Real-world prevalence of adverse events with first-line systemic therapies among patients with metastatic castration-sensitive prostate cancer.

BACKGROUND: The current guidelines for treating metastatic castration-sensitive prostate cancer (mCSPC) recommend treatment intensification of androgen deprivation therapy (ADT) with the addition of an androgen receptor pathway inhibitor (ARPI), with or without docetaxel. However, the adoption of these treatment options has been slow, leading to therapeutic inertia. This real-world study was conducted to investigate the occurrence of adverse events (AEs) among treated patients diagnosed with mCSPC in the United States. METHODS: This retrospective claim review estimated the occurrence of AEs among patients with mCSPC from January 2014 to June 2021 in the PharMetrics® Plus data set. The study focused on 10 common AEs (fatigue/asthenia, gastrointestinal [GI] AEs, skin/nail/hair AEs, immunodeficiency/thrombocytopenia, hot flash, sexual function AEs, anemia, hypertension, pain, and edema) known to occur in ≥10% of patients and ≥2% more prevalent than those treated with ADT alone as selected from the US Food and Drug Administration prescribing information and published results from clinical trials. Proportions of patients experiencing these AEs at Day 90, 180, and then every 180 days until month 30 during the follow-up period were estimated using cumulative hazard plots. Results were adjusted using inverse probability of treatment weighting (IPTW) across four treatment groups: ADT alone, ADT + nonsteroidal anti-androgen (NSAA) (bicalutamide, nilutamide, or flutamide), ADT + docetaxel, and ADT + ARPIs (abiraterone, apalutamide, or enzalutamide). ADT-alone cohort was the reference group for all comparisons. RESULTS: A total of 4145 patients were included (ADT alone: 2318, ADT + NSAA: 632, ADT + docetaxel: 471, ADT + ARPIs: 724). At baseline, median (interquartile range [IQR]) age was 64.3 (60.1-73.1) years; most common sites of metastasis were bone only (n = 1886, 45.5%) and node only (n = 1237, 29.8%); most used medications were pain medications (n = 2182, 52.6%) and corticosteroids (n = 1213, 29.3%). Median (IQR) duration of follow-up 10.2 (6.1-16.6) months in ADT alone, 6.7 (4.1-11.5) months in ADT + NSAA, 5.1 (4.3-5.9) months in ADT + docetaxel, and 11.0 (6.6-17.0) months in ADT + ARPI cohort. The reported AEs increased over time for all assessed AEs, across all treatment groups. Compared with ADT alone, no statistically significant difference in the proportion of patients with AEs was seen in the ADT + ARPI or ADT + NSAA cohorts at months 3 and 12; a significantly higher proportion of patients in the ADT + docetaxel cohort experienced 6 of the 10 assessed AEs at month 3 (fatigue/asthenia, GI AEs, skin/nail/hair AEs, immunodeficiency/thrombocytopenia, hot flash, anemia). During the follow-up period, on IPTW analysis, compared with ADT alone, a significantly higher proportion of patients experienced AEs with seven AEs in the ADT + docetaxel group (fatigue/asthenia, GI AEs, skin/nail/hair AEs, immunodeficiency/thrombocytopenia, hot flash, anemia, edema; p < 0.001 for all seven), three AEs in the ADT + ARPI group (hot flash, p = 0.05; anemia, p = 0.01; edema, p = 0.019), and one AE in the ADT + NSAA group (anemia, p = 0.029). The proportion of patients with sexual function AE did not significantly differ between the treatment groups and ADT alone. CONCLUSION: Results of this large, real-world study demonstrated that all treatment groups experienced an increase in the rates of AEs over time, including ADT alone. Most AE rates with ADT + ARPIs were comparable with ADT + NSAA and not significantly different from ADT alone. ADT + docetaxel cohort was associated with significantly higher rates for all AEs over time except hypertension, sexual dysfunction, and pain. This study provides real-world evidence on AEs, beyond controlled clinical trials, and may assist healthcare providers to make better-informed decisions about disease management among patients with mCSPC.

The real world experience of pediatric primary hyperoxaluria patients in the PEDSnet clinical research network.

The rarity of primary hyperoxaluria (PH) challenges our understanding of the disease. The purpose of our study was to describe the course of clinical care in a United States cohort of PH pediatric patients, highlighting health service utilization. We performed a retrospective cohort study of PH patients < 18 years old in the PEDSnet clinical research network from 2009 to 2021. Outcomes queried included diagnostic imaging and testing related to known organ involvement of PH, surgical and medical interventions specific to PH-related renal disease, and select PH-related hospital service utilization. Outcomes were evaluated relative to cohort entrance date (CED), defined as date of first PH-related diagnostic code. Thirty-three patients were identified: 23 with PH type 1; 4 with PH type 2; 6 with PH type 3. Median age at CED was 5.0 years (IQR 1.4, 9.3 years) with the majority being non-Hispanic white (73%) males (70%). Median follow-up between CED and most recent encounter was 5.1 years (IQR 1.2, 6.8). Nephrology and Urology were the most common specialties involved in care, with low utilization of other sub-specialties (12%-36%). Most patients (82%) had diagnostic imaging used to evaluate kidney stones; 11 (33%) had studies of extra-renal involvement. Stone surgery was performed in 15 (46%) patients. Four patients (12%) required dialysis, begun in all prior to CED; four patients required renal or renal/liver transplant.    Conclusion: In this large cohort of U.S. PH children, patients required heavy health care utilization with room for improvement in involving multi-disciplinary specialists. What is Known: • Primary hyperoxaluria (PH) is rare with significant implications on patient health. Typical involvement includes the kidneys; however, extra-renal manifestations occur. • Most large population studies describe clinical manifestations and involve registries. What is New: • We report the clinical journey, particularly related to diagnostic studies, interventions, multispecialty involvement, and hospital utilization, of a large cohort of PH pediatric patients in the PEDSnet clinical research network. • There are missed opportunities, particularly in that of specialty care, that could help in the diagnosis, treatment, and even prevention of known clinical manifestations.

Real-world use, dose intensity, and adherence to enfortumab vedotin in locally advanced or metastatic urothelial cancer.

BACKGROUND: Enfortumab vedotin (EV) monotherapy is approved for the treatment of advanced urothelial cancer as later-line therapy (post-immunotherapy and -platinum-chemotherapy) and as earlier-line therapy (cisplatin-ineligible, at least 1 prior therapy). We examined real-world EV monotherapy use, dose intensity and adherence across 280 US cancer clinics. METHODS: This postmarketing study used data from a nationwide (United States) deidentified patient-level electronic health record-derived database. Included were patients with advanced urothelial cancer initiating EV on or after December 19, 2019 (date of accelerated approval). We summarized characteristics of EV users using descriptive statistics and computed metrics of EV use, EV dose intensity, and EV treatment adherence. RESULTS: We identified 416 advanced urothelial cancer patients initiating EV monotherapy. More than half of patients (55.3%) received EV as later-line therapy (3L+), and nearly half (44.7%) received EV as earlier line therapy (1 or 2L). Dosing frequency (mean [SD] 2.4 [0.5] treatments per 28 day cycle) and dose (1.1 [0.2] mg/kg) were lower than label indication guidelines (1.25 mg/kg, Day 1, 8, 15 of a 28 day cycle). Only 58.8% of patients received an average of >2 treatments per 28-day cycle. CONCLUSIONS: Among patients with advanced urothelial cancer treated with EV monotherapy in contemporary practice, EV dosing frequency, and dosage was lower in clinical practice than recommended in the product labeling. Further research is required to understand clinical factors and outcomes associated with the differences observed.

Patient Preferences for First-Line Treatment of Locally Advanced or Metastatic Urothelial Carcinoma: An Application of Multidimensional Thresholding.

OBJECTIVES: Patient preferences have the potential to influence the development of new treatments for locally advanced/metastatic urothelial carcinoma (la/mUC), and therefore we explored how patients with la/mUC value different attributes of first-line treatments. METHODS: An online preference survey and multidimensional thresholding (MDT) exercise were developed following a targeted literature review and qualitative interviews with physicians, patients with la/mUC, and their caregivers. Treatment attributes included two benefits (overall response rate [ORR], pain related to bladder cancer [scored 0-100; 100 being the worst pain possible]) and four treatment-related risks (peripheral neuropathy, severe side effects, mild to moderate nausea, mild to moderate skin reactions). A Dirichlet regression was used to estimate average preference weights. Marginal utility and the reduction in ORR that patients would accept in exchange for a 10-point decrease or a 10% decrease in other attributes were calculated. RESULTS: A total of 100 patients were recruited and self-completed the survey and MDT. Mean patient age was 64.9 years (standard deviation, 7.6), 54% were female, and 38% identified as white. All included treatment attributes had a statistically significant impact on preferences. Changes in ORR had the largest impact, followed by cancer-related pain and treatment-related risks. Patients were willing to accept an 8.4% decrease in ORR to reduce their pain level by 10 points or a 7.8% decrease in ORR to reduce the risk of peripheral neuropathy by 10%. For a 10% decrease in severe side effects, mild to moderate nausea, or skin reaction, patients would accept decreases in ORR of 5.5%, 3.7%, or 3.4%, respectively. CONCLUSIONS: Of the attributes tested, changes in ORR were most important to patients. Patients made tradeoffs between treatment attributes indicating that a lower ORR may be acceptable for an improvement in other attributes such as reduced cancer-related pain or the risk of treatment-related adverse events.

Staging dementia from symptom profiles on a care partner website.

BACKGROUND: The World Wide Web allows access to patient/care partner perspectives on the lived experience of dementia. We were interested in how symptoms that care partners target for tracking relate to dementia stage, and whether dementia could be staged using only these online profiles of targeted symptoms. OBJECTIVES: To use clinical data where the dementia stage is known to develop a model that classifies an individual's stage of dementia based on their symptom profile and to apply this model to classify dementia stages for subjects from a Web-based dataset. METHODS: An Artificial Neural Network (ANN) was used to identify the relationships between the dementia stages and individualized profiles of people with dementia obtained from the 60-item SymptomGuide (SG). The clinic-based training dataset (n=320), with known dementia stages, was used to create an ANN model for classifying stages in Web-based users (n=1930). RESULTS: The ANN model was trained in 66% of the 320 Memory Clinic patients, with the remaining 34% used to test its accuracy in classification. Training and testing staging distributions were not significantly different. In the 1930 Web-based profiles, 309 people (16%) were classified as having mild cognitive impairment, 36% as mild dementia, 29% as moderate, and 19% as severe. In both the clinical and Web-based symptom profiles, most symptoms became more common as the stage of dementia worsened (eg, mean 5.6 SD 5.9 symptoms in the MCI group versus 11.9 SD 11.3 in the severe). Overall, Web profiles recorded more symptoms (mean 7.1 SD 8.0) than did clinic ones (mean 5.5 SD 1.8). Even so, symptom profiles were relatively similar between the Web-based and clinical datasets. CONCLUSION: Symptoms targeted for online tracking by care partners of people with dementia can be used to stage dementia. Even so, caution is needed to assure the validity of data collected online as the current staging algorithm should be seen as an initial step.

Validation of an informant-reported web-based data collection to assess dementia symptoms.

BACKGROUND: The Web offers unprecedented access to the experience of people with dementia and their care partners, but data gathered online need to be validated to be useful. OBJECTIVE: To test the construct validity of an informant Web-based data collection to assess dementia symptoms in relation to the 15-point Dependence Scale (DS). METHODS: In an online survey posted on the DementiaGuide website, care partners of people with dementia built individualized profiles from the 60-item SymptomGuide and completed a questionnaire, which included the DS and a staging tool. RESULTS: In the 250 profilees (155, 62% women, mean age 77 years), increasing dependence was associated with a greater chance of institutionalization. For example, no one at the lowest levels of dependence (DS score < 5, n = 33) was in long-term care, compared with half (13/25) of the profilees at the highest levels of dependence (DS score > 12) being in institutions (χ(2)(4) = 27.9, P < .001). The Web-based DS was correlated with the number of symptoms: higher DS scores were associated with a higher stage of dementia (F > 50, P < .001). CONCLUSION: In an online survey, the Web-based DS showed good construct validity, potentially demonstrating how the Web can be used to learn more about dementia progression and how it relates to symptoms experienced by patients across the course of dementing illnesses. Even so, caution is needed to assure the validity of data collected online.

Clinical and economic impact of primary hyperoxaluria: a retrospective claims analysis.

BACKGROUND: Primary hyperoxaluria (PH) is a family of rare, life-threatening genetic liver disorders characterized by elevated production and excretion of oxalate. To date, the clinical and economic burden associated with PH has not been well characterized due to the rarity of the disease and previous challenges with diagnostic coding that prevented proper identification of patients with PH in claims data. OBJECTIVE: To characterize the clinical and economic costs, as well as health care resource utilization (HCRU), associated with PH relative to a matched cohort of patients without PH. METHODS: Data from the IQVIA PharMetrics Plus Database were used to conduct a retrospective matched-cohort study to compare differences in clinical characteristics, HCRU, and pharmacy and medical costs in patients with PH compared with a matched cohort of patients without PH from January 2014 to December 2019. RESULTS: Overall, 324 patients were included in the PH cohort and 1,620 patients were in the non-PH cohort. The mean age of PH patients was 48.1 years, and approximately 58% of the sample were male. Significantly more patients in the PH cohort than the non-PH cohort were diagnosed with stage 2 chronic kidney disease (CKD; 3.1% vs 0.4%, respectively; P < 0.001), stage 3 CKD (4.6% vs 0.5%; P < 0.001), stage 4 CKD (2.5% vs 0.1%; P < 0.001), and stage 5 CKD or end-stage renal disease (ESRD; 2.2% vs 0.1%; P < 0.001). PH patients had a significantly higher mean Charlson Comorbidity Index composite score than patients in the non-PH cohort (0.79 vs 0.37; P < 0.001). HCRU was significantly higher in patients with PH. The PH cohort had a significantly higher proportion of patients with at least 1 visit to clinicians specializing in nephrology (19% vs 0.4%, respectively; P < 0.001), cardiology (22% vs 12%; P < 0.001), ophthalmology (16% vs 7%; P < 0.001), general surgery (9% vs 6%; P = 0.011), and urology (65% vs 6%; P < 0.001) compared with patients without PH. Mean total annual health care costs in the PH cohort were 65% higher than in the non-PH cohort ($22,549 vs $7,852, respectively; P < 0.001). Similar results were found for total prescription drug costs ($4,125 vs $2,464; P = 0.012). CONCLUSIONS: Despite the rarity of PH, patients with this disease incur substantial clinical and economic burden and may cause financial strain on the health care system. Additional research is warranted to understand the economic and clinical burden of PH stratified by the 3 subtypes of the disease. DISCLOSURES: Funding for this research was provided by Dicerna Pharmaceuticals. Mucha and Hoppe are employed by Dicerna Pharmaceuticals. Silber Miyasoto, Skaar, and Wang are employed by Trinity Life Sciences, which was contracted by Dicerna Pharmaceuticals to conduct the study analysis. Langman is consultant to Dicerna Pharmaceuticals. This study was presented as a poster at the AMCP Nexus 2020 (virtual), October 19-23, 2020, and American Society of Nephrology 2020 (virtual), October 19-25, 2020.

Cost-effectiveness of vortioxetine compared with levomilnacipran and vilazodone in patients with major depressive disorder switching from an initial antidepressant.

Introduction: Many patients with major depressive disorder (MDD) do not achieve remission with their first antidepressant (AD), resulting in a high burden due to treatment failure. Vortioxetine is a valid treatment option for patients with MDD only partially responding to their first AD. Characterization of vortioxetine's potential benefits versus other approved treatments is important. Areas covered: The cost-effectiveness of vortioxetine, including cognitive outcomes, was modeled in comparison with levomilnacipran and vilazodone for patients switched to these medications after inadequate responses to a first AD. Expert opinion: Vortioxetine was associated with incremental quality-adjusted life-year (QALY) gains versus levomilnacipran (0.008) or vilazodone (0.009). Vortioxetine was dominant versus levomilnacipran and cost-effective versus vilazodone (incremental cost-effectiveness ratio [ICER],33,829 USD/QALY). In sensitivity analyses using residual cognitive dysfunction rates (vortioxetine, 49%; levomilnacipran, 58%, and vilazodone, 64%), incremental QALY gains for vortioxetine versus levomilnacipran (0.0085) or vilazodone (0.0109) were found. Vortioxetine remained dominant versus levomilnacipran and cost-effective versus vilazodone (ICER, 27,633 USD/QALY). ICER reduction was found with cognition outcomes inclusion. This model provides additional support for considering vortioxetine for patients requiring a switch of MDD treatments, although its conclusions are limited by the data available for inclusion. Additional research and real-world trials are needed to confirm the findings.

Dependence as a unifying construct in defining Alzheimer's disease severity.

This article reviews measures of Alzheimer's disease (AD) progression in relation to patient dependence and offers a unifying conceptual framework for dependence in AD. Clinicians typically characterize AD by symptomatic impairments in three domains: cognition, function, and behavior. From a patient's perspective, changes in these domains, individually and in concert, ultimately lead to increased dependence and loss of autonomy. Examples of dependence in AD range from a need for reminders (early AD) to requiring safety supervision and assistance with basic functions (late AD). Published literature has focused on the clinical domains as somewhat separate constructs and has given limited attention to the concept of patient dependence as a descriptor of AD progression. This article presents the concept of dependence on others for care needs as a potential method for translating the effect of changes in cognition, function, and behavior into a more holistic, transparent description of AD progression.

Modeling the impact of patient treatment preference on health outcomes in relapsing-remitting multiple sclerosis.

Aims: Model how moving from current disease-modifying drug (DMD) prescribing patterns for relapsing-remitting multiple sclerosis (RRMS) observed in the United Kingdom (UK) to prescribing patterns based on patient preferences would impact health outcomes over time.Materials and methods: A cohort-based Markov model was used to measure the effect of DMDs on long-term health outcomes for individuals with RRMS. Data from a discrete choice experiment were used to estimate the market shares of DMDs based on patient preferences (i.e. preference shares). These preference shares and real-world UK market shares were used to calculate the effect of prescribing behavior on relapses, disability progression, and quality-adjusted life-years (QALYs). The incremental benefit of patient-centered prescribing over current practices for the UK RRMS population was then estimated; scenario and sensitivity analyses were also conducted.Results: Compared to current prescribing practices, when UK patients with RRMS were treated following patient preferences, health outcomes were improved. This population was expected to experience 501,690 relapses and gain 1,003,263 discounted QALYs over 50 years under patient-centered prescribing practices compared to 538,417 relapses and 958,792 discounted QALYs under current practices (-6.8% and +4.6%, respectively). Additionally, less disability progression was observed when prescribed treatment was based on patient preferences. In a scenario analysis where only oral treatments were considered, the results were similar, although the magnitude of benefit was smaller. Number of relapses was most sensitive to how the annualized relapse rate was modeled; disability progression was most sensitive to mortality rate assumptions.Limitations: Treatment efficacy estimates applied to various models in this study were based on data derived from clinical trials, rather than real-world data; the impact of patient-centered prescribing on treatment adherence and/or switching was not modeled.Conclusions: The population of UK RRMS patients may experience overall health gains if patient preferences are better incorporated into prescribing practices.

Economic burden of relapse/recurrence in patients with major depressive disorder.

Objective: This study was conducted to determine the incremental healthcare resource utilization (HRU) and costs associated with relapse or recurrence (R/R) in patients with major depressive disorder (MDD) treated with antidepressants (AD) in US clinical practice. Methods: In this retrospective cohort study, adult patients with MDD treated with a branded AD were selected from the Truven Health Analytics MarketScan Databases (January 1, 2004-March 31, 2015). Time to first indicator of R/R was described. Characteristics, HRU, and costs were compared between patients with and without R/R. Among patients with R/R, HRU and costs were also compared between the pre- and post-R/R period. Results: From the 22,236 selected patients, 5,541 had ≥ 1 indicator of R/R and 16,695 did not. The 3-year R/R rate varied between 21.3% and 36.4% based on pattern of AD use (continuous, switch/augmentation, or early discontinuation). Patients with and without R/R presented different characteristics-notably, more intensive prior AD use and a higher comorbidity burden. HRU and costs were high in both patients with and without R/R but substantially higher among those with R/R ($20,590 vs $12,368 per-patient-per-year (PPPY); adjusted difference [aDiff] = $7,037), mainly driven by increased inpatient (IP) services (adjusted incidence rate ratio IP days = 3.95; aDiff IP costs = $3,433 PPPY). Among patients with R/R, emergency department visits, IP days, and IP admissions were over 2-times higher during the post-R/R period and total costs increased by over 50% from $19,267 to $29,419 in the post-R/R period. Conclusions: The economic burden in MDD patients is substantial, but is significantly higher among those who experience R/R.

Adapting the Goal Attainment Approach for Major Depressive Disorder.

The need for patient-centered care has become a focal point of healthcare improvement initiatives. Shared decision making-in which patients and clinicians communicate about various treatment options and goals and patient input is considered when making treatment decisions-has been associated with improved health and quality of life. A method of treatment evaluation allowing incorporation of patient-specific goals and perspectives is of increasing interest to healthcare providers, payers, and patients. An approach that allows incorporation of shared goal setting is possible via use of an instrument called the Goal Attainment Scale (GAS). This scale provides the structure for measuring progress toward treatment goals set through patient-clinician collaboration. The goal attainment approach has been used as a primary outcomes measure in numerous studies but not in major depressive disorder (MDD). As MDD is a complex, multidimensional disorder affecting each patient differently, the use of GAS methodology is a relevant framework for setting personalized meaningful treatment goals. Initial research into the feasibility of using the GAS in MDD (GAS-D) to measure patient-centric outcomes that may be neglected when more traditional scales are used has been encouraging. The objective of this Commentary is to provide background and rationale for implementation of the GAS-D in clinical practice.Funding Takeda Pharmaceutical Company, Ltd., and Lundbeck LLC.

Patient attitudes toward and goals for MDD treatment: a survey study.

Background/Objectives: Major depressive disorder (MDD) is a highly prevalent disorder, frequently diagnosed and treated in a primary care setting; however, little information is available about the treatment decision-making process between MDD patients and their providers. A shared decision-making and goal attainment approach to establishing and tracking progress toward treatment goals that are meaningful to individual patients is explored in this survey study. In addition, information about patient perspectives on setting treatment goals, medication selection/switching, and engaging patients with their health care professionals was also collected and evaluated. Methods: A 50-question online survey was administered to members of the PatientsLikeMe community who indicated an MDD diagnosis and a switch in antidepressant medications within the past 2 years. Follow-up interviews were also conducted with a small subset of these participants. Results: Of the 200 participants who completed the survey, 42% reported currently having goals for MDD treatment. These goals were typically in the areas of physical health (62.7%), cognitive functioning (60.2%), and social aspects of life (57.8%). A majority of survey participants (61%) believed the goal attainment approach would be helpful to set and evaluate treatment goals. Conclusions: The data provide important insights into patient perspectives on the development of formal treatment plans and goals for MDD. In addition, the data also support the use of a patient-centric approach to shared decision-making by using a goal attainment scale to establish and track progress toward treatment goals that are meaningful to MDD patients in real-world clinical practice. The results of this study can be used to inform best practices in patient-clinician communication when developing an MDD treatment plan and goals.

Comparison of cholinesterase inhibitor utilization patterns and associated health care costs in Alzheimer's disease.

BACKGROUND: Sustained treatment with a cholinesterase inhibitor (ChEI) is used in the management of the symptoms of Alzheimer's disease (AD). However, the characteristic declines in learning and memory seen in AD may erode the patient's ability to adhere to medication regimens with or without caregiver support. OBJECTIVES: To examine differences by type of ChEI in (1) monthly prevalence of use, (2) nonpersistence, (3) switching from the index drug to another ChEI, (4) number of days on therapy, (5) medication possession ratio (MPR), and (6) an estimate of the relationship of these characteristics to total annual health care expenditures. METHODS: Data were from the MarketScan Medicare Supplemental and Coordination of Benefits 2001-2003 database, which comprised 1.47 million Medicare beneficiaries during this 3-year time period. Inclusion criteria were: (1) aged 65 years or older; (2) at least 1 claim with an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) code 331.0 for AD in any of 15 diagnosis fields on outpatient claims or any of 2 diagnosis fields on inpatient claims at any time during 18 months of observation; (3) at least 1 pharmacy claim for donepezil, galantamine, or rivastigmine preceded by a 6-month period without a ChEI claim; and (4) at least 12 months of follow-up data, for a minimum 18 months continuous enrollment. Multivariate analyses, including logistic regression and exponential conditional mean models, tested for cohort differences in ChEI utilization, controlling for demographics, region of the country, type of insurer, and the Charlson Comorbidity Index (comorbid diagnoses). Using exponential conditional mean models, we also examined the relationship between utilization characteristics and all-cause (i.e., not specific to AD) health care expenditures for a 12-month period, including inpatient and outpatient (physician) care, laboratory and radiology services, emergency room (ER) use, prescription drugs, and long-term care services (e.g., nursing home care, home health visits) paid by Medicare or private insurance, but excluding long-term care services paid by Medicaid. Expenditure was defined as allowed charge (i.e., the total payment received by the service provider including plan and patient paid amounts.) RESULTS: More than 70% of the patients who received ChEI therapy and who otherwise met the inclusion criteria were excluded from this study due to the absence of at least 1 claim with a diagnosis for AD. Of the 3,177 patients included in the study, the index ChEI was donepezil for 62.8% of the patients (n=1,994); 17.2% received galantamine (n=546) and 20.1% received rivastigmine (n=637). The total number of days of index therapy dispensed was greater for those starting on donepezil (mean [median, SD] days=226 [263, 115]) compared with rivastigmine (206 [233, 120], P<0.001), but was not significantly different compared with galantamine (216 [250, 119], P=0.085). Monthly prevalence of use was similar for the 3 drugs until month 5 when a smaller proportion of rivastigmine patients had index medication on hand (65.9%) compared with 72.1% of donepezil patients (P=0.003) and 72.7% of galantamine patients (P=0.012). At 12 months, the likelihood of receiving the index ChEI was higher for donepezil (61.1%) than for either rivastigmine (50.1%, P<0.001) or galantamine (56.4%, P=0.048) and was higher for galantamine than for rivastigmine (P=0.030). The rate of switching for donepezil patients was significantly lower (14.5%) than the switch rate for rivastigmine patients (21.5%, P<0.001) and was similar to the switch rate for galantamine patients (15.0%, P=0.781 for donepezil vs. galantamine; P=0.004 for galantamine vs. rivastigmine). Rates of nonpersistence, measured as having at least 1 gap in therapy of 30 days or more during the 1-year follow-up, were 63.5% for donepezil, 63.7% for galantamine (P=0.933 for donepezil vs. galantamine), and 68.0% for rivastigmine (P=0.042 for donepezil vs. rivastigmine). MPRs and total days supply of any ChEI did not significantly differ among the 3 drugs. Results of multivariate models showed that, controlling for index ChEI drug, each additional month of ChEI treatment was associated with a reduction of 1% in total all-cause health care costs. The mean (SD) total all-cause 1-year health care costs for patients initiated on the 3 ChEIs were not significantly different: $12,112 ($16,437) for donepezil, $12,137 ($19,154) for galantamine (P=0.978), and $12,853 ($14,543) for rivastigmine (P=0.278). CONCLUSIONS: During the first year following initiation of ChEI therapy, patients initiated on donepezil had a greater days supply of the index medication than did patients initiated on rivastigmine. At 12 months following treatment initiation, the proportion of patients in therapy was higher for donepezil than for either rivastigmine or galantamine and was higher for galantamine than for rivastigmine. Patients treated with either donepezil or galantamine were less likely to switch from the index drug to another ChEI than were patients treated with rivastigmine. All-cause 1-year health care costs for patients initiated on the 3 ChEIs were not significantly different.

Cost sharing and branded antidepressant initiation among patients treated with generics.

OBJECTIVES: To determine the relationship between consumer cost sharing for branded antidepressants and the initiation of branded therapy among patients with major depressive disorder (MDD) filling a prescription for generic MDD medication. STUDY DESIGN: Retrospective cross-sectional analyses. METHODS: Patients aged 18 to 64 years with MDD who filled a generic antidepressant were identified in commercial claims data for 2012 to 2014. For each year-specific analysis, an average cost-sharing index for branded antidepressants at the level of the plan was computed. Multivariable models were used to estimate the relationship between plan-level cost sharing for branded antidepressant medications and the filling of branded prescriptions, with demographic and clinical variables as covariates. RESULTS: For patients with MDD filling a generic prescription, increases in branded cost sharing were associated with significant decreases in the likelihood of filling a branded antidepressant in each year (P <.001). Results in 2012 imply that a shift from the 0th to 90th percentile in the branded cost-sharing index corresponded with a 9.5% decrease in the relative likelihood of a branded fill among patients receiving a generic antidepressant. The corresponding figures for 2013 and 2014 were 9.3% and 3.5%, respectively. CONCLUSIONS: In MDD, patients and clinicians who dutifully adhere to guidelines requiring a trial of first-line medication may ultimately require therapy with alternate agents to achieve adequate disease control. A "reward the good soldier" benefit design would lower cost sharing for higher-tier evidence-based therapies when clinically indicated. Results suggest that narrowing the gap in cost sharing between branded and generic medications following a trial of a generic agent might improve access to second-line treatment in MDD.

Impact of adherence to antidepressants on healthcare outcomes and costs among patients with type 2 diabetes and comorbid major depressive disorder.

OBJECTIVE: To evaluate the association between adherence to antidepressants and an effect on clinical outcomes and healthcare costs in patients with major depressive disorder (MDD) and comorbid type 2 diabetes (T2D). METHODS: This retrospective study used MarketScan claims data from January 2012 to March 2014. Study entry was the first claim for an antidepressant and a diagnosis code for MDD and T2D in the prior 6 months. Adherence and persistence with antidepressant therapy in the first 180 days were defined as medication possession ratio (MPR) ≥ 80% and length of therapy (LOT), with no treatment gap of >15 days, respectively. T2D control (HbA1c <7%), oral diabetes medication adherence, and healthcare costs were measured in the 12 month post-index period. The impact of antidepressant adherence and persistence on outcomes was assessed using multivariable analyses. RESULTS: Among the 1361 patients included, the mean age was 59 years and 55% were women. About one-third of the patients were adherent (35.9%, mean MPR = 40%), persistent (32.0%, average LOT = 100 days), and adherent/persistent (31.2%) on antidepressants. Being adherent, persistent, or adherent/persistent to antidepressants was associated with a two-fold improvement in adherence to oral diabetes medications. Of those with HbA1c data (n = 121), adherence or adherence/persistence to antidepressants was associated with patients being five times more likely to have T2D control (odds ratio [OR]: 4.95; 95% confidence interval [CI]: 1.39, 17.59, p = .0134). Comparison between antidepressant-persistent and non-persistent patients was not significant. Mean difference in adjusted all-cause annual costs showed lower costs among antidepressant-adherent and adherent/persistent patients (adherent: -$350, 95% CI: -$462, -$247; adherent/persistent: -$1165; 95% CI: -$1280, -$1060). CONCLUSIONS: Patients with better antidepressant adherence and adherence/persistence demonstrated better HbA1c control, with lower all-cause total and medical costs. Adherence, persistence, or adherence/persistence to antidepressants was associated with improved adherence to oral diabetes medications.

Per-patient-per-month drug costs in Medicare Part D protected classes.

OBJECTIVE: The objective of this study was to estimate the per-patient-per-month (PPPM) costs of medications in the six Medicare Part D protected classes based on findings among Medicare and dual eligible beneficiaries with drug coverage before the enactment of the benefit. DESIGN: Data were from the Thomson Medstat MarketScan Medicare and Medicaid claims databases. The study sample was constructed by identifying patients who were enrolled either in Medicare or dually in Medicare and Medicaid. PPPM costs were calculated for each protected class. Drugs covered under Part B were excluded. OUTCOMES MEASURE: PPPM aggregated costs within each class. RESULTS: The classes in which generic formulations are available (antidepressants and anticonvulsants) show low PPPM costs ($ US 45.31 and $ US 50.97, respectively). The most expensive class is the antiretrovirals ($ US 829.73). This class is the costliest for all dual eligible patients including those aged 64 years and under. Among the dual eligible aged 65 years and older, the immunosuppressants are the most expensive class. The same result is seen qualitatively in the Medicare group. CONCLUSIONS: PPPM costs are not uniformly high among the protected classes. The claims data in this study allowed a 'real world' check of how much the protected classes may impact the finances of Part D. There are differences within the classes between the dual eligible and Medicare patients, and also within the dual eligible by age. This is an important message to policy makers that a change to the structure of the protected classes in Part D may have differential effects across classes and also within classes.

Meta-analysis of disease risk associated with smoking, by gender and intensity of smoking.

BACKGROUND: The risks associated with cigarette smoking can be substantial, particularly for females. In 2000, the mortality rate for lung cancer among women was higher than that for breast cancer. OBJECTIVE: To obtain overall risk for intensity of smoking for both males and females, a meta-analysis was performed on recent studies that assessed the morbidity and mortality associated with smoking. METHODS: Using the PubMed database, a literature search was conducted for cohort and case-control studies on the effect of smoking on morbidity and mortality. Only studies that had quantified the risk of disease associated with smoking were included. Nineteen studies were selected, with data obtained on the disease affected by smoking, point estimates of risk, 95% CIs, sample size, type of study, and the number of patients of each sex. Meta-analyses were performed for low level of use, defined as 1 to 20 cigarettes per day, and for high level of use, >20 cigarettes per day. RESULTS: For low level of use, the rate ratio point estimate of 1.77 (95% CI, 1.40-2.24) for females was higher than that of 1.42 (95% CI, 1.23-1.64) for males, indicating a gender effect associated with smoking as a disease risk. The point estimate for females who smoked at high levels was 2.75 (95% CI, 2.14-3.52), well beyond the estimate of 1.95 (95% CI, 1.70-2.24) for males, indicating there was a substantial gender effect with high-level use. All point estimates for low and high levels of smoking were significant; those for each sex at high levels of smoking exceeded those found for low levels. The increase in risk from low to high levels of smoking was greater for females than for males. CONCLUSIONS: Few systems in the body were unaffected by smoking, and intensity was a risk factor for disease. Results were consistent with and strengthened previous research demonstrating an increase in overall risk with an increase in smoking intensity. In addition, gender differences were noted that may contribute to risk magnitude.

Road to the nursing home: costs and disease progression among medicare beneficiaries with ADRD.

OBJECTIVES: To estimate long-term care costs and disease progression among Medicare beneficiaries aged 65+ with ADRD. METHODS: Retrospective analysis of Medicare Part A claims and nursing home (NH) Minimum Data Set (MDS) records among beneficiaries 1999-2007. Expenditures were grouped into 3 periods; PRE, events occurring between date of ADRD diagnosis, before first NH admission; PERI, from first NH admission to at least 100 days; and, PERM, after 120 days. Utilization and reimbursements were computed for each period. RESULTS: Demographics of the3,681,702 ADRD beneficiaries showed average age of 83 (+/-7), female (67.7%) and white (87.4%). Medicare reimbursements per person increased by 58% from the PRE ($47,912) to PERM period ($75,654). Age, ethnicity, gender (male), and comorbidities were significantly related to total reimbursements in each phase. CONCLUSIONS: Applying a taxonomy of NH phases, Medicare expenditures per person year are higher among patients in their terminal phase and higher still with comorbidities.

A review of the methods used to estimate the cost of Alzheimer's disease in the United States.

UNLABELLED: BACKGROUN/RATIONALE: To determine the suitability of published estimates of the US cost of Alzheimer's disease (AD) for use in cost-effectiveness models for new AD treatments. METHODS: A systematic literature review of published information on direct medical, direct nonmedical, indirect, and informal care costs for different levels of disease severity. RESULTS: Nineteen studies were included in the review. In studies presenting mean costs by disease severity, the change in different types of costs with increasing disease severity varied, depending on the data sources and characteristics of patients with AD. In studies presenting the results of regression analyses, costs were shown to be independently associated with cognition, functional status, behavioral symptoms, and dependence. CONCLUSIONS: Published US studies (1) did not include all the types of costs and AD populations, and (2) generally did not include all the measures of disease severity that are needed for cost-effectiveness models.