Mortality risk in patients with autosomal dominant polycystic kidney disease.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the leading inheritable cause of end-stage renal disease (ESRD). Mortality data specific to patients with ADPKD is currently lacking; thus, the aim of this study was to estimate mortality in patients with ADPKD. METHODS: We analyzed data from the United States Renal Data System (USRDS) for patients with ADPKD available during the study period of 01/01/2014-12/31/2016, which included a cohort of patients with non-ESRD chronic kidney disease (CKD) and a cohort of patients with ESRD. Mortality rates with 95% confidence intervals (CIs) were calculated overall and by age group, sex, and race for the full dataset and for a subset of patients aged ≥ 65 years. Adjusted mortality hazard ratios (HRs) were calculated using Cox regression modeling by age group, sex, race, and CKD stage (i.e., non-ESRD CKD stages 1-5) or ESRD treatment (i.e., dialysis and transplant). RESULTS: A total of 1,936 patients with ADPKD and non-ESRD CKD and 37,461 patients with ADPKD and ESRD were included in the analysis. Age-adjusted mortality was 18.4 deaths per 1,000 patient-years in the non-ESRD CKD cohort and 37.4 deaths per 1,000 patient-years in the ESRD cohort. As expected, among the non-ESRD CKD cohort, patients in CKD stages 4 and 5 had a higher risk of death than patients in stage 3 (HR = 1.59 for stage 4 and HR = 2.71 for stage 5). Among the ESRD cohort, patients receiving dialysis were more likely to experience death than patients who received transplant (HR = 2.36). Age-adjusted mortality among patients aged ≥ 65 years in the non-ESRD CKD cohort was highest for Black patients (82.7 deaths per 1,000 patient-years), whereas age-adjusted mortality among patients aged ≥ 65 years in the ESRD cohort was highest for White patients (136.1 deaths per 1,000 patient-years). CONCLUSIONS: Mortality rates specific to patients aged ≥ 65 years suggest racial differences in mortality among these patients in both non-ESRD CKD and ESRD cohorts. These data fill an important knowledge gap in mortality estimates for patients with ADPKD in the United States.

A disease progression model estimating the benefit of tolvaptan on time to end-stage renal disease for patients with rapidly progressing autosomal dominant polycystic kidney disease.

BACKGROUND: Tolvaptan was approved in the United States in 2018 for patients with autosomal dominant polycystic kidney disease (ADPKD) at risk of rapid progression as assessed in a 3-year phase 3 clinical trial (TEMPO 3:4). An extension study (TEMPO 4:4) showed continued delay in progression at 2 years, and a trial in patients with later-stage disease (REPRISE) provided confirmatory evidence of efficacy. Given the relatively shorter-term duration of the clinical trials, estimating the longer-term benefit associated with tolvaptan via extrapolation of the treatment effect is an important undertaking. METHODS: A model was developed to simulate a cohort of patients with ADPKD at risk of rapid progression and predict their long-term outcomes using an algorithm organized around the Mayo Risk Classification system, which has five subclasses (1A through 1E) based on estimated kidney growth rates. The model base-case population represents 1280 patients enrolled in TEMPO 3:4 beginning in chronic kidney disease (CKD) stages G1, G2, and G3 across Mayo subclasses 1C, 1D, and 1E. The algorithm was used to predict longer-term natural history health outcomes. The estimated treatment effect of tolvaptan from TEMPO 3:4 was applied to the natural history to predict the longer-term treatment benefit of tolvaptan. For the cohort, analyzed once reflecting natural history and once assuming treatment with tolvaptan, the model estimated lifetime progression through CKD stages, end-stage renal disease (ESRD), and death. RESULTS: When treated with tolvaptan, the model cohort was predicted to experience a 3.1-year delay of ESRD (95% confidence interval: 1.8 to 4.4), approximately a 23% improvement over the estimated 13.7 years for patients not receiving tolvaptan. Patients beginning tolvaptan treatment in CKD stages G1, G2, and G3 were predicted to experience estimated delays of ESRD, compared with patients not receiving tolvaptan, of 3.8 years (21% improvement), 3.0 years (24% improvement), and 2.1 years (28% improvement), respectively. CONCLUSIONS: The model estimated that patients treated with tolvaptan versus no treatment spent more time in earlier CKD stages and had later onset of ESRD. Findings highlight the potential long-term value of early intervention with tolvaptan in patients at risk of rapid ADPKD progression.

Mental Health and Health-Related Quality of Life Among Nephrology Nurses: A Survey-Based Cross-Sectional Study.

Nephrology nurses face health and wellness challenges due to significant work-related stressors. This survey, conducted online between July 24 and August 17, 2020, assessed the psychological well-being of nephrology nurses in the United States during the COVID-19 pandemic (n = 393). Respondents reported feeling burned out from work (62%), symptoms of anxiety (47% with Generalized Anxiety Disorder-7 [GAD-7] scores ≥ 5), and major depressive episodes (16% with Patient Health Questionnaire-2 [PHQ-2] scores ≥ 3). Fifty-six percent (56%) of survey respondents reported caring for COVID-19 patients, and 62% were somewhat or very worried about COVID-19. Factors, including high workload, age, race, and the COVID-19 pandemic, may partially explain the high proportion of nephrology nurses who reported symptoms of burnout, anxiety, and depression.

Variation in health plan coverage of ESAs for anemia due to chronic kidney disease.

BACKGROUND: Because health plans each issue their own policies, drug coverage can vary. This variation can result in patients having unequal access to treatment. In this study, we evaluate commercial health plans' coverage policies for erythropoiesis-stimulating agents (ESAs) for patients with anemia resulting from chronic kidney disease (CKD). OBJECTIVES: To assess how a set of US commercial health plans cover ESAs for patients with anemia due to CKD. Our second objective was to examine the evidence that the plans reviewed when formulating their coverage policies. METHODS: We used the Tufts Medical Center Specialty Drug and Evidence and Coverage Database to identify coverage policies issued by 17 of the largest US commercial health plans for ESAs. The following drugs were indicated for anemia due to CKD: darbepoetin alfa, methoxy polyethylene glycol-epoetin beta, epoetin alfa (available as two brands), and epoetin alfa-epbx. Coverage policies were current as of May 2019. We determined whether the health plans applied any restrictions, such as step therapy protocols or patient subgroup restrictions, in their coverage policies. We categorized the evidence that plans cited to support their policies into seven categories: randomized controlled trials (RCTs), real-world evidence (RWE) studies (studies based on data collected in a real-world setting), other clinical studies (eg, single arm trials), systematic reviews and/or meta-analyses, clinical or treatment guidelines, health technology assessments, and economic evaluations. RESULTS: We categorized 72.5% of coverage policies (58/80 policies) as equivalent to the FDA label and 27.5% (22/80 policies) as more restrictive. In restricted policies, plans most often applied step therapy protocols (18/22 policies), followed by prescriber requirements (4/22 policies), and patient subgroup restrictions (3/22 policies). Five health plans applied restrictions in at least half of their coverage policies; seven plans did not apply restrictions in any policy. Plans that cited evidence reviewed an average of 10 citations across their ESA coverage policies, ranging from one to 29 studies. Plans varied with respect to the types of cited studies: at least 50% of evidence cited by five health plans was RCTs, while half or more of the evidence cited by four health plans was clinical or treatment guidelines. CONCLUSIONS: Health plans varied in how they covered ESAs for patients with anemia due to CKD and in the evidence cited in their coverage policies. Inconsistencies in plans' coverage policies may have implications for patients' access to ESAs. DISCLOSURES: This study was funded by Otsuka Pharmaceutical Development and Commercialization. Sanon, Redmond, and Mogahadam are employed by Otsuka Pharmaceutical. Michalopoulos was employed by Otsuka Pharmaceutical at the time of this study. Margaretos, Panzer, and Chambers are employed by Tufts Medical Center, Institute for Clinical Research and Health Policy Studies, Center for the Evaluation of Value and Risk in Health. Lai was with Tufts Medical Center, Institute for Clinical Research and Health Policy Studies, Center for the Evaluation of Value and Risk in Health at the time of this study.

Excess healthcare costs in patients with autosomal dominant polycystic kidney disease by renal dysfunction stage.

AIM: To build upon previous outdated studies by comprehensively assessing the direct healthcare burden of autosomal dominant polycystic kidney disease (ADPKD). MATERIALS AND METHODS: Patients with ≥2 diagnoses for ADPKD (ADPKD cohort) were identified in the US fee-for-use IBM Truven Health Analytics MarketScan Commercial Claims and Encounters and IBM Truven Health Analytics MarketScan Medicare Supplemental databases (01 January 2015-31 December 2017) and matched (1:3) to controls without ADPKD (non-ADPKD cohort). The index date was the last calendar date followed by 12 months continuous enrollment (study period). Patients with ADPKD were stratified into one of seven mutually exclusive groups based on chronic kidney disease (CKD) stages (I-V), end-stage renal disease requiring renal replacement therapy (ESRD-RRT), and unknown stage. RESULTS: During the 12-month study period, patients with ADPKD incurred significantly higher total healthcare costs than those without ADPKD (mean cost difference = $22,879 per patient per year [PPPY]; p < .001). Besides CKD stages I and II, total healthcare cost differences increased as patients progressed beyond CKD stage III, with the greatest difference observed among patients with ESRD-RRT. Total healthcare cost differences between cohorts were more pronounced in subgroups of patients with hypertension ($29,347) and with high risk of rapid progression ($39,976). Similar results were observed in the Medicare Supplemental population, with a total mean cost difference of $42,694 PPPY (p < .001); cost difference was also higher in the hypertension ($46,461 PPPY) and high risk of rapid progression ($45,708 PPPY) subgroups. LIMITATIONS: Results may not be representative of the overall ADPKD US population; CKD stage was based on diagnosis and procedure codes; criteria used to identify ADPKD at risk of rapid progression did not rely on laboratory values; there may be billing inaccuracies and omissions in health insurance claims data. CONCLUSIONS: This study demonstrated the substantial healthcare costs associated with ADPKD, which increased as patients progressed through more severe CKD stages.

P016 Impact of Non-Remission on Health-Related Quality of Life and Patient Reported Outcomes in Patients With Crohn's Disease: Targeted Literature Review.

BACKGROUND: Crohn's disease (CD) leads to chronic inflammation of the gastrointestinal tract that significantly impacts patients over an entire lifetime. The decrease in health-related quality of life (HRQoL) may have an impact on patient's level of functioning, work productivity, and other activities. The goal of treatment for CD is clinical remission based on clinical, endoscopic, and biological parameters. There has been introduction of new treatments in recent years. A review was conducted to assess the impact of non-remission on HRQoL and patient reported outcomes (PROs) in patients with CD. METHODS: Literature search of English language publications from 2015-2021 was conducted in Embase® and MEDLINE®. Real world studies meeting predefined criteria (adult CD patients in non-remission presenting data for HRQoL or PROs) were included in the review. Data on study characteristics, disease characteristics, HRQoL and PROs were extracted from the included studies. RESULTS: The review retrieved 1384 records from which only 10 studies presented data for HRQoL and/or PROs. The definition of remission varied across the included studies. In most studies (90%), remission was defined using Harvey-Bradshaw Index and/or Crohn's disease activity index. Different tools were used to assess HRQoL and sleep quality. In a study, no normalization of long-term HRQoL was observed in patients who did not achieve clinical remission. A negative correlation was found between utility indexes & disease activity in a study (ρ = -0.586, p < 0.001). A significant correlation was also observed in a study between HRQoL and disease activity where HRQoL in patients with active disease was poor compared to patients in remission. The HRQoL domains of anxiety, depression and pain were impacted in non-remitters. The mean IBDQ score was 189 ± 16.1 in remitters and 145 ± 15.9 in non-remitters (p < 0.001). A strong negative correlation between IBDQ and disease activity was reported by a study. In a study, work productivity was moderately but significantly correlated with disease activity indicating reduction in work productivity of patients with active disease (mild, moderate, and severe) compared to remitters. In another study, severe disease activity was significantly associated with an increased amount of fragmented sleep. Patients with moderate to severe disease had a significantly longer time awake after falling asleep compared to patients in remission or with mild disease activity (65.8 minutes, 44.3 minutes, 49.1 minutes, respectively). Patients with active disease also reported poor sleep quality and suffered from excessive daytime sleepiness. There was a significant difference in the median sleep efficiency for patients with moderate to severe disease compared to patients with remission. CONCLUSION: This targeted review found in general that not being able to achieve/maintain remission had an impact on the HRQoL of patients with CD. Patients not achieving remission were associated with decreased work productivity, poor sleep quality, lower sleep efficiency, daytime sleepiness and poor HRQoL. However, studies assessing HRQoL and PROs in the real-world are scarce, with discrepancies based on remission status. Further research is warranted, and health care providers and payers should consider the impact of therapies on the improvement in HRQoL of patients with CD.

P025 The Impact of Non-Remission on Costs and Resource Use In Patients With Crohn's Disease: Targeted Literature Review.

BACKGROUND: The incidence of Crohn's disease (CD) has been rising globally. Patients with CD are at an increased risk of mortality compared to general population. The goal of treatment for CD is clinical remission based on clinical, endoscopic, and biological parameters. There has been introduction of new treatments in recent years. A review was conducted to assess the impact of non-remission on cost and resource use in patients with CD. METHODS: Literature search of English language publications from 2015-2021 was conducted in Embase® and MEDLINE®. Real world studies meeting predefined review criteria were included and data were extracted in pre-defined extraction form. RESULTS: The review retrieved 1384 records; 24 fulfilled eligibility criteria. The definition of remission varied across the included studies. In most studies (66.67%), remission was defined using Crohn's disease activity index and/or Harvey-Bradshaw Index. Among included evidence, 21 studies reported proportion of non-remitters undergoing surgery, 11 studies reported the data for hospitalizations and 2 studies reported cost of treatment for non-remitters. Proportion of non-remitters requiring hospitalizations ranged from 6.7% to 30.6%. Univariate analysis suggested that deep remission was significantly associated with lower hazards for being hospitalized (HR: 0.18 [95%CI: 0.08, 0.25]); suggesting a significantly higher risk of hospitalization in non-remitters. In a study, the mean duration of cumulative hospital stays was significantly higher in patients with a pathological MRI (19.7 ± 7.4 days) compared to patients in deep remission (0.75 ± 0.52 days, p < 0.05). The proportion of non-remitters undergoing surgery ranged from 1.5% to 57%. The proportion of patients undergoing surgery were high in non-remitters compared to remitters. Hematopoietic stem cell transplantation was needed in 4.1% non-remitters and repeat surgery in 3.5% non-remitters. In a study, surgery was required by 11.6% patients with no healing (due to refractory strictures, penetrating complications, and severe refractory disease) and 11.5% patients presenting with mucosal healing (due to structuring and penetrating complications), while no patient with transmural healing required surgery. Non-remission led to higher total costs, especially in patients undergoing surgery or dependent on in-hospital administrated drugs. The costs were 4 to 6 times higher in patients in an active period and 19 times higher for patients requiring surgery compared to patients in remission. Adjusted total indirect cost among participants with disease remission was reduced by 60% compared to patients with active disease (€243.44 per patient per month, p < 0.001). The number of consultations in the last month, monthly consultation cost, current treatment cost, amount of benefits from public organisations, and self-reported expenses on all categories were significantly higher in non-remitters compared to patients in remission. CONCLUSION: This targeted review found in general that not being able to achieve/maintain remission has an impact on the economic outcomes of patients with CD. Non-remission in patients with CD was associated with an increased number of hospitalizations and surgeries. The cost of treatment for non-remitters was significantly higher than patients in remission. None of the studies presented data for patients who respond to treatment but are not able to achieve remission. Further research is warranted in these patients.

P043 Resource Utilization and Productivity Loss among Patients with Inflammatory Bowel Disease in Sweden: A Longitudinal Nationwide Population-based Study.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are the two most prevalent forms of inflammatory bowel disease (IBD) causing frequent diarrhea, rectal bleeding, fatigue, and abdominal pain. IBD may result in complications requiring hospitalizations and surgical procedure, hence IBD can negatively impact patients' quality of life, work productivity, and increase societal economic burden. Limited data exists assessing epidemiologic trends and population-level health outcomes among patients with IBD in Sweden. This study assessed the trends in annual incidence and prevalence of CD, annual inpatient and outpatient visits, employment status and sickness absence among adults with IBD in Sweden from 2001 to 2017. METHODS: Data were acquired from four nationwide registers provided by the National Board of Health and Welfare in Sweden and linked through the unique personal identity number. Individuals aged ≥18 years with ≥2 primary diagnoses of CD (ICD-10 K50) or ≥2 primary diagnoses of UC (ICD-10 K51) from 01/01/2001 to 12/30/2017 were selected. Date of the first CD or UC diagnosis was designated as index date. All individuals were followed until death, lost to follow up or end of study. RESULTS: A total of 30,895 patients with CD and 50,415 with UC were included in the analysis, respectively. The mean follow-up for patients was 10.1 (±5.33) and 10.4 (±5.21) years for CD and UC. The mean (±SD) age among CD patients was 40.4 (±18.4) years and 42.6 (±18.2) years for UC. The most frequently observed comorbid condition was noninfective enteritis and colitis for patients with CD (24.2%) and UC (15.7%). The annual incidence of CD was 10 per 100,000 person-years in 2017, while the incidence of UC was 3 per 100,000 in 2017. 40.6% of CD patients and 30.8% of UC patients had ≥ 1 inpatient admission during 1-year post-index period, of which 53.5% and 51.2% had inpatient care lasting more than 1 week. Among patients with ≥ 1 outpatient services (CD: n = 30,675; UC: n = 50,183), 41.7% and 29.2% of patients had more than 5 visits during 1-year post-index period. Among patients who were eligible for employment and disability benefit analyses who had at least 1-year follow-up (CD: n = 23,731; UC: n = 39,391), 27.9% of CD patients and 23.1% of UC patients were not in employment; among those who were in employment (CD: n = 17,039; UC: n=30,302), 30% and 24.6% reported sickness absence within the calendar year after the index date, respectively. CONCLUSION: Findings from this study of a large national cohort of patients followed for many years demonstrates the significant epidemiological, clinical, and socioeconomic impact of patients with CD and UC. Further research is needed to understand underlying factors driving inpatient admissions among patients with IBD. With an increasing annual prevalence, IBD continues to impose a substantial public health burden to patients, their families and health care services.

Association of the US Food and Drug Administration Antipsychotic Drug Boxed Warning With Medication Use and Health Outcomes in Elderly Patients With Dementia.

Importance: Atypical antipsychotics (AAPs) are often used off-label to manage dementia-associated neuropsychiatric symptoms. In 2005, the US Food and Drug Administration (FDA) issued a boxed warning for the use of AAPs in elderly patients. The long-term association of this warning with health outcomes is unknown to date. Objective: To assess the long-term association of the 2005 FDA boxed warning on AAPs with psychiatric medication and opioid use, health events, and quality of life among elderly individuals with dementia. Design, Setting, and Participants: For this cross-sectional study, data were analyzed from the household component of the Medical Expenditure Panel Survey (MEPS), the National Ambulatory Medical Care Survey (NAMCS), and the National Hospital Ambulatory Medical Care Survey (NHAMCS) fielded between January 1, 1996, and December 31, 2014. This interrupted time-series analysis applied to 3-year moving means derived from the 1996-2014 MEPS, NAMCS, and NHAMCS. All survey respondents included in this analysis were 65 years or older and had dementia. Data analysis was performed from December 1, 2017, to March 15, 2018. Exposures: The 2005 FDA boxed warning on AAPs. Main Outcomes and Measures: Use of psychiatric medications and opioids, prevalence of cerebrovascular and cardiovascular events, prevalence of falls and/or fractures, 2-year mortality, and health-related quality of life assessed by the Medical Outcomes Study 12-Item Short-Form Health Survey scores. Results: A total of 2430 (MEPS) and 5490 (NAMCS and NHAMCS) respondents were identified, corresponding to weighted populations of 22 996 526 (MEPS) and 65 502 344 (NAMCS and NHAMCS) noninstitutionalized elderly individuals with dementia (mean [SD] age, 81.06 [1.13] years; 63.1% female). In the MEPS sample, compared with before 2005, AAP use (from an annual slope of 0.99 to -0.18 percentage points), cerebrovascular events (0.75 to -0.50 percentage points), and falls and/or fractures (-1.72 to -0.40 percentage points) decreased and opioid use (0.04 to 1.29 percentage points), antiepileptic use (-0.42 to 1.21 percentage points), cardiovascular events (-0.13 to 1.30 percentage points), and 2-year mortality risk (-0.68 to 0.18 percentage points) increased. Health-related quality of life remained relatively unchanged. The NAMCS and NHAMCS sample yielded similar findings. Conclusions and Relevance: These data suggest that the 2005 FDA boxed warning was associated with some unintended negative patient outcomes.

Economic Burden and Health-Related Quality of Life Associated with Current Treatments for Anaemia in Patients with CKD not on Dialysis: A Systematic Review.

BACKGROUND: The cost and health-related quality of life (HRQoL) burden associated with treatments for anaemia of chronic kidney disease (CKD) is not well characterized among non-dialysis-dependent (NDD) patients. OBJECTIVE: Our objective was to review the literature on costs and HRQoL associated with current treatments for anaemia of CKD among NDD patients. METHODS: The Cochrane Library, MEDLINE, Embase, NHS EED, and NHS HTA databases were searched for original studies published in English between 1 January 2000 and 17 March 2017. The following inclusion criteria were applied: adult population; primary focus was anaemia of CKD; patients received iron supplementation, red blood cell transfusion, or erythropoiesis-stimulating agents (ESAs); and reported results on HRQoL and/or costs. Studies that included NDD patients, did not compare different treatments, and had relevant designs were retained. HRQoL and cost outcomes were summarized in a narrative synthesis. RESULTS: In total, 16 studies met the inclusion criteria: six randomized controlled trials, four prospective single-arm trials, three retrospective studies, one prospective observational study, one simulation study, and one cross-sectional survey. All included ESAs. Treatment of anaemia (compared with no treatment) was associated with HRQoL improvements in five of six studies and lower costs in four of four studies. Treatment aiming for higher haemoglobin targets (compared with lower targets) resulted in modest HRQoL improvements, higher healthcare resource utilization (HRU), and higher costs. CONCLUSIONS: In NDD patients, untreated anaemia of CKD leads to higher costs, higher HRU, and lower HRQoL compared with initiating anaemia treatment. Relative to aiming for lower haemoglobin targets with ESAs, higher targets conferred modest HRQoL improvements and were associated with higher HRU.

Economic and quality of life burden of anemia on patients with CKD on dialysis: a systematic review.

Aims: The overall cost and health-related quality of life (HRQoL) associated with current treatments for chronic kidney disease (CKD)-related anemia are not well characterized. A systematic literature review (SLR) was conducted on the costs and HRQoL associated with current treatments for CKD-related anemia among dialysis-dependent (DD) patients. Materials and methods: The authors searched the Cochrane Library, MEDLINE, EMBASE, NHS EED, and NHS HTA for English-language publications. Original studies published between January 1, 2000 and March 17, 2017 meeting the following criteria were included: adult population; study focus was CKD-related anemia; included results on patients receiving iron supplementation, red blood cell transfusion, or erythropoiesis stimulating agents (ESAs); reported results on HRQoL and/or costs. Studies which included patients with DD-CKD, did not directly compare different treatments, and had designs relevant to the objective were retained. HRQoL and cost outcomes, including healthcare resource utilization (HRU), were extracted and summarized in a narrative synthesis. Results: A total of 1,625 publications were retrieved, 15 of which met all inclusion criteria. All identified studies included ESAs as a treatment of interest. Two randomized controlled trials reported that ESA treatment improves HRQoL relative to placebo. Across eight studies comparing HRQoL of patients achieving high vs low hemoglobin (Hb) targets, aiming for higher Hb targets with ESAs generally led to modest HRQoL improvements. Two studies reported that ESA-treated patients had lower costs and HRU compared to untreated patients. One study found that aiming for higher vs lower Hb targets led to reduced HRU, while two other reported that this led to a reduction in cost-effectiveness. Limitations: Heterogeneity of study designs and outcomes; a meta-analysis could not be performed. Conclusions: ESA-treated patients undergoing dialysis incurred lower costs, lower HRU, and had better HRQoL relative to ESA-untreated patients. However, treatment to higher Hb targets led to modest HRQoL improvements compared to lower Hb targets.

The conceptual relevance of assessment measures in patients with mild/mild-moderate Alzheimer's disease.

INTRODUCTION: This study aims to evaluate the conceptual relevance of four measures of disease activity in patients with mild/mild-moderate Alzheimer's disease (AD): (1) the Alzheimer's Disease Assessment Scale-Cognitive Subscale; (2) the Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory; (3) the Neuropsychiatry Inventory; and (4) the Dependence Scale. METHODS: A conceptual model depicting patient experience of mild AD was developed via literature review; concepts were compared with the items of the four measures. Relevance of the concepts included in the four measures was evaluated by patients with mild AD in a survey and follow-up interviews. RESULTS: The four measures assessed few of the symptoms/impacts of mild AD identified within the literature. Measured items addressing emotional impacts were deemed most relevant by participants but were included in the measures only superficially. DISCUSSION: The four assessment measures do not appear to capture the concepts most relevant to/important to patients with mild/mild-moderate AD.

A retrospective, observational study of patient outcomes for critically ill patients receiving parenteral nutrition.

OBJECTIVE: To evaluate health care-related utilization for critically ill patients receiving parenteral nutrition (PN) administered via a premixed multichamber bag (MCB) or compounded solutions (COM). DESIGN: A retrospective database analysis of critically ill patients (intensive care unit stay ≥ 3 days) receiving PN and discharged between January 1, 2010, and June 30, 2011, using the Premier Hospital Database. Patients were identified as receiving MCB or COM on the basis of product description codes. Primary outcomes were length of stay (LOS) and total costs. Comorbidities and clinical outcomes were identified using International Classificaion of Diseases, Ninth Revision diagnosis codes. All costs reported were for inpatient services only. Patients receiving MCB and COM were matched on key patient and hospital characteristics using a propensity score methodology. Multivariate regression models for cost and LOS used generalized linear models with a log link and gamma distribution. RESULTS: A total of 42,631 patients met the inclusion criteria (MCB = 5,679; COM = 36,952), and the final matched population included 3,559 patients from each cohort. Baseline patient and hospital characteristics were well matched between groups. Adjusted multivariate models demonstrated a small difference between groups for LOS (MCB = 9.40 days vs. COM = 9.65 days; P = 0.014). In addition, patients receiving MCB incurred approximately 9.1% less in total costs (MCB = $37,790 vs. COM = $41,569; P < 0.001). CONCLUSIONS: Overall, patients receiving MCB and COM experienced similar LOS, though patients receiving MCB had significantly lower overall costs. Interpretation of the study findings is subject to several limitations, and additional studies that include explicit identification of the method for compounding are needed.

Cost-effectiveness of 3-years of adjuvant imatinib in gastrointestinal stromal tumors (GIST) in the United States.

BACKGROUND: Recent clinical trial data have demonstrated that 3 years vs 1 year of adjuvant imatinib therapy for patients with surgically resected Kit+ Gastrointestinal Stromal Tumors (GIST) leads to a significant improvement in recurrence-free survival and overall survival. This study assesses the cost-effectiveness of treating patients with 3 years vs 1 year of imatinib from a US payer's perspective. METHODS: A Markov model was developed to predict GIST recurrence and treatment costs. Patients enter the model after surgery and transition among three health states: free of recurrence, recurrence, and death. Recurrence, mortality, costs, and utilities were derived from clinical trial and published literature. Expected costs and quality-adjusted life years (QALYs) were estimated and discounted at 3%/year. Deterministic and probabilistic sensitivity analyses were conducted. RESULTS: Patients receiving 3 years of imatinib had higher QALYs (8.53 vs 7.18) than those receiving 1 year of imatinib. Total lifetime per-patient cost was $302,100 for 3 years vs $217,800 for 1 year of imatinib. Incremental cost effectiveness ratio of 3 years vs 1 year of imatinib was $62,600/QALY. Model results were sensitive to long-term rate of GIST recurrence (beyond 5 years) and cost of imatinib. At a threshold of $100,000/QALY, 3 years vs 1 year of imatinib was cost-effective in 100% of simulations. LIMITATIONS: The model is a simplified representation of disease natural history and may not account for all possible health states and complications associated with disease. Resource utilization on treatment was estimated using the resource use data from previous trials, therefore calculated medical costs might be over-estimated compared to the real-world setting. CONCLUSIONS: Model results suggest that treatment with 3 years vs 1 year of imatinib is cost-effective at a $100,000/QALY threshold. Clinical and economic results suggest treating surgically resected Kit+ GIST patients with 3 years of imatinib would result in improved quality-adjusted survival.

Incorporating calibrated model parameters into sensitivity analyses: deterministic and probabilistic approaches.

OBJECTIVE: The aim of this study was to examine how calibration uncertainty affects the overall uncertainty of a mathematical model and to evaluate potential drivers of calibration uncertainty. METHODS: A lifetime Markov model of the natural history of human papillomavirus (HPV) infection and cervical disease was developed to assess the cost effectiveness of a hypothetical HPV vaccine. Published data on cervical cancer incidence and mortality and prevalence of pre-cursor lesions were used as endpoints to calibrate the age- and HPV-type-specific transition probabilities between health states using the Nelder-Mead simplex method of calibration. A conventional probabilistic sensitivity analysis (PSA) was performed to assess uncertainty in vaccine efficacy, cost and utility estimates. To quantify the uncertainty around calibrated transition probabilities, a second PSA (calibration PSA) was performed using 25 distinct combinations of objective functions and starting simplexes. RESULTS: The initial calibration produced an incremental cost-effectiveness ratio (ICER) of $US 4300 per QALY for vaccination compared with no vaccination, and the conventional PSA gave a 95% credible interval of dominant to $US 9800 around this estimate (2005 values). The 95% credible interval for the ICERs in the calibration PSA ranged from $US 1000 to $US 37,700. CONCLUSIONS: Compared with a conventional PSA, the calibration PSA results reveal a greater level of uncertainty in cost-effectiveness results. Sensitivity analyses around model calibration should be performed to account for uncertainty arising from the calibration process.

Epidemiology, survival, and costs of localized gastrointestinal stromal tumors.

PURPOSE: The aim of this study is to examine the epidemiologic and economic burden in surgically resected localized gastrointestinal stromal tumor (GIST) patients versus age- and gender-matched controls. METHOD: Two data sources were used to conduct a series of complementary analyses. First, the Surveillance, Epidemiology, and End Results (SEER) cancer registry was used to identify diagnosed GIST patients from 1993 to 2002 and determine incidence, prevalence, and 3-year survival. Second, using the SEER-Medicare linked database, a matched case-control analysis was conducted to determine resource utilization, GIST recurrence, and costs. Because GIST recurrence is not explicitly defined in the database, patterns in resource use were used to identify probable recurrence. Kaplan-Meier Sample Average (KMSA) Estimator technique was used to estimate costs of GIST and recurrence. RESULTS: SEER registry results show over the 10-year time horizon average annual GIST incidence was 0.32 per 100,000 persons in the United States, 15-year limited-duration prevalence was 1.62 per 100,000 persons, and 3-year survival was 73%. A total of 292 GIST patients were included in the SEER-Medicare analyses; 35 were identified with probable recurrence. GIST patients had increased risk of mortality (hazard ratio: 1.23; 95% confidence intervals: 0.94-1.61) compared to controls. Median recurrence-free and postrecurrence survival was 45 and 46 months, respectively. GIST patients incurred significantly higher medical care costs in the first year after initial resection, with $23,221 attributable to GIST. GIST recurrence costs totaled $101,700 over 5 years after initial resection. CONCLUSIONS: GIST is associated with substantial medical care costs, estimated recurrence costs more than $100,000; treatments that delay or reduce recurrence could substantially reduce the burden of GIST.

Budgetary impact of treatment with adjuvant imatinib for 1 year following surgical resection of Kit-positive localized gastrointestinal stromal tumors.

BACKGROUND: Imatinib mesylate, an orally administered kinase inhibitor that targets the Kit (CD117) protein, currently has 10 approved indications including treatment of chronic myelogenous leukemia and metastatic gastrointestinal stromal tumors (GIST). Treatment with adjuvant imatinib following surgical resection of localized Kit-positive GIST, the most recent FDA-approved indication (December 2008), has been shown to significantly improve recurrence-free survival (RFS) compared with surgical resection alone. Although adjuvant imatinib has proven effective in clinical trials, it is important to consider the economic impact to health plans of introducing imatinib in accordance with its new labeled indication. OBJECTIVE: To evaluate the budgetary impact over a 3-year time horizon of treating patients with localized Kit-positive GIST with 1 year of adjuvant imatinib following surgical resection. METHODS: A Markov model was developed to predict patients' transitions across health states defined by initial treatment (surgical resection followed by adjuvant imatinib 400 milligrams [mg] daily versus surgical resection alone), recurrence, and progression. Treatments for a first recurrence were (a) imatinib 400 mg daily for recurrences following resection only or after completion of 1 year of treatment with imatinib 400 mg daily and (b) imatinib 800 mg daily for recurrence during active treatment with imatinib 400 mg daily. Treatments for further progression were imatinib 800 mg daily, sunitinib, or best supportive care (BSC) following imatinib 400 mg per day, and sunitinib or BSC following imatinib 800 mg daily. Recurrence rates were derived from the American College of Surgeons Oncology Group (ACOSOG) Z9001 clinical trial, which compared 1 year of adjuvant imatinib following surgical resection with surgical resection only. The total number of patients with localized and surgically resected GIST (incidence rate of 0.36 per 100,000) was estimated from epidemiologic studies of GIST. Uptake of treatment with imatinib was estimated from unpublished data from qualitative market research funded by the study sponsor. The uptake rate assumptions reflected both (a) the percentage of patients with Kitpositive disease and (b) the percentage of clinically eligible patients who would use imatinib. Costs were estimated by combining unit costs from published sources with expected resource utilization based on the clinical trial publication and National Comprehensive Cancer Network guidelines on the treatment of patients with GIST. To obtain estimates of the budgetary impact, we compared estimated health care costs with versus without adjuvant imatinib, where health care costs with imatinib reflected the costs of treatment minus cost offsets associated with delayed or avoided recurrence or progression. All "with" scenarios assumed no additional uses other than surgically resected localized Kit-positive GIST (i.e., no change in off-label use of imatinib). The budgetary impact was estimated for the first 3 years after the introduction of adjuvant imatinib in accordance with its new labeled indication in a hypothetical plan population of 10 million persons. Results were calculated both as total budgetary impact and as per member per month (PMPM) cost in 2009 dollars. Sensitivity analyses were performed to test the robustness of model results to changes in parameter estimates. RESULTS: The model predicted 36 incident resected GIST cases per year in a health plan of 10 million members. The estimated counts of cases treated with adjuvant imatinib were 10.8, 16.2, and 21.6 in the first, second, and third years after introduction, respectively, with the annual increases attributable to changes in the proportion of patients with resected GIST assumed to use imatinib (30% in year 1, rising to 45% in year 2 and 60% in year 3). The model predicted that treatment of these cases with imatinib will increase pharmacy costs by an additional $505,144 in the first year, $757,717 in the second year, and $1,010,289 in the third year. Increased resource use associated with monitoring patients during and after treatment with adjuvant imatinib would cost an additional $21,564, $38,145, and $56,605 in the first, second, and third years, respectively. Recurrence would be avoided or delayed in 7 patients over the 3-year period. Avoided or delayed recurrences would result in cost offsets of $61,583 in the first year, $156,702 in the second year, and $233,849 in the third year. The net budgetary impact was estimated to be $465,126 in the first year (less than $0.01 PMPM), $639,159 in the second year ($0.01 PMPM), and $833,044 in the third year ($0.01 PMPM). Results of sensitivity analyses indicated that the budgetary impact in the third year is most sensitive to changes in the price of adjuvant imatinib and recurrence rates. CONCLUSIONS: The model predicted that the introduction of adjuvant imatinib for treatment of surgically resected, localized, Kit-positive GIST will lead to a net budgetary impact of $0.01 PMPM in the third year after introduction assuming change in use only in accordance with the new labeled indication. Approximately 11.7%-21.9% of the cost of adjuvant imatinib is offset by the reduction in costs associated with GIST recurrence.