Assessment of women's treatment preferences for vasomotor symptoms due to menopause.

BACKGROUND: Several therapies for vasomotor symptoms (VMS) due to menopause are available. Treatment preferences and willingness-to-pay for VMS treatment among US women with VMS were evaluated. METHODS: An online survey of women with perimenopausal or postmenopausal VMS was conducted (3/15/21-4/23/21). A discrete choice experiment quantified the impact of 7 treatment attributes on VMS treatment choice: VMS frequency/severity reduction, sleep improvement, risk of breast cancer/cardiovascular events in 6 years, risk of short-term side effects, and out-of-pocket costs. Preference weights (PWs) with 95% confidence intervals (CIs) were estimated and reported. RESULTS: Among 467 women, 86.5% and 87.8% reported moderate to very severe VMS and sleep problems during the preceding month, respectively. Sleep improvement (PW: 0.843; 95% CI: 0.721, 0.965) and reduction in VMS frequency (PW: 0.658; 95% CI: 0.520, 0.796) and severity (PW: 0.628; 95% CI: 0.500, 0.756) most influenced treatment preference; risk of cardiovascular events (PW: 0.150; 95% CI: 0.069, 0.232) or breast cancer (PW: 0.401; 95% CI: 0.306, 0.496) in 6 years had lesser effect. Willingness-to-pay was an additional $35-$46/month for substantially improved sleep, 80% VMS frequency reduction, and reduction from severe to mild VMS. CONCLUSIONS: Sleep improvement and reductions in VMS frequency/severity were the most important treatment attributes.

Hormone and non-hormone treatments are available to reduce vasomotor symptoms (hot flashes and night sweats) due to menopause. We conducted an online survey of 467 women with moderate to very severe vasomotor symptoms during perimenopause or postmenopause to learn what treatment attributes are most important to women when selecting from among the available therapies and how much women were willing to pay for the attributes. Women were shown 14 cards, each with a side-by-side comparison of 2 treatments with varying descriptions of the following 7 treatment attributes: reduction in frequency of vasomotor symptoms, reduction in severity of vasomotor symptoms, improvement in sleep, risk of breast cancer in 6 years, risk of cardiovascular events in 6 years, risk of short-term side effects, and out-of-pocket costs. Women picked their preferred treatment on each card. Results showed that improvement in sleep was the most important attribute to women, and they were willing to pay an extra $46/month for a treatment that substantially improved sleep. The next most important attributes were reduction in frequency and reduction in severity of vasomotor symptoms. Women were willing to pay $36/month more for a treatment that reduced symptom frequency by 80% compared with one that reduced frequency by 50%, and they were willing to pay $35/month more for treatment that reduced symptoms from severe to mild compared with one that did not reduce symptom severity. These results may help guide development of new treatment options and may help physicians recommend treatments that best fit women's preferences.

Handling Missing Data in Health Economics and Outcomes Research (HEOR): A Systematic Review and Practical Recommendations.

BACKGROUND: Missing data in costs and/or health outcomes and in confounding variables can create bias in the inference of health economics and outcomes research studies, which in turn can lead to inappropriate policies. Most of the literature focuses on handling missing data in randomized controlled trials, which are not necessarily always the data used in health economics and outcomes research. OBJECTIVES: We aimed to provide an overview on missing data issues and how to address incomplete data and report the findings of a systematic literature review of methods used to deal with missing data in health economics and outcomes research studies that focused on cost, utility, and patient-reported outcomes. METHODS: A systematic search of papers published in English language until the end of the year 2020 was carried out in PubMed. Studies using statistical methods to handle missing data for analyses of cost, utility, or patient-reported outcome data were included, as were reviews and guidance papers on handling missing data for those outcomes. The data extraction was conducted with a focus on the context of the study, the type of missing data, and the methods used to tackle missing data. RESULTS: From 1433 identified records, 40 papers were included. Thirteen studies were economic evaluations. Thirty studies used multiple imputation with 17 studies using multiple imputation by chained equation, while 15 studies used a complete-case analysis. Seventeen studies addressed missing cost data and 23 studies dealt with missing outcome data. Eleven studies reported a single method while 20 studies used multiple methods to address missing data. CONCLUSIONS: Several health economics and outcomes research studies did not offer a justification of their approach of handling missing data and some used only a single method without a sensitivity analysis. This systematic literature review highlights the importance of considering the missingness mechanism and including sensitivity analyses when planning, analyzing, and reporting health economics and outcomes research studies.

Evaluating and understanding combination therapy decision drivers for the treatment of overactive bladder in the United States.

OBJECTIVE: To understand factors guiding overactive bladder (OAB) therapy selection and experience with combination therapy (antimuscarinics and beta-3 agonists). METHODS: Cross-sectional surveys of OAB patients and OAB-treating physicians in the USA were conducted. Patients receiving monotherapy with antimuscarinics were categorized by OAB treatment history: monotherapy only; third-line procedures (e.g., onabotulinumtoxinA injections) and combination therapy; third-line therapy only; and combination therapy only. The patient survey assessed therapy choice drivers and barriers, treatment satisfaction and sociodemographic/clinical characteristics. The physician survey assessed drivers of and barriers to OAB treatment choices. RESULTS: Of 200 patients, 86.5% reported involvement in treatment decision-making; doctor's recommendation was the most frequently considered factor (84.4%). Most patients (71%) were unaware of combination therapy. The primary reason why those patients aware of combination therapy had not used it (N = 43/200; 21%) was physician recommendation of other treatments (69.8%). For physicians (N = 50), the most frequently considered factors when prescribing OAB treatment were effectiveness (92.0%) and side effects (84.0%); 70% prescribed combination therapy, primarily for symptom severity (82.9%). The main reasons for not prescribing combination therapy were cost/insurance coverage (80%) and lack of information (53.3%). CONCLUSIONS: Shared decision-making guided treatment decisions; the main considerations were treatment safety and efficacy.

Clinical experience with regadenoson SPECT myocardial perfusion imaging: insights into patient characteristics, safety, and impact of results on clinical management.

The Henry Ford Hospital (HFH) regadenoson (REG) registry includes patients with a variety of comorbidities allowing for the evaluation of outcomes in a large, unselected population. Using a database of electronic medical records and nuclear cardiology reports, patients aged > 18 years who underwent REG-facilitated single-photon emission computed tomography (SPECT) testing at HFH between January 2009 and August 2012 were identified. The primary objective was to describe the clinical and demographic characteristics of patients who had undergone REG only vs REG WALK (REG + low-level exercise) SPECT. A total of 2104 patients were included in the analysis (mean age 65.3 years; 50% women; 51% African American, 43% Caucasian). For the REG only (n = 1318) and REG WALK (n = 786) cohorts, SPECT was abnormal in 37% of patients (REG only, 39%; REG WALK, 34%; P < 0.01). No differences in diagnostic modalities or interventions in 90 days after SPECT were observed. Immediate safety analysis showed no deaths 48 h after REG SPECT testing. Although they guide invasive therapy, abnormal scans do not automatically lead to invasive testing. This demonstrates the focus on initial medical management, which reflects the existing evidence of initial goal-directed medical management of stable coronary disease.

Evaluating the use of pharmacological stress agents during single-photon emission computed tomography myocardial perfusion imaging tests after inadequate exercise stress test.

BACKGROUND: Past clinical trial findings suggest that the availability of regadenoson in a nuclear imaging center may affect real-world center practices related to the transition of patients from an inadequate exercise stress test (EST) to a pharmacological stress agent (PSA). METHODS AND RESULTS: This was a cross-sectional study using one-on-one telephone interviews with nuclear imaging center staff to facilitate survey development, followed by an online survey to evaluate patterns and processes around use of PSAs during single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in patients with inadequate ESTs. Of the 50 participants, 35 (70%) used only regadenoson, 3 (6%) only adenosine, 3 (6%) regadenoson and adenosine, 7 (14%) regadenoson and dipyridamole, and 2 (4%) all 3 agents for converting patients from an inadequate EST to a PSA. Nearly all centers (94%) used protocols to guide conversions. Of 12 centers using > 1 PSA, 11 reported regadenoson to be the most preferred PSA. Total staff time required from PSA transition to post-test monitoring was shortest for regadenoson. CONCLUSIONS: Compared to adenosine and dipyridamole, regadenoson is preferred by nuclear imaging center staff and associated with operational efficiencies after inadequate EST in real-world practice SPECT-MPI.

Persistence with mirabegron or antimuscarinic treatment for overactive bladder syndrome: Findings from the PERSPECTIVE registry study.

OBJECTIVES: This analysis from the PERSPECTIVE (a Prospective, Non-interventional Registry Study of Patients Initiating a Course of Drug Therapy for Overactive Bladder) study evaluated treatment persistence with mirabegron or antimuscarinics over a 12-month period. METHODS: Participants were adults diagnosed with overactive bladder (OAB) by their health care provider (HCP), who were initiating mirabegron or antimuscarinic treatment. The HCP made all treatment decisions, and patients were followed for 12 months with no mandatory scheduled visits. Information requests were sent to patients at baseline and months 1, 3, 6, and 12. Patients were nonpersistent if they switched, discontinued, or added OAB medications/therapies to their initial treatment. Reasons for discontinuation and switching patterns were investigated. RESULTS: Overall, 1514 patients were included (613 mirabegron and 901 antimuscarinic initiators). Persistence rates decreased steadily over time in both groups. A low proportion of patients added or switched medication at each time point. Unadjusted Kaplan-Meier analysis showed similar persistence rates for both groups. When the data were adjusted for patient characteristics (age, sex, and OAB treatment status), mirabegron initiators had higher persistence rates. No significant differences were noted in unadjusted median time to end of persistence. However, end of treatment persistence by any cause was longer with mirabegron (median: 9.5 vs 6.7 months for antimuscarinics). HCPs stated that the most common reasons for nonpersistence were no symptomatic improvement and side effect aversion. CONCLUSIONS: Treatment persistence was longer for mirabegron compared with antimuscarinic initiators after controlling for patient characteristics. End of treatment persistence by any cause was also longer with mirabegron.

Mirabegron Vs Placebo Add-on Therapy in Men With Overactive Bladder Symptoms Receiving Tamsulosin for Underlying Benign Prostatic Hyperplasia: A Safety Analysis From the Randomized, Phase 4 PLUS Study.

OBJECTIVE: To analyze the safety of mirabegron add-on therapy in men with overactive bladder symptoms concurrently receiving tamsulosin for lower urinary tract symptoms associated with benign prostatic hyperplasia. METHODS: The Phase 4 PLUS study comprised a 4-week run-in period (tamsulosin [0.4 mg]) and a 12-week randomized treatment period (add-on treatment: mirabegron [25 mg] or placebo). Doses were increased to mirabegron 50 mg or matched placebo after 4 weeks. Safety assessments: treatment-emergent adverse events (TEAEs), vital signs, 12-lead electrocardiograms, and changes in postvoid residual volume and maximum urinary flow (Qmax). RESULTS: The safety analysis set included 352 tamsulosin plus mirabegron (TAM + MIRA) and 354 tamsulosin plus placebo (TAM + PL) patients. The frequency of overall TEAEs was higher with TAM + PL, although a higher incidence of drug-related TEAEs was observed with TAM + MIRA. Most TEAEs were mild or moderate in severity. Drug-related serious TEAEs were reported for 3 patients (2 TAM + MIRA patients: acute myocardial infarction with cerebral infarction and angina pectoris, 1 TAM + PL patient: lacunar stroke). Hypertension, headache, and nasopharyngitis were the most common TEAEs. Special interest TEAEs were infrequently reported. The most common was urinary retention and 2 TAM + MIRA patients required catheterization (neither led to discontinuation). No major changes in blood pressure or pulse rate were noted and similar electrocardiogram parameters were observed for both groups. Changes in mean postvoid residual volume and Qmax were not clinically meaningful. CONCLUSION: No unexpected safety concerns were noted in men receiving tamsulosin for lower urinary tract symptoms associated with benign prostatic hyperplasia who subsequently received mirabegron add-on therapy.

Factors that impact a patient's experience when undergoing single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in the US: A survey of patients, imaging center staff, and physicians.

BACKGROUND: Single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) is commonly used for coronary artery disease diagnosis/assessment in the United States (US); however, the factors that most significantly affect patients' experience when undergoing SPECT-MPI are not well known. METHODS: In this US-based cross-sectional study, an online questionnaire was used to identify and quantify attributes of the SPECT-MPI process that impact patients' experience, according to adults who underwent SPECT-MPI in the prior month, cardiac imaging center staff, and referring physicians. Participants were asked to rate the importance of 32 factors using an 11-point scale; congruence between groups (physicians vs patients, patients vs imaging center staff, and physicians vs imaging center staff) was assessed. RESULTS: The survey was completed by 101 patients, 101 center staff, and 100 physicians, who gave similar ratings for the highest-rated factors (high-quality results/decreasing likelihood of having to retest, highly skilled and knowledgeable staff, and compassionate and respectful staff). Congruence was higher between patients and imaging center staff compared with physicians and patients, and was notably low between imaging center staff and physicians. CONCLUSIONS: We identified areas for improvement in the patient SPECT-MPI experience that could translate into improved quality and value.

Comparative Safety and Efficacy of Treatments for Overactive Bladder Among Older Adults: A Network Meta-analysis.

BACKGROUND: Cumulative exposure to one or more anticholinergic medications ("anticholinergic burden") is associated with an increased risk of adverse outcomes, particularly among older individuals. Mirabegron, an oral selective ß3-adrenergic receptor agonist, has demonstrated efficacy in managing the symptoms of overactive bladder without contributing to anticholinergic burden. However, it is not known whether the favorable safety profile of mirabegron relative to antimuscarinics varies with increasing age among a patient population who may have a high anticholinergic burden. OBJECTIVE: The primary objective of this study was to indirectly compare the safety and efficacy profile of mirabegron relative to antimuscarinics in older adults with overactive bladder. METHODS: A systematic literature review was conducted to identify randomized controlled trials that reported safety and efficacy endpoints among patients aged ≥ 65 years. Identified randomized controlled trials were subsequently synthesized via a network meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines in designing, performing, and reporting the literature review were followed. In line with current best practices, the network meta-analysis was conducted using a Bayesian approach and according to the overall general guidance for evidence synthesis developed by the National Institute for Health and Care Excellence decision support unit. Estimates of relative safety were assessed via the odds ratio and estimates of relative efficacy were assessed via means and credible intervals. RESULTS: A total of 3078 abstracts, 300 of which underwent full-text screening, were identified using the search criteria. Twenty articles reporting on 21 randomized controlled trials were eligible for data extraction and synthesis. Following review, five safety and five efficacy endpoints were considered for inclusion in the network meta-analysis. Regarding findings typical of anticholinergic exposure in older adults, mirabegron was not associated with an increased odds of dry mouth (odds ratio 95% credible interval 0.76 [0.26-2.37]) or constipation (1.08 [0.39-3.02]) relative to placebo, whereas antimuscarinics were strongly associated with these events (odds ratio range 3.78-7.85 and 2.12-4.66, respectively). In this older population, mirabegron was associated with a similar odds of experiencing adverse event-related treatment discontinuations relative to placebo (0.99 [0.57-1.70]), while the odds of experiencing an adverse event-related treatment discontinuation for antimuscarinics had a range of 1.14-3.03 (in most cases, the association was mild). No increased odds of experiencing overall treatment-emergent adverse events was observed for mirabegron or antimuscarinics (odds ratio range 1.25-1.55), apart from fesoterodine (2.23 [1.37-3.37]). Finally, a similar treatment effect was observed across all efficacy endpoints between mirabegron and antimuscarinics in this older population. CONCLUSIONS: This study indicates that the safety and efficacy profile of mirabegron remains favorable compared with antimuscarinics among older adults. This includes safety outcomes typically associated with anticholinergic burden, which were less frequently observed in patients treated with mirabegron.

Safety and Tolerability Results from the PILLAR Study: A Phase IV, Double-Blind, Randomized, Placebo-Controlled Study of Mirabegron in Patients ≥ 65 years with Overactive Bladder-Wet.

BACKGROUND: In older patients with overactive bladder (OAB), mirabegron, a ß3-adrenoreceptor agonist, represents an alternative treatment that may have a favorable risk-benefit profile. OBJECTIVES: Our objective was to further examine the safety and tolerability of mirabegron versus placebo treatment in patients aged ≥ 65 years with OAB-wet. METHODS: We conducted a 12-week, double-blind, randomized, placebo-controlled phase IV study to compare mirabegron with placebo. Community-dwelling patients aged ≥ 65 years with OAB-wet (one or more incontinence episode and three or more urgency episodes, and an average of eight or more micturitions/24 h over a 3-day diary) were randomized to receive placebo or mirabegron 25 mg/day (optional dose escalation to 50 mg/day at week 4 or 8). Safety analyses were performed for adverse events (AEs) and vital signs on all randomized patients who received one or more dose of study drug. RESULTS: Treatment-emergent AEs (TEAEs), the majority mild or moderate in severity, were reported in 39.4% of placebo patients and 44.2 and 49.8% of those who received mirabegron 25 mg or 50 mg, respectively. The most common TEAEs in mirabegron-treated patients were urinary tract infection, headache, and diarrhea. The incidence of TEAEs was slightly higher in mirabegron patients aged ≥ 75 years than in those aged < 75 years. There were no clinically meaningful differences in changes in vital signs from baseline to end of treatment for any treatment group, and no differences were observed between mirabegron and placebo treatment groups. TEAEs tended to occur early post exposure and were not dose related. CONCLUSIONS: Mirabegron treatment was well-tolerated in older adults with OAB-wet. Safety and tolerability were consistent with the known mirabegron safety profile. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov: NCT02216214.

Overactive bladder in an integrated delivery system: a longitudinal cohort study.

BACKGROUND: Overactive bladder (OAB) is common and morbid. Medication and diagnosis claims may be specific, but lack sensitivity to identify patients with overactive bladder. We used an "electronic health record (EHR) phenotype" to identify cases and describe treatment choices and anticholinergic burden for OAB. METHODS: We conducted a retrospective cohort study in a large, integrated health delivery system between July 2011 and June 2012 (2-year follow-up). We examined care from primary care and specialty clinics, medication and procedure use, and anticholinergic burden for each patient. RESULTS: There were 7362 patients with an EHR OAB phenotype; 50% of patients were > 65 years old, 74% were female, and 83% were white. The distribution of care included primary care physician (PCP)/specialty co-management (25% of patients); PCP care only (18%); urology only (13%); or some other combination of specialty care (33%). Only 40% of patients were prescribed at least 1 OAB medication during the study. The mean duration of prescribed medication was 1.5 months (95% confidence interval [CI], 1.4 to 1.6 months; range, < 1 month to 24 months). Independent predictors of receipt of an OAB medication included increasing age (odds ratio [OR], 1.4 for every 10 years; 95% CI, 1.4 to 1.5), women (OR, 1.6 compared with men; 95% CI, 1.4 to 1.8), diabetes (OR, 1.3; 95% CI, 1.1 to 1.5), and certain sources of care compared with PCP-only care: PCP/specialty co-management (OR, 1.8; 95% CI, 1.5 to 2.0), urology (OR, 2.2; 95% CI, 1.8 to 2.6), and multiple specialists (OR, 1.4; 95% CI, 1.2 to 1.8). Very few patients received other treatments: biofeedback (< 1%), onabotulinumtoxinA (2%), or sacral nerve stimulation (1%). Patients who received OAB medications had significantly higher anticholinergic burden than patients who did not (anticholinergic total standardized daily dose, 125 versus 46; P < .001). CONCLUSIONS: Although OAB is common and morbid, in a longitudinal study using an EHR OAB phenotype 40% of patients were treated with OAB medication and only briefly.

Efficacy and Safety of Mirabegron versus Placebo Add-On Therapy in Men with Overactive Bladder Symptoms Receiving Tamsulosin for Underlying Benign Prostatic Hyperplasia: A Randomized, Phase 4 Study (PLUS).

PURPOSE: PLUS investigated the efficacy and safety of mirabegron add-on therapy in men with overactive bladder symptoms receiving tamsulosin for underlying lower urinary tract symptoms attributable to benign prostatic hyperplasia. MATERIALS AND METHODS: In this phase 4 study a 4-week 0.4 mg tamsulosin run-in period was followed by a 12-week, randomized, double-blind, treatment period in which patients initially received 25 mg mirabegron or placebo add-on therapy. At 4 weeks doses were titrated to 50 mg mirabegron or placebo equivalent. Efficacy end points were changes from baseline to end of treatment in mean number of micturitions per day (primary), mean volume voided per micturition, number of urgency episodes per day, total urgency and frequency score, and total International Prostate Symptom Score (secondary). Safety assessments included treatment emergent adverse events, and post-void residual volume, and maximum urinary flow measurements. RESULTS: Of the 676 men most were 65 years old or older (380, 56.2%). Tamsulosin plus mirabegron was statistically superior to tamsulosin plus placebo in reducing the mean number of micturitions per day (-2.00 vs -1.62; adjusted difference -0.39; 95% CI -0.76, -0.02). Statistically superior results were noted for tamsulosin plus mirabegron in mean volume voided per micturition, urgency episodes per day, and total urgency and frequency score (not International Prostate Symptom Score). Higher overall treatment emergent adverse event rates were observed with tamsulosin plus placebo, although higher rates of drug related treatment emergent adverse events were noted with tamsulosin plus mirabegron. Urinary retention rates were higher in the tamsulosin plus mirabegron group. Post-void residual volume and maximum urinary flow results were not clinically meaningful. CONCLUSIONS: The results of PLUS underscore the utility of mirabegron add-on therapy to treat men with overactive bladder symptoms receiving tamsulosin for benign prostatic hyperplasia.

Efficacy, safety, and tolerability of mirabegron in patients aged ≥65yr with overactive bladder wet: a phase IV, double-blind, randomised, placebo-controlled study (PILLAR).

BACKGROUND: The majority of patients with overactive bladder (OAB) are aged >65yr. There has been no prospectively designed study assessing treatment efficacy with the ß3-adrenoreceptor agonist, mirabegron, specifically in this age group. OBJECTIVE: A phase IV study comparing flexibly dosed mirabegron versus placebo in elderly patients with OAB and urgency incontinence. DESIGN, SETTING, AND PARTICIPANTS: Community-dwelling patients aged ≥65yr with OAB for ≥3mo. INTERVENTION: Following a 2-wk placebo run in, patients with one or more incontinence episodes, three or more urgency episodes, and an average of eight or more micturitions/24h were randomised 1:1 to double-blind 25mg/d mirabegron or matched placebo, for 12wk. After week 4 or 8, the dose could be increased to 50mg/d mirabegron/matched placebo based on patient and investigator discretion. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Coprimary endpoints: change from baseline to end of treatment (EOT) in the mean numbers of micturitions/24h and incontinence episodes/24h. Secondary endpoints: change from baseline to EOT in the mean volume voided/micturition, mean number of urgency episodes/24h, and mean number of urgency incontinence episodes/24h. Analysis of covariance (ANCOVA) was used for the mean number of micturitions/24h, mean volume voided/micturition, and mean number of urgency episodes/24h. Stratified rank ANCOVA was used for the mean numbers of incontinence episodes/24h and urgency incontinence episodes/24h. RESULTS AND LIMITATIONS: Statistically significant improvements were observed for mirabegron versus placebo in change from baseline to EOT in the mean number of micturitions/24h, mean number of incontinence episodes/24h, mean volume voided/micturition, mean number of urgency episodes/24h, and mean number of urgency incontinence episodes/24h. Safety and tolerability were consistent with the known mirabegron safety profile. CONCLUSIONS: Mirabegron efficacy, safety, and tolerability over 12 wk were confirmed in patients aged ≥65yr with OAB and incontinence. PATIENT SUMMARY: We examined the effect of mirabegron compared with placebo in people aged 65yr or older with overactive bladder and incontinence. Mirabegron improved the symptoms of overactive bladder compared with placebo. Side effects were similar to those already known for mirabegron.

Factors Associated with Improvements in Patient-Reported Outcomes During Mirabegron or Antimuscarinic Treatment of Overactive Bladder Syndrome: A Registry Study (PERSPECTIVE).

INTRODUCTION: Patient-reported outcomes (PROs) provide valuable insights about the effectiveness of overactive bladder (OAB) treatments. The aim of PERSPECTIVE (a Prospective, non-intErventional Registry Study of PatiEnts initiating a Course of drug Therapy for overactIVE bladder) was to provide real-world evidence from the USA and Canada on patient-perceived effectiveness and safety of mirabegron and antimuscarinics for treating OAB symptoms. METHODS: This prospective, non-interventional registry followed adult patients with OAB who were starting treatment with mirabegron or antimuscarinics. All treatment decisions were made at the discretion of the treating healthcare provider with no mandatory visits after enrollment. The primary objective was to identify factors associated with improved treatment effectiveness from a patient perspective mainly using the OAB Questionnaire Short-Form (OAB-q SF). The form was sent to patients via email link at baseline and months 1, 3, 6, and 12. Treatment-emergent adverse event (TEAE) data were collated from investigator reports. RESULTS: Overall, 1514 patients were included (female 73.5%, mean age 62.2 years). Mirabegron was initiated by 613 patients and antimuscarinics by 901 patients. A PRO response rate of approximately 60% was achieved (575 patients did not complete baseline PROs). Similar improvements in OAB-q SF symptom bother score and health-related quality of life (HRQoL) total score were observed for mirabegron and antimuscarinic initiators. Covariate-adjusted models demonstrated that worse baseline PRO score, Hispanic ethnicity, being treatment naïve, and use of complementary/supportive OAB therapies at baseline were significantly associated with greater improvements in both scores. The most frequent TEAEs were gastrointestinal disorders (dry mouth, constipation, and nausea) and nervous system disorders (headache, somnolence, and dizziness). CONCLUSION: There are no differences between mirabegron and antimuscarinics in terms of patient-reported OAB symptom bother and HRQoL. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02386072. FUNDING: Astellas Pharma Global Development, Inc. Plain language summary available for this article.

Use of Initial Noninvasive Cardiac Testing and Association with Downstream Healthcare Resource: A Retrospective Review of Resources Used Across a 12-Month Window for Probable Type I Myocardial Infarction Patients.

BACKGROUND: Clinical guidelines provide clinicians with substantial discretion in the use of noninvasive cardiac testing for patients with suspected coronary artery disease. Repeat testing, frequent emergency department (ED) visits, and increases in other cardiac-related procedures can be a burden on patients and payers and can complicate treatment planning. We assessed downstream healthcare resource utilization (HCRU) for patients undergoing initial single-photon emission computed tomography (SPECT), myocardial perfusion imaging (MPI), stress echocardiography (ECHO), or exercise treadmill testing (ETT) with probable type I myocardial infarction (MI). METHODS: Electronic medical records data from 12,130 patients with probable type I MI presenting to EDs within a large healthcare system comprised of 11 adult hospitals were retrospectively analyzed. Logistic and linear regression determined the individual contribution of SPECT-MPI, ETT, and ECHO on repeat cardiovascular (CV) testing, inpatient visits, outpatient visits, and cardiac-related costs within 12 months of the index visit. RESULTS: The majority of patients received SPECT-MPI for the index-testing event (56.5%), followed by ETT (29.2%) and ECHO (14.3%). Patients who had SPECT-MPI at the index visit were less likely to have a repeat CV testing visit (odds ratio [OR] 0.77, 95% confidence interval [CI] 0.62‒0.96; p = 0.020) or an inpatient visit (OR 0.70, 95% CI 0.49‒0.98; p = 0.039) than those who underwent ETT or ECHO. ETT and ECHO were not predictive of any outcome. CONCLUSIONS: SPECT-MPI does not result in more downstream HCRU than ETT or ECHO and is associated with a lower likelihood of repeat non-invasive CV testing and inpatient visits.

A Novel, Dose-Adjusted Tacrolimus Trough-Concentration Model for Predicting and Estimating Variance After Kidney Transplantation.

BACKGROUND AND OBJECTIVE: Given that a high intrapatient variability (IPV) of tacrolimus whole blood concentration increases the risk for a poor kidney transplant outcome, some experts advocate routine IPV monitoring for detection of high-risk patients. However, attempts to estimate the variance of tacrolimus trough concentrations (TTC) are limited by the need for patients to receive a fixed dose over time and/or the use of linear statistical models. A goal of this study is to overcome the current limitations through the novel application of statistical methodology generalizing the relationship between TTC and dose through the use of nonparametric functional regression modeling. METHODS: With TTC as a response and dose as a covariate, the model employs an unknown bivariate function, allowing for the potentially complex, nonlinear relationship between the two parameters. A dose-adjusted variance of TTC is then derived based on standard functional principal component analysis (FPCA). To assess the model, it was compared against an FPCA-based model and linear mixed-effects models using prediction error, bias, and coverage probabilities for simulated data as well as phase III data from the Astellas new drug application studies for extended-release tacrolimus. RESULTS: Our numerical investigation indicates that the new model better predicts dose-adjusted TTCs compared with the prediction of linear mixed effects models. Estimated coverage probabilities also indicate that the new model accurately accounts for the variance of TTC during the periods of large fluctuation in dose, whereas the linear mixed effects model consistently underestimates the coverage probabilities because of the inaccurate characterization of TTC fluctuation. CONCLUSION: This is the first known application of a functional regression model to assess complex relationships between TTC and dose in a real clinical setting. This new method has applicability in future clinical trials including real-world data sets due to flexibility of the nonparametric modeling approach.

A Prospective, non-intErventional Registry Study of PatiEnts initiating a Course of drug Therapy for overactIVE bladder (PERSPECTIVE): Rationale, design, and methodology.

INTRODUCTION: Pharmacotherapy of overactive bladder (OAB) typically involves treatment with an antimuscarinic or mirabegron, a ß3-adrenoceptor agonist, but real-world evidence on their use, including treatment access, persistence, and switching, is limited. Here, we describe the design of a prospective, multicenter, non-interventional registry of patients beginning a new course of OAB pharmacological therapy in routine clinical practice. METHODS: Adults with an OAB diagnosis for at least 3 months who either initiated a new course of mirabegron or antimuscarinic, or who switched therapy were enrolled into PERSPECTIVE (a Prospective, non-intErventional Registry Study of PatiEnts initiating a Course of drug Therapy for overactIVE bladder). The primary objective was to identify factors associated with improved OAB treatment effectiveness from a patient perspective. Secondary objectives were to compare persistence rates, reasons for discontinuation, and switching patterns between patients taking mirabegron or antimuscarinics. Healthcare centers and sites involving medical specialties who routinely participate in the care and treatment of patients with OAB (e.g., gynecology, urology, and primary care practices) were targeted for recruitment. Patient-reported outcomes (PROs), including quality of life, symptom bother, and treatment satisfaction from OAB-validated scales, were collected at baseline, months 1, 3, 6, and 12, and when patients switched or discontinued their current OAB medication. CONCLUSIONS: PERSPECTIVE is the first real-world observational study in the United States and Canada on clinical and patient perspectives in OAB management. Recruitment was reflective of centers where patients are treated for OAB to maximize generalizability to the real-world population. TRIAL REGISTRATION: ClinicalTrials.gov, ID number NCT02386072 (date of registration March 6, 2015).

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.

Attributes of nuclear imaging centers impacting physician referrals for single-photon emission computed tomography myocardial perfusion imaging tests.

AIM: To evaluate nuclear imaging center attributes that cardiologists and primary care physicians (PCPs) consider when referring patients for single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) tests, and how these attributes impact physician referral decisions in the United States. METHODS: A targeted literature review and seven one-to-one interviews with physicians and imaging center directors were conducted to identify attributes that could impact physicians' referral decisions. The impact of the identified attributes was assessed via an online discrete choice survey among eligible PCPs and cardiologists randomly selected from a nationally representative panel, and quantified with an odds ratio (OR) scale estimated with a multivariable logistic regression. RESULTS: Nine two-level attributes were identified: ease of the referral process, waiting time for tests, insurance preauthorization assistance, time to receive results, conclusive test reports, patient satisfaction, a protocol for rapid conversion from an exercise to a pharmacological stress test, patient communication, and assistance with parking/wheelchair access. A total of 410 physicians, including 208 (50.7%) cardiologists and 202 (49.3%) PCPs completed the survey. Among all physicians, a protocol that allows for a rapid conversion from an exercise to a pharmacological stress test (OR = 2.9) and preauthorization assistance (OR = 2.6) were the most impactful attributes. Additionally, cardiologists preferred imaging centers that provide an easy referral process (OR = 2.7), while PCPs favored centers offering a conclusive test report (OR = 2.4). LIMITATIONS: Some center features that might impact physician referral decision were not evaluated in this study, if they were not easily changeable from an imaging center's perspective. CONCLUSIONS: The availability of a protocol for rapid conversion from an exercise to a pharmacological stress test and preauthorization assistance had the most significant impact on physician referral decisions for SPECT-MPI. Additionally, cardiologists preferred centers providing an easy referral process, while PCPs favored those offering a concluding statement and actionable steps in test reports.