Economic burden during remission and after relapse among older patients with newly diagnosed acute myeloid leukemia without hematopoietic stem cell transplant: A retrospective study using the SEER-Medicare database.

Acute myeloid leukemia (AML) is associated with a substantial clinical and economic burden. This study characterized the magnitude of this burden following initial treatment with standard or less intensive therapies (hypomethylating agents [HMAs]) and throughout different treatment phases post-remission. The Surveillance, Epidemiology, and End Results (SEER) cancer registry (2007-2016) linked with Medicare beneficiary claims (2007-2015) was analyzed. Patients were ≥ 65 years old with AML who initiated chemotherapy or HMAs and achieved remission. Outcomes included baseline characteristics, treatment patterns, clinical outcomes, healthcare resource utilization (HRU), and costs (2019 United States dollar). Economic impacts were stratified by treatment phase (initial treatment, early post-remission, late post-remission, and post-relapse). Early and late post-remission were defined as treatment initiated ≤ 60 days and > 60 days following initial treatment, respectively. A subgroup analysis of patients receiving only HMAs as initial treatment was also conducted. Overall, 530 patients were included (mean age: 74.1 years; 53.6 % male). In the overall analysis, 68.1 % of patients received post-remission treatment; 31.9% had no post-remission treatment. Mean monthly per patient healthcare costs by treatment phase were $45,747 (initial treatment), $30,248 (early post-remission), $23,173 (late post-remission), and $37,736 (post-relapse), driven predominantly by inpatient visits. The HMA subgroup analysis comprised 71 patients (mean age: 78.8 years; 50.7 % male); mean monthly per patient healthcare costs were highest post-relapse. The economic burden of AML among older patients is substantial across all treatment phases. AML treatments that induce and prolong remission may reduce HRU and the economic burden of disease.

The implementation of value-based frameworks, clinical care pathways, and alternative payment models for cancer care in the United States.

BACKGROUND: Cancer treatment is a significant driver of rising health care costs in the United States, where the annual cost of cancer care is estimated to reach $246 billion in 2030. As a result, cancer centers are considering moving away from fee-for-service models and transitioning to value-based care models, including value-based frameworks (VBFs), clinical care pathways (CCPs), and alternative payment models (APMs). OBJECTIVE: To assess the barriers and motivations for using value-based care models from the perspectives of physicians and quality officers (QOs) at US cancer centers. METHODS: Sites were recruited from cancer centers in the Midwest, Northeast, South, and West regions in a 15/15/20/10 relative distribution. Cancer centers were identified based on prior research relationships and known participation in the Oncology Care Model or other APMs. Based on a literature search, multiple choice and open-ended questions were developed for the survey. A link to the survey was emailed to hematologists/oncologists and QOs at academic and community cancer centers from August to November 2020. Results were summarized using descriptive statistics. RESULTS: A total of 136 sites were contacted; 28 (21%) centers returned completed surveys, which were included in the final analysis. 45 surveys (23 from community centers, 22 from academic centers) were completed: 59% (26/44), 76% (34/45), and 67% (30/45) of physicians/QOs respondents had used or implemented a VBF, CCP, and APM, respectively. The top motivator for VBF use was "producing real-world data for providers, payers, and patients" (50% [13/26]). Among those not using CCPs, the most common barrier was a "lack of consensus on pathway choices" (64% [7/11]). For APMs, the most common difficulty was that "innovations in health care services and therapies must be adopted at the site's own financial risk" (27% [8/30]). CONCLUSIONS: The ability to measure improvements in cancer health outcomes was a large motivator for implementing value-based models. However, heterogeneity in practice size, limited resources, and potential increase in costs were possible barriers to implementation. Payers need to be willing to negotiate with cancer centers and providers to implement the payment model that will most benefit patients. The future integration of VBFs, CCPs, and APMs will depend on reducing the complexity and burden of implementation. DISCLOSURES :Dr Panchal was affiliated with the University of Utah at the time this study was conducted and discloses current employment with ZS. Dr McBride discloses employment with Bristol Myers Squibb. Dr Huggar and Dr Copher report employment, stock, and other ownership interests in Bristol Myers Squibb. The other authors have no competing interests to disclose. This study was funded by an unrestricted research grant from Bristol Myers Squibb to the University of Utah.

Indirect treatment comparison of oral versus injectable azacitidine as maintenance therapy for acute myeloid leukemia.

Aim: Evaluate the relative efficacy of oral versus injectable azacitidine (AZA) maintenance therapy in acute myeloid leukemia (AML) after complete remission. Materials & methods: Systematic literature review identified QUAZAR AML-001, HOVON 97 AML, UK NCRI AML16 and QoLESS-AZA-AMLE (sensitivity analysis) trials. Network meta-analysis and matching-adjusted indirect comparisons assessed survival outcomes. Results: In the network meta-analysis, combining the HOVON 97 and UK NCRI trials, oral AZA (QUAZAR) was associated with significantly improved overall survival (OS) versus injectable AZA (hazard ratio: 0.744; 95% credible interval: 0.557-0.998). After matching-adjusted indirect comparisons, to address differences in patient characteristics across trials, OS improvements were maintained with oral versus injectable AZA (hazard ratio: 0.753; credible interval: 0.563-0.998). Conclusion: In AML, maintenance therapy with oral AZA was associated with improved OS versus injectable AZA.

Older people with acute myeloid leukemia (AML) may have remission with or without blood count recovery, after first-line chemotherapy; however, remission is short lived and overall survival is limited (7­12 months). Ongoing treatment (maintenance therapy) after response to initial chemotherapy may prolong remission. Maintenance therapy with azacitidine (AZA) given by injection beneath the skin (subcutaneous) or into a vein (intravenous) can extend disease-free survival compared with no further treatment and best supportive care. However, treatment with intravenous AZA may only extend overall survival in certain patients. ONUREG^® is a novel formulation of AZA that can be taken by mouth (orally), remains in the body for longer periods and has the potential for significant clinical benefits compared with intravenous AZA. Presently, there are no studies directly comparing outcomes of maintenance therapy with oral and injectable AZA in older people with AML. In this analysis, we used an indirect treatment comparison method including four clinical trials to explore the survival benefit associated with ONUREG and injectable AZA when used as maintenance therapies after response to initial chemotherapy in older people with AML. Findings showed ONUREG significantly improved overall survival compared with injectable AZA, with an almost 26% reduction in the risk of death. These results suggest that maintenance therapy with ONUREG significantly improves overall survival compared with injectable AZA in older people with AML who may have remission with or without blood count recovery, after first-line chemotherapy.

Economic burden in US patients with newly diagnosed acute myeloid leukemia receiving intensive induction chemotherapy.

Aim: This retrospective, observational study assessed healthcare resource utilization (HCRU) and costs for newly diagnosed acute myeloid leukemia (AML) patients receiving intensive induction chemotherapy. Materials & methods: Adult AML patients with inpatient hospitalization or hospital-based outpatient visit receiving intensive induction chemotherapy (CPX-351 or 7 + 3 treatments) were identified from the Premier Healthcare Database (US). Results: All 642 patients had inpatient hospitalizations (median number = 2; median length of stay = 16 days); 22.4% had an ICU admission. Median total outpatient hospital cost was US$2904 per patient, inpatient hospital cost was $83,440 per patient, and ICU cost was $16,550 per patient. Discussion: In the US hospital setting, substantial HCRU and costs associated with intensive induction chemotherapy for AML were driven by inpatient hospitalizations.

Real-world clinical outcomes with enasidenib in relapsed or refractory acute myeloid leukemia.

Enasidenib was approved by the Food and Drug Administration in 2017 for the treatment of patients with relapsed or refractory (RR) acute myeloid leukemia (AML) with an isocitrate dehydrogenase-2 (IDH2) mutation. Given limited data in clinical practice, this study assessed real-world clinical outcomes and healthcare resource use in patients with RR AML. Physicians performed chart abstraction of patients with RR IDH2-mutated AML treated with enasidenib (between 1/2018 and 6/2019) or other first-line (1 L) RR therapy (between 1/2016 and 7/2017). Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method, and adjusted risk of progression and death were estimated by multivariable Cox proportional hazard models. Among 124 patients treated with enasidenib and 76 patients treated with other 1 L RR therapy, overall response rate was higher among patients treated with enasidenib vs. other 1 L RR therapies (77% vs. 52%, p < 0.01). After a median follow-up of 9 and 6 months, median PFS was 8 months in enasidenib-treated patients and 5 months in patients receiving other 1 L RR therapy, respectively (adjusted HR=0.36, 95% CI: 0.23-0.57, p < 0.01). Median OS was 11 and 6 months in enasidenib-treated patients and patients receiving other 1 L RR therapy, respectively (adjusted HR=0.37, 95% CI: 0.22-0.60, p < 0.01). Fewer enasidenib-treated patients were hospitalized during 1 L RR therapy vs. those receiving other therapies (14% vs. 46%, p < 0.01). Results from this real-world study confirm the effectiveness of enasidenib among patients with IDH2-mutated RR AML and demonstrate that hospitalizations were significantly lower vs. other 1 L RR treatment in clinical practice.

The impact of remission duration on the long-term economic burden of acute myeloid leukemia among patients without hematopoietic stem cell transplant in the United States.

BACKGROUND AND AIMS: Acute myeloid leukemia (AML) prognosis is poor, with sustained remission occurring in <35% of young adults and <15% of older adults. This descriptive study examined the potential benefit of prolonged remission on the economic burden of AML. METHODS: Using the IBM MarketScan Commercial and Medicare Supplemental databases, we identified newly diagnosed patients with AML without hematopoietic stem cell transplantation from January 1, 2012 to December 31, 2018; AML diagnosis was the index date. Patients had 6 months of pre-index eligibility and were followed until the end of continuous eligibility, study data, or death. Active treatment and supportive care cohorts were defined; duration-of-remission subgroups (0 to <3, 3 to <6, 6 to <12, and ≥12 months) were established among active treatment patients with remission. Healthcare service utilization and costs were reported over follow-up and mutually exclusive treatment, remission, and post-relapse periods. RESULTS: This study included 1,558 active treatment and 1,127 supportive care patients who were followed for a median of 232 and 62 days, respectively. Over follow-up, active treatment and supportive care patients incurred mean ± standard deviation all-cause healthcare costs of $55,723 ± $61,994 and $68,596 ± $100,375 per-patient-per-month (PPPM), respectively. Decreasing PPPM costs were observed with increased remission duration (0 to <3 months: $71,823 ± $62,635; 3 to <6 months: $54,262 ± $44,734; 6 to <12 months: $35,287 ± $23,699; and ≥12 months: $15,615 ± $10,560). Although median follow-up varied by up to 5-fold, total costs were largely similar across duration-of-remission subgroups (0 to <3 months: $438,569 ± $332,675; 3 to <6 months: $590,411 ± $598,245; 6 to <12 months: $482,902 ± $369,115; and ≥12 months: $448,867 ± $316,133). CONCLUSIONS: The economic burden of AML is substantial, even among untreated patients. Further, among patients with remission, longer durations in remission are associated with reduced PPPM healthcare costs, suggesting that remission-prolonging treatments could help mitigate healthcare costs.

Treatment Patterns, Health Care Resource Utilization, and Cost in Patients with Myelofibrosis in the United States.

BACKGROUND: This study analyses treatment patterns, health care resource utilization (HCRU), and costs in patients with myelofibrosis (MF) and a subgroup treated with ruxolitinib (RUX). MATERIALS AND METHODS: Treatment patterns, all-cause and MF-related HCRU, and costs were analyzed in adults with MF with continuous enrollment in a commercial or the Medicare Advantage health plan in the pre-index period, defined as the 12 months immediately prior to the index date (date of primary or secondary MF diagnosis), and the post-index period, defined as ≥6 months following the index date. In a subgroup analysis, outcomes were analyzed in patients treated with optimal RUX (OPT RUX, ≥30 mg) and suboptimal RUX (SUB RUX, <30 mg) in the pre-index RUX period, defined as the 3 months immediately prior to the index RUX date (first date for an RUX claim), and the post-index RUX period, defined as ≥6 months following the index RUX date. RESULTS: Of 2830 patients with an MF diagnosis, 1191 met eligibility requirements. The median age of patients was 72 years, 54% were male, and comorbidities were frequent. Sixty percent of patients received ≥1 line of therapy (LOT), of which 46% (n = 331) had ≥2 LOTs during the post-index MF period. Costs increased considerably 6-month pre-index to 6-month post-index (all-cause: cause ($24,216 to $48,966) and MF-related ($16,502 to $39,383), driven by inpatient stays and pharmacy costs. In the subgroup analysis, patients treated with RUX (n = 495) experienced significant disease burden and high costs, regardless of dose. A shorter duration of therapy and a higher rate of discontinuation were observed in patients treated with SUB RUX (n = 191) versus OPT RUX (n = 304). CONCLUSION: These findings suggest a significant disease and economic impacts associated with MF patients that persists with RUX therapy, highlighting the need for additional therapeutic options for MF.

Real-World Treatment Patterns Among Patients Initiating Small Molecule Kinase Inhibitor Therapies for Thyroid Cancer in the United States.

INTRODUCTION: Little is known about real-world use of small molecule kinase inhibitors (SMKI) for advanced thyroid cancer in the United States. This study examined prescribing patterns of SMKI agents recommended by the National Comprehensive Cancer Center (NCCN). METHODS: This retrospective study used a national health insurance database to identify patients diagnosed with thyroid cancer during 1/1/2006-6/30/2016 and with prescription claims for NCCN-recommended SMKI during 1/1/2010-5/31/2016 whose first claim date was the index date. Inclusion also required continuous enrollment in a health plan for 3 months pre-index (baseline) and ≥ 1 month post-index (follow-up) with no claims for SMKI during baseline. Lines of therapy (LOT) were defined by the date of SMKI claims and days of drug supply. Median time to SMKI discontinuation in each LOT was estimated by Kaplan-Meier method. RESULTS: The study included 217 patients. During follow-up (mean duration 499.0 days), 35.5% of patients (n = 77) received a second or later LOT; among patients with ≥ 12 months follow-up after first LOT (LOT1) initiation, 53.1% (n = 60) received a second or later LOT. Median treatment duration was 5.0 months for LOT1 and 5.1 months for LOT2. Over the entire follow-up period (2010-2016), sorafenib was the most common regimen in LOT1 (36.9% of patients) and LOT2 (24.7%) followed by sunitinib and levantinib (13.4% each) in LOT1 and sunitinib (19.5%) in LOT2. Starting in 2015, the year lenvatinib was approved for differentiated thyroid cancer, lenvatinib was the most common first-line regimen among patients initiating LOT1 in 2015 (43.4%) and 2016 (66.7%). CONCLUSION: Sorafenib was the most common first-line agent during 2010-2014 but was supplanted by lenvatinib starting in 2015. Approximately 36-53% of patients received a second-line treatment. Median treatment duration results suggested potential benefit of SMKI in second-line therapy. SMKI treatment after first-line failure may be considered for appropriately selected patients. FUNDING: Eisai, Inc. (Woodcliff Lake, NJ).

Cost-effectiveness analysis of lenvatinib treatment for patients with unresectable hepatocellular carcinoma (uHCC) compared with sorafenib in Japan.

BACKGROUND: Lenvatinib demonstrated a treatment effect on overall survival by the statistical confirmation of non-inferiority to sorafenib for the first-line treatment of uHCC. The objective of this study was to evaluate the cost-effectiveness of lenvatinib compared with sorafenib for patients with uHCC in Japan. METHODS: A partitioned-survival model was developed to estimate the cost-effectiveness of lenvatinib versus sorafenib when treating uHCC patients over a lifetime horizon and considering total public healthcare expenditure. Efficacy and safety data were extracted from the REFLECT trial. Utility values were derived from the European Quality-of-Life 5-Dimension Questionnaire, conducted with patients enrolled in the REFLECT trial. Direct medical costs, such as primary drug therapy, outpatient visits, diagnostic tests, hospitalization, post-progression therapy, and adverse-event treatments, were included. Cost parameters unavailable in the clinical trial or publications were obtained based on the consolidated clinical standards from a Delphi panel of four Japanese medical experts. RESULTS: For lenvatinib versus sorafenib, the incremental cost was - 406,307 Japanese Yen (JPY), and the incremental life years and quality-adjusted life years (QALYs) were 0.27 and 0.23, respectively. Thus, lenvatinib dominated sorafenib, due to the mean incremental cost-effectiveness ratio falling in the fourth quadrant, conferring more benefit at lower costs compared with sorafenib. The probabilistic sensitivity analysis showed that 81.3% of the simulations were favorable to lenvatinib compared with sorafenib, with a payer's willingness-to-pay-per-QALY of 5 million JPY. CONCLUSIONS: Lenvatinib was cost-effective compared with sorafenib for the first-line treatment of uHCC in Japan.

Clinical benefit of treatment with eribulin mesylate for metastatic triple-negative breast cancer: Long-term outcomes of patients treated in the US community oncology setting.

INTRODUCTION: Real-world data are critical to demonstrate the consistency of evidence and external generalizability of randomized controlled trials (RCTs). This study examined characteristics and outcomes of metastatic triple-negative breast cancer (mTNBC) patients treated with eribulin mesylate at community oncology practices in the United States. METHODS: Physicians identified mTNBC patients initiating eribulin between 1 January 2011 and 1 January 2014 and abstracted data into an electronic case report form (eCRF). Eribulin treatment in the metastatic setting was categorized as early use (EU, first-/second-line) and late use (LU, third-line or later). Patient characteristics, overall survival (OS), disease response (per treating physician), and adverse events (AEs) rates in each group, respectively, are reported. RESULTS: Overall 252 eCRFs were completed: 125 (49.6%) EU and 127 (50.4%) LU. The median age at metastatic diagnosis was 53 years and 42.1% were stage IV at their initial diagnosis. The median duration of follow-up from the initiation of first-line treatment was 24 months. Rates of disease response (complete or partial per treating physician) were 69.9% in the EU group and 48.8% in the LU group. The five most commonly reported adverse events during eribulin were as follows: fatigue (65.1%), weakness (40.1%), decreased appetite (32.5%), neutropenia (31.0%), and leukopenia (27.4%). Discontinuation of eribulin due to AE was observed in 4.0% of patients. Median OS from initiation of eribulin was 23.0 months (95% CI: 18.7-27.3) among EU and 14.7 (95% CI: 12.6-16.9) among LU. CONCLUSION: In the real-world eribulin-treated mTNBC, patients have more sites of metastatic disease and exposure to greater numbers of prior therapies compared to RCTs. The median OS of 14.7 months among LU patients is consistent with, and slightly longer than the 13.1 months and 14.4 months reported in the EMBRACE and Study 301 clinical trials, respectively.

Number needed to treat in indirect treatment comparison.

AIM: For dichotomous outcomes, odds ratio (OR) is one of the usual summary measures of indirect treatment comparison. A corresponding number needed to treat (NNT) estimate may facilitate understanding of the treatment effect. METHODS: We show how to estimate NNT based on OR results of a matching adjusted indirect comparison. We also have derived the explicit formula of its 95% CIs by applying the delta method, and as an alternative, a simulation-based method. RESULTS: The method was applied in a case study example in radioiodine-refractory differentiated thyroid cancer (RR-DTC) patients, comparing lenvatinib to sorafenib. For every two RR-DTC patients treated with lenvatinib instead of sorafenib, one fewer would have progressed and for every eight RR-DTC patients treated with lenvatinib instead of sorafenib, one fewer would have died. CONCLUSION: Using NNT to summarize the results of a matching adjusted indirect comparison can help the clinicians to better understand the results in addition to OR.

Measuring the Value of New Drugs: Validity and Reliability of 4 Value Assessment Frameworks in the Oncology Setting.

BACKGROUND: Several organizations have developed frameworks to systematically assess the value of new drugs. OBJECTIVE: To evaluate the convergent validity and interrater reliability of 4 value frameworks to understand the extent to which these tools can facilitate value-based treatment decisions in oncology. METHODS: Eight panelists used the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), Institute for Clinical and Economic Review (ICER), and National Comprehensive Cancer Network (NCCN) frameworks to conduct value assessments of 15 drugs for advanced lung and breast cancers and castration-refractory prostate cancer. Panelists received instructions and published clinical data required to complete the assessments, assigning each drug a numeric or letter score. Kendall's Coefficient of Concordance for Ranks (Kendall's W) was used to measure convergent validity by cancer type among the 4 frameworks. Intraclass correlation coefficients (ICCs) were used to measure interrater reliability for each framework across cancers. Panelists were surveyed on their experiences. RESULTS: Kendall's W across all 4 frameworks for breast, lung, and prostate cancer drugs was 0.560 (P= 0.010), 0.562 (P = 0.010), and 0.920 (P < 0.001), respectively. Pairwise, Kendall's W for breast cancer drugs was highest for ESMO-ICER and ICER-NCCN (W = 0.950, P = 0.019 for both pairs) and lowest for ASCO-NCCN (W = 0.300, P = 0.748). For lung cancer drugs, W was highest pairwise for ESMO-ICER (W = 0.974, P = 0.007) and lowest for ASCO-NCCN (W = 0.218, P = 0.839); for prostate cancer drugs, pairwise W was highest for ICER-NCCN (W = 1.000, P < 0.001) and lowest for ESMO-ICER and ESMO-NCCN (W = 0.900, P = 0.052 for both pairs). When ranking drugs on distinct framework subdomains, Kendall's W among breast cancer drugs was highest for certainty (ICER, NCCN: W = 0.908, P = 0.046) and lowest for clinical benefit (ASCO, ESMO, NCCN: W = 0.345, P = 0.436). Among lung cancer drugs, W was highest for toxicity (ASCO, ESMO, NCCN: W = 0. 944, P < 0.001) and lowest for certainty (ICER, NCCN: W = 0.230, P = 0.827); and among prostate cancer drugs, it was highest for quality of life (ASCO, ESMO: W = 0.986, P = 0.003) and lowest for toxicity (ASCO, ESMO, NCCN: W = 0.200, P = 0.711). ICC (95% CI) for ASCO, ESMO, ICER, and NCCN were 0.800 (0.660-0.913), 0.818 (0.686-0.921), 0.652 (0.466-0.834), and 0.153 (0.045-0.371), respectively. When scores were rescaled to 0-100, NCCN provided the narrowest band of scores. When asked about their experiences using the ASCO, ESMO, ICER, and NCCN frameworks, panelists generally agreed that the frameworks were logically organized and reasonably easy to use, with NCCN rated somewhat easier. CONCLUSIONS: Convergent validity among the ASCO, ESMO, ICER, and NCCN frameworks was fair to excellent, increasing with clinical benefit subdomain concordance and simplicity of drug trial data. Interrater reliability, highest for ASCO and ESMO, improved with clarity of instructions and specificity of score definitions. Continued use, analyses, and refinements of these frameworks will bring us closer to the ultimate goal of using value-based treatment decisions to improve patient care and outcomes. DISCLOSURES: This work was funded by Eisai Inc. Copher and Knoth are employees of Eisai Inc. Bentley, Lee, Zambrano, and Broder are employees of Partnership for Health Analytic Research, a health services research company paid by Eisai Inc. to conduct this research. For this study, Cohen, Huynh, and Neville report fees from Partnership for Health Analytic Research. Outside of this study, Cohen receives grants and direct consulting fees from various companies that manufacture and market pharmaceuticals. Mei reports a grant from Eisai Inc. during this study. The other authors have no disclosures to report. Study concept and design were contributed by Bentley and Broder, with assistance from Elkin and Cohen. Bentley took the lead in data collection, along with Elkin, Huynh, Mukherjea, Neville, Mei, Popescu, Lee, and Zambrano. Data interpretation was performed by Bentley and Broder, along with Elkin, Cohen, Copher, and Knoth. The manuscript was written primarily by Bentley, along with Elkin and Broder, and revised by Bentley, Broder, Elkin, Cohen, Copher, and Knoth. Select components of this work's methods were presented at ISPOR 19th Annual European Congress held in Vienna, Austria, October 29-November 2, 2016, and Society for Medical Decision Making 38th Annual North American Meeting held in Vancouver, Canada, October 23-26, 2016.

Validity and Reliability of Value Assessment Frameworks for New Cancer Drugs.

BACKGROUND: Several organizations have developed frameworks to systematically assess the value of new drugs. These organizations include the American Society of Clinical Oncology (ASCO), the European Society for Medical Oncology (ESMO), the Institute for Clinical and Economic Review (ICER), and the National Comprehensive Cancer Network (NCCN). OBJECTIVES: To understand the extent to which these four tools can facilitate value-based treatment decisions in oncology. METHODS: In this pilot study, eight panelists conducted value assessments of five advanced lung cancer drugs using the ASCO, ESMO, and ICER frameworks. The panelists received instructions and published clinical data required to complete the assessments. Published NCCN framework scores were abstracted. The Kendall's W coefficient was used to measure convergent validity among the four frameworks. Intraclass correlation coefficients were used to measure inter-rater reliability among the ASCO, ESMO, and ICER frameworks. Sensitivity analyses were conducted. RESULTS: Drugs were ranked similarly by the four frameworks, with Kendall's W of 0.703 (P = 0.006) across all the four frameworks. Pairwise, Kendall's W was the highest for ESMO-ICER (W = 0.974; P = 0.007) and ASCO-NCCN (W = 0.944; P = 0.022) and the lowest for ICER-NCCN (W = 0.647; P = 0.315) and ESMO-NCCN (W = 0.611; P = 0.360). Intraclass correlation coefficients (confidence interval [CI]) for the ASCO, ESMO, and ICER frameworks were 0.786 (95% CI 0.517-0.970), 0.804 (95% CI 0.545-0.973), and 0.281 (95% CI 0.055-0.799), respectively. When scores were rescaled to 0 to 100, the ICER framework provided the narrowest band of scores. CONCLUSIONS: The ASCO, ESMO, ICER, and NCCN frameworks demonstrated convergent validity, despite differences in conceptual approaches used. The ASCO inter-rater reliability was high, although potentially at the cost of user burden. The ICER inter-rater reliability was poor, possibly because of its failure to distinguish differential value among the sample of drugs tested. Refinements of all frameworks should continue on the basis of further testing and stakeholder feedback.

Health-care costs and utilization related to long- or short-acting antiepileptic monotherapy use.

PURPOSE: This study aimed to compare health-care utilization and costs in patients treated with long-acting (LA) vs. short-acting (SA) antiepileptic drug (AED) monotherapy. METHODS: We conducted a cross-sectional study of claims from the OptumInsight™ database. Our analysis was restricted to adults diagnosed with epilepsy and who used AED monotherapy. Patients were excluded if they used >1 type of AED, had <9months of treatment, or had a treatment gap of >60days. Antiepileptic drugs were classified as LA or SA based on published data and expert opinion. Medical and pharmacy claims were used to estimate health-care utilization and costs, and baseline group differences were adjusted using multivariate analyses. RESULTS: There were 4058 (49.6%) LA AED users and 4122 (50.4%) SA AED users. Medication possession ratios (MPRs) were not significantly different between LA AED users and SA AED users (P=0.125). Long-acting AED users had lower mean overall health-care costs ($9757 vs. $12,689), lower epilepsy-related costs ($3539 vs. $5279), and lower rate of overall (8.8% vs. 10.9%) and epilepsy-related hospitalizations (5.7% vs. 7.6%) compared with SA AED users (all P<0.01). After adjusting for demographics and clinical characteristics, mean overall costs were lower by $686 and the mean epilepsy-related costs were lower by $894 in LA AED users. CONCLUSION: Although MPRs were similar in LA AED and SA AED groups, patients treated with LA monotherapy had a lower economic burden compared with those treated with SA monotherapy, indicating that using AEDs with extended duration of action is associated with decreased health-care use and lower health-care costs.

Patient preferences and treatment adherence among women diagnosed with metastatic breast cancer.

BACKGROUND: Given the various profiles (eg, oral vs intravenous administration, risk of hot flashes vs fatigue) of treatment options (eg, endocrine therapy, chemotherapy) for metastatic breast cancer (mBC), how patients value these attributes of their medications has implications on making treatment decisions and on adherence. OBJECTIVES: To understand how patients trade off medication side effects with improved effectiveness and/or quality of life, to provide estimates of nonadherence among women with mBC, and to quantify the association of medication nonadherence with health outcomes. METHODS: The study was a cross-sectional, Internet-based survey of 181 women diagnosed with mBC who were recruited from cancer-specific online panels (response rate, 7%). Treatment information, demographics, nonadherent behaviors, and quality of life assessed by the Functional Assessment of Cancer Therapy-Breast (FACT-B) were collected in the survey, and each respondent completed a choice-based conjoint exercise to assess patient preferences. The patients' preferences were analyzed using hierarchical Bayesian logistic regression models, and the association between the number of nonadherent behaviors and the health outcomes was analyzed using general linear models. RESULTS: The mean age of the patient sample was 52.2 years (standard deviation, ±9.1), with 93.9% of participants being non-Hispanic white. Results from the conjoint model indicated that effectiveness (overall survival) was of primary importance to patients, followed by side effects-notably alopecia, fatigue, neutropenia, motor neuropathy, and nausea/vomiting-and finally, dosing regimen. In all, 34.8% of survey respondents either discontinued their treatment or were nonadherent to their treatment regimen. Among those who have ever used oral chemotherapy (N = 95; 52.5%) and those currently using oral chemotherapy (N = 44; 24.3%), the number of nonadherent behaviors was significantly associated with a decrease in functional well-being (b [unstandardized regression coefficient] = -2.01 for patients who had ever used a targeted therapy and b = -3.14 for current users of a targeted therapy), FACT-General total score (b = -4.30 and b = -7.37, respectively), FACT-B total score (b = -3.93 and b = -6.11, respectively), and FACT trial outcome index (b = -5.22 and b = -8.63, respectively; all P <.05). CONCLUSIONS: Patients were willing to accept substantial additional risks from side effects for gains in overall survival. Approximately 33% of women with mBC reported engaging in nonadherent behaviors. Because forgetfulness and adverse events were among the most frequent reasons for nonadherence, these results suggest that less complex treatment regimens, as well as regimens with less toxic profiles, may be associated with improvements in adherence and, subsequently, could correspond to perceptible patient benefits.

Effectiveness of antiepileptic drug combination therapy for partial-onset seizures based on mechanisms of action.

IMPORTANCE: To our knowledge, the current study is the first to describe antiepileptic drug (AED) combination therapy patterns according to their mechanism of action (MOA) in a real-world setting and to evaluate the differences in outcomes comparing different-MOA combination therapy with same-MOA combination therapy for patients with partial-onset seizure. OBJECTIVE: To compare treatment persistence and health care use with AED combinations categorized by MOA in patients with partial-onset seizures. DESIGN, SETTING, AND PARTICIPANTS: Using the Truven Health MarketScan Commercial Claims Database containing 96 million covered lives from July 1, 2004, through March 31, 2011, adults with concomitant use of 2 different AEDs and a recent partial-onset seizure diagnosis were selected. Antiepileptic drugs were categorized by MOA: sodium channel blockers (SC), gamma-aminobutyric acid analogs (G), synaptic vesicle protein 2A binding (SV2), and multiple mechanisms (M). Patients were assigned a combination category based on their concomitant AED use. MAIN OUTCOMES AND MEASURES: Treatment persistence was measured from the start of AED combination therapy until the end of the combination. Health care resource use was measured during the combination treatment duration. Multivariate analyses evaluated AED discontinuation risk and health care use according to MOA combinations. RESULTS: Distribution of 8615 selected patients by combination was 3.3% for G+G, 7.5% for G+SV2, 8.6% for G+M, 13.9% for SC+SC, 19.0% for G+SC, 21.5% for SC+M, and 26.3% for SC+SV2. The same-MOA (G+G and SC+SC) combinations had the shortest persistence (mean [SD], 344 [345] days and 513 [530] days, respectively) and greater hazard of discontinuation compared with different-MOA combinations. Patients with different-MOA G combinations had a significantly lower risk for inpatient admission (odds ratio, 0.716; 95% CI, 0.539-0.952; P = .02) compared with G+G combinations. Patients with different-MOA SC combinations had significantly lower risks for emergency department visits (odds ratio, 0.853; 95% CI, 0.742-0.980; P = .03) compared with SC+SC combinations. CONCLUSIONS AND RELEVANCE: The findings suggest that AED combinations with different MOAs have greater effectiveness as measured by treatment persistence and lower risks for hospitalization and emergency department visits. Further research is needed to more fully understand the role of the MOA in achieving optimal outcomes.

Healthcare utilization and costs in children with stable and uncontrolled epilepsy.

OBJECTIVE: Epilepsy adversely affects childhood development, possibly leading to increased economic burden in pediatric populations. We compared annual healthcare utilization and costs between children (<12 years old) with stable and uncontrolled epilepsy treated with antiepileptic drugs (AEDs). METHODS: Children (<12 years old) with epilepsy (ICD-9-CM 345.xx or 780.39) in 2008 were identified in the MarketScan claims database from 2007 to 2009. Patients with "stable" epilepsy used the same AED for ≥12 months, and patients with "uncontrolled" epilepsy were prescribed additional AED(s) during that period. For patients with uncontrolled epilepsy, the study index date was the start of additional AED(s); for patients with stable epilepsy, the study index date was a random AED fill date. Epilepsy-related utilization included medical services with 345.xx or 780.39 in any diagnosis field and AED fills. Epilepsy-related costs included AEDs, medical claims with epilepsy in any diagnosis field, and certain tests. We adjusted for baseline cohort differences (demographics, region, usual-care physician specialty, and comorbidities) using logistic regression and analysis of covariance. RESULTS: Two thousand one hundred seventy patients were identified (mean: 7.5 years; 45.3% were female; Charlson comorbidity index: 0.3; 422 (19.4%) patients with uncontrolled epilepsy). Patients with uncontrolled epilepsy faced more hospitalizations (30.1% vs. 12.0%) and greater overall ($30,343 vs. $18,206) and epilepsy-related costs ($16,894 vs. $7979) (all p<.001). Adjusting for baseline measures, patients with uncontrolled epilepsy had greater odds of hospitalization (OR: 2.5; 95% CI: 1.9-3.3) and costs (overall: $3908, p=.087; epilepsy-related: $5744, p<.001). CONCLUSIONS: Children with uncontrolled epilepsy use significantly more healthcare resources and have a greater economic burden than children with stable epilepsy. However, epilepsy accounted for only half of overall costs, indicating that comorbid conditions may add substantially to the disease burden.

Healthcare utilization and costs in adults with stable and uncontrolled epilepsy.

Despite the availability of numerous antiepileptic drugs (AEDs), some epilepsies remain resistant to treatment. We compared utilization and costs in patients with uncontrolled epilepsy to those with stable epilepsy. Claims data (2007-2009) were used to identify adults with epilepsy requiring additional AED therapy (having uncontrolled epilepsy) and those not requiring additional AED therapy (having stable epilepsy). The date in 2008 on which an additional AED was started was the index date for patients with uncontrolled epilepsy, and a randomly selected date was used for patients with stable epilepsy, whose AED use was unchanged in the preceding year. In the postindex year, all pharmacy and medical claims were used to estimate overall utilization and costs; claims with epilepsy in any diagnosis field were used to estimate epilepsy-related outcomes. Outcomes were adjusted using multivariate analyses. We identified 1536 patients with uncontrolled epilepsy and 8571 patients with stable epilepsy (mean age: 42.8years; female: 48%). Patients with uncontrolled epilepsy had higher comorbidity rates (p<.02). A greater proportion of patients with uncontrolled epilepsy had ≥1 hospitalization or emergency department visit (p<.001). Patients with uncontrolled epilepsy had a greater mean length of hospital stay and more physician office visits (p<.034). After adjustment, the odds of hospitalization (OR: 1.8, any diagnosis; 2.2, epilepsy-related) and emergency department visit (OR: 1.6, any diagnosis; 1.9, epilepsy-related) were greater for patients with uncontrolled epilepsy. Annual overall ($23,238 vs. $13,839) and epilepsy-related ($12,399 vs. $5511) costs were higher in patients with uncontrolled epilepsy and remained higher after adjustment (p<.001). Patients with uncontrolled epilepsy use more services and incur higher costs compared with those with stable epilepsy. Epilepsy-related costs accounted for <50% of the total costs, suggesting that comorbid conditions and/or underidentification of utilization may substantially contribute to costs.

Retrospective analysis of variation in heavy menstrual bleeding treatments by age and underlying cause.

OBJECTIVE: To describe treatment patterns associated with heavy menstrual bleeding (HMB) in US practice. STUDY DESIGN: A retrospective claims-based analysis of organic (ICD-9 codes 218.x, 621.0, 622.7, 219.x, and bleeding disorders) or idiopathic (no underlying condition identified) HMB treatment patterns among newly diagnosed, commercially insured women who were enrolled in a large US health plan. First HMB claim (index date; ICD-9-CM 626.2 and 627.0), second HMB claim within 180 days of index date, and continuous enrollment ≥6 months prior to (pre-index period) and 18 months following (post-index period) index date were required. RESULTS: The database included 13,579 organic and 21,362 idiopathic HMB patients. More organic HMB patients received only one treatment type (64% vs 58%; p < 0.001) or two treatments types (14% vs 11%; p < 0.001) compared to idiopathic HMB patients. During the 18 month post-index period, fewer organic HMB patients had no observed treatment compared to idiopathic HMB patients (21% vs 31%; p < 0.001). The idiopathic cohort had significantly higher rates (p < 0.001) of medication use and endometrial ablation, whereas the organic HMB cohort had a higher rate of hysterectomy (p < 0.001). Women <35 years were more frequently prescribed medical treatments (p ≤ 0.037), while women aged >35 years utilized significantly more surgical approaches (p < 0.001). CONCLUSIONS: Among organic and idiopathic HMB patients, considerable variation was observed in the medications and procedures used to treat HMB. Current treatment pattern awareness may improve HMB management. Future research is needed to understand factors that influence women's treatment choices (including newer medications LNG-IUS and tranexamic acid) and age in relation to child-bearing preference.