Lessons learned from a multi-data source research collaboration: The mirabegron post-authorization safety study program.

BACKGROUND: Many factors contribute to developing and conducting a successful multi-data source, non-interventional, post-authorization safety study (NI-PASS) for submission to multiple health authorities. Such studies are often large undertakings; evaluating and sharing lessons learned can provide useful insights to others considering similar studies. OBJECTIVES: We discuss challenges and key methodological and organizational factors that led to the delivery of a successful post-marketing requirement (PMR)/PASS program investigating the risk of cardiovascular and cancer events among users of mirabegron, an oral medication for the treatment of overactive bladder. RESULTS: We provide context and share learnings, including sections on research program collaboration, scientific transparency, organizational approach, mitigation of uncertainty around potential delays, validity of study outcomes, selection of data sources and optimizing patient numbers, choice of comparator groups and enhancing precision of estimates of associations, potential confounding and generalizability of study findings, and interpretation of results. CONCLUSIONS: This large PMR/PASS program was a long-term commitment from all parties and benefited from an effective coordinating center and extensive scientific interactions across research partners, scientific advisory board, study sponsor, and health authorities, and delivered useful learnings related to the design and organization of multi-data source NI-PASS.

Anticholinergic exposure and its association with dementia/Alzheimer's disease and mortality in older adults.

BACKGROUND: Use of anticholinergic (ACH) medications is associated with increased risk of cognitive decline in the elderly. However, little is known about this association from a health plan perspective. METHODS: This retrospective cohort study used the Humana Research Database to identify individuals with at least one ACH medication dispensed in 2015. Patients were followed until incidence of dementia/Alzheimer's disease, death, disenrollment or end of December 2019. Multivariate Cox regression models were used to assess the association between ACH exposure and study outcomes, adjusting for demographics and clinical characteristics. RESULTS: A total of 12,209 individuals with no prior ACH use or dementia/Alzheimer's disease diagnosis were included. As ACH polypharmacy increased (i.e., from no ACH exposure, to one, two, three, and four or more ACH medications), there was a stair-step increase in the incidence rate of dementia/Alzheimer's disease (15, 30, 46, 56 and 77 per 1,000 person-years of follow-up) and in the incidence of mortality (19, 37, 80, 115 and 159 per 1,000 person-years of follow-up). After adjusting for confounders, ACH exposure to one, two, three and four or more ACH medications was associated with a 1.6 (95% CI 1.4-1.9), 2.1 (95% CI 1.7-2.8), 2.6 (95% CI 1.5-4.4), and 2.6 (95% CI 1.1-6.3) times, respectively, increased risk of a dementia/Alzheimer's disease diagnosis compared to periods of no ACH exposure. ACH exposure to one, two, three and four or more medications was associated with a 1.4 (95% CI 1.2-1.6), 2.6 (95% CI 2.1-3.3), 3.8 (95% CI 2.6-5.4), and 3.4 (95% CI 1.8-6.4) times, respectively, increased risk of mortality compared to periods of no ACH exposure. CONCLUSIONS: Reducing ACH exposure may potentially minimize long-term adverse effects in older adults. Results suggest populations which may benefit from targeted interventions to reduce ACH polypharmacy.

Heart Failure Among Patients with Multiple Myeloma Treated with Carfilzomib-Based Versus Non-Carfilzomib-Based Regimens in the United States by Race.

BACKGROUND: Carfilzomib treatment for multiple myeloma (MM) can increase heart failure risk. Whether this risk differs by race is unknown. PATIENTS AND METHODS: We sought to estimate the incidence rates (IRs) of heart failure hospitalization among mostly 65-years-and-older US patients with MM by race treated with carfilzomib- and non-carfilzomib-based regimens in the real-world using Centers for Medicare & Medicaid Services Medicare Fee-for-Service data, Optum Clinformatics Data Mart, and Humana Research Database. The risk of heart failure hospitalization associated with a carfilzomib-based regimen was evaluated using propensity score matching among Black and White patients receiving second or later lines of therapy. RESULTS: Most patient-episodes (88%) were in persons 65 years or older for the 3 cohorts combined. The IR (95% CI) of heart failure hospitalization was higher for patient-episodes treated with a carfilzomib-based regimen than those with a non-carfilzomib-based regimen for both White (14.5 [12.2-17.0] vs. 10.7 [10.3-11.2] events per person-years) and Black patients (15.8 [10.1-23.5] vs. 12.1 [10.9-13.4] events per person-years) in the Medicare cohort. After propensity score matching, the hazard ratio (95% CI) of increased heart failure hospitalization comparing carfilzomib-based to non-carfilzomib-based regimens for White patients (1.6 [1.3-2.0]) was similar to that of Black patients (1.7 [1.0-2.9]) in the Medicare Database, and in the Humana Database (1.4 [0.8-2.6] and 1.2 [0.4-3.5], respectively). CONCLUSION: Although the IR of heart failure among patients with MM treated with a carfilzomib-based regimen was slightly higher, no evidence suggested the relative risk was different between White and Black patients with MM.

Real-world treatment, clinical outcomes and healthcare resource utilization among persons with hemophilia A by age.

Aim: Examine real-world characteristics, treatment patterns, and outcomes among treated persons with hemophilia A (PwHA) stratified by age. Patients & methods: This study utilized US claims data from 1 January 2007-31 July 2018 from the Humana Research Database. Unadjusted comparisons were conducted across PwHA (<18, 18-55, 56-89 years) enrolled in commercial or Medicare Advantage Prescription Drug plans. Results: A total of 294 PwHA were identified; 21.1% experienced ≥1 bleeding event, and 41.2 and 53.1% had evidence of arthropathy or related disorders, and pain, respectively. Along with all-cause and hemophilia-related healthcare resource utilization (HCRU), these were highest among PwHA aged 56-89 years. Conclusion: Insights into treatment, outcomes and HCRU may identify opportunities for enhanced disease management, particularly in older PwHA.

Cardiovascular Risk in Users of Mirabegron Compared with Users of Antimuscarinic Treatments for Overactive Bladder: Findings from a Non-Interventional, Multinational, Cohort Study.

INTRODUCTION: During clinical trials, mirabegron, a ß3-adrenoreceptor agonist, was associated with increased vital signs vs placebo in patients with overactive bladder. OBJECTIVE: The purpose of this study was to compare incidence rates of adverse cardiovascular (CV) outcomes following mirabegron or antimuscarinic use. METHODS: We conducted an observational post-marketing safety study utilising real-world data. The study population was identified within five sources: Danish and Swedish National Registers, Clinical Practice Research Datalink (UK), Optum (USA) and Humana (USA). Episodes of time when patients were new users of mirabegron or antimuscarinics (October 2012-December 2018) were sourced from prescriptions and matched on propensity scores. Occurrences of major adverse cardiovascular events (MACE), acute myocardial infarction (AMI), stroke, CV mortality and all-cause mortality were identified. Outcome incidence rates and hazard ratios from Cox models were estimated. RESULTS: Overall, 152,026 mirabegron and 152,026 antimuscarinic episodes were matched. The population consisted of 63.1% women and 72.6% were ≥ 65 years old. There were no appreciable differences in the incidence rates of MACE, AMI or stroke between users of mirabegron and antimuscarinics. Incidence rates of CV mortality (hazard ratio 0.83, 95% confidence interval 0.73-0.95) and all-cause mortality (hazard ratio 0.80, 95% confidence interval 0.76-0.84) were no higher with mirabegron vs antimuscarinics. Results restricted to episodes at high risk for CV events or stratified by age (< 65 years, ≥ 65 years) or prior overactive bladder medication use were consistent with overall findings. CONCLUSIONS: This large, multinational study found no higher risk of MACE, AMI, stroke, CV mortality or all-cause mortality among users of mirabegron relative to users of antimuscarinics.

During clinical trials, mirabegron, which is a treatment for overactive bladder, was associated with small increases in heart rate and blood pressure. This study was conducted to compare the frequency of cardiac events following the use of mirabegron or antimuscarinics, a group of treatments also used to treat overactive bladder. We obtained the data for this study from four countries: Denmark, Sweden, the UK and the USA. We identified people who were new users of mirabegron or antimuscarinics from 2012 to 2018 using prescription or dispensing records. Occurrences of major cardiac events, heart attack, stroke, death due to cardiac events and death from any cause were evaluated. Overall, we identified 152,026 times when mirabegron or antimuscarinics were each used as new treatments. Most of the people in the study were women (63.1%) and at least 65 years old (72.6%). There were no notable differences between the treatment groups with regard to how often major cardiac events, heart attack or stroke occurred. Further, death due to cardiac events and death from any cause were no higher with mirabegron compared with antimuscarinics. We obtained similar results when the data were assessed for patients who were at high risk for cardiac events or split by age (less than 65 years or at least 65 years) or a history of overactive bladder medication use. In conclusion, this large study involving data from several countries found no higher risk of major cardiac events, heart attack, stroke or death among people prescribed mirabegron compared with antimuscarinics.

Novel Approach Using Administrative Claims to Evaluate Trends in Oncology Multigene Panel Testing for Patients Enrolled in Medicare Advantage Health Plans.

PURPOSE: To develop an approach to identify and evaluate recent use of multigene panel testing over time. METHODS: We conducted a retrospective database analysis using medical and pharmacy claims data. Medicare Advantage Prescription Drug Plan members diagnosed with select malignant solid tumors were identified. The pattern of somatic genetic testing for each patient was evaluated from January 2016 through December 2018. Tests were classified by the number of genes tested in the panel: < 50 (small or medium) and ≥ 50 (large). RESULTS: An initial feasibility study using our novel approach for identifying panel tests resulted in 2.4 and 1.2 times more large and medium panels, respectively, identified compared with using procedure codes alone. A total of 121,675 eligible patients were identified, with 131,915 unique cancer cases. Overall, 5,457 (4.5%) patients received any panel test from 2016 to 2018. We found the number of tests performed each quarter increased from 238 in Q1 of 2016 to 755 in Q4 of 2018. The highest number of cases were genitourinary cancers; however, the highest proportion of cancer-related genetic testing was among patients with respiratory cancer. Across all tumor types, the proportion of large-panel tests performed as a function of all multigene panel tests increased from 20.7% of tests in Q1 of 2016 to 46.4% of tests in Q4 of 2018. The three cancer categories with the highest count of cancer-related panel tests, respiratory cancer, GI cancer, and female reproductive cancer, had a consistently greater proportion receiving a panel test at any point postindex. CONCLUSION: Across a variety of cancers, use of somatic, large-panel cancer-related genetic testing, as a proportion of all somatic cancer-related genetic testing, increased from 2016 to 2018, although testing overall was low.

Removal of prior authorization for medication-assisted treatment: impact on opioid use and policy implications in a Medicare Advantage population.

BACKGROUND: More than 30% of Medicare beneficiaries and 40% of patients dually eligible for Medicare and Medicaid use opioids. With an estimated 8%-12% of patients developing an opioid use disorder (OUD) after initiating opioids, opioid misuse is a significant public health challenge, especially among high-risk Medicare populations. Medication-assisted treatment (MAT) is the use of medications for the treatment of OUD and to prevent relapse to opioid use. MAT is the most effective treatment for OUD. There are a variety of barriers to MAT therapy that may delay access to treatment. OBJECTIVE: To study the impact of the removal of prior authorization requirements for MAT medications on MAT utilization, opioid utilization, and clinical outcomes, including emergency department visits, inpatient admission, relapse rates, behavioral health services, and nonopioid pain medication utilization, among opioid-using individuals with Medicare Advantage Prescription Drug (MAPD) coverage. METHODS: This retrospective, cross-sectional study used administrative medical, pharmacy, and enrollment data to identify chronic opioid users and a subset cohort initiating MAT use in 2017, when prior authorization requirements were in effect, and 2018 after removal of prior authorization requirements. Opioid and MAT utilization and clinical outcomes from emergency department visits were also examined before and after prior authorization requirements. A logistic regression analysis was conducted to examine the impact of the policy change on relapse rates, comparing relapse rates in 2017 and 2018, after controlling for potentially confounding demographic and clinical factors. RESULTS: This policy change was followed by a decrease in opioid utilization, an increase in MAT initiation, and a 4% decline in relapse rates. Patients initiating MAT after removal of prior authorizations had a 19% decrease in likelihood of relapse, and those with an OUD diagnosis were 47% less likely to relapse. The majority of MAT recipients were aged younger than 65 years, had a mental or behavioral health disorder diagnosis, and initially used relatively low doses (< 90 MME) of prescription opioids. There were no statistically significant differences in the use of behavioral health services or the use of nonopioid medications from 2017 to 2018. CONCLUSIONS: Utilization management policies should ensure appropriate MAT use, while minimizing impediments to access. Providing patients with evidence-based therapy effective for the treatment of OUD is essential to patient recovery and combating the consequences of the opioid epidemic. Further strides are needed to eliminate additional obstacles to OUD care. DISCLOSURES: No outside funding supported this study. All authors are or were employees of Humana, Inc., at the time of the study and have no other potential conflicts of interest to disclose.

A study of cancer occurrence in users of mirabegron and antimuscarinic treatments for overactive bladder.

OBJECTIVE: This post-authorization safety study (EU PAS Register Number: EUPAS16088) was designed to compare the incidence of cancer outcomes in patients treated with mirabegron versus antimuscarinic medications. METHODS: Cohorts of mirabegron initiators during 2012-2018 were propensity-score matched to antimuscarinic medication initiators within real-world data sources (Danish National Registers, Swedish National Registers, Clinical Practice Research Datalink [UK], Optum [US], and Humana [US]). Incident cancer cases were identified during follow-up from direct linkage to cancer registers or validated through medical record review or through physician questionnaires. Comparisons of sex-specific composite cancer outcomes (cancer of the lung/bronchus, colon/rectum, melanoma of skin, urinary bladder, non-Hodgkin lymphoma, kidney/renal pelvis, pancreas, prostate in men and breast and uterus in women) were made overall and for person-time in the first year and after the first year following start of treatment, for all ages and for the subgroup ≥65 years. RESULTS: Among the 80,637 mirabegron initiators matched to 169,885 antimuscarinic medication initiators, 68% were at least 65 years of age and 66% were women. Over 5000 incident cancer cases were observed overall. Incidence rates were higher for men than women for composite and individual cancer outcomes. The pooled fixed effects hazard ratios for composite cancer outcomes (all ages) were 1.05 (95% confidence interval [CI]: 0.98-1.14) for women and 1.06 (95% CI: 0.98-1.14) for men. Results were similar in persons ≥65 years. CONCLUSIONS: The results suggest no association between mirabegron use and risk of cancer, compared with antimuscarinic medications, in either men or women. Registration: EU PAS Register Number: EUPAS16088.

An Evaluation of Longitudinal Measures of Anticholinergic Exposure for Application in Retrospective Administrative Data Analyses.

INTRODUCTION: As continuous exposure to anticholinergics has been associated with adverse outcomes, accurately measuring exposure is important. However, no gold standard measure is available, and the performance of existing measures has not been compared. Our objective was to compare the properties of the Cumulative Anticholinergic Burden (CAB) measure against two existing measures of anticholinergic exposure and to assess their compatibility for use in observational studies based on claims data. METHODS: The average daily dose, cumulative dose and CAB measures were evaluated on: the applicability for use with anticholinergic burden scales, the ability to consider duration and/or accumulation of exposure, and consideration of anticholinergic dose, potency, and residual effect. To calculate each measure empirically, Truven MarketScan claims data from 2012 to 2015 were analyzed. Cumulative anticholinergic exposure over 1-year post-enrollment was calculated for each measure using Anticholinergic Cognitive Burden scale scores. Median [interquartile range (IQR)] and ranges of measure scores, and Spearman's correlation coefficients between measures, were estimated. Due to the differing methods of calculation, the absolute values of each score cannot be compared. RESULTS: The properties of the different measures varied, with only the CAB considering both dose and theoretical potency. The cohort included 99,742 individuals (mean age = 73.1 years; 54.9% female). Among individuals prescribed anticholinergics (n = 55,969), 1-year median (IQR) scores based on average daily dose, cumulative dose and CAB measures were 0.9 (0.3-1.5), 16.9 (7.3-33.9) and 203 (68-500), respectively. Measures were highly inter-correlated (r2 = 0.74-0.83). CONCLUSIONS: Considering both potency and dose, the CAB may prove a more comprehensive measure of anticholinergic burden; however, additional research is necessary to demonstrate whether it has any association with relevant health-related outcomes. FUNDING: Astellas Pharma Global Development, Inc.

The Relationship Between Anticholinergic Exposure and Falls, Fractures, and Mortality in Patients with Overactive Bladder.

BACKGROUND: Understanding risk factors associated with falls is important for optimizing care and quality of life for older patients. OBJECTIVE: Our objective was to determine the relationship between anticholinergic exposure and falls, fractures, and all-cause mortality. METHODS: An observational retrospective cohort study was conducted using administrative claims data from 1 January 2007 to 30 September 2015. Individuals aged 65-89 years newly diagnosed or treated for overactive bladder (OAB) were identified. Index date was the first OAB diagnosis or OAB medication prescription claim. Follow-up began on the index date and continued until death, disenrollment, or end of study period. The Anticholinergic Cognitive Burden (ACB) scale was used to define and quantify daily anticholinergic exposure and intensity. The primary study outcome was a combined endpoint of falls or fractures. All-cause mortality was a secondary endpoint. RESULTS: There were 113,311 patients with mean age of 74.8 ± standard deviation (SD) 6.2 years included. Current anticholinergic exposure was associated with a 1.28-fold increased hazard of a fall/fracture (95% confidence interval [CI] 1.23-1.32) compared with unexposed person-time, and past exposure was associated with a 1.14-fold increased hazard of a fall/fracture (95% CI 1.12-1.17). Compared with unexposed person-time, low-, moderate-, and high-intensity anticholinergic exposure was associated with a 1.04-fold (95% CI 1.00-1.07), 1.13-fold (95% CI 1.09-1.17), and 1.31-fold (95% CI 1.26-1.36) increased hazard of falls/fractures, respectively. A similar pattern was observed for all-cause mortality. CONCLUSIONS: Anticholinergic exposure is associated with an increased risk of falls or fractures in older patients and is an important consideration when evaluating treatment options for such patients with OAB.

Impact of Coexisting Overactive Bladder in Medicare Patients With Dementia on Clinical and Economic Outcomes.

BACKGROUND: Patients with dementia commonly suffer from symptoms of overactive bladder (OAB); however, limited research exists on the clinical impact of coexisting OAB among patients with dementia. As such, the objective of this study was to examine the impact of OAB on clinical outcomes, health-care resource use, and associated costs among patients with dementia. METHODS: We conducted a retrospective cohort analysis of patients with dementia using 3861 matched pairs of patients with and without OAB. Analyses were based on administrative claims data from January 1, 2007, to September 30, 2015, and compared clinical outcomes, health services use, and associated costs. RESULTS: Patients with dementia and OAB were more likely than those without OAB to have least one fall (incidence rate ratio [IRR]: 1.43, 95% confidence interval [CI], 1.22-1.68, P < .001), fracture (IRR: 1.23, 95% CI, 1.05-1.44, P = .008), combined fall/fracture (IRR: 1.25, 95% CI, 1.11-1.42, P < .001), or urinary tract infection (IRR: 2.75, 95% CI, 2.55-2.96, P < .001). Patients with dementia and OAB demonstrated greater utilization of all-cause encounter types compared to similar patients without coexisting OAB (P < .01). All-cause and dementia-related total health-care costs were approximately 23% (95% CI, 0.19-0.28, P < .001) and 13% (95% CI, 0.05-0.20, P = .001), respectively, greater than similar patients without coexisting OAB. CONCLUSION: Coexisting OAB was associated with impacts on clinical outcomes, health-care resource utilization, and costs in patients with dementia.

Healthcare utilization and costs with fixed-source versus variable-source tacrolimus in patients receiving a kidney transplant.

AIMS: Switching drug manufacturers in transplant patients may require an increased intensity of therapeutic monitoring, leading to additional healthcare visits, associated laboratory tests, and perhaps hospitalizations. As real-world studies examining the interchangeability of tacrolimus from different manufacturers are limited, the purpose of this study was to examine the healthcare resource utilization (HRU) and economic impact of tacrolimus-switching in kidney transplantation. MATERIALS AND METHODS: This cross-sectional, retrospective study examined HRU and healthcare costs (HCCs) among patients with a kidney transplant who were prescribed tacrolimus from fixed-source (FS) vs variable-source (VS) manufacturers using claims data from the large US health plan Humana from October 1, 2012, to December 31, 2013. RESULTS: Overall, 1,024 patients were identified (FS: n = 674, 66%; VS: n = 350, 34%). The number of therapeutic drug monitoring (TDM) events for the VS group was 13% greater than for the FS group after controlling for demographics, comorbidity score, and number of medications (incidence rate ratio = 1.13, p = .033). Adjusted total HCCs were 9% lower for VS (US$28,054 vs US$30,823, p = .045). In the unadjusted analysis, VS had greater emergency department (ED) utilization (45% vs 35%, p < .002). In the VS group, the mean (standard deviation [SD]) number of days from manufacturer switch to first outpatient visit was 23.8 (33.6), and the number of days (SD) to first TDM event was 43.6 (56.2). LIMITATIONS: Study limitations include the lack of availability of many transplant-specific variables within the Humana database, potential errors/omissions in claims coding, and restriction of cross-sectional data examination to a 1-year period. CONCLUSIONS: VS patients had greater TDM and lower total HCCs. Further research is warranted to understand the drivers of ED use among the VS group, and to determine factors associated with delayed TDM after regimen modification. Opportunities may exist to improve the quality of care for patients receiving immunosuppressant treatment with tacrolimus.

Adherence and economic impact of paliperidone palmitate versus oral atypical antipsychotics in a Medicare population.

Aim: To compare adherence, healthcare utilization and costs among real world, Medicare-eligible patients with schizophrenia using long-acting injectable paliperidone palmitate (PP) versus oral atypical antipsychotics. Patients & methods: Historical cohort study used Medicare Advantage claims data. Inverse probability of treatment weighting was applied to adjust for baseline differences. 12-month adherence, healthcare utilization and costs were compared. Results: Patients using PP were more adherent (proportion of days covered ≥0.8; 48.1 vs 32.6%; p < 0.001), had lower odds of hospitalization (odds ratio [OR]: 0.81; 95% CI: 0.68-0.96) and lower medical costs ($11,095; 95% CI: $10,374-11,867 vs $15,551; 95% CI: $14,584-16,583), but higher pharmacy costs ($14,787; 95% CI: $14,117-15,488 vs $5781; 95% CI: $5530-6043). Conclusion: Compared with patients using oral atypical antipsychotics, PP had lower hospitalizations and medical costs with greater medication adherence accompanied by higher pharmacy costs.

Association of obesity with healthcare resource utilization and costs in a commercial population.

OBJECTIVE: To examine the association of obesity with healthcare resource utilization (HRU) and costs among commercially insured individuals. METHODS: This retrospective observational cohort study used administrative claims from 1 January 2007 to 1 December 2013. The ICD-9-CM status codes (V85 hierarchy) from 2008 to 2012 classified body mass index (BMI) into the World Health Organizations' BMI categories. The date of first observed BMI code was defined as the index date and continuous eligibility for one year pre- and post- index date was ensured. Post-index claims determined individuals' HRU and costs. Sampling weights developed using the entropy balance method and National Health and Nutrition Examination Survey data ensured representation of the US adult commercially insured population. Baseline characteristics were described across BMI classes and associations between BMI categories, and outcomes were examined using multivariable regression. RESULTS: The cohort included 9651 individuals with BMI V85 codes. After weighting, the BMI distribution was: normal (31.1%), overweight (33.4%), obese class I (22.0%), obese class II (8.1%) and obese class III (5.4%). Increasing BMI was associated with greater prevalence of cardiometabolic conditions, including hypertension, type 2 diabetes and metabolic syndrome. The use of antihypertensives, antihyperlipidemics, antidiabetics, analgesics and antidepressants rose with increasing BMI. Greater BMI level was associated with increased inpatient, emergency department and outpatient utilization, and higher total healthcare, medical and pharmacy costs. CONCLUSIONS: Increasing BMI was associated with higher prevalence of cardiometabolic conditions and higher HRU and costs. There is an urgent need to address the epidemic of obesity and its clinical and economic impacts.

A prospective study of elderly initiating mirabegron versus antimuscarinics: Patient reported outcomes from the Overactive Bladder Satisfaction Scales and other instruments.

AIMS: To understand differences in patient reported outcomes (PRO) between patients initiating mirabegron or an antimuscarinic using a validated PRO instrument, OAB-Satisfaction (OAB-S). METHODS: This prospective observational study used real-time prescription claims from Humana to identify Medicare patients initiating mirabegron or an antimuscarinic to participate in a series of three phone surveys over ninety days. RESULTS: A total of 1897 mirabegron and 2444 randomly selected antimuscarinic initiators were identified; 174 mirabegron and 193 antimuscarinic initiators completed all three surveys. Among responders, mirabegron initiators were slightly older (76 vs 75 years, P = 0.032), included more males (32% vs 23%, P = 0.044), more likely to have prior OAB treatment (21% vs 13%, P = 0.048), and had greater medication burden (number of unique medications: 10.0 vs 8.7, P = 0.014). There were no between-group differences at any time or on any OAB-S scale. There were significant within-group differences at follow-up compared to baseline for OAB-S scales: "impact on daily living," with improvement over the 90-day survey period for both mirabegron (P = 0.008) and antimuscarinic (P < 0.001); "interruption of day-to-day life," with improvement for both mirabegron (P < 0.001) and antimuscarinic (P < 0.001); and improvement in "OAB control" for mirabegron (P < 0.001) and antimuscarinic (P < 0.001). CONCLUSIONS: Mirabegron initiators tended to be older, had a greater number of unique medications and previously tried prescriptions to treat OAB; nonetheless, mirabegron, and antimuscarinic initiators reported similar trends in improvement in PROs over the first 90 days of treatment. Significant improvement in daily impact of OAB was observed after treatment initiation; however, no significant differences between groups were observed.

Impact of coexisting overactive bladder in Medicare patients with osteoporosis.

BACKGROUND: Osteoporosis and overactive bladder (OAB) are prevalent conditions in older adults and are independent risk factors for falls and fractures. A paucity of evidence exists examining the impact of coexisting OAB in patients with osteoporosis. OBJECTIVE: To examine the impact of OAB on healthcare resource utilization (HRU), clinical outcomes, and healthcare costs among older adult patients with osteoporosis. METHODS: This retrospective analysis compared patients with osteoporosis with and without OAB. Patients with an osteoporosis diagnosis, enrolled in a Medicare Advantage plan, and aged 65-89 inclusive were eligible. Incident OAB among patients with prevalent osteoporosis was identified. A comparison group of patients with osteoporosis but no evidence of OAB was propensity score matched on baseline characteristics. Fall and/or fracture outcomes, HRU and healthcare costs were evaluated during 12 months of follow-up. Bivariate comparisons of outcomes were conducted. Ordinary least squared regression was used to examine the relationship between OAB and total healthcare costs. RESULTS: After matching, 5,526 patients in each group were included. Patients with osteoporosis and OAB demonstrated greater all-cause HRU across all encounter types compared to patients without OAB (all P values<0.001). Patients with osteoporosis and OAB had a greater frequency of any fall/fracture (17.7% vs. 14.9%, P<0.001). Patients with osteoporosis and OAB had 35% greater all-cause total healthcare costs than patients without OAB (P<0.001). CONCLUSIONS: Patients with OAB and osteoporosis had significantly greater all-cause HRU and costs. Falls and fractures were significantly more common in patients with osteoporosis and OAB compared to patients with osteoporosis without OAB.

Association of obesity with healthcare utilization and costs in a Medicare population.

OBJECTIVES: To examine the association of obesity with healthcare resource utilization and costs in a Medicare population. METHODS: This study was a retrospective cohort study using Humana Medicare Advantage (MA) claims data. Body mass index (BMI) was assessed using ICD-9-CM status codes (V85 hierarchy) that have been validated in the data source to classify patients into BMI categories: normal (N), overweight (Ow), obese class I (ObI), obese class II (ObII), and obese class III (ObIII). Healthcare resource utilization (HRU) and costs were determined based on claims data. Descriptive statistics were used to examine baseline characteristics and HRU across BMI classes. Multivariable analysis was used to examine the association between BMI class and outcome measures. RESULTS: Among the 172,866 patients aged ≥65 years that were identified, BMI distribution was: N, 21%; Ow 37%; ObI, 24%, ObII, 10%; and ObIII, 9%. Inpatient, emergency department and outpatient utilization increased with greater BMI level, and greater BMI level was associated with higher total healthcare, medical and pharmacy costs. Greater prevalence of several cardiometabolic conditions, total medication use, and use of specific medication classes was observed with increasing BMI class. CONCLUSIONS: Greater BMI was associated with greater HRU and costs and observed increase in prevalence of cardiometabolic conditions. These results reflect an urgent need to address the epidemic of obesity and the resulting excessive clinical and economic burden on the healthcare system.

Predictors of all-cause 30 day readmission among Medicare patients with type 2 diabetes.

OBJECTIVE: Readmission is costly among patients with type 2 diabetes (T2DM) in Medicare Advantage Prescription Drug Plans; identifying high-risk patients is necessary for targeting reduction programs. The objective of this study was to develop a claims-based algorithm to predict all-cause 30 day readmission among patients with T2DM. METHODS: This study used administrative data from 1 January 2012 through 31 January 2014. The cohort included hospitalized T2DM patients, aged 18-90 with ≥12 months' continuous enrollment before an unplanned hospital admission and ≥1 month of enrollment post-discharge, excluding patients in long-term care >30 days pre-index. Multivariate logistic regression predicted the likelihood of readmission following hospitalization in 2013. The analytic file was randomly split into training and test datasets to build and validate the model. Candidate variables included physician and patient demographics, baseline clinical conditions, and healthcare utilization metrics. Clinical conditions were classified using the Healthcare Cost and Utilization Project clinical classification system for ICD-9-CM. RESULTS: Of 63,237 individuals, 17.1% experienced a readmission. Of nearly 200 candidate variables, 14 were predictors of readmission, including total cumulative number of days for inpatient stays and the number of emergency department visits in the baseline period. Male gender, older age, and certain comorbidities were associated with higher likelihood of readmission. The final model demonstrated good discriminant ability (c-statistic = 0.82). CONCLUSIONS: This study provided evidence that certain patient characteristics and healthcare utilization are predictive of readmission. An algorithm with good discriminant ability was developed which could be used to target readmission reduction programs. Physician gender, specialty, and ownership status did not appear to influence the likelihood of readmission.

Impact of 2015 Update to the Beers Criteria on Estimates of Prevalence and Costs Associated with Potentially Inappropriate Use of Antimuscarinics for Overactive Bladder.

BACKGROUND: Research has demonstrated that the use of potentially inappropriate medication (PIM) is highly prevalent among older individuals and may lead to increased healthcare costs, adverse drug reactions, hospitalizations, and mortality. OBJECTIVES: The purpose of this study was to examine the impact of the 2015 updates to the Beers Criteria on estimates of prevalence and cost associated with potentially inappropriate use of antimuscarinic medications indicated for treatment of overactive bladder (OAB). METHODS: A retrospective database analysis was conducted using a historical cohort design and including data collected between 2007 and 2013. Claims data were used to identify Medicare Advantage patients aged ≥65 years newly initiated on antimuscarinic OAB treatment. Patients were classified with potentially inappropriate use of antimuscarinic OAB drugs based on either the 2012 Beers Criteria or the 2015 Beers Criteria. Prevalence of PIM at the time of antimuscarinic initiation was determined. Bivariate comparisons of healthcare costs and medical condition burden were conducted to compare the marginal groups of patients (who qualified based on the 2012 Beers Criteria only or the 2015 Beers Criteria only). Differences in healthcare costs for patients with and without potentially inappropriate use of urinary antimuscarinics based on the 2012 and 2015 Beers Criteria were also examined. RESULTS: Of 66,275 patients, overall prevalence of potentially inappropriate use of OAB antimuscarinics was higher using 2015 Beers Criteria than when using the 2012 Beers Criteria (25.0 vs. 20.6%). Dementia was the most common PIM-qualifying condition under both versions. The 2015 Beers Criteria identified more females, more White people, and a younger population with PIM. Comorbid medical condition burden was lower using the 2015 Beers Criteria. The 2015 Beers Criteria only group had lower median unadjusted healthcare costs ($7104 vs. 8301; p < 0.001). The incremental net cost associated with potentially inappropriate use of antimuscarinic medication was higher under the 2012 Beers Criteria than under the 2015 Beers Criteria. CONCLUSIONS: In this cohort of patients newly initiated on antimuscarinic OAB treatment, substantial overlap of patients identified with PIM based on the 2015 Beers Criteria compared with the 2012 Beers Criteria was observed. In addition, the findings suggest that, when applied to antimuscarinic initiators, the 2015 Beers Criteria result in a greater prevalence of PIM and the identification of patients with less overall medical morbidity than the 2012 Beers Criteria.

A Historical Retrospective Analysis of the Impact of Diabetes Quality Measure Attainment on Outcomes in Medicare Advantage Members.

The objective of this study was to assess achievement of 4 diabetes mellitus (DM)-related quality measures (QMs) and examine the relationship between QM attainment, concurrent health care costs, and DM complications over 1 year by conducting a retrospective analysis of claims data for Medicare Advantage Prescription Drug plan members with DM. Claims and member-level quality data were used to assess QM achievement, concurrent health care costs, and presence of new or worsening DM complications during the QM year. Multivariable regression models were used to examine the relationship between QM achievement and outcome measures controlling for potentially confounding baseline characteristics. QM attainment rates ranged from 54.2% for DM Treatment measure to 83.4% for Cholesterol Screening measure. Odds of new or worsening complications were greater for members who did not meet the Blood Sugar Controlled performance goal (odds ratio [OR]: 1.12, P < 0.001), DM Treatment goal (OR: 1.40, P < 0.001), or Cholesterol Screening goal (OR: 1.32, P < 0.001). Failure to attain the DM Medication Adherence goal was associated with lower odds of new or worsening complications (OR: 0.94, P < 0.001). In the regression models, all-cause health care costs were greater for members who achieved the Blood Sugar Controlled quality goal (P < 0.001), but lower for members who attained DM Treatment (P < 0.001) and low-density lipoprotein Cholesterol Screening goals (P < 0.001). There was no statistically significant relationship between attaining the DM Medication Adherence measure and all-cause costs. Achievement rates for individual QMs varied across the study population and relationships between QM attainment, health care costs, and DM complications during the QM measurement year were mixed.