Racial disparities in medication use: imperatives for managed care pharmacy

The COVID-19 pandemic and the social unrest pervading U.S. cities in response to the killings of George Floyd and other Black citizens at the hands of police are historically significant. These events exemplify dismaying truths about race and equality in the United States. Racial health disparities are an inexcusable lesion on the U.S. health care system. Many health disparities involve medications, including antidepressants, anticoagulants, diabetes medications, drugs for dementia, and statins, to name a few. Managed care pharmacy has a role in perpetuating racial disparities in medication use. For example, pharmacy benefit designs are increasingly shifting costs of expensive medications to patients, creating affordability crises for lower income workers, who are disproportionally persons of color. In addition, the quest to maximize rebates serves to inflate list prices paid by the uninsured, among which Black and Hispanic people are over-represented. While medication cost is a foremost barrier for many patients, other factors also propagate racial disparities in medication use. Even when cost sharing is minimal or zero, medication adherence rates have been documented to be lower among Blacks as compared with Whites. Deeper understandings are needed about how racial disparities in medication use are influenced by factors such as culture, provider bias, and patient trust in medical advice. Managed care pharmacy can address racial disparities in medication use in several ways. First, it should be acknowledged that racial disparities in medication use are pervasive and must be resolved urgently. We must not believe that entrenched health system, societal, and political structures are impermeable to change. Second, the voices of community members and their advocates must be amplified. Coverage policies, program designs, and quality initiatives should be developed in consultation with those directly affected by racial disparities. Third, the industry should commit to dramatically reducing patient cost sharing for essential medication therapies. Federal and state efforts to limit annual out-of-pocket pharmacy spending should be supported, even though increased premiums may be an undesirable (yet more equitable) consequence. Finally, information about race should be incorporated into all internal and external reporting and quality improvement activities

Comparison of persistence rates of acetylcholine-esterase inhibitors in a state Medicaid program

Objective: To compare levels of persistency between cholinesterase inhibitors (ChEIs) among a Medicaid patient population of older adults. Methods: Survival analysis was used to assess differences in discontinuation between ChEIs (donepezil versus rivastigmine and galantamine), and for difference in patient gender, age, race, and care setting. Results: Rates of discontinuation increased from 42.7% (95% CI = 39.9-45.5) at 12 months to 84.8% (95% CI = 82.3-87.3) at 24 months. In multivariate models, no significant difference in discontinuation existed prior to 365 days. However, patients dispensed donepezil were less likely to discontinue as compared with users of the other two ChEIs after the first year (RR = 0.70; CI = 0.499-0.983; p \u3c 0.04). Patients of white race were less likely to discontinue (RR = 0.549; 95% CI = 0.43-0.82; p = 0.0015), while gender, care setting, and age were not associated with discontinuation. Conclusions: One-year persistence rates were similar between different ChEIs. Among patients persisting with ChEI medication for at least 12 months, users of donepezil were slightly more likely to continue to persist at 24 months. Nearly half of patients failed to persist with ChEI therapy for at least 12 months. Our findings underscore the limitations of the ChEI medications and the urgent need for effective and tolerable therapeutic options for patients having dementia. © 2008 Abughosh and Kogut, publisher and licensee Dove Medical Press Ltd

Costs of medical care of mesothelioma

Malignant mesothelioma is a rare and devastating form of cancer with an increasing economic burden. We sought to describe the direct cost burden of mesothelioma to the US health system. A systematic literature review was performed to locate published estimates of the medical cost of mesothelioma. In addition, we performed an analysis of hospital discharge data from the National Inpatient Sample, Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. We also reviewed publicly available legal settlements. We found that published estimates of the cost of medical care for mesothelioma are sparse, and differ with respect to nation, timeframe, and types of cost included. For the year 2014 in the United States, we estimated a mean cost per mesothelioma hospitalization of US$24,124 (95$20,819–US$28,983) and a total cost for hospital care of US$44,214,835. In conclusion, we found that reports describing the direct medical cost of care for mesothelioma in the United States are lacking, yet the per-patient cost of care is substantial, as evidenced by analyses of inpatient care and legal settlements

Impact of Depression Treatment on Health-Related Quality of Life Among Adults with Cancer and Depression: A Population-Level Analysis.

PURPOSE: Cancer diagnosis in adults is often accompanied by negative impacts, which increase the risk of depression thereby lowering health-related quality of life (HRQoL). We examined the association between depression treatment and HRQoL among US adults with cancer and depression. METHODS: Patients age 18 and above, with self-reported cancer and depression diagnoses were identified from Medical Expenditure Panel Survey database for 2006-2013. Baseline depression treatment was categorized as antidepressants only, psychotherapy with or without antidepressant use, and no reported use of antidepressants or psychotherapy. HRQoL was measured using SF-12 physical component summary (PCS) and mental component summary (MCS) scores. Adjusted ordinary least squares regressions estimated the association between type of depression treatment and HRQoL. RESULTS: Out of 450 (weighted per calendar year: 2.1 million) cancer adults included in the study, 51% received antidepressants only, while 16% received psychotherapy with or without antidepressants. In bivariate analyses, the mean MCS score was lowest among those who received psychotherapy with or without antidepressants compared to those receiving antidepressants only and those with no reported use of either modality, p \u3c 0.05. In multivariate analyses, there was no significant difference in HRQoL by type of depression treatment. CONCLUSION: Despite treatment for depression, HRQoL did not improve during the measurement timeframe. Quality of life is a priority health outcome in cancer treatment, yet our findings suggest that current clinical approaches to ameliorate depression in cancer patients appear to be suboptimal. IMPLICATIONS FOR CANCER SURVIVORS: Adults with cancer and comorbid depression should receive appropriate depression care in order to improve their HRQoL

Prescribing of Antipsychotic Medication in a Medicaid Population: Use of Polytherapy and Off-Label Dosages

OBJECTIVES: To describe the use of atypical antipsychotic medications in a Medicaid-enrolled population composed primarily of elderly and disabled patients. Our analyses focused upon the frequency of use of polytherapy with multiple antipsychotic medications and the prescribing of off-label dosages. METHODS: We conducted a cross-sectional retrospective analysis of oral antipsychotic medication use, as prescribed for this population in 2003. The unit of analysis was the patient. We determined the prevalence of use of each type of antipsychotic medication according to gender and age group and determined the extent of use of combination therapies with multiple oral antipsychotic medications. Using the dosage ranges described in the product labeling, we identified the percentage of patients prescribed in-range dosages, overall and for each atypical antipsychotic medication studied. Those identified as receiving out-of-range (off-label) dosages were further stratified by gender and age group. The statistical significance of differences between these proportions was assessed using the chi-square test. RESULTS: Of the 8,616 patients meeting our inclusion criteria, 7,748 (90%) received monotherapy with an oral antipsychotic medication and 868 patients (10%) received polytherapy with multiple oral antipsychotic medications. Approximately 2 of 3 patients receiving atypical antipsychotic medications were prescribed a dosage that was within the range recommended in the product labeling. Dosages lower than recommended in the product labeling were prescribed for 27% of patients receiving atypical antipsychotics, while 6% of patients received an above-range dosage. The frequency of patients receiving in-range dosages varied substantially among medications. Younger patients and male patients were more frequently prescribed above-range dosages while older patients and female patients were more frequently prescribed below-range dosages of these medications (P less than 0.001 for both findings). CONCLUSION: In this subpopulation of Medicaid enrollees who were prescribed antipsychotic medications, we found a 10% incidence of use of antipsychotic polytherapy and a 33% incidence of prescribing of dosages outside the range listed in the product labeling. These findings suggest that physicians commonly prescribe antipsychotic medications in a manner that differs from the recommendations described in the prescribing information. The off-label use of atypical antipsychotic medications raises important questions regarding the purpose and applicability of the product labeling and the role and ability of the pharmacist to provide information regarding the risks and benefits of therapy as commonly prescribed

The Influence of US Drug Price Dynamics on Cost-Effectiveness Analyses of Biologics

Objectives: This study aimed to evaluate the influence of drug price dynamics in cost-effectiveness analyses. Methods: We evaluated scenarios involving typical US drug price increases during the exclusivity period and price decreases after the loss of exclusivity (LOE). Worked examples are presented using the Institute for Clinical and Economic Review’s assessments of tezepelumab for the treatment of severe asthma and targeted immune modulators for rheumatoid arthritis. Results: Tezepelumab case: yearly 2% price increases during the period of exclusivity and a post-LOE price decrease of 25% yielded an incremental cost per quality-adjusted life-year (QALY) gained that increased over the base case from $430 300 to$444 600 (+3.2%). Yearly 2% price increases followed by a steeper post-LOE price reduction of 40% resulted in a cost per QALY gained of $401 400 (6.8$121 000 and $122 300, respectively (\u3c 3$119 200/QALY). Including a 2% yearly price increase during the projected exclusivity periods of both intervention and comparator increased the cost per QALY gained by \u3e 60%. Conclusion: Two biologic treatment cases incorporating price dynamics in cost-effectiveness analyses had varied impacts on the cost-effectiveness ratio depending on the magnitude of pre-LOE price increase and post-LOE price decrease and whether the LOE also affected the comparator. Yearly price increase magnitude during the period of exclusivity, among other factors, may counterbalance the effects of lower post-LOE intervention prices

Evaluation of a Program to Improve Diabetes Care Through Intensified Care Management Activities and Diabetes Medication Copayment Reduction

BACKGROUND: Medication copayment reduction can be integrated with disease management programs to incentivize patient engagement in chroniccare management. While disease management programs in diabetes havebeen evaluated across a range of settings and designs, less is knownregarding the effectiveness of copayment reduction as a component ofdisease management. OBJECTIVE: To evaluate the short-term results of a diabetes-focused disease management program that included copayment reduction, care coordination, and patient goal setting, focusing on rates of evidence-based care processes and all-cause pharmacy and health care costs. METHODS: Blue Cross & Blue Shield of Rhode Island offered large employer groups the opportunity to participate in a diabetes disease management initiative that featured reduced copayments (from $7/$25/$40 for generic, tier 2, and tier 3 drugs, respectively, to$ 0 for generic and $0-$2 for brand drugs) for diabetes-related medications. In return for the copayment reduction, participants agreed to the following: (a) participate in care coordination with a case manager, (b) have an annual physical examination, (c) have a hemoglobin A1c blood test at least twice annually, and (d) have a low-density lipoprotein cholesterol (LDL-C) test at least once annually. Patients received personalized support provided by a registered nurse and dietician, disease-related education provided by nurses, and intensified case management services, including working with a health coach to establish healthy behavioral change goals. All study subjects were aged 18 years or older and had at least 1 ICD-9-CM code for diabetes and at least 1 claim for an antidiabetic drug during a 12-month measurement period, which was each subject’s most recent 12-month period of continuous enrollment from January 1, 2008, through May 31, 2010. Administrative claims data were used to determine the percentage of intervention (participating) and nonintervention (nonparticipating) subjects from among all of the plan’s employer groups who received at least once-yearly monitoring of A1c, high-density lipoprotein cholesterol (HDL-C), and LDL-C; medical attention (or drug therapy) for nephropathy; and an eye examination. We conducted multivariate logistic regression analyses to assess the effect of the intervention and other patient characteristics and comorbidities on rates of performance of these care processes, aggregating the 5 processes of care into an “all or none” single composite outcome. We also developed a propensity score-weighted model to attempt to adjust for differences between the intervention and nonintervention groups resulting from the nonrandomized study design. Additionally, we quantified average plan payments to providers less patient copayments (i.e., net plan cost) per patient per year (PPPY) for the 12-month follow-up period and compared these costs for the intervention versus nonintervention groups. RESULTS: The study sample consisted of 9,698 patients with diabetes; 649 (6.7%) of whom participated in the intervention. 9,049 (93.3%) patients were identified by the insurer as patients with diabetes receiving usual care. Patients in the intervention and nonintervention groups were similarly likely to have all 5 recommended processes of care performed (40.1% vs. 38.9%, respectively, P = 0.543). Younger patients received all 5 recommended care processes less frequently than older patients (30.5%, 38.0%, and 47.0% for ages 18-48 years, 49-59 years, and 60 years or older, respectively, P \u3c 0.001); in adjusted analyses, patients aged 60 years or older were approximately twice as likely to receive all 5 care processes compared with patients aged 18-48 years (odds ratio [OR] = 1.97, 95% CI = 1.75-2.21). Users of oral antidiabetic monotherapy were least likely to have these processes of care performed compared with users of multiple oral therapies (OR = 1.23, 95% CI = 1.11-1.36) and insulin (OR = 1.59, 95% CI = 1.41-1.78). PPPY prescription drug costs incurred by the plan were greater for intervention than comparison patients (means [SDs] of $3,139 [$3,426] vs. $2,854 [$3,938], respectively, P \u3c 0.001); and the generic-dispensing ratio was slightly lower (means [SDs] of 62.1% [22.4%] and 65.4% [23.0%], respectively, P \u3c 0.001). There were no significant differences between the intervention and comparison groups in mean [SD] PPPY all-cause medical care costs ($7,475 [$17,601] vs. $8,577 [$22,972], respectively, P = 0.213) or total all-cause costs ($10,613 [$18,590] vs. $11,431 [$24,060], P = 0.666). CONCLUSIONS: Patients participating in this incentive program featuring diabetes medication copayment reduction and disease management components did not receive recommended care any more or less frequently than other enrolled members with diabetes. Younger patients and those utilizing oral antidiabetic monotherapy as their drug regimens were less likely to have the recommended processes of care performed. While prescription drug expenditures incurred by the plan were greater for intervention patients, between-group differences in total costs for medications and all-cause medical care were not statistically significant. Further follow-up is required to determine the success of this program over the longer term in promoting quality of care and achieving cost reductions and improved health outcomes

In utero and childhood polybrominated diphenyl ether (PBDE) exposures and neurodevelopment in the CHAMACOS study.

BackgroundCalifornia children's exposures to polybrominated diphenyl ether flame retardants (PBDEs) are among the highest worldwide. PBDEs are known endocrine disruptors and neurotoxicants in animals.ObjectiveHere we investigate the relation of in utero and child PBDE exposure to neurobehavioral development among participants in CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas), a California birth cohort.MethodsWe measured PBDEs in maternal prenatal and child serum samples and examined the association of PBDE concentrations with children's attention, motor functioning, and cognition at 5 (n = 310) and 7 years of age (n = 323).ResultsMaternal prenatal PBDE concentrations were associated with impaired attention as measured by a continuous performance task at 5 years and maternal report at 5 and 7 years of age, with poorer fine motor coordination-particularly in the nondominant-at both age points, and with decrements in Verbal and Full-Scale IQ at 7 years. PBDE concentrations in children 7 years of age were significantly or marginally associated with concurrent teacher reports of attention problems and decrements in Processing Speed, Perceptual Reasoning, Verbal Comprehension, and Full-Scale IQ. These associations were not altered by adjustment for birth weight, gestational age, or maternal thyroid hormone levels.ConclusionsBoth prenatal and childhood PBDE exposures were associated with poorer attention, fine motor coordination, and cognition in the CHAMACOS cohort of school-age children. This study, the largest to date, contributes to growing evidence suggesting that PBDEs have adverse impacts on child neurobehavioral development

Hepatotoxicity reports in the FDA adverse event reporting system database: A comparison of drugs that cause injury via mitochondrial or other mechanisms

Drug-induced liver injury (DILI) is a leading reason for preclinical safety attrition and post-market drug withdrawals. Drug-induced mitochondrial toxicity has been shown to play an essential role in various forms of DILI, especially in idiosyncratic liver injury. This study examined liver injury reports submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) for drugs associated with hepatotoxicity via mitochondrial mechanisms compared with non-mitochondrial mechanisms of toxicity. The frequency of hepatotoxicity was determined at a group level and individual drug level. A reporting odds ratio (ROR) was calculated as the measure of effect. Between the two DILI groups, reports for DILI involving mitochondrial mechanisms of toxicity had a 1.43 (95% CI 1.42–1.45; P \u3c 0.0001) times higher odds compared to drugs associated with non-mitochondrial mechanisms of toxicity. Antineoplastic, antiviral, analgesic, antibiotic, and antimycobacterial drugs were the top 5 drug classes with the highest ROR values. Although the top 20 drugs with the highest ROR values included drugs with both mitochondrial and non-mitochondrial injury mechanisms, the top 4 drugs (ROR values \u3e18: benzbromarone, troglitazone, isoniazid, rifampin) were associated with mitochondrial mechanisms of toxicity. The major demographic influence for DILI risk was also examined. There was a higher mean patient age among reports for drugs that were associated with mitochondrial mechanisms of toxicity [56.1 ± 18.33 (SD)] compared to non-mitochondrial mechanisms [48 ± 19.53 (SD)] (P \u3c 0.0001), suggesting that age may play a role in susceptibility to DILI via mitochondrial mechanisms of toxicity. Univariate logistic regression analysis showed that reports of liver injury were 2.2 (odds ratio: 2.2, 95% CI 2.12–2.26) times more likely to be associated with older patient age, as compared with reports involving patients less than 65 years of age. Compared to males, female patients were 37% less likely (odds ratio: 0.63, 95% CI 0.61–0.64) to be subjects of liver injury reports for drugs associated with mitochondrial toxicity mechanisms. Given the higher proportion of severe liver injury reports among drugs associated with mitochondrial mechanisms of toxicity, it is essential to understand if a drug causes mitochondrial toxicity during preclinical drug development when drug design alternatives, more clinically relevant animal models, and better clinical biomarkers may provide a better translation of drug-induced mitochondrial toxicity risk assessment from animals to humans. Our findings from this study align with mitochondrial mechanisms of toxicity being an important cause of DILI, and this should be further investigated in real-world studies with robust designs