QD vs 61.6 yr BID, P<0.001), insurance type (Medicare, 65.4% QD vs 46.8% BID, P<0.001), being previously untreated (67.6% QD vs 63.7% BID, P=0.019), and Charlson's comorbidity score (mean: 1.61 QD vs 1.44 BID, P<0.001). After 1:1 PS matching, demographics, baseline comorbidities, cancer histology, and line of therapy were well-balanced. The matched cohort comprised 936 patients receiving QD oral oncolytics and 936 patients receiving BID oral oncolytics. Table 1 summarizes refill adherence among patients with hematological malignancies receiving QD versus BID oral oncolytics. The proportion of patients with ≥80% of drug coverage during follow-up was higher for QD versus BID recipients at 3 mo: numerically higher by PDC (70.8% vs 66.9%, P=0.065) and statistically significantly higher by MPR (72% vs 67.8%, P=0.049). The proportion of adherent patients was significantly higher for QD vs BID for both PDC and MPR at 6 mo (PDC: 62% vs 56.8%, P=0.024; MPR: 62.7% vs 57.5%, P=0.021) and at variable-length follow-up (PDC: 82.4% QD vs 77.7% BID, P=0.011; MPR: 84.9% QD vs 80.9%, P=0.020). These results suggest QD dosing is associated with improved tx adherence to oral hematological oncolytics compared to BID dosing. Conclusions: This study demonstrates significantly higher refill adherence in patients receiving QD versus BID oral hematological oncolytics at 6 mo and variable-length follow-up, highlighting the potential benefit of dosing convenience in improving adherence to oral oncolytics in the real-world setting. As suboptimal tx adherence may result in reduced tx effectiveness, real-world characterization of refill adherence rates of oral oncolytics can better inform on tx effectiveness outside of a controlled clinical trial environment. Figure 1 Figure 1. Disclosures Challagulla: Pharmacyclics LLC, an AbbVie Company: Current Employment; AbbVie: Current equity holder in publicly-traded company. Kebede: Pharmacyclics LLC, an AbbVie Company: Consultancy; ObsEva: Other. Rege: Pharmacyclics LLC, an AbbVie Company (paid to institution): Consultancy. Volodarsky: AbbVie: Current equity holder in publicly-traded company; Pharmacyclics LLC, an AbbVie Company: Current Employment. Osei-Bonsu: AbbVie: Current equity holder in publicly-traded company; Pharmacyclics LLC, an AbbVie Company: Current Employment. Karve: AbbVie: Current Employment, Current equity holder in publicly-traded company.

Association Between Patient‐Clinician Relationships and Adherence to Antihypertensive Medications Among Black Adults: An Observational Study Design

Background We assessed the associations between patient‐clinician relationships (communication and involvement in shared decision‐making [SDM]) and adherence to antihypertensive medications. Methods and Results The 2010 to 2017 Medical Expenditure Panel Survey (MEPS) data were analyzed. A retrospective cohort study design was used to create a cohort of prevalent and new users of antihypertensive medications. We defined constructs of patient‐clinician communication and involvement in SDM from patient responses to the standard questionnaires about satisfaction and access to care during the first year of surveys. Verified self‐reported medication refill information collected during the second year of surveys was used to calculate medication refill adherence; adherence was defined as medication refill adherence ≥80%. Survey‐weighted multivariable‐adjusted logistic regression models were used to measure the odds ratio (OR) and 95% CI for the association between both patient‐clinician constructs and adherence. Our analysis involved 2571 Black adult patients with hypertension (mean age of 58 years; SD, 14 years) who were either persistent (n=1788) or new users (n=783) of antihypertensive medications. Forty‐five percent (n=1145) and 43% (n=1016) of the sample reported having high levels of communication and involvement in SDM, respectively. High, versus low, patient‐clinician communication (OR, 1.38; 95% CI, 1.14–1.67) and involvement in SDM (OR, 1.32; 95% CI, 1.08–1.61) were both associated with adherence to antihypertensives after adjusting for multiple covariates. These associations persisted among a subgroup of new users of antihypertensive medications. Conclusions Patient‐clinician communication and involvement in SDM are important predictors of optimal adherence to antihypertensive medication and should be targeted for improving adherence among Black adults with hypertension.

The association between a free medicine program and functioning in people with schizophrenia: a cross-sectional study in Liuyang, China

Background Persons with schizophrenia frequently discontinue or avoid medications. Under a national community-based mental health program many places in China have started to provide free medications to people with severe mental health disorders in their communities. In the free medication program (FMP) in Liuyang, China, peripatetic psychiatrists prescribed and dispensed antipsychotic medications free of charge at regular intervals and places convenient for all patients through the primary health care system since 2006. Our study aims to test whether adherence to this FMP improves the functioning of people with schizophrenia. Methods The research was conducted in Liuyang, a rural county in central China. Data were obtained from three sources: an ad-hoc survey and the program’s management system in 2013 and in-home interviews in 2014 in Liuyang. We conducted a cross-sectional propensity-score based analysis of the “dose” effect of FMP participation on their level of functioning, using medication refill adherence as a proxy for the participatory intensity in the program. Results Only 50.9% of 2,332 participants came for all refills in 2012. Higher refill adherence was associated with slightly worse functional outcomes. The main reasons for refill non-adherence were “unwilling to take medication or only took medication when unwell” (23.6%), “forgot or missed the appointment” (20.6%) and “hospitalized” (20.1%). Conclusions The FMP program in Liuyang seemed to have successfully removed barriers in cost and access. However, better refill adherence was not associated with better functional outcomes in this study, which might have been the result of reverse causation. To improve the effectiveness of the FMP, patient-centered measures should be considered.

Refill Adherence Measures and Its Association with Economic, Clinical, and Humanistic Outcomes Among Pediatric Patients: A Systematic Review

Although refill adherence measures (RAMs) are widely reviewed on their use among adult patients, existing reviews on adherence among children have only focused on self-report measures and electronic monitoring. Hence, this systematic review aims to examine the use of RAMs and their association with economic, clinical, and humanistic outcomes (ECHO) among pediatric patients. A literature search was conducted in Pubmed, Embase, CINAHL, and PsycINFO. Studies published in English involving subjects aged ≤18 years were included if RAMs were analyzed with ECHO. Of the 35 included studies, the majority (n = 33) were conducted in high-income countries. Asthma was the most common condition (n = 9) studied. Overall, 60.6% of 33 clinical outcomes reported among 22 studies was positive (improved clinical outcomes with improved adherence), while 21.9% of 32 economic outcomes reported among 16 studies was positive (reduced healthcare utilization or cost outcomes with improved adherence). Only four studies evaluated the relationship of adherence with 11 humanistic outcomes, where the majority (72.7%) were considered unclear. RAMs are associated with ECHO and can be considered for use in the pediatric population. Future studies could explore the use of RAMs in low-income countries, and the association of RAMs with quality of life.

Inhaler Refill Adherence among Patients with COPD/Asthma at a General Hospital in Northern Peninsular Malaysia

Background: Most adherence studies are based on self-report measures. There are limited studies on medication refill adherence (MRA) conducted in Malaysia, especially on bronchial asthma (BA) and chronic obstructive pulmonary disease (COPD). The study aimed to investigate the MRA for inhalers with fixed dosing indicated for BA or COPD, prescribed from paediatric and medical clinics in Hospital Tuanku Fauziah and the factors that may affect MRA of COPD/BA inhalers. Methods: A cross-sectional study was conducted on repeat prescriptions (fixed-dose inhalers dispensed as the units of analysis) collected from 1st January 2015 to 31st December 2015 from the specialist clinic pharmacy. Descriptive analysis was conducted based on satisfactory MRA which was set as the dispensed refill of inhalers covering 80-120% of the prescribed treatment time. Logistic regression analysis was used to explore each variable (diagnosis, gender, ethnicity and age) in relation to MRA: overall satisfactory MRA (≥80% MRA) with undersupply (<80% MRA) as the reference group. Results: Out of the repeat prescriptions analysed (N=199), the majorities were COPD (N=118; 64.3%), male (N=122; 61.4%), Malay (N=175; 88.0%), and aged 60-69 years old (N=56; 28.3%). 44.5% of repeat prescriptions (N=57) for COPD showed satisfactory MRA, compared to only 25.4% (N=18) in BA. Repeat prescriptions for fluticasone/salmeterol accuhalers showed the highest satisfactory MRA at 18.1% (N=36). Diagnosis, gender and ethnicity did not significantly influence the overall MRA while age marginally influenced the overall MRA. Conclusion: More than half of the repeat prescriptions for BA and COPD inhalers showed undersupply and oversupply: patients may not be compliant nor using the inhaler correctly.

Risk of cardiovascular event and mortality in relation to refill and guideline adherence to lipid-lowering medications among patients with type 2 diabetes mellitus in Sweden

ObjectiveTo analyze the risk of cardiovascular (CV) events and mortality in relation to adherence to lipid-lowering medications by healthcare centers and patients with type 2 diabetes mellitus (T2DM).Research design and methodsWe included 121 914 patients (12% secondary prevention) with T2DM reported by 1363 healthcare centers. Patients initiated lipid-lowering medications between July 2006 and December 2012 and were followed from cessation of the first filled supply until multidose dispensed medications, migration, CV events, death or December 2016. The study period was divided into 4-month intervals through 2014, followed by annual intervals through 2016. Adherence measures were assessed for each interval. Patients’ (refill) adherence was measured using the medication possession ratio (MPR). Healthcare centers’ (guideline) adherence represented the prescription prevalence of lipid-lowering medications according to guidelines. The risk of CV events and mortality was analyzed for each interval using Cox proportional hazard regression and Kaplan-Meier.ResultsCompared with high-adherent patients (MPR >80%), low-adherent primary prevention patients (MPR ≤80%) showed higher risk of all outcomes: 44%–51 % for CV events, doubled for all-cause mortality and 79%–90% for CV mortality. Corresponding risks for low-adherent secondary prevention patients were 17%–19% for CV events, 88%–97% for all-cause and 66%–79% for CV mortality. Primary prevention patients treated by low-adherent healthcare centers (guideline adherence <48%) had a higher risk of CV events and CV mortality. Otherwise, no difference in the risk of CV events or mortality was observed by guideline adherence level.ConclusionsOur results demonstrate the importance of high refill adherence and thus the value of individualized care among patients with T2DM.