Health Economic Assessments of Hyaluronic Acid Treatments for Knee Osteoarthritis: A Systematic Review.

INTRODUCTION: Hyaluronic acid (HA) use to treat knee osteoarthritis (OA) has been extensively investigated in the literature. There are also multiple economic assessments comparing intra-articular HAs with oral anti-inflammatory medicines and other conservative measures (NSAIDs), as well as different types and formulations of HA. Owing to the broad landscape of evidence across this area, it is important to further understand the empirical data comparing HA products, as well as the health economic implications that exist between commercially available HAs. This systematic review aims to identify and summarize the available evidence comparing commercially available HA products in the USA, as well as the health economic evidence and socioeconomic outcomes associated with HA use for knee OA. METHODS: A systematic literature review within the OVID Medline, Embase, HealthStar, and Cochrane EBM HTA databases was conducted. Articles were screened for eligibility, and a qualitative summary of the findings was provided based on specific themes: (1) trials comparing the safety and/or efficacy of two or more HA products in knee OA, (2) economic/cost analyses of HA use in knee OA, and (3) studies investigating healthcare resource utilization in patients treated with HA for knee OA. RESULTS: The search strategy identified 398 studies, 27 of which were deemed eligible: 21 health economic analyses with US relevance and six head-to-head trials of HA products available in the USA, cumulatively assessing 5,782,156 patients with knee OA. The evidence demonstrates a clear distinction between high and low molecular weight HAs, as both efficacy and cost analyses provided favorable results for the high molecular weight options. In all but one cost analysis, HA use was a cost-effective option when compared to routine nonoperative care, captured in administrative databases, which typically included NSAID use and/or corticosteroids. HA saw benefits in delaying the need for total knee arthroplasty (TKA), decreasing the use of rescue medication, and limiting the need for additional corticosteroid injection. The included evidence highlights that the treatment's cost-effectiveness is improved when HA is utilized in earlier stages of the disease, as opposed to when HA is reserved for late stages of knee OA. Additionally, among HAs, Bio-HA and Hylan G-F 20 evidence made up the majority of available literature with beneficial efficacy and cost outcomes. Head-to-head evidence between them indicated similar pain outcomes; however, Bio-HA required less rescue with acetaminophen and had fewer joint effusions in this comparison. CONCLUSIONS: The available efficacy and safety data as well as health economic analyses on the use of HA for knee OA management suggest that there are economic benefits of this treatment option. From a healthcare system perspective, the body of HA literature summarizes favorable costs profile, decreased opioid and corticosteroid use as rescue medication, and a delay to the need for TKA in patients who have HA included in their treatment regimen.

Economic Impact of Recurrent Clostridioides difficile Infection in the USA: A Systematic Literature Review and Cost Synthesis.

INTRODUCTION: Up to 35% of patients with a first episode of Clostridioides difficile infection (CDI) develop recurrent CDI (rCDI), and of those, up to 65% experience multiple recurrences. A systematic literature review (SLR) was conducted to review and summarize the economic impact of rCDI in the United States of America. METHODS: English-language publications reporting real-world healthcare resource utilization (HRU) and/or direct medical costs associated with rCDI in the USA were searched in MEDLINE, MEDLINE In-Process, Embase, and the Cochrane Library databases over the past 10 years (2012-2022), as well as in selected scientific conferences that publish research on rCDI and its economic burden over the past 3 years (2019-2022). HRU and costs identified through the SLR were synthesized to estimate annual rCDI-attributable direct medical costs to inform the economic impact of rCDI from a US third-party payer's perspective. RESULTS: A total of 661 publications were retrieved, and 31 of them met all selection criteria. Substantial variability was found across these publications in terms of data source, patient population, sample size, definition of rCDI, follow-up period, outcomes reported, analytic approach, and methods to adjudicate rCDI-attributable costs. Only one study reported rCDI-attributable costs over 12 months. Synthesizing across the relevant publications using a component-based cost approach, the per-patient per-year rCDI-attributable direct medical cost was estimated to range from $67,837 to $82,268. CONCLUSIONS: While real-world studies on economic impact of rCDI in the USA suggested a high-cost burden, inconsistency in methodologies and results reporting warranted a component-based cost synthesis approach to estimate the annual medical cost burden of rCDI. Utilizing available literature, we estimated the average annual rCDI-attributable medical costs to allow for consistent economic assessments of rCDI and identify the budget impact on US payers.

Cost-Effectiveness Analysis of REBYOTA™ (Fecal Microbiota, Live-jslm [FMBL]) Versus Standard of Care for the Prevention of Recurrent Clostridioides difficile Infection in the USA.

INTRODUCTION: Recurrent Clostridioides difficile infection (rCDI) is common and associated with considerable clinical and economic consequences. REBYOTA™ (fecal microbiota, live-jslm [FMBL]) is a microbiota-based live biotherapeutic approved for the prevention of rCDI following antibiotic treatment for rCDI. We sought to evaluate cost-effectiveness of FMBL compared to standard of care (SOC) from a US third-party payer perspective among patients with one or more (≥ 1) recurrences. METHODS: A Markov model with a lifetime time horizon was developed. The model population included adult patients who had ≥ 1 recurrence after a primary CDI episode and had completed ≥ 1 round of antibiotics, or had ≥ 2 severe CDI episodes resulting in hospitalization within the last year. The model consisted of six health states with an 8-week model cycle: rCDI, absence of CDI after recurrence, colectomy, ileostomy, ileostomy reversal, and death. Drug costs and rCDI-related medical costs were estimated in 2022 US dollars and discounted at 3% annually. Deterministic sensitivity analyses were performed. RESULTS: Compared to SOC, FMBL at $9000/course resulted in an incremental cost-effectiveness ratio (ICER) of $18,727 per quality-adjusted life year (QALY) gained. The incremental cost was $5336 (FMBL $79,236, SOC $73,900) and the incremental effectiveness was 0.285 QALYs (FMBL 10.346, SOC 10.061). The cumulative drug acquisition and administration costs for the FMBL and SOC arms were $24,245 and $16,876, while rCDI-related medical costs for FMBL and SOC were $54,991 and $57,024, respectively. The ICER in the subgroup of patients at first recurrence was $13,727 per QALY gained. FMBL remained cost-effective across all sensitivity analyses. CONCLUSIONS: FMBL was found to be cost-effective compared to SOC for the prevention of rCDI with more benefits among patients at first recurrence, with an ICER far below the payer ICER threshold of $100,000. Patients treated with FMBL experienced higher total QALYs and reduced healthcare resource utilization, including reduced hospitalizations.

Budget Impact Analysis of REBYOTA™ (Fecal Microbiota, Live-jslm [FMBL]) for Preventing Recurrent Clostridioides difficile Infection in the US.

INTRODUCTION: Patients with Clostridioides difficile infection (CDI) often experience recurrences (rCDI), which are associated with high morbidity, mortality, and healthcare expenditures. REBYOTA™ (fecal microbiota, live-jslm [FMBL]) is a microbiota-based live biotherapeutic approved for the prevention of rCDI following antibiotic treatment for rCDI. We quantified the budget impact of FMBL during the first 3 years following introduction from a third-party US payer perspective. METHODS: A decision-tree model was used to estimate the budget impact of one-course FMBL by comparing costs under the scenario with FMBL to the scenario without FMBL (standard of care) in patients with one or more (≥ 1) recurrences after a primary episode of CDI and had completed ≥ 1 round of antibiotic treatments. Drug costs, rCDI-related medical costs, and budget impact over 1-3 years were estimated in 2022 US dollars. One-way sensitivity analyses were performed. RESULTS: For an insurance plan with a population size of 1,000,000, 468 patients per year were estimated to have ≥ 1 rCDI. The budget impact of one-course FMBL at $9000/course was cost-saving at an¼ average of -$0.0039 on a per-member-per-month (PMPM) basis, an average of -$8.30 on a per-treated-member-per-month (PTMPM) basis, and a total of -$139,865 on a plan level assuming 5%, 15%, and 20% of patients receive FMBL over 1-3 years, respectively. The scenario with FMBL entry was associated with higher drug costs (difference at $0.0474 PMPM; $101.26 PTMPM; $1,706,445 total plan) and lower rCDI-related medical costs (difference at -$0.0513 PMPM; -$109.56 PTMPM; -$1,846,309 total plan). The budget impact of FMBL in patients at first rCDI was cost-saving at -$0.0139 PMPM, -$84.78 PTMPM, corresponding to an annual savings of $500,022. CONCLUSIONS: FMBL has a cost-saving budget impact for a US payer, with higher initial drug costs being offset by savings in rCDI-related medical costs. Greater cost saving was found in patients at first recurrence.

The Impact of Progression on Healthcare Resource Utilization and Costs Among Patients with High-Grade Non-Muscle Invasive Bladder Cancer After Bacillus Calmette-Guérin Therapy: A Retrospective SEER-Medicare Analysis.

INTRODUCTION: We evaluated the real-world healthcare resource utilization (HRU) and costs among patients with high-grade non-muscle invasive bladder cancer (HG-NMIBC) following Bacillus Calmette-Guérin (BCG) therapy. METHODS: Patients aged ≥ 65 years diagnosed with HG-NMIBC between 2008 and 2015 who received adequate BCG induction and were identified in the SEER-Medicare database. Those who received intravesical chemotherapy or radical cystectomy within 12 months of the last BCG induction dose, and had ≥ 6 months of data availability after treatment (index date), were included. Annualized HRU and mean medical costs (2020 United States dollars) were estimated and compared between patients with versus without progression. Inverse probability of treatment weighting was used to adjust for differences in baseline characteristics. RESULTS: Of 986 patients diagnosed with HG-NMIBC who met the inclusion criteria, 257 (26.1%) progressed; the mean ages were similar between patients who did and did not progress (77.6 vs. 77.0 years). The overall population had a mean of 0.96 [standard deviation (SD): 1.18] inpatient admissions, 6.47 (11.40) hospitalization days, 1.38 (2.19) emergency department (ED) visits, and 48.03 (44.97) outpatient visits per patient-year during the study period; total annualized costs per patient post-BCG were $39,102 ($44,244). Patients experiencing progression had significantly higher mean numbers of inpatient admissions [1.61 (SD 1.40) vs. 0.72 (0.99)], hospitalization days [11.77 (14.96) vs. 4.59 (9.29)], ED visits [2.34 (2.92) vs. 1.03 (1.76)], and outpatient visits [65.97 (44.72) vs. 41.63 (43.09)] per patient-year compared with patients without progression (all p < 0.05). Total mean annualized costs per patient after BCG among those who progressed [$65,668 (SD $53,943)] were more than double compared with patients who did not [$29,780 ($36,425)]. CONCLUSIONS: Existing treatments for HG-NMIBC after BCG therapy are associated with substantial HRU and medical costs, particularly after progression. Novel treatments and earlier detection are needed to reduce progression rates and associated costs in this difficult-to-treat population.

Factors associated with water quality, sanitation, and hygiene in rural schools in 14 low- and middle-income countries.

Improving access to water, sanitation, and hygiene (WaSH) and menstrual hygiene management (MHM) in schools is important to achieve Sustainable Development Goals (SDGs) 3 and 6. Inadequate WaSH and MHM in schools adversely affect student health and educational performance, as well as teacher satisfaction. However, there is little evidence describing factors associated with WaSH services and MHM in schools. We conducted 2690 surveys and collected 1946 water samples at randomly selected schools in rural areas of 14 low- and middle-income countries (LMICs). We developed multilevel mixed-effects logistic regression models to identify factors associated with basic water services, water quality, basic sanitation facilities, basic handwashing facilities, and availability of MHM materials. We found that 51% of schools had at least a basic, on-premises water service. Twenty-eight percent of schools had at least basic sanitation services, 12% had at least a basic handwashing facility, and 26% had MHM materials available. Four percent of schools had all basic WaSH services. Half (52%) of schools had drinking water compliant with the WHO guideline value for E. coli. In regression models, we found that schools that did not share their water point with a community, had a parent-teacher association that supported WaSH, or had support from an external WaSH program were more likely to have access to basic, continuous, on-premises water service versus worse access. Schools with an on-premises water point, water available on the day of survey, a health club, or handwashing stations near toilets were more likely to have a basic sanitation service versus a lower service. Schools with limited or basic sanitation, health clubs, an MHM curriculum, a designated MHM focal person, or school funds for WaSH were more likely to have MHM materials. We conclude that improved institutional management and external support, accountability mechanisms, and enhanced training and hygiene curriculum will support sustained WaSH service delivery in schools in LMICs.

Inpatient Admissions and Costs Associated with Persistent Use of Dalfampridine Extended-Release in Multiple Sclerosis: A Claims Database Analysis.

BACKGROUND: While the clinical benefits of dalfampridine extended-release (D-ER) have been established in patients with multiple sclerosis (MS) through multiple clinical trials, there is limited real-world data on D-ER use, in particular the persistent use of D-ER, and associated acute care resource utilization and costs. OBJECTIVE: To examine the real-world association of D-ER use and inpatient admissions and costs among patients with MS. METHODS: This study was a retrospective observational claims analysis of the MarketScan database (April 2009-March 2014). Eligible patients consisted of adult enrollees aged 18-64 years who had (a) 12 months of continuous private plan enrollment preceding (baseline) and following (follow-up) the first D-ER claim; (b) ≥ 2 MS diagnosis codes with ≥ 1 during the baseline period; (c) ≥ 2 consecutive D-ER claims; and (d) no alternate gait-impairing etiologies during the baseline and follow-up periods. Patients were separated into 2 D-ER cohorts in the main analysis: persistent (≥ 360 days of D-ER supply) and nonpersistent (< 360 days of supply) users. Sensitivity analyses were conducted, examining additional breakdowns of days of supply within the nonpersistent cohort. Inpatient admissions (all-cause and MS-related) and health care expenditures were calculated and compared between the cohorts during follow-up using Wilcoxon rank-sum and chi-square tests. Regression models were conducted, controlling for age, sex, MS relapses, comorbidities, disease-modifying therapy use, and other baseline factors, including inpatient admissions and costs. RESULTS: Of 1,598 eligible patients, 719 (45.0%) were persistent D-ER users, and 879 (55.0%) were nonpersistent D-ER users. The 2 cohorts had similar demographic and clinical characteristics, with mean (SD) ages of 51.0 (8.4) and 50.6 (8.6) years and were 71.3% and 66.6% female, respectively. Compared with nonpersistent D-ER use, persistent D-ER use was associated with lower odds of all-cause inpatient admissions (OR = 0.58, P = 0.010) and MS-related inpatient admissions (OR = 0.50, P = 0.004). Persistent use was also associated with lower inpatient expenditures for all-cause admissions ($669 vs. $1,515, P = 0.002) and MS-related admissions ($388 vs. $891, P = 0.008). CONCLUSIONS: Persistent D-ER use was associated with significantly lower rates of all-cause and MS-related inpatient admissions and costs. DISCLOSURES: Funding for this research and medical writing assistance was provided by Acorda Therapeutics. The study sponsor was involved in all stages of the study research and manuscript preparation. Guo and Niyazov were employees of Acorda Therapeutics at the time of this study and may own stock/stock options. Wu, Macaulay, Terasawa, and Schmerold are employees of Analysis Group, which received consultancy fees from Acorda Therapeutics for this project. Krieger was a consultant for Acorda Therapeutics for this project and has the following additional financial interests to report: consulting/advisory board work with Bayer, Biogen, EMD Serono, Novartis, Genentech, Genzyme, and Teva. Study concept and design were contributed by Guo, Niyazov, Macaulay, and Wu. Macaulay, Terasawa, Schmerold, and Wu helped prepare the data, and data interpretation was performed by Krieger, Guo, Niyazov, and Macaulay, along with Terasawa and Wu. The manuscript was written by Terasawa and Schmerold, along with Macaulay, and revised by all the authors. A portion of the current research was presented in poster format at the 2106 American Academy of Neurology Annual Meeting, which took place in Vancouver, BC, Canada, on April 15-21, 2016.

The economic burden of pleural effusions in patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors.

OBJECTIVE: Tyrosine kinase inhibitors (TKI), the standard of care for patients with chronic myeloid leukemia (CML) patients, may in some cases lead to the development of pleural effusion (PE). The purpose of this study is to compare healthcare resource utilization and costs associated with PE among CML patients treated with a TKI therapy. METHODS: Two large retrospective claims databases (1999-2009) were combined to identify adult CML patients who received ≥1 TKI prescription before the index date, which was defined as 30 days before the first PE diagnosis for patients with PE and a randomly selected date for PE-free patients. Patients were followed for 6 months after the index date. PE and PE-free patients were matched on a 1:1 ratio. PE-related resource utilization and costs (measured in 2009 US dollars) were estimated for PE patients. All-cause and CML-related resource utilization and costs were compared between PE and PE-free patients. Multivariate regression models were used to control for confounding factors. RESULTS: The study included 186 matched pairs. PE-free and PE patients were on average 65.4 and 63.6 years old and 39.8% and 48.9% were female, respectively. PE patients had a significantly higher number of inpatient (IP) days, IP admissions, outpatient (OP) visits and emergency room (ER) visits than PE-free patients (all p < 0.01). All-cause medical services costs were $88,526 and $30,434 for PE and PE-free patients, respectively. After adjusting for confounding factors, the PE-related total medical costs were $47,288 (p < 0.01), which was mostly accounted for by higher IP (difference: $34,123, p < 0.01) and OP (difference: $9563, p < 0.05) costs. PE patients also incurred higher CML-related medical costs compared to PE-free patients (difference: $39,599; p < 0.01). CONCLUSION: PE presents a substantial economic burden for CML patients treated with TKI.

Economic impact on US Medicare of a new diagnosis of myelodysplastic syndromes and the incremental costs associated with blood transfusion need.

BACKGROUND: Recent retrospective studies suggest myelodysplastic syndromes (MDSs) are more common than previously recognized and patients who develop transfusional dependence may be at risk for increased comorbid complications. STUDY DESIGN AND METHODS: A retrospective review was undertaken of Medicare claims focusing on costs associated with patients with a new claim listing ICD-9-CM Diagnosis Code 238.7 in first quarter of 2003. Patients were followed until 2005 to assess resource use and costs. RESULTS: A total of 512 patients aged 65 years or more with newly diagnosed MDS were identified. Forty percent had received red blood cell transfusions between 2003 and 2005. During the 3-year follow-up, transfused patients experienced increased prevalence of cardiac diseases, dyspnea, and infections. Cumulative 3-year mean Medicare costs for MDS patients were $49,156. Transfused patients had greater use of hospital inpatient and outpatient services and incurred significantly higher mean costs than nontransfused patients ($88,824 vs. $29,519, p < 0.001). After adjustment for baseline characteristics and clinical complications, transfusion was independently associated with a 48% increase in monthly costs in addition to the cost of transfusion administration. CONCLUSION: MDS places a significant economic burden on the US Medicare system. MDS patients requiring transfusions experience higher prevalence of new comorbid conditions and incur significantly higher Medicare costs than nontransfused patients during the initial 3 years after diagnosis.

Surgical resection of subependymal giant cell astrocytomas (SEGAs) and changes in SEGA-related conditions: a US national claims database study.

OBJECTIVES: To compare the prevalence rates of clinical conditions related to subependymal giant cell astrocytomas (SEGAs) before and after SEGA surgery among patients with tuberous sclerosis complex (TSC). METHODS: Based on three US national claims databases, we analyzed and compared the prevalence rates of 21 SEGA-related conditions (including seizures, hydrocephalus, headaches and stroke or hemiparesis) in the six months preceding surgery with the rates in the second through sixth post-surgery months and in the seventh through twelfth post-surgery months among TSC patients who underwent SEGA surgery during 2000-2009. Repeated measures analysis with a bootstrapping method was used to assess the surgery impact. RESULTS: Patients (N = 47) had a mean age of 11.5 years at their first SEGA surgery, and 66% were male. Compared with the six months preceding surgery, the post-surgery prevalence rates increased by 23-26% for seizures, 21-26% for hydrocephalus, 17-19% for headache and 6-9% for stroke or hemiparesis (all p < 0.05). Repeated measures analysis confirmed the impact of surgery on the prevalence rate of these five conditions (all p < 0.05). CONCLUSIONS: SEGA surgery has its important role in SEGA treatment. However, after SEGA surgery this group of TSC patients had increased prevalence rates of seizures, hydrocephalus, vision disorders, headaches, stroke or hemiparesis, and autism. Future research to examine the causes of these symptoms is imperative. LIMITATIONS: The study results have limitations in data source representativeness, coding accuracy, and study design.

Outcomes of resecting subependymal giant cell astrocytoma (SEGA) among patients with SEGA-related tuberous sclerosis complex: a national claims database analysis.

OBJECTIVE: To examine the outcomes following resection of subependymal giant cell astrocytoma (SEGA) among patients with SEGA-associated tuberous sclerosis complex (TSC). METHODS: Using three large US national healthcare claims databases, we retrospectively examined the outcomes of SEGA surgery among TSC patients who underwent SEGA surgery between 2000 and 2009. The examined outcomes were: prevalence rates of post-surgery SEGA, repeated SEGA surgery, and postoperative complications (surgical procedure complications, nervous system complications, postoperative infections, complications of subdural empyemas, and complications of epidural abscesses). Descriptive data analysis and two-sided one sample t-test for mean or proportion were used to assess the characteristics of patients and the outcomes of SEGA surgery. RESULTS: The selected patients (N = 47) had a mean age of 11.6 years at their first SEGA surgery and 66% were male. During the third through twelfth months following surgery, 34% had post-surgery SEGA (diagnosis) and 12% underwent repeated SEGA surgeries. During the first post-surgery year, 48.9% of patients developed postoperative complications (34.0% had complications relating to the surgical procedure, 12.8% had nervous system complications, 6.4% developed postoperative infections, 17.0% had complications of subdural empyemas, and 2.1% had complications of epidural abscesses). CONCLUSIONS: SEGA surgery was associated with statistically significant risks of developing post-surgery SEGA, requiring repeated SEGA surgery and developing postoperative complications. Future efforts in reducing these outcomes, either through improving surgical procedures or through alternative treatments, are urgently needed. LIMITATIONS: This study has its limitation in data source representativeness and measurement accuracy.

Economic evaluation of denosumab compared with zoledronic acid in hormone-refractory prostate cancer patients with bone metastases.

BACKGROUND: Bone metastases are common in patients with hormone-refractory prostate cancer. In a study of autopsies of patients with prostate cancer, 65%-75% had bone metastases. Bone metastases place a substantial economic burden on payers with estimated total annual costs of $1.9 billion in the United States. Skeletal-related events (SREs), including pathologic fractures, spinal cord compression, surgery to bone, and radiation to bone, affect approximately 50% of patients with bone metastases. They are associated with a decreased quality of life and increased health care costs. Zoledronic acid is an effective treatment in preventing SREs in solid tumors and multiple myeloma. Recently, denosumab was FDA-approved for prevention of SREs in patients with bone metastases from solid tumors. A Phase 3 clinical trial (NCT00321620) demonstrated that denosumab had superior efficacy in delaying first and subsequent SREs compared with zoledronic acid. However, the economic value of denosumab has not been assessed in patients with hormone-refractory prostate cancer. OBJECTIVE: To compare the cost-effectiveness of denosumab with zoledronic acid in the treatment of bone metastases in men with hormone-refractory prostate cancer. METHODS: An Excel-based Markov model was developed to assess costs and effectiveness associated with the 2 treatments over a 1- and 3-year time horizon. Because the evaluation was conducted from the perspective of a U.S. third-party payer, only direct costs were included. Consistent with the primary outcome in the Phase 3 trial, effectiveness was assessed based on the number of SREs. The model consisted of 9 health states defined by SRE occurrence, SRE history, disease progression, and death. A hypothetical cohort of patients with hormone-refractory prostate cancer received either denosumab 120 mg or zoledronic acid 4 mg at the model entry and transitioned among the 9 health states at the beginning of each 13-week cycle. Transition probabilities associated with experiencing the first SRE, subsequent SREs, disease progression, and death were primarily derived from the results of the Phase 3 clinical trial and were supplemented with published literature. The model assumed that a maximum of 1 SRE could occur in each cycle. Drug costs included wholesale acquisition cost, health care professional costs associated with drug administration, and drug monitoring costs, if applicable. Nondrug costs included incremental costs associated with disease progression, costs associated with SREs, and terminal care costs, which were derived from the literature. Adverse event (AE) costs were estimated based on the incidence rates reported in the Phase 3 trial. Resource utilization associated with AEs was estimated based on consultation with a senior medical director employed by the study sponsor. All costs were presented in 2010 dollars. The base case estimated the incremental total cost per SRE avoided over a 1-year time horizon. Results for a 3-year time horizon were also estimated. One-way sensitivity analyses and probabilistic sensitivity analyses (PSA) were performed to test the robustness of the model. RESULTS: In the base case, the total per patient costs incurred over 1 year were estimated at $35,341 ($19,230 drug costs and $16,111 nondrug costs) for denosumab and $27,528 ($10,960 drug costs and $16,569 nondrug costs) for zoledronic acid, with an incremental total direct cost of $7,813 for denosumab. The estimated numbers of SREs per patient during the 1-year period were 0.49 for denosumab and 0.60 for zoledronic acid, resulting in an incremental number of SREs of -0.11 in the denosumab arm. The estimated incremental total direct costs per SRE avoided with the use of denosumab instead of zoledronic acid were $71,027 for 1 year and $51,319 for 3 years. The 1-way sensitivity analysis indicated that the results were sensitive to the drug costs, median time to first SRE, and increased risk of SRE associated with disease progression. Results of the PSA showed that based on willingness-to-pay thresholds of $70,000, $50,000, and $30,000 per SRE avoided, respectively, denosumab was cost-effective compared with zoledronic acid in 49.5%, 17.5%, and 0.3% of the cases at 1 year, respectively, and 79.0%, 49.8%, and 4.1% of the cases at 3 years, respectively. CONCLUSIONS: Although denosumab has demonstrated benefits over zoledronic acid in preventing or delaying SREs in a Phase 3 trial, it may be a costly alternative to zoledronic acid from a U.S. payer perspective.

Retrospective real-world comparison of medical visits, costs, and adherence between nilotinib and dasatinib in chronic myeloid leukemia.

OBJECTIVE: To compare healthcare resource utilization, costs, and treatment adherence associated with dasatinib versus nilotinib treatment as second-line therapies in chronic myeloid leukemia (CML) patients. METHODS: Two large retrospective claims databases (01/1999-06/2009) were combined to identify CML patients (ICD-9 code 205.1x) who received one or more prescriptions of dasatinib or nilotinib. Studied patients had continuous enrollment ≥ 1 month prior to and after the index date, defined as the first prescription for dasatinib or nilotinib. Patients were followed for up to 6 months from the index date to the earliest of the termination of healthcare plan enrollment or end of data availability. Patients with bone marrow or stem cell transplant during the study period were excluded. Poisson regression models were used to compare healthcare resource utilization between the two groups. Results were reported as incidence rate ratios (IRR). Healthcare cost differences were estimated for each cost component using generalized linear models or two-part models. Treatment adherence was measured by the proportion of days covered (PDC) and compared using generalized linear models. Multivariate regressions were used to control for potential confounding factors. RESULTS: A total of 521 CML patients receiving second-line tyrosine kinase inhibitors (TKI) (452 dasatinib and 69 nilotinib) were studied. During the study period, dasatinib patients were estimated to have more than twice as many inpatient days (IRR = 2.44; p < 0.001) and nearly double the number of inpatient admissions (IRR = 1.99; p = 0.047) compared to nilotinib patients. Over the follow-up period, dasatinib patients incurred $8828 more in total medical service costs (p < 0.001); cost differences were mainly driven by an adjusted inpatient cost difference of $8520 (p = 0.003). Dasatinib patients were less adherent, with a PDC value approximately 13% lower compared to nilotinib patients (p = 0.009). CONCLUSIONS: Among CML patients treated with second-line TKIs, nilotinib patients were more adherent and experienced lower healthcare resource utilization, resulting in medical service cost savings compared to dasatinib patients.

Cost effectiveness of letrozole versus anastrozole in postmenopausal women with HR+ early-stage breast cancer.

BACKGROUND: The Breast International Group (BIG) 1-98 and Arimidex, Tamoxifen Alone or in Combination (ATAC) trials demonstrated that, in postmenopausal women with hormone receptor positive (HR+) early-stage breast cancer, 5 years of initial adjuvant endocrine therapy with letrozole or anastrozole is superior to tamoxifen. With expected generic availability of anastrozole in July 2010 and letrozole in June 2011, there may be financial pressures prior to letrozole's generic availability to start treatment-naïve patients on anastrozole vs. letrozole or to switch patients already receiving letrozole to anastrozole. METHODS: A Markov model was used to estimate cost per quality-adjusted life-year (QALY) gained with letrozole vs. anastrozole from the US healthcare system perspective. Cost effectiveness was examined separately in treatment-naïve patients and in patients already receiving letrozole. For the latter, cost effectiveness of continued letrozole vs. therapeutic substitution (TS) to generic anastrozole was evaluated separately in cohorts defined on years of endocrine therapy remaining. TS to generic anastrozole was assumed to result in an additional 5% of patients discontinuing endocrine therapy. Probabilities of distant recurrence and death were taken from reports of BIG 1-98, ATAC, the Early Breast Cancer Trialists' Collaborative Group meta-analysis of tamoxifen, and other published sources. Carry-over effects of aromatase inhibitors were assumed to be proportional to treatment duration. Costs of aromatase inhibitors were assumed to decline by 75% with generic availability. RESULTS: In treatment-naïve patients, total expected lifetime costs are $3916 greater with letrozole vs. anastrozole. However, initiation of treatment with letrozole results in a gain of 0.15 QALYs. Cost per QALY gained with letrozole vs. anastrozole is $25,846. In patients already receiving letrozole, the increase in total expected lifetime costs with continued letrozole vs. TS to anastrozole is between $4200 and $4500 in all cohorts. QALYs gained with letrozole range from 0.21 in those with 4 years of endocrine therapy remaining to 0.13 in those with 1 year of therapy remaining. Cost per QALY gained ranges from $20,276 to $34,356. CONCLUSION: For postmenopausal women with HR+ early-stage breast cancer, letrozole is more likely to be cost effective vs. anastrozole in treatment-naïve patients and in patients already receiving letrozole. Limitations of the study include a lack of direct evidence comparing letrozole and anastrozole and lack of data on rates of discontinuation due to therapeutic substitution with aromatase inhibitors.

Incidence and clinical complications of myelodysplastic syndromes among United States Medicare beneficiaries.

PURPOSE: To determine the incidence and complications of myelodysplastic syndromes (MDS) among Medicare beneficiaries. METHODS: Retrospective review of 2003 Medicare Standard Analytic Files utilizing International Classification of Diseases for Oncology ninth edition CM code 238.7 to identify new MDS patients, with 3-year follow-up. RESULTS: Among 1,394,343 individuals in Medicare Standard Analytic Files age > or = 65 years, 162 per 100,000 were coded as newly diagnosed MDS during 2003 yielding a calculated 45,000 new cases in the United States Medicare > or = 65 years population. Patients with MDS were older (median age, 77 years), and over-represented by males. Among patients with MDS diagnosed during first quarter of 2003, 73.2% suffered cardiac-related events during 3-year follow-up, which exceeded the Medicare population (54.5%; P < .01) even when age adjusted (odds ratio, 2.10; P < .01). Significant increases in prevalence of diabetes (40.0% v 33.1%), dyspnea (49.4% v 28.5%), hepatic diseases (0.8% v 0.2%), and infections (sepsis: 22.5% v 6.1%) were noted in MDS (all P < .01) compared with the Medicare population. Patients with MDS requiring RBC transfusions had greater prevalence of these comorbidities. Acute myeloid leukemia developed within 3 years in 9.6%, with increased transformation among transfused (24.6%; P < .001). The 3-year Kaplan-Meier age-adjusted survival for MDS was 60.0%, which was significantly lower than the Medicare population (84.7%; hazard ratio, 3.08; P < .001), and mortality was further increased among transfused MDS (P < .01). In 2003, median payment for MDS was $16,181, compared to $1,575 for the Medicare population (P < .001). CONCLUSION: MDS is a common hematologic malignancy of the elderly, which places patients at risk for comorbid conditions. Transfusion dependency identifies patients with MDS at additional increased risk of organ impairment and shortened survival.

Healthcare resource utilization and costs associated with non-adherence to imatinib treatment in chronic myeloid leukemia patients.

BACKGROUND: Patients with chronic myeloid leukemia (CML) who do not adhere to treatment may experience suboptimal outcomes. OBJECTIVE: To examine the association between adherence with imatinib and direct healthcare costs and resource utilization in a large group of privately insured CML patients. PATIENTS AND METHODS: CML patients under age 65 were identified with ICD-9 code 205.1X using MarketScan Commercial Claims data between 1/1/02 and 7/31/08. Patients were required to be continuously enrolled in a private insurance plan during the baseline and study periods, defined respectively as the 4 months prior to and the 12 months following imatinib initiation. Non-adherence was evaluated by the medication possession ratio (MPR), defined as the fraction of days during the study period that patients had filled prescriptions for imatinib, and stratified into two groups (low MPR: <85%, high MPR: > or =85%). Costs, inpatient admissions, and hospital days were compared between high and low adherence groups using Wilcoxon tests. Regression models compared utilization and costs controlling for age, sex, CML severity, Charlson comorbidity index, baseline costs, and other factors. RESULTS: The study sample consisted of 592 patients, where 242 (40.9%) patients were classified with a low MPR, while 350 (59.1%) had a high MPR. Mean MPR was 79% (95% confidence interval 76-81%). Patients with a low MPR incurred more all-cause inpatient visits (4.1 vs. 0.4; p < 0.001) and all-cause inpatient days (14.8 vs. 1.8; p < 0.001). Regression models demonstrated a 283% increase (US$56 324; p < 0.001) in non-imatinib costs within the low- vs. high-MPR group. The generalizability of this study is limited by the use of a privately insured population under 65 years of age as well as by the limitations common to claims data analyses. CONCLUSIONS: Imatinib adherence is an important issue for patients and physicians. Better imatinib adherence was associated with significantly lower resource utilization and costs in CML patients, as lower imatinib costs in low MPR patients were more than offset by higher non-imatinib costs mostly driven by inpatient services.

Cost effectiveness of breast cancer screening with contrast-enhanced MRI in high-risk women.

PURPOSE: The aim of this study was to estimate the cost effectiveness of breast cancer screening with contrast-enhanced magnetic resonance imaging (MRI), with and without adjunctive x-ray mammography (XM), compared with XM alone in high-risk women. MATERIALS AND METHODS: A model was developed to depict the consequences of screening with MRI and/or XM for cohorts of 10,000 women with BRCA1/2 mutations and women with other high-risk characteristics, respectively. The model predicted the number of women correctly and incorrectly diagnosed with each strategy and lifetime consequences in terms of additional care, patient utilities, life expectancy, and quality-adjusted life-years (QALYs). Cost effectiveness was calculated in terms of cost per QALY gained. RESULTS: Among the 400 women (of 10,000) with BRCA1/2 mutations and undiagnosed breast cancer, 361 cases would be detected with MRI and XM, 290 with MRI, and 160 with XM. False-positive results would total 1,526, 1,190, and 528, respectively. Cost per QALY gained with MRI and XM compared with XM alone for women with BRCA1/2 mutations was $25,277. Among other high-risk women, cost per QALY gained with MRI and XM compared with XM alone varied depending on the prevalence of breast cancer, ranging from $45,566 (300 cases) to $310,616 (50 cases). The cost effectiveness of MRI alone compared with XM alone was similar. CONCLUSION: Screening with MRI, alone or in combination with XM, in women with BRCA1/2 mutations is cost effective by current standards compared with XM alone. In women with other high-risk characteristics, MRI screening may also be cost effective, depending on the expected prevalence of undiagnosed breast cancer at the time of screening.

Cost impact of diagnostic imaging for lower extremity peripheral vascular occlusive disease.

OBJECTIVE: The evaluation of peripheral vascular disease in the primary care setting is routinely performed by contrast-enhanced magnetic resonance angiography (CE-MRA) and digital subtraction angiography (DSA). However, limited data are available on the relative costs and clinical outcomes following these diagnostic procedures. The objective of this study is to assess and compare costs associated with diagnostic imaging in peripheral vascular occlusive disease (PAOD). METHODS: US veterans (n = 19,209) with CE-MRA or DSA for the assessment of PAOD from fiscal year (FY) 1999 to FY 2004. Main outcome measure(s) using the Department of Veterans Affairs' (VA) costing algorithms, cost, and log-cost of interventions (e.g., revascularization, stent, angioplasty), amputations or mortality rates within 30/90 days and 1 year of DSA or CE-MRA were compared, and adjusted for patient characteristics and disease severity using multivariate regression. Imaging modality selection bias was evaluated with propensity score, instrumental variables, and Heckman methods using untransformed costs and log-costs with smearing retransformation. RESULTS: Initial CE-MRA imaging was significantly more likely among patients with prior renal disease or bypass surgery [odds ratio (OR) > 2; P < 0.001], and less likely among patients with prior amputation, peripheral vascular disease (PVD), claudication, or other cardiovascular disease (OR < 0.7; P < 0.001). After adjusting for endogenous choice of initial imaging modality, 30-day treatment costs were US$3500-$4300 lower (P < 0.001) for patients with initial CE-MRA. Eighty-two percent of DSA imaging patients had no additional procedures or events within 30 days, and 65% at 90 days. Less than 3.2% (3.6%) of patients had any repeat imaging within 30 (90) days of initial imaging. CONCLUSIONS: Relative to DSA, CE-MRA imaging was associated with substantial treatment episode savings, beyond the US$950 direct savings in imaging cost per procedure. Substituting CE-MRA for DSA among those not planning or requiring any follow-up procedures within 30 days, could have reduced outpatient imaging costs by up to 55%, and reduced VA system costs by US$13.2 million over the six-year period.

Development and validation of the Premenstrual Symptoms Impact Survey (PMSIS): a disease-specific quality of life assessment tool.

OBJECTIVE: To develop and validate the Premenstrual Symptoms Impact Survey (PMSIS), a brief web-based instrument for evaluating the impact of premenstrual symptoms on health-related quality of life (HRQOL). METHODS: An item bank of 68 questions was administered to a nationally representative sample of 971 women using the web, aged 18-45, who experienced regular menstrual cycles in the past 3 months, were not currently pregnant or breastfeeding, and were not being treated or taking medications for depression-related disorders in the last 2 years. Item reduction was performed using forward stepwise linear regression of an overall symptom severity score onto item scores. Three standards were used to validate the instrument: (1) the American College of Obstetricians and Gynecologists retrospective diagnostic criteria for identifying participants "at risk" for clinically significant premenstrual syndrome (PMS), (2) the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders retrospective diagnostic criteria for identifying participants at risk for premenstrual dysphoric disorder (PMDD), and (3) the Medical Outcomes Study Short Form (SF-12) Health Survey. RESULTS: Six items met entry criteria in the model. Approximately 6.0% of the participants were identified as being at risk for PMDD, and 17.3% were identified as being at risk for clinically significant PMS. PMSIS scale score differed significantly between participants who were and were not at risk for PMDD/clinically significant PMS. PMSIS scale score also differed significantly between participants having either high, average, or low HRQOL as defined by SF-12 physical and mental component summary scores. CONCLUSIONS: These results demonstrate that the PMSIS has excellent discriminative ability to detect differences in groups that are known to differ in terms of clinical criteria. The PMSIS can be used to educate consumers about the impact of their symptoms on QOL.

Burden of premenstrual dysphoric disorder on health-related quality of life.

OBJECTIVE: The purpose of this study was to document the burden of premenstrual dysphoric disorder (PMDD) on health-related quality of life (HRQoL) in comparison to the U.S. general population and specific chronic health conditions. METHODS: The disease burden that PMDD placed on HRQoL was estimated by comparing SF-12v2 scores between women who were identified as being at risk for PMDD with those observed in the general U.S. female population. Additional comparisons were made to several chronic health conditions. Regression methods were used to estimate SF-12v2 normative values from the general population sample and statistically adjust them to match age and the presence of disease comorbidity of the PMDD patient group. Significance tests were used to compare the means across samples. RESULTS: After adjusting for multiple comparisons, six SF-12v2 scales and two summary measures of PMDD were significantly below the adjusted U.S. general population norms. Both summary measures of PMDD had mean differences greater than 3 points below the norm (threshold for clinical meaningful difference). The burden of PMDD was greater on mental/emotional HRQoL domains than on physical HRQoL. The HRQoL burden of PMDD was (1) greater than that of chronic back pain in bodily pain and mental health (MH) scales and greater than type 2 diabetes and hypertension in bodily pain scale while comparable in all other scales of the three conditions, (2) comparable to osteoarthritis and rheumatoid arthritis in all scales, and (3) less burden than depression in vitality and MH scales and mental component summary measure while comparable in other scales. CONCLUSIONS: PMDD is associated with substantial burden on both physical and mental aspects of HRQoL.