Evaluating patient-reported adherence and outcomes in specialty disease states: A dual-site initiative.

BACKGROUND: Patient-reported outcomes (PROs) are often used by clinicians to evaluate patient response to specialty medications used to treat multiple sclerosis (MS) and rheumatologic conditions. Identifying associations among PROs and patient characteristics could inform patient-centered treatment monitoring. OBJECTIVE: To examine the association among patient characteristics and PROs, including patient-reported adherence (defined as no missed doses), medication tolerance, patient perceived effectiveness, and health care resource utilization (HCRU; defined as emergency department visits or hospitalizations), for patients prescribed specialty medications in 2 health system specialty pharmacies. METHODS: A dual-center, retrospective review of monthly medication assessments completed by Vanderbilt Specialty Pharmacy and University of Illinois Hospital and Health Sciences System specialty pharmacy was conducted. Patients were included if they received at least 3 fills of a specialty medication from rheumatology or MS clinics from October 2019 to March 2022, excluding patients with more than a 30-day supply. Primary outcomes were the PROs of patient-reported adherence, medication tolerability, perceived effectiveness, and HCRU. For each of the 2 primary outcomes (adherence and tolerability), a mixed-effects logistic regression model was used to test for associations with age, sex, race, clinic, site, and the other PROs. RESULTS: A total of 61,926 assessments were completed from 3,677 patients (Site 1 = 3,346; 91.0% and Site 2 = 331; 9.0%). Patients were predominantly White (75.6%) and female (71.7%) with a median age of 50 years (IQR = 37-61). Assessments most frequently originated from rheumatology (76.0%). Nonadherence was reported 4.0% of the time, with the most common explanations being forgetfulness (33.1%) and medication being held because of a procedure or illness (29.5%). Most responses indicated perceived effectiveness as good/excellent (93.9%), with 98.5% of responses indicating no issues with tolerability. Patients who reported tolerability issues were 2.5 times more likely to report a missed dose (95% CI = 1.87-3.23, P < 0.001). An effectiveness rating of fair was associated with a 61% increase in the odds of a missed dose compared with a rating of good/excellent (95% CI = 1.33-1.94). CONCLUSIONS: Patients filling rheumatology or MS specialty medications within health system specialty pharmacies reported high rates of medication effectiveness and adherence and low rates of issues with tolerability and HCRU. Patients who report tolerability issues or lower perceived effectiveness may benefit from additional monitoring to prevent nonadherence.

Using electronic health records for clinical pharmacology research: Challenges and considerations.

Electronic health records (EHRs) contain a vast array of phenotypic data on large numbers of individuals, often collected over decades. Due to the wealth of information, EHR data have emerged as a powerful resource to make first discoveries and identify disparities in our healthcare system. While the number of EHR-based studies has exploded in recent years, most of these studies are directed at associations with disease rather than pharmacotherapeutic outcomes, such as drug response or adverse drug reactions. This is largely due to challenges specific to deriving drug-related phenotypes from the EHR. There is great potential for EHR-based discovery in clinical pharmacology research, and there is a critical need to address specific challenges related to accurate and reproducible derivation of drug-related phenotypes from the EHR. This review provides a detailed evaluation of challenges and considerations for deriving drug-related data from EHRs. We provide an examination of EHR-based computable phenotypes and discuss cutting-edge approaches to map medication information for clinical pharmacology research, including medication-based computable phenotypes and natural language processing. We also discuss additional considerations such as data structure, heterogeneity and missing data, rare phenotypes, and diversity within the EHR. By further understanding the complexities associated with conducting clinical pharmacology research using EHR-based data, investigators will be better equipped to design thoughtful studies with more reproducible results. Progress in utilizing EHRs for clinical pharmacology research should lead to significant advances in our ability to understand differential drug response and predict adverse drug reactions.

Efficacy and safety of outpatient fludarabine, cyclophosphamide, and rituximab based allogeneic hematopoietic cell transplantation in adults with severe aplastic anemia.

The age effect in severe aplastic anemia (SAA) following allogeneic hematopoietic cell transplantation (HCT) favors the use of reduced intensity conditioning (RIC) regimens in older adults. We implemented a non-myeloablative regimen consisting of fludarabine, cyclophosphamide, and rituximab (FCR) to improve HCT outcomes in SAA. Patients who underwent first HCT for SAA utilizing an FCR regimen between January 2016 and May 2022 were included. Outcomes analyzed included time to engraftment, incidence of graft failure, GVHD, viral reactivation, disease recurrence, and GVHD-free, relapse-free survival (GRFS). Among 24 patients included, median age was 43.5 years (22-62) and a variety of donor types and stem cell sources were represented. At median follow-up of 26.9 months (2.4-72.7), no cases of grade III-IV acute (aGVHD) or severe chronic GVHD (cGVHD) were recorded. Viral reactivation was minimal, and there were no cases of graft failure or PTLD, with 100% disease-free and overall survival at last follow up. The estimate of 1-year GRFS was 86.3% (95% CI: 72.8-100%), with moderate cGVHD accounting for all events. The FCR regimen in SAA was well tolerated, even in older adults, with 100% disease-free survival with low GVHD and infection rates. These encouraging findings should be validated in larger prospective trials.

Financial impact of integrated specialty pharmacy efforts to avoid oral anticancer medication waste.

BACKGROUND: The growing number of oral anticancer medications represents a significant portion of pharmacy spending and can be costly for patients. Patients taking oral anticancer medications may experience frequent treatment changes following necessary safety and effectiveness monitoring, often resulting in medication waste. Strategies to avoid medication waste could alleviate the financial burden of these costly therapies on the payer and the patient. OBJECTIVE: To evaluate the impact on waste and cost avoidance of reviewing the amount of medication patients have on hand and the presence of upcoming follow-up (ie, provider visit, laboratory testing, or imaging) before requesting a prescription refill renewal for patients taking oral anticancer medications through an integrated health system specialty pharmacy. METHODS: We performed a retrospective review of patients filling oral anticancer medications prescribed by a Vanderbilt University Medical Center provider and dispensed by Vanderbilt Specialty Pharmacy between January 1, 2020, and December 31, 2020. Specialty pharmacists received a system-generated refill renewal request for oral anticancer medications when the final prescription refill was dispensed, prompting the pharmacist to review the patient's medical record for continued therapy appropriateness and to request a new prescription. If the patient had a sufficient supply on hand to last until an upcoming follow-up (ie, provider visit, imaging, or laboratory assessment), the pharmacist postponed the renewal until after the scheduled follow-up. Patients were included in the analysis if the refill renewal request was postponed after review of the amount of medication on hand and the presence of an upcoming follow-up. Medication outcomes (ie, continued, dose changed, held, medication changed to a different oral anticancer medication, or discontinued) resulting from the follow-up were collected. Cost avoidance in US dollars was assigned based on the outcome of follow-up by calculating the price per unit times the number of units that would have been unused or in excess of what was needed if the medication had been dispensed before the scheduled follow-up. The average wholesale price minus 20% (AWP-20%) and wholesale acquisition cost (WAC) were used to report a range of costs avoided over 12 months. RESULTS: The total cost avoidance over 12 months associated with postponing refill renewal requests in a large academic health system with an integrated specialty pharmacy ranged from $549,187.03 using WAC pricing to $751,994.99 using AWP-20% pricing, with a median cost avoidance per fill of $366.04 (WAC) to $1,931.18 (AWP-20%). Refill renewal requests were postponed in 159 instances for 135 unique patients. After follow-up, medications were continued unchanged in only 2% of postponed renewals, 56% of follow-ups resulted in medication discontinuations, 32% in dose changes, 5% in medication changes, and 5% in medication holds. CONCLUSIONS: Integrated health system specialty pharmacist postponement of refill requests after review of the amount of medication on hand and upcoming follow-up proved effective in avoiding waste and unnecessary medication costs in patients treated with oral anticancer medications at a large academic health system.

Cost avoidance from health system specialty pharmacist interventions in patients with multiple sclerosis.

BACKGROUND: Specialty pharmacists monitor patients taking multiple sclerosis (MS) disease-modifying therapies (DMTs) to evaluate response to therapy and intervene on adverse effects. These interventions have the potential to avoid health care costs by discontinuing inappropriate therapies and avoiding downstream health care utilization. OBJECTIVE: To calculate the costs avoided by specialty pharmacist interventions in MS. METHODS: A retrospective observational cohort study including patients at the Vanderbilt MS Clinic who received a specialty pharmacist intervention between February 1, 2022, and July 31, 2022, was performed. A panel of 3 investigators categorized each intervention based on the potential for cost avoidance: (1) no cost avoidance, (2) direct cost avoidance, and (3) indirect cost avoidance. A single intervention may have one or both cost avoidance types. Direct costs avoided included the cost of the potential service or medication avoided due to the intervention. Medication costs were calculated using the range of the average wholesale price and average wholesale price - 20%. For indirect costs avoided, the range of costs of a consequence (self-care, ambulatory visit, emergency department visit, hospitalization, or death) occurring had the intervention not been performed were multiplied by the range of probabilities for the consequence occurring (from zero [0] to very likely [0.5]). Self-care indirect cost savings equated to $0. Descriptive statistics summarized types of pharmacist interventions, the patients impacted, and costs avoided. In patients with an intervention that resulted in cost avoidance, chart review was performed to collect patient demographics, disease history, and MS-related health care usage during the 12 months prior to the pharmacist intervention. RESULTS: 485 pharmacist interventions in 354 individual patients were included. Fifty interventions in 38 individual patients (76% female, median age 51 years, 68% White) resulted in cost avoidance. The total estimated costs avoided in 6 months ranged from $123,733 to $156,265. In total, $138,410 were direct costs and $1,890 were indirect costs. Reasons for direct costs avoided (n = 13) were often safety monitoring (69%) or common side effects management (23%). Indirect costs avoidance (n = 37) resulted primarily from interventions on common side effects management (57%) and safety monitoring (22%). Self-care was the most common type of indirect cost avoided (n = 27). Interventions resulting in costs avoided were commonly seen in patients with relapsing-remitting MS (82%). The median time from MS diagnosis was 15 years and 42% of patients had previously trialed 1 other MS DMT. CONCLUSIONS: There is a potential for significant health care savings after specialty pharmacist interventions in MS, primarily from preventing the dispensing of inappropriate therapies.

Adherence and discontinuation of prescription cannabidiol for the management of seizure disorders at an integrated care center.

OBJECTIVE: Evaluate adherence, discontinuation rates, and reasons for non-adherence and discontinuation of prescription CBD during the 12-months post-initiation period at an integrated care center. METHODS: This was a prospective study of patients prescribed CBD by a neurology clinic provider with initial prescription fulfillment through the center's specialty pharmacy from January 2019 through April 2020. Baseline demographics and reasons for non-adherence and/or discontinuation were collected from the electronic health record and pharmacy claims history was used to calculate adherence using proportion of days covered (PDC). Patients were included in the PDC analysis if they had at least 3 fills during the study period. Non-adherence was defined as a PDC < 0.8. Descriptive statistics were used to summarize data with categorical variables represented as frequencies and percentages and continuous variables as medians and interquartile ranges (IQRs). RESULTS: We included 136 patients with a median age of 14 years (IQR 9 - 21). Most patients were white (n = 115, 85%), with a diagnosis of intractable epilepsy (n = 100, 74%). Among the 128 patients with 3 or more fills, the median PDC was 0.99 (IQR 0.95 - 1.00) with non-adherence seen in 6% (n = 8) of patients. The most common reason for non-adherence was side effects (n = 2, 25%). Prescription CBD was discontinued by 23% (n = 31) of patients with a median time to discontinuation of 117 days (IQR 68 - 216). The most common reason for discontinuation was major side effects (n = 12, 39%). The most common side effects leading to discontinuation were agitation/irritability (n = 4), mood changes (n = 4), aggressive behavior (n = 3), and increased seizure frequency (n = 3). CONCLUSION: Adherence to prescription CBD at an integrated care center was high with approximately 94% of patients considered adherent. Providers and pharmacists may improve adherence and discontinuation rates by educating patients on the timeline of response, potential side effects, and potential for dose adjustments.

Denosumab treatment lapses, discontinuation, and off-treatment fracture risk: A retrospective study of patients with osteoporosis in a real-world clinical setting.

INTRODUCTION: The purpose of this study was to retrospectively examine predictors of fracture risk when adult patients experienced a denosumab treatment lapse or discontinuation in a real-world clinic setting. MATERIALS AND METHODS: Eligible patients were adults who had received ≥2 doses of denosumab at an academic health center in the United States. Demographics, treatment doses, reasons for missed doses, and fractures, were collected retrospectively from electronic health records, from an 8-year period (2010-2018). The number of times each patient incurred a treatment lapse, defined as ≥240 days between two doses (excluding lapse due to discontinuation, death, or transfer of care) was computed. The occurrence of denosumab discontinuation (excluding discontinuation due to death or transfer of care), whether the patient initiated alternative therapy, and the reason for each lapse and discontinuation were collected. Cox proportional hazards models assessed characteristics associated with risk of fracture and treatment discontinuation. A logistic regression model was used to determine if cumulative amount of time off medication (i.e., cumulative lapse time) was associated with a higher likelihood of incurring a fracture. RESULTS: We included 534 patients: 95 % White, 86 % women, 33 % tobacco users, 13 % diagnosed with diabetes, median age 69 years (Interquartile Range (IQR): 62-77), and median Body Mass Index (BMI) 25 kg/m2 (IQR: 22-28). Thirty-six percent of patients incurred 250 lapses; 10 % discontinued therapy. Dental problems/procedures and logistical barriers were the most common reasons for lapses and discontinuations. Nineteen percent (n = 103) incurred a total of 190 fractures; of these, 121 were osteoporotic, 50 were vertebral. Risk of any, osteoporotic, and vertebral fractures were associated with off-treatment status (hazard ratio [HR] = 1.7, p = 0.043; HR = 2.0, p = 0.026; and HR = 4.2, p = 0.001, respectively) and older age (HR = 1.3, p = 0.015; HR = 1.5, p = 0.001; and HR = 1.8, p = 0.005, respectively). Older age was associated with higher risk of discontinuation (HR = 1.4, p = 0.022). There was a non-significant trend of a nonlinear association between incurring a fracture and cumulative lapse time (p = 0.087). CONCLUSION: Denosumab treatment lapses are common, and off-treatment status may be associated with a higher risk of fractures. Clinical teams should proactively identify and address adverse effects and potential logistical barriers to reduce the risk of treatment lapses.

Therapy outcomes associated with prescription cannabidiol use at 12 months post-initiation.

OBJECTIVE: This study evaluated prescription cannabidiol (CBD) outcomes during the first 12 months of therapy. METHODS: A single-center, prospective cohort study was performed including patients prescribed CBD from January 2019 - April 2020, excluding clinical trial patients and those using external specialty pharmacy services. The primary outcome wasepilepsy-related emergency healthcare service (EHS) use within 12 months of initation. Secondary outcomes included prescription CBD discontinuation rate and reason and concomitant anti-seizure medication (ASM) use. A multiple logistic regression model evaluated the odds of EHS use, adjusting for initial concomitant ASM count, age, and insurance type. RESULTS: The 136 patients included were 85% white, 50% female, and 68% pediatric. EHS utilization occurred in 37% (n = 50) of patients; 29 patients (21%, n = 20 pediatric, n = 9 adult) had at least one emergency department (ED) visit, 9 patients (7%) had two or more; 30 patients (22%, n = 22 pediatric, n = 8 adult) had at least one hospitalizaion. Median time to first ED and hospitalization was 69 (IQR 31-196) and 104 (IQR 38-179) days, respectively. Prescription CBD was discontinued in 31 patients (23%, n = 18 pediatric, n = 13 adult), due to major side effects (n = 12, 39%), common side effects (n = 11, 36%), and unsatisfactory response (n = 11, 36%). There was no significant change in concomitant ASM use. CONCLUSION: Despite potential benefits of prescription CBD, many patients utilize EHSs in the first 12 months of treatment with minimal changes in concomitant ASM use.

Insurance Approval Delay of Biologic Therapy Dose Escalation Associated with Disease Activity in Patients with Inflammatory Bowel Disease.

BACKGROUND: Dose escalation of self-injectable biologic therapy for inflammatory bowel diseases may be required to counteract loss of response and/or low drug levels. Payors often require completion of a prior authorization (PA), which is a complex approval pathway before providing coverage. If the initial PA request is denied, clinic staff must complete a time and resource-intensive process to obtain medication approval. AIMS: This study measured time from decision to dose escalate to insurance approval and evaluated impact of approval time on disease activity. METHODS: This was a single-center retrospective analysis of adult patients with IBD prescribed an escalated dose of biologic therapy at an academic center with an integrated specialty pharmacy team from January to December 2018. Outcomes included time to insurance approval and the association between approval time and follow-up C-reactive protein (CRP) and Short Inflammatory Bowel Disease Questionnaire (SIBDQ) scores. Associations were tested using linear regression analyses. RESULTS: 220 patients were included, median age 39, 53% female, and 96% white. Overall median time from decision to dose escalate to insurance approval was 7 days [interquartile range (IQR) 1, 14]. Approval time was delayed when an appeal was required [median of 29 days (IQR 17, 43)]. Patients with a longer time to insurance approval were less likely to have CRP improvement (p = 0.019). Time to insurance approval did not significantly impact follow-up SIBDQ scores. CONCLUSION: Patients who had a longer time to insurance approval were less likely to have improvement in CRP, highlighting the negative clinical impact of a complex dose escalation process.

Patient-reported outcomes and pharmacist actions in patients with multiple sclerosis managed by health-system specialty pharmacies.

PURPOSE: This study evaluated patient-reported outcomes (PROs) and pharmacist actions for patients on disease-modifying therapies (DMTs) for multiple sclerosis (MS) through health-system specialty pharmacies (HSSPs). METHODS: A multisite, prospective cohort study of patients utilizing an HSSP for DMT fulfillment was performed. Primary outcomes were affirmative answers to PRO questions regarding impacted productivity, hospitalization, and relapse and pharmacist actions. Rates of pharmacist actions were reported as the number of person-years of treatment per action. Univariate and multivariate logistic regression were used to evaluate the association between each PRO and covariates, including the number of pharmacist actions performed, age, sex, insurance, site, and route of administration. RESULTS: The 968 patients included had 10,562 fills and 6,946 PRO assessments. The most common affirmative PRO was impacted productivity (14.6%). Pharmacists performed 3,683 actions, most commonly general medication education (42.6%) and safety (33.3%). Rates of general medication education and nonfinancial coordination of care actions were similar across medication classes; other pharmacist actions varied by medication class. Insurance type was significantly associated with reporting impacted productivity; patients with Medicare and Medicaid were 2.2 and 3.1 times more likely to have reported impacted productivity, respectively (P < 0.001) than commercially insured patients. Patients who reported impacted productivity had more pharmacist actions (P < 0.001). CONCLUSION: Patients on DMTs through an HSSP reported low rates of impacted productivity, relapse, and hospitalization due to MS, although patients with noncommercial insurance were more likely to have impacted productivity. Patients reporting impacted productivity and those taking certain DMTs may require more frequent pharmacist actions.

Low rates of primary medication nonadherence in patients prescribed oral oncology agents across health system specialty pharmacies.

BACKGROUND: New oral oncology medications bring novel challenges when patients are initiating treatment. Rates of primary medication nonadherence (PMN), the rate at which a medication is prescribed but not obtained, of up to 30% have been reported for oral oncology medications. More research is needed to identify causes and develop strategies for health system specialty pharmacies (HSSPs) to improve cancer treatment initiation rates. OBJECTIVE: To evaluate the rate and reasons for PMN to specialty oral oncology medications in an HSSP setting. METHODS: We performed a multisite retrospective cohort study across 7 HSSP sites. Patients were included if they had an orally self-administered oncology medication referral generated by the health system of the affiliated specialty pharmacy between May 1, 2020, and July 31, 2020. Data collected at each site using pharmacy software and the electronic health record were deidentified and aggregated for analysis. After identifying unfilled referrals within a 60-day fill window, a retrospective chart review was performed to identify final referral outcomes and reasons for unfilled referrals. Referral outcomes were categorized as unknown fill outcomes (because of being referred to another fulfillment method or if received for benefits investigation only), filled by the HSSP, or not filled. The primary outcome was PMN for each PMN-eligible referral and secondary outcomes included reason for PMN and time to fill. The final PMN rate was calculated by dividing the number of unfilled referrals by total referrals with a known fill outcome. RESULTS: Of 3,891 referrals, 947 were PMN eligible, representing patients with a median age of 65 years (interquartile range = 55-73), near equal distribution between male and female (53% vs 47%), and most commonly with Medicare pharmacy coverage (48%). The most referred medication was capecitabine (14%), and the most common diagnosis was prostate cancer (14%). Among PMN-eligible referrals, 346 (37%) had an unknown fill outcome. Of the 601 referrals with known fill outcome, 69 referrals were true instances of PMN, yielding the final PMN rate of 11%. Most referrals were filled by the HSSP (56%). Patient decision was the most common reason for not filling (25%; 17/69 PMN cases). The median time to fill after initial referral was 5 days (interquartile range = 2-10). CONCLUSIONS: HSSPs have a high percentage of patient initiation of new oral oncology medication treatments in a timely manner. More research is needed to understand patient reasons for deciding not to start therapy and to improve patient-centered cancer treatment planning decisions. DISCLOSURES: Dr Crumb was a planning committee member with Horizon CME for the Nashville APPOS 2022 Conference. Dr Patel received funding and support for attending meetings and/or travel from the University of Illinois Chicago College of Pharmacy.

Primary medication nonadherence rates to specialty disease-modifying antirheumatic drugs for rheumatoid arthritis within a health system specialty pharmacy.

BACKGROUND: Assessing primary medication nonadherence, the rate at which a medication is prescribed for a patient but is not obtained or replaced with an alternative medication within a reasonable time period, can provide a better understanding of the frequency and impact of these barriers to medication access. Previous literature has reported high rates of primary medication nonadherence, ranging from approximately 20% to 55% in patients with rheumatoid arthritis (RA) treated with specialty disease-modifying antirheumatic drugs (DMARDs). The high primary medication nonadherence rate may reflect the difficulties associated with obtaining specialty medications, such as high costs, extended prior authorizations, and pretreatment safety requirements. OBJECTIVE: To evaluate reasons for and rates of primary medication nonadherence to specialty DMARDs in patients with RA referred to an integrated health systems specialty pharmacy. METHODS: We conducted a retrospective cohort study examining eligible patients with a specialty DMARD referral from a health system rheumatology provider to the health system specialty pharmacy. Initially, pharmacy claims were used to identify primary medication nonadherence, defined as the lack of a fill event within 60 days following the medication referral for patients without a specialty DMARD claim in the 180 days prior. Referrals from July 1, 2020, to July 1, 2021, were eligible. Exclusion criteria included duplicate referrals, use for non-RA indications, switches to clinic-administered therapies, and alternate filling methods. Medical record reviews were conducted to confirm referral outcomes. Outcomes included rate of and reasons for primary medication nonadherence. RESULTS: We included 480 eligible patients, 100 of whom had no documented fill event. After medical record review, 27 patients were removed due to having a non-RA diagnosis and 65 patients were removed due to having alternative fill methods, most due to external prescription routing (83.1%). The final primary medication nonadherence rate was 2.1%. Out of the 8 cases of true primary medication nonadherence, 3 patients held specialty DMARD therapy because of other existing disease states, 3 patients were unreachable, and 2 patients were unable to afford medication. CONCLUSIONS: Rates of primary medication nonadherence to specialty DMARDs were low in patients with RA managed by a health system specialty pharmacy. A total of 8 primary medication nonadherence cases were related to safety concerns in non-RA diseases states, patient unreachability, and affordability. However, the limited number of primary medication nonadherence cases limits the generalizability of reasons for primary medication nonadherence found in this study. Key elements of the health systems specialty pharmacy model that likely contribute to low primary medication nonadherence include dedicated financial assistance navigation services, in-clinic pharmacist availability, and open communication between provider offices.

Optimizing HIV PrEP Persistence: Does Your Pharmacy Matter?

Persistence to human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) is integral to preventing new HIV infections. Previous studies have shown real-world PrEP persistence is low and insight is needed into PrEP delivery strategies that improve persistence. This single-center, retrospective, cohort study measured persistence in patients filling PrEP through an integrated health-system specialty pharmacy (HSSP) compared to those filling at external pharmacies. The Kaplan-Meier estimates for persistence probability at 6, 12, and 18 months were 0.87 (95% CI 0.79-0.95), 0.75 (95% CI 0.66-0.86), and 0.64 (95% CI 0.53-0.76) for the HSSP cohort compared to 0.65 (95% CI 0.51-0.83), 0.41 (95% CI 0.28-0.62), and 0.32 (95% CI 0.2-0.53), respectively, for the non-HSSP cohort (log-rank p < 0.001, [Formula: see text] = 11.2). Cox PH modeling showed that patients using a non-HSSP were 2.7 times more likely to be non-persistent than HSSP patients (HR 2.7, 95% CI 1.6-4.7, p < 0.001, [Formula: see text] = 12.61), demonstrating patients were better maintained on PrEP therapy when their prescriptions were filled with the HSSP.

Variant-based heritability assessment of dexmedetomidine and fentanyl clearance in pediatric patients.

Despite complex pathways of drug disposition, clinical pharmacogenetic predictors currently rely on only a few high effect variants. Quantification of the polygenic contribution to variability in drug disposition is necessary to prioritize target drugs for pharmacogenomic approaches and guide analytic methods. Dexmedetomidine and fentanyl, often used in postoperative care of pediatric patients, have high rates of inter-individual variability in dosing requirements. Analyzing previously generated population pharmacokinetic parameters, we used Bayesian hierarchical mixed modeling to measure narrow-sense (additive) heritability ( h SNP 2 ) of dexmedetomidine and fentanyl clearance in children and identify relative contributions of small, moderate, and large effect-size variants to h SNP 2 . We used genome-wide association studies (GWAS) to identify variants contributing to variation in dexmedetomidine and fentanyl clearance, followed by functional analyses to identify associated pathways. For dexmedetomidine, median clearance was 33.0 L/h (interquartile range [IQR] 23.8-47.9 L/h) and h SNP 2 was estimated to be 0.35 (90% credible interval 0.00-0.90), with 45% of h SNP 2 attributed to large-, 32% to moderate-, and 23% to small-effect variants. The fentanyl cohort had median clearance of 8.2 L/h (IQR 4.7-16.7 L/h), with estimated h SNP 2 of 0.30 (90% credible interval 0.00-0.84). Large-effect variants accounted for 30% of h SNP 2 , whereas moderate- and small-effect variants accounted for 37% and 33%, respectively. As expected, given small sample sizes, no individual variants or pathways were significantly associated with dexmedetomidine or fentanyl clearance by GWAS. We conclude that clearance of both drugs is highly polygenic, motivating the future use of polygenic risk scores to guide appropriate dosing of dexmedetomidine and fentanyl.

Adherence and persistence to self-administered disease-modifying therapies in patients with multiple sclerosis: A multisite analysis.

BACKGROUND: Though there are several disease-modifying therapy (DMT) options for patients with multiple sclerosis (MS), treatment outcomes rely on patient adherence and persistence. Previous studies have demonstrated suboptimal adherence rates and high rates of early treatment discontinuation. Health-system specialty pharmacies (HSPPs) are a growing practice model that have demonstrated adherence and persistence benefits through single site evaluations. Research is needed across multiple HSSPs to understand and validate the outcomes of this practice model. METHODS: A multisite prospective cohort study was performed including patients with at least three fills of a DMT between January 2020 and June 2021 at an HSSP. Patients were excluded due to pregnancy or death. Enrollment occurred for 6 months followed by 12 months of follow-up. Adherence was measured using pharmacy claims to calculate proportion of days covered (PDC) during the follow-up period. Time to non-persistence was calculated as the time from an index DMT fill to the first date of a gap of >60 days between medication exhaust and fulfillment dates. Adherence and persistence calculations were assessed at the therapeutic class level (any self-administered DMT dispensed by the HSSPs). The Kaplan-Meier method was used to present the probability of being persistent, and Cox proportional hazards regression analysis was used to estimate hazard ratios of factors associated with non-persistence, which included age, sex, study site, insurance type, and whether the patient switched medication as potential factors. RESULTS: The most common self-administered DMTs filled among 968 patients were glatiramer acetate (32%), fingolimod (18%), and dimethyl fumarate (18%). Most patients (96%) did not switch DMT during the study period. The median PDC was 0.97 (interquartile range 0.90-0.99), which was similar across all sites. Patients who had at least one DMT switch were 76% less likely to have a higher PDC than those who did not have any switch after adjusting for other covariates (Odds ratio: 0.24, 95% confidence interval [CI]: 0.14-0.40, p<0.001). Most patients (86%) were persistent to DMT over the 12-month study period. Among those non-persistent, median time to non-persistence was 231 (IQR 177-301) days. Patients who switched medications were 2.4 times more likely to be non-persistent (95% CI: 1.3 - 4.5, p = 0.005). The most common reasons for non-persistence were discontinuation/medication held for an extended period (30%), often due to patient or prescriber decision (75%). CONCLUSION: High rates of DMT adherence and persistence were seen among patients serviced by HSSPs, indicating potential benefits of this model for patients with MS. Switching DMTs was associated with lower adherence and persistence and may be an opportunity for added care coordination or resources to optimize therapy transitions.

Patient-Tailored Interventions to Improve Specialty Medication Adherence: Results from a Prospective Randomized Controlled Trial.

BACKGROUND: Specialty medication nonadherence results in poor clinical outcomes and increased costs. This study evaluated the impact of patient-tailored interventions on specialty medication adherence. METHODS: A pragmatic, randomized controlled trial was conducted at a single-center health-system specialty pharmacy from May 2019 to August 2021. Participants included recently nonadherent patients prescribed self-administered specialty medications from multiple specialty clinics. Eligible patients were stratified by historical clinic rates of nonadherence and randomized 1:1 to usual care or intervention arms. Intervention patients received patient-tailored interventions and 8 months of follow-up. A Wilcoxon test was used to analyze the difference in 6-, 8-, and 12-month post-enrollment adherence, calculated using proportion of days covered, between the intervention and usual care arms. RESULTS: Four hundred and thirty eight patients were randomized. Baseline characteristics were similar between groups: mostly women (68%), white (82%), with a median age of 54 years (interquartile range, 40, 64). The most common reasons for nonadherence in the intervention arm were memory (37%) and unreachability (28%). There was a significant difference in median proportion of days covered between patients in the usual care and intervention arms at 8-months (0.88 vs 0.94, P < .001), 6-months (0.90 vs 0.95, P = .003), and 12-months post-enrollment (0.87 vs 0.93, P < .001). CONCLUSIONS: Patient-tailored interventions resulted in significant specialty medication adherence improvement compared with standard of care. Specialty pharmacies should consider targeting nonadherent patients for adherence interventions.

2022 ASHP Survey of Health-System Specialty Pharmacy Practice: Clinical Services.

PURPOSE: Results of the first ASHP national survey of clinical services provided by health-system specialty pharmacies (HSSPs) are presented. METHODS: A survey questionnaire was developed by 26 HSSP contacts after reviewing available literature on the role and services of HSSPs. After pilot and cognitive testing resulting in a final questionnaire of 119 questions, a convenience sample of 441 leaders in HSSPs was contacted using email and invited to participate in the survey. RESULTS: The survey response rate was 29%. Almost half of respondents (48%) had offered pharmacy services for 7 years or more, and most (60%) dispensed more than 15,000 prescriptions annually. Respondents most commonly (42%) reported a specialist model wherein staff are dedicated to specific specialty disease states. Over half of respondents reported providing several medication access, pretreatment assessment, and initial counseling services to patients referred to them, regardless of whether the HSSP was used for medication fulfillment. All HSSP activities were noted to be documented in the electronic health record and visible to providers frequently or always. Almost all respondents noted that HSSP pharmacists have a role in specialty medication selection. Disease-specific outcomes were tracked in 95% of responding HSSPs, with 67% reporting that outcomes were used to drive patient monitoring. HSSPs were often involved in continuity of care services such as transitions of care (reported by 89% of respondents), referral to other health-system services (53%), and addressing social determinants of health (60%). Most respondents (80%) reported providing clinical education to specialty clinic staff, including medicine learners (62%). Though only 12% of respondents had dedicated outcomes research staff, many reported annually publishing (47%) or presenting (61%) outcomes research. CONCLUSION: HSSPs are a clinical and educational resource for specialty clinics and have developed robust patient care services that encompass the patient journey from before specialty medication selection through treatment monitoring and optimization.

Pharmacist Review of Chronic Inhaler Therapy Appropriateness for Hospitalized Patients with COPD or Asthma.

INTRODUCTION: Patients with asthma and chronic obstructive pulmonary disease rely on inhaler therapy to reduce disease progression and exacerbation risk. Patients admitted to the hospital are at an increased risk for exacerbations and readmission if their inhaler therapy upon discharge is not aligned with current guidelines and/or affordable. OBJECTIVE: Assess the appropriateness of the chronic inhaler regimen for patients admitted to the hospital based on clinical practice guidelines and insurance coverage. METHODS: A sub-study was designed to analyze a cohort of a single-center, pragmatic, prospective randomized controlled trial at a large academic medical center. Patients admitted to a medicine service with a pharmacist and prescribed a long-acting inhaler were included. Participants randomized to a pharmacist-led intervention were assessed for inhaler appropriateness based on clinical guidelines and patient insurance. The objective of this sub-study is to assess the number of inhalers identified as inappropriate based on the pharmacist's review. A patient was considered to have an inappropriate inhaler regimen if any of their inhalers were inconsistent with guideline recommendations or not covered by insurance. Descriptive statistics were used to characterize appropriate inhaler use. RESULTS: The study pharmacist reviewed 552 unique inhalers for 348 patients. Overall, 42% of inhalers were inappropriate, affecting 50.3% of participants. 20% of inhalers were inappropriate based on insurance, 26% were inappropriate based on guidelines, and 7% were inappropriate based on both criteria. Recommendations were placed via a pharmacy consult for 198 patients (57%), most recommending an inhaler initiation (55%), followed by inhaler discontinuation (38%). CONCLUSION: A pharmacist-led review of chronic inhaler therapy for patients admitted to the hospital identified the need for a change in therapy based on financial or clinical guidelines in over half of the patients reviewed. Interventions to increase the appropriateness of prescribed inhalers are needed to reduce disease progression and disease exacerbation.

Individual and Community-Level Characteristics and Adherence to Specialty Medications.

Background: Understanding risk factors for nonadherence can help specialty pharmacies optimize resources to prevent nonadherence and inform risk-stratification processes. Objective: To determine which individual and community-level characteristics are associated with nonadherence to specialty medications. Methods: We analyzed a cohort of patients enrolled in a prospective randomized controlled trial having filled a specialty medication at least 4 times in the previous 12 months with a proportion of days (PDC) covered < 0.90. We collected patient age, gender, race, medication administration type, therapy start date, home address, insurance type, and online patient portal status from the electronic health record. An ordinal logistic regression model was used to assess the association of nonadherence with individual and community-level patient characteristics. Results: Most patients were female (68%), white (82%), and held commercial insurance (58%) with a median age of 53 (interquartile range [IQR] 40, 64) years. Patients were mostly from the adult rheumatology (35%), multiple sclerosis (20%) and lipid (17%) clinics. Given a 10-year increase in age, patients had lower odds of having lower PDC (odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.71-0.94, P = 0.005). Patients on therapy greater than or equal to 1 year had half the odds of having lower PDC relative to patients on therapy less than 1 year (OR = 0.52, CI = 0.35 - 0.75, P < 0.001). No statistically significant associations were found between PDC and gender, race, insurance type, route of administration, clinic type, patient portal status, median income, percent receiving government assistance, or percent with no health insurance. Conclusion: Patients with younger age and shorter duration on treatment may be at-risk for lower adherence. Specialty pharmacies may benefit from targeting adherence interventions to these groups.

Specialty pharmacy integration and the role of an advanced certified pharmacy technician in prescription cannabidiol access.

BACKGROUND: Insurance requirements that limit access to prescription cannabidiol (CBD), an adjunct therapy for uncontrolled seizure disorders, may lead to treatment initiation delays. Integrated health-system specialty pharmacies (IHSSPs) use pharmacists and advance certified pharmacy technicians (CPhTs) to help navigate prescription CBD access requirements. OBJECTIVE(S): Evaluate time from initial specialty pharmacy referral to prescription CBD shipment. METHODS: This was a single-center, retrospective analysis of patients prescribed CBD from January 2019 to April 2020 by the outpatient neurology clinic and dispensed by the center's IHSSP. The primary outcome was the time to prescription CBD access, defined as days between the specialty pharmacy completing an initial patient assessment and first medication shipment. Secondary outcomes were percentage of patients requiring financial assistance and days between key steps in the access pathway. Data were collected from electronic health records and the specialty pharmacy patient management database. The CPhT was responsible for completing most portions of the access pathway under supervision of the clinical pharmacist. RESULTS: After screening, 136 patients were included: 50% male, 85% white, 60% insured by Medicaid, and median age 14 years (interquartile range [IQR] 9-21). The most common indication was Lennox-Gastaut syndrome (n = 117, 86%). Of the 129 patients (95%) who required a prior authorization (PA), 92% were approved (n = 119). Median time from initial assessment to first shipment was 7 days (IQR 4-13). Of patients for whom the CPhT helped obtain financial assistance (n = 14, 10%), all had $0 costs after assistance. Median times for secondary outcomes led by the CPhT in days were as follows: initial assessment completion to benefits investigation (BI) = 0 (IQR 0-0), BI to PA submission = 0 (IQR 0-0), and PA denial to appeal submission = 4 (IQR 1-7). CONCLUSION: IHSSP teams, particularly advanced CPhT roles, helped patients afford and initiate prescription CBD quickly.