The societal economic burden of autosomal dominant polycystic kidney disease in the United States.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited kidney diseases characterized by progressive development of renal cysts and numerous extra-renal manifestations, eventually leading to kidney failure. Given its chronic and progressive nature, ADPKD is expected to carry a substantial economic burden over the course of the disease. However, there is a paucity of evidence on the impact of ADPKD from a societal perspective. This study aimed to estimate the direct and indirect costs associated with ADPKD in the United States (US). METHODS: A prevalence-based approach using data from scientific literature, and governmental and non-governmental organizations was employed to estimate direct healthcare costs (i.e., medical services, prescription drugs), direct non-healthcare costs (i.e., research and advocacy, donors/recipients matching for kidney transplants, transportation to/from dialysis centers), and indirect costs (i.e., patient productivity loss from unemployment, reduced work productivity, and premature mortality, caregivers' productivity loss and healthcare costs). The incremental costs associated with ADPKD were calculated as the difference between costs incurred over a one-year period by individuals with ADPKD and the US population. Sensitivity analyses using different sources and assumptions were performed to assess robustness of estimates and account for variability in published estimates. RESULTS: The estimated total annual costs attributed to ADPKD in 2018 ranged from $7.3 to $9.6 billion in sensitivity analyses, equivalent to $51,970 to $68,091 per individual with ADPKD. In the base scenario, direct healthcare costs accounted for $5.7 billion (78.6%) of the total $7.3 billion costs, mostly driven by patients requiring renal replacement therapy ($3.2 billion; 43.3%). Indirect costs accounted for $1.4 billion (19.7%), mostly driven by productivity loss due to unemployment ($784 million; 10.7%) and reduced productivity at work ($390 million; 5.3%). Total excess direct non-healthcare costs were estimated at $125 million (1.7%). CONCLUSIONS: ADPKD carries a considerable economic burden, predominantly attributed to direct healthcare costs, the majority of which are incurred by public and private healthcare payers. Effective and timely interventions to slow down the progression of ADPKD could substantially reduce the economic burden of ADPKD.

Treatment patterns and burden of behavioral disturbances in patients with dementia in the United States: a claims database analysis.

BACKGROUND: Although patients with dementia frequently experience neuropsychological symptoms (NPS) such as agitation, which profoundly impacts patients, caregivers, and the healthcare system, few studies have evaluated the associated burden of agitation or agitation-related symptoms in dementia. METHODS: This retrospective analysis of claims data from the Truven Health MarketScan® database (2012-2015) compared clinical characteristics, treatment patterns, healthcare resource utilization, and costs among patients with dementia with behavioral disturbances (BD) versus patients with dementia without BD. Existing BD diagnosis codes 294.11 or 294.21 were used as a means to identify patients with agitation/agitation-related symptoms. RESULTS: From a starting sample of 6.4 million beneficiaries, 103,402 patients with dementia were identified, of whom 16,440 (16%) had BD during an average of 17 months of follow-up. Patients with BD had significantly more medical and psychiatric comorbidities and greater comedication use (i.e., antidementia drugs, antidepressants, and antipsychotics; all values, P < .0001) compared with patients without BD. A significantly greater number of hospitalizations, hospital days, outpatient hospital/clinic visits, number of skilled nursing visits, and number of patients with hospice visit were reported during follow-up in patients with BD compared with patients without BD (all values, P <  0.0001). Costs were also significantly higher among patients with BD versus those patients without BD ($42,284 vs. $32,640, respectively; P <  0.0001). CONCLUSIONS: Patients with dementia with BD had a higher prevalence of comorbidities, greater use of comedications, and greater healthcare utilization and costs than patients with dementia without BD.

Using electronic health records to estimate the prevalence of agitation in Alzheimer disease/dementia.

BACKGROUND: Agitation is a common neuropsychiatric symptom of Alzheimer disease (AD). Data are scarce regarding agitation prevalence among community-dwelling patients with AD. OBJECTIVE: To estimate agitation prevalence in a sample of US patients with AD/dementia overall and by AD/dementia disease severity, using data from electronic health records (EHR). METHODS: This retrospective database study examined community-dwelling patients with ≥1 EHR record indicating AD/dementia from January 2008 to June 2015 and no evidence of non-Alzheimer dementia during the 12-month preindex and postindex periods. Agitation was identified using diagnosis codes for dementia with behavioral disturbance and EHR abstracted notes records indicating agitation symptoms compiled from the International Psychogeriatric Association provisional consensus definition. RESULTS: Of 320 886 eligible patients (mean age, 76.4 y, 64.7% female), 143 160 (44.6%) had evidence of agitation during the observation period. Less than 5% of patients with agitation had a diagnosis code for behavioral disturbance. The most prevalent symptom categories among patients with agitation, preindex and postindex, were agitation (31.4% and 41.3%), falling (22.6% and 21.7%), and restlessness (18.3% and 23.3%). Among the 78 827 patients (24.6%) with known AD/dementia severity, agitation prevalence was 61.3%. Agitation during the observation period was most prevalent for moderate-to-severe and severe AD/dementia (74.6% and 68.3%, respectively) and lowest for mild AD/dementia (56.4%). CONCLUSIONS: Agitation prevalence was 44.6% overall and 61.3% among patients with staged AD/dementia. Behavioral disturbance appeared to be underdiagnosed. While agitation has previously been shown to be highly prevalent in the long-term care setting, this study indicates that it is also common among community-dwelling patients.

Patient and Care Partner Burden in CKD Patients With and Without Anemia: A US-Based Survey.

Rationale & Objective: Chronic kidney disease (CKD) has a far-reaching impact on both patients and care partners, which can be further compounded by frequent complications such as anemia. This study assessed the burden experienced by patients with CKD and the care partners of patients with CKD, with and without anemia. Study Design: Online survey. Setting & Participants: Adult patients with CKD and the care partners of adult patients with CKD living in the United States were recruited through the American Association of Kidney Patients and a third-party online panel (January 9, 2020-March 12, 2020). Outcomes: Patient and care partner characteristics, care received or provided; health-related quality of life, and work productivity. Analytical Approach: Descriptive statistics were reported separately based on the presence or absence of anemia. Results: In total, 410 patients (anemia: n=190, no anemia: n=220) and 258 care partners (anemia: n=110, no anemia: n=148) completed the survey. Most patients reported receiving paid or unpaid care because of their health condition (anemia: 58.9%, no anemia: 50.9%), with an overall average of 14.2 and 11.3 h/wk among the anemia and no anemia patients, respectively. The care partners also reported providing numerous hours of care (anemia: 33.6 h/wk, no anemia: 38.0 h/wk), especially care partners living with their care recipient (anemia: 52.6 h/wk, no anemia: 42.8 h/wk). Among the patients, those with anemia reported a numerically lower average health-related quality of life (Functional Assessment of Cancer Therapy-Anemia score, anemia: 110.1; no anemia: 121.6). Most care partners reported a severe or very severe burden (Burden Scale for Family Caregivers-Short Version score≥15, anemia: 69.1%; no anemia: 58.8%). The work productivity impairment was substantial among employed patients (anemia: 44.9%, no anemia: 35.4%) and employed care partners (anemia: 47.9%, no anemia: 40.7%). Limitations: The survey results may have been subject to selection and recall biases; moreover, the observational nature of the study does not allow for causal inferences. Conclusions: Patients with CKD and the care partners of patients with CKD experience a considerable burden, especially when anemia is present.

Agitation in Dementia: Real-World Impact and Burden on Patients and the Healthcare System.

BACKGROUND: At least 90%of patients with dementia experience behavioral or neuropsychiatric symptoms including agitation, psychotic symptoms, apathy, depression, and sleep disturbances. Agitation has been reported to be experienced by 60%of patients with mild cognitive impairment and 76%of patients with Alzheimer's disease. OBJECTIVE: We aimed to assess the impact of agitation in patients with dementia on healthcare resource utilization (HCRU) and healthcare costs. METHODS: This was a retrospective analysis of physician-reported patient data from a point-in-time survey. Patients included were aged≥50 years, with early cognitive impairment or dementia. Agitated and non-agitated patients were compared. Regression analyses assessed the relationship of agitation score (calculated from number/severity of agitation symptoms) with outcomes, with covariates including age and Mini-Mental State Examination score. Sensitivity analyses compared patients with 0 and≥2 agitation symptoms following propensity score matching on the base-case covariates. RESULTS: Data were included for 1,349 patients (agitated, n = 693; non-agitated, n = 656). Based on regression analyses, agitation score was correlated with proportion of patients with professional caregivers (p < 0.01), institutionalized (p < 0.01), hospitalized in a psychiatric ward (p < 0.05), and receiving an antipsychotic/antidepressant (both p < 0.001); number of consultations with a healthcare professional (HCP), psychiatrist, or psycho-geriatrician; number and cost of hospitalizations (p < 0.01); cost of HCP consultations (p < 0.001); and total direct healthcare costs (p < 0.001). Sensitivity analyses generally supported the base-case analysis. CONCLUSION: Agitation in dementia is associated with increased HCRU and healthcare costs. Effective therapies are needed to address agitation in dementia, with the potential to alleviate patient impact, HCRU, and healthcare costs.

Regional variations in prevalence and severity of autosomal dominant polycystic kidney disease in the United States.

OBJECTIVES: To evaluate geographic variation in the prevalence of autosomal dominant polycystic kidney disease (ADPKD) in the US, including ADPKD at risk of rapid progression. METHODS: Claims data from the IBM MarketScan Commercial and Medicare Supplemental databases (01/16/2016-12/31/2017) were used to estimate the 2017 annual and 2016-2017 two-year prevalence of diagnosed ADPKD and ADPKD at risk of rapid progression in the US overall, and stratified by census regions and states. Risk of rapid progression was identified based on either: hypertension <35 years, hematuria <30 years, albuminuria, stage 2 chronic kidney disease (CKD) <30 years, stage 3 CKD <50 years, and stage 4/5 CKD or kidney transplant <55 years. RESULTS: Annual prevalence was estimated at 2.34 and two-year prevalence at 3.61 per 10,000 in the US. Across census regions, two-year prevalence per 10,000 was highest in the Northeast (4.14) and lowest in the West (3.35). Prevalence was significantly correlated with the proportion of individuals in urban areas (r = .34, one-sided p = .026). In 2017, 37.5% of patients were identified as being at risk for rapid progression, and this proportion was larger among patients in the South (42.1%, p < .001). CONCLUSION: This estimate for ADPKD prevalence is consistent with previously reported national estimates, with regional variation suggesting that ADPKD might be under-diagnosed in rural areas with more limited access to care. More than one-third of ADPKD patients presented risk factors associated with rapid progression, highlighting the need for timely identification, as disease-modifying therapy may delay progression to end-stage renal disease.

Real-World Treatment Patterns and Characteristics Among Patients with Agitation and Dementia in the United States: Findings from a Large, Observational, Retrospective Chart Review.

BACKGROUND: Few studies have examined patient characteristics and treatment patterns among patients with dementia and agitation in the United States (US). OBJECTIVE: To examine real-world treatment patterns and characteristics of patients with agitation related to dementia who were treated with antipsychotics in US residential care and community-based settings. METHODS: This retrospective chart review collected US physician-level data from patients 55 to 90 years old initiated on an antipsychotic medication for the treatment of agitation related to dementia from January 2018 to May 2018. Clinical characteristics and treatment patterns were assessed overall and stratified by residential care and community-based settings. RESULTS: A total of 313 participating physicians, 59.5% of whom were primary care physicians, abstracted 801 patient charts (residential care: n = 312; community-based: n = 489). Of patients with agitation who were initiated on an antipsychotic, most patients (74.5%) were initiated within 3 months of the onset of their studied agitation episode, and 62.8% experienced multiple agitation episodes before initiation. While non-pharmacological therapies are recommended first-line approach for agitation in dementia, use of non-pharmacological therapy before initiation of antipsychotics was reported for only 37.8% of patients in residential care and 21.3% in community-based settings. CONCLUSION: Most patients were initiated on an antipsychotic treatment after multiple episodes of agitation and largely without initial non-pharmacological therapy, suggesting that current treatment guideline recommendations for first-line non-pharmacological intervention may not be adequately followed in clinical practice. Understanding the clinical burden and treatment patterns among dementia patients with agitation is imperative for effective disease management.

Severity of memory impairment in the elderly: Association with health care resource use and functional limitations in the United States.

INTRODUCTION: Dementia is a prevalent condition in older adults associated with decline in cognitive and functional abilities and substantial burden. This study assessed the prevalence and impact of subjective memory impairment in the United States. METHODS: The 2011 to 2014 National Health and Nutrition Examination Survey, a population-based, nationally representative survey, was analyzed. Data included medical examinations, self-reported cognitive and functional limitations, and health care utilization over 1 year. Participants were aged ≥65 years and completed both interview and medical examination components. Descriptive analyses of patient characteristics were performed, and complex survey regression models were used to test associations. RESULTS: Of 2431 survey participants included, 53.1% had no memory impairment, 40.1% had early-stage memory impairment, and 6.6% had late-stage memory impairment. In adjusted analyses, late-stage versus no impairment was associated with more functional limitations (odds ratio [OR] = 7.26, P < .001), greater health care utilization (OR = 2.46, P < .001), and higher likelihood of seeing a mental health specialist (OR = 3.06, P = .001). DISCUSSION: Consistent with previous research, individuals with late-stage memory impairment had significantly greater functional limitations and higher health care utilization versus individuals with early-stage or no memory impairment.

Cost-effectiveness of brexpiprazole adjunctive treatment for major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is a debilitating psychiatric illness with a high cost burden. This analysis evaluates the cost-effectiveness of adjunctive brexpiprazole versus comparator branded adjunctive treatment for MDD and background antidepressant therapy (ADT) alone from a US payer perspective. METHODS: An economic model was developed to assess the cost-effectiveness of brexpiprazole versus comparator adjunctive treatment and ADT alone on total direct medical costs using a 6-week cycle time frame for a total of 48 weeks, with treatment response and remission as primary outcomes. The model consisted of 3 parts, 1 to represent the acute treatment phase and 2 to represent the maintenance stage. RESULTS: In the base-case analysis, brexpiprazole as reference treatment resulted in cost per additional responder ranging from $19,442-$48,745 and cost per additional remitter ranging from $27,196-$71,839 versus comparator treatments over 48 weeks. Sensitivity analyses showed treatment with brexpiprazole was more costly, but more clinically effective in all probabilistic simulations. LIMITATIONS: This representation of disease natural history over 48 weeks may not account for all possible health states. Resource utilization on treatment was estimated using the resource use data from previous trials, and may overestimate medical costs compared to the real-world setting. Treatment comparators were limited to branded therapies, and head-to-head studies were not available to obtain data inputs. CONCLUSION: Compared to other branded adjunctive therapies, brexpiprazole increases response and remission at 6 weeks; medical care cost savings were observed with the use of brexpiprazole. These findings may assist clinicians and formulary decision makers when selecting treatment for MDD.

A Real-world Analysis of Treatment Patterns for Cholinesterase Inhibitors and Memantine among Newly-diagnosed Alzheimer's Disease Patients.

INTRODUCTION: Alzheimer's disease (AD) is the most common neurodegenerative form of dementia. Pharmacological therapies for symptomatic treatment, such as acetylcholinesterase inhibitors (AChEIs) and memantine, have been available in the USA since 2000. Over the past decade, few studies have analyzed real-world anti-dementia treatment patterns in the USA. This study evaluated monotherapy AChEIs and memantine treatment patterns among newly diagnosed AD patients. METHODS: A retrospective cohort study was conducted using Medicare data and the Minimum Data Set from 2008 to 2012. Patients aged 65-100 years with newly diagnosed AD (ICD-9 code: 331.0) and monotherapy AChEI or memantine treatment initiated after diagnosis were included. Descriptive treatment pattern analyses, including discontinuation and switch, were undertaken. Kaplan-Meier curves were developed to examine the treatment duration. RESULTS: A total of 9812 newly diagnosed AD patients were identified, with 56.7% (n = 5567) first receiving anti-dementia treatment after the initial AD diagnosis. Among patients initiating monotherapy AChEIs or memantine after AD diagnosis (N = 5200), 51.6% continued index treatment during the entire follow-up period (mean follow-up: 659.7 days) and 21.7% discontinued treatment. Of those who initiated monotherapy treatment with an AChEI, 11.1% received adjunct therapy with memantine. Among patients with ≥1 year of continuous treatment (mean follow-up: 834 days), 75.6% remained on the index drug, 10.2% discontinued during the remaining follow-up period, and 9.5% of the AD patients initiating AChEIs received adjunct memantine therapy during the remaining follow-up period. CONCLUSION: In the USA Medicare population, about 50% of the patients who initiated treatment with AChEI or memantine after diagnosis continued the index treatment, and more than 20% discontinued and were untreated afterwards over the observation period. AD patients initiating AChEIs or memantine were more likely to remain on their treatment if they were persistently treated for the first year.

Pharmaceutical Innovation in the Treatment of Schizophrenia and Mental Disorders Compared with Other Diseases.

OBJECTIVES: The objectives of this study were to assess the level of private and public investment in research and development of treatments for schizophrenia and other mental disorders compared to other diseases in order to present data on the economic burden and pharmaceutical innovation by disease area, and to compare the level of investment relative to burden across different diseases. DESIGN: The levels of investment and pharmaceutical innovation relative to burden across different diseases were assessed. Disease burden and prevalence for mental disorders (schizophrenia, bipolar disorder, and major depressive disorder); cancer; rheumatoid arthritis; chronic obstructive pulmonary disorder; diabetes; cardiovascular disease; and neurological disorders (dementia and epilepsy) were estimated from literature sources. SETTING: Pharmaceutical treatment innovation was measured by the total number of drug launches and the number of drugs launched categorized by innovativeness. Research and development expenditures were estimated using published information on annual public and domestic private research and development expenditures by disease area. Lastly, investment relative to disease burden was measured among the set of disease classes for which all three measures were available: schizophrenia, bipolar disorder, major depressive disorder, cancer, rheumatoid arthritis, chronic obstructive pulmonary disease, diabetes, cardiovascular disease, and neurology (dementia and epilepsy combined). RESULTS: The level of investment and pharmaceutical innovation in mental disorders was comparatively low, especially relative to the burden of disease. For mental disorders, investment was $3.1 per $1,000 burden invested in research and development for schizophrenia, $1.8 for major depressive disorder, and $0.4 for bipolar disorder relative to cancer ($75.5), chronic obstructive pulmonary disease ($9.4), diabetes ($7.6), cardiovascular disease ($6.3), or rheumatoid arthritis ($5.3). Pharmaceutical innovation was also low for mental disorders. CONCLUSION: Despite the significant burden mental disorders impose on society, investment and pharmaceutical innovation in this disease area remains comparatively low. Policymakers should consider new strategies to stimulate public and private investment in the research and development of novel and effective therapies to treat schizophrenia and other mental disorders.

The Economic Burden of Schizophrenia in the United States in 2013.

OBJECTIVE: The objective of this study was to estimate the US societal economic burden of schizophrenia and update the 2002 reported costs of $62.7 billion given the disease management and health care structural changes of the last decade. METHODS: A prevalence-based approach was used to assess direct health care costs, direct non-health care costs, and indirect costs associated with schizophrenia (ICD-9 codes 295.xx) for 2013, with cost adjustments where necessary. Direct health care costs were estimated using a retrospective matched cohort design using the Truven Health Analytics MarketScan Commercial Claims and Encounters, Medicare Supplemental, and Medicaid Multistate databases. Direct non-health care costs were estimated for law enforcement, homeless shelters, and research and training. Indirect costs were estimated for productivity loss from unemployment, reduced work productivity among the employed, premature mortality (ie, suicide), and caregiving. RESULTS: The economic burden of schizophrenia was estimated at $155.7 billion ($134.4 billion-$174.3 billion based on sensitivity analyses) for 2013 and included excess direct health care costs of $37.7 billion (24%), direct non-health care costs of $9.3 billion (6%), and indirect costs of $117.3 billion (76%) compared to individuals without schizophrenia. The largest components were excess costs associated with unemployment (38%), productivity loss due to caregiving (34%), and direct health care costs (24%). CONCLUSIONS: Schizophrenia is associated with a significant economic burden where, in addition to direct health care costs, indirect and non-health care costs are strong contributors, suggesting that therapies should aim at improving not only symptom control but also cognition and functional performance, which are associated with substantial non-health care and indirect costs.