Overall survival, costs and healthcare resource use by number of regimens received in elderly patients with newly diagnosed metastatic triple-negative breast cancer.

AIM: This analysis estimated the overall survival, treatment patterns and economic burden of elderly metastatic triple-negative breast cancer patients. MATERIALS & METHODS: Patients (≥66 years) with metastatic triple-negative breast cancer were identified from the SEER-Medicare database. Treatment patterns were defined in terms of first, second and third or more regimens. Healthcare resource use and costs were reported over the follow-up period and over the treatment duration of each regimen. RESULTS:  A total of 51% of patients did not receive chemotherapy. Taxanes were most commonly used. Median survival was 7 months. The mean cumulative (per patient per month) cost per patient was US$73,586 (US$10,084). Mean cost in first and second regimen were US$26,950 and US$33,347. CONCLUSION: About half of patients did not receive chemotherapy. Receipt of increasing regimens led to higher mean costs and healthcare resource use.

Estimating the global prevalence of transthyretin familial amyloid polyneuropathy.

INTRODUCTION: This study sought to estimate the global prevalence of transthyretin familial amyloid polyneuropathy (ATTR-FAP). METHODS: Prevalence estimates and information supporting prevalence calculations was extracted from records yielded by reference-database searches (2005-2016), conference proceedings, and nonpeer reviewed sources. Prevalence was calculated as prevalence rate multiplied by general population size, then extrapolated to countries without prevalence estimates but with reported cases. RESULTS: Searches returned 3,006 records; 1,001 were fully assessed and 10 retained, yielding prevalence for 10 "core" countries, then extrapolated to 32 additional countries. ATTR-FAP prevalence in core countries, extrapolated countries, and globally was 3,762 (range 3639-3884), 6424 (range, 1,887-34,584), and 10,186 (range, 5,526-38,468) persons, respectively. DISCUSSION: The mid global prevalence estimate (10,186) approximates the maximum commonly accepted estimate (5,000-10,000). The upper limit (38,468) implies potentially higher prevalence. These estimates should be interpreted carefully because contributing evidence was heterogeneous and carried an overall moderate risk of bias. This highlights the requirement for increasing rare-disease epidemiological assessment and clinician awareness. Muscle Nerve 57: 829-837, 2018.

Quality-adjusted survival with combination nal-IRI+5-FU/LV vs 5-FU/LV alone in metastatic pancreatic cancer patients previously treated with gemcitabine-based therapy: a Q-TWiST analysis.

BACKGROUND: In the NAPOLI-1 Phase 3 trial, nal-IRI+5-fluorouracil and leucovorin (5-FU/LV) significantly improved median overall survival (6.1 vs 4.2 months, P=0.012) and progression-free survival (3.1 vs 1.5 months, P=0.0001) vs 5-FU/LV alone in metastatic pancreatic adenocarcinoma patients previously treated with gemcitabine-based therapy. This analysis evaluated between treatment differences in quality-adjusted time without symptoms of disease progression or toxicity (Q-TWiST). METHODS: Overall survival was partitioned into time with grade ⩾3 toxicity (TOX), disease progression (REL), and time without disease progression symptoms or grade ⩾3 toxicity (TWiST). Mean Q-TWiST was calculated by weighting time spent by a utility of 1.0 for TWiST and 0.5 for TOX and REL. In threshold analyses, utility for TOX and REL were varied from 0.0 to 1.0. RESULTS: Patients in nal-IRI+5-FU/LV (n=117) vs 5-FU/LV (n=119) had significantly more mean time in TWiST (3.4 vs 2.4 months) and TOX (1.0 vs 0.3 months) but similar REL (2.5 vs 2.7 months). In the base case, nal-IRI+5-FU/LV patients had 1.3 months (95% CI, 0.4-2.1; 5.1 vs 3.9) greater Q-TWiST (threshold analyses range: 0.9-1.6 months). CONCLUSIONS: Within NAPOLI-1, nal-IRI+5-FU/LV resulted in statistically significant and clinically meaningful gains in quality-adjusted survival vs 5-FU/LV alone.

Economic Burden of Atopic Dermatitis in High-Risk Infants Receiving Cow's Milk or Partially Hydrolyzed 100% Whey-Based Formula.

OBJECTIVE: To estimate the health and economic impact of feeding partially hydrolyzed formula-whey (PHF-W) instead of standard cow's milk formula (CMF) for the first 4 months of life among US infants at high risk for developing atopic dermatitis (AD). STUDY DESIGN: A Markov model was developed integrating published data, a survey of US pediatricians, costing sources and market data, and expert opinion. Key modeled outcomes included reduction in AD risk, time spent post AD diagnosis, days without AD flare, and AD-related costs. Costs and clinical consequences were discounted at 3% annually. RESULTS: An estimated absolute 14-percentage point reduction in AD risk was calculated with the use of PHF-W compared with CMF (95% CI for difference, 3%-22%). Relative to CMF, PHF-W decreased the time spent post-AD diagnosis by 8.3 months (95% CI, 2.78-13.31) per child and increased days without AD flare by 39 days (95% CI, 13-63) per child. The AD-related, 6-year total cost estimate was $495 less (95% CI, -$813 to -$157) per child with PHF-W ($724 per child; 95% CI, $385-$1269) compared with CMF ($1219 per child; 95% CI, $741-$1824). CONCLUSION: Utilization of PHF-W in place of CMF as the initial infant formula administered to high-risk US infants not exclusively breastfed during the first 4 months of life may reduce the incidence and economic burden of AD. Broad implementation of this strategy could result in a minimum savings of $355 million per year to society.

Patterns of clinical management of atopic dermatitis in infants and toddlers: a survey of three physician specialties in the United States.

OBJECTIVE: To describe atopic dermatitis (AD) management patterns in children ≤36 months old as reported by pediatricians, dermatologists, and allergists in the US. STUDY DESIGN: A nationally-representative survey was administered to pediatricians (n = 101), dermatologists (n = 26), and allergists (n = 26). Main outcomes included referrals to health care professionals, suggested/ordered laboratory tests, management approach (dietary, pharmacologic, or combination of both) by age, AD location, and severity. RESULTS: Significant differences were observed in referrals to healthcare professionals (P < .001). Pediatricians more frequently referred to dermatologists than allergists in mild (52.4% vs 32.0%) and moderate/severe (60.6% vs 38.1%) cases. Dermatologists referred to allergists less frequently for mild (9.1%) than moderate/severe (40.7%) AD cases. Pediatricians (59%), allergists (61.5%), and dermatologists (26.9%) reported treating at least some of their patients with AD with dietary management (infant formula change) alone (with or without emollients). Soy-based formulas were often used. For mild AD, the most commonly reported first-line pharmacologic treatments included topical emollients, topical corticosteroids, and barrier repair topical therapy/medical devices. Over 80% of physicians used a dietary and pharmacologic combination approach. Dermatologists were most likely to manage AD symptoms with a pharmacologic-only approach. AD lesion location influenced pharmacologic treatment in >80% of physicians. CONCLUSIONS: Significant and distinct differences in AD treatment approach exist among physicians surveyed. Most pediatricians and allergists use formula change as a management strategy in some patients, whereas dermatologists favor a pharmacologic approach. This diversity may result from inadequate evidence for a standard approach. Consistent methods for managing AD are needed.

The impact of second-line agents on patients' health-related quality of life in the treatment for non-small cell lung cancer: a systematic review.

PURPOSE: In advanced non-small cell lung cancer (NSCLC), progressive disease burdens patients considerably. Second-line (2L) chemotherapy improves survival marginally but humanistic outcomes (i.e., quality of life, QOL) are underreported. The impact of 2L therapy remains an important consideration for patients and caregivers, and there have been QOL reviews for 1L, but not 2L, therapies. This review assessed QOL outcomes of approved, guideline-supported 2L chemotherapy with docetaxel, erlotinib, gefitinib, and pemetrexed in advanced NSCLC. METHODS: Clinical trial reports of approved, guideline-supported 2L or maintenance therapy for NSCLC published from 2000 to 2010 were identified from PubMed/Medline and clinical meetings. Outcomes were stratified by overall QOL impact, domain/symptom-specific effects, effect over time, and subgroup effects. RESULTS: Of 145 studies identified, 24 full-text articles were retained. Studies with docetaxel versus best supportive care (n = 1) and active comparators (n = 4) reported non-significant overall QOL improvements, as did studies of gefitinib versus placebo and active comparator (n = 7). Overall QOL improvements were seen for gefitinib versus docetaxel (n = 2) and gefitinib in a single-arm study (n = 1). At the symptom level, studies of docetaxel (n = 4/7), gefitinib (n = 7/9), and pemetrexed (n = 1) reported non-significant results. Subgroup analyses indicated improved QOL outcomes for gefitinib-treated responders versus non-responders, worse QOL for gefitinib-treated smokers versus placebo, worse QOL for gefitinib-treated Asian patients versus placebo, and longer time to symptom deterioration in erlotinib versus placebo-treated elderly patients. CONCLUSIONS: Significant improvements in overall QOL with 2L chemotherapy for advanced NSCLC were infrequent. Single-arm studies and those with less toxic regimens more commonly provided statistically significant improvements in QOL outcomes. Methodological heterogeneity impedes cross-study QOL comparisons.

Eliciting health state utilities for Dupuytren's contracture using a discrete choice experiment.

BACKGROUND AND PURPOSE: An internet-based discrete choice experiment (DCE) was conducted to elicit preferences for a wide range of Dupuytren's contracture (DC)-related health states. An algorithm was subsequently developed to convert these preferences into health state utilities that can be used to assess DC's impact on quality of life and the value of its treatments. METHODS: Health state preferences for varying levels of DC hand severity were elicited via an internet survey from a sample of the UK adult population. Severity levels were defined using a combination of contractures (0, 45, or 90 degrees) in 8 proximal interphalangeal and metacarpophalangeal joints of the index, middle, ring, and little fingers. Right-handed, left-handed, and ambidextrous respondents indicated which hand was preferable in each of the 10 randomly-selected hand-pairings comparing different DC severity levels. For consistency across comparisons, anatomically precise digital hand drawings were used. To anchor preferences onto the traditional 0-1 utility scale used in health economic evaluations, unaffected hands were assigned a utility of 1.0 whereas the utility for a maximally affected hand (i.e., all 8 joints set at 90 degrees of contracture) was derived by asking respondents to indicate what combination of attributes and levels of the EQ-5D-5L profile most accurately reflects the impact of living with such hand. Conditional logistic models were used to estimate indirect utilities, then rescaled to the anchor points on the EQ-5D-5L. RESULTS: Estimated utilities based on the responses of 1,745 qualified respondents were 0.49, 0.57, and 0.63 for completely affected dominant hands, non-dominant hands, or ambidextrous hands, respectively. Utility for a dominant hand with 90-degree contracture in t h e metacarpophalangeal joints of the ring and little fingers was estimated to be 0.89. Separately, reducing the contracture of metacarpophalangeal joint for a little finger from 50 to 12 degrees would improve utility by 0.02. INTERPRETATION: DC is associated with substantial utility decrements. The algorithms presented herein provide a robust and flexible framework to assess utility for varying degrees of DC severity.

Assessing the value of orphan drugs using conventional cost-effectiveness analysis: Is it fit for purpose?

Conventional cost-effectiveness analysis-i.e., assessing pharmaceuticals through a cost per quality-adjusted life year (QALY) framework-originated from a societal commitment to maximize population health given limited resources. This "extra-welfarist" approach has produced pricing and reimbursement systems that are not well- aligned with the unique considerations of orphan drugs. This framework has been slow to evolve along with our increased understanding of the impact of rare diseases, which in turn has complicated the assessment of orphan drugs meant to treat rare diseases. Herein, we (i) discuss the limitations of conventional cost-effectiveness analysis as applied to assessing access to, as well as the pricing and reimbursement of, orphan drugs, (ii) critically appraise alternative and supplemental approaches, and (iii) offer insights on plausible steps forward.

Mapping of the Insomnia Severity Index and other sleep measures to EuroQol EQ-5D health state utilities.

BACKGROUND: This study sought to map the Insomnia Severity Index (ISI) and symptom variables onto the EQ-5D. METHODS: A cross-sectional survey was conducted among adult US residents with self-reported sleep problems. Respondents provided demographic, comorbidity, and sleep-related information and had completed the ISI and the EQ-5D profile. Respondents were classified into ISI categories indicating no, threshold, moderate, or severe insomnia. Generalized linear models (GLM) were used to map the ISI's 7 items (Model I), summary scores (Model II), clinical categories (Model III), and insomnia symptoms (Model IV), onto the EQ-5D. We used 50% of the sample for estimation and 50% for prediction. Prediction accuracy was assessed by mean squared errors (MSEs) and mean absolute errors (MAEs). RESULTS: Mean (standard deviation) sleep duration for respondents (N = 2,842) was 7.8 (1.9) hours, and mean ISI score was 14.1 (4.8). Mean predicted EQ-5D utility was 0.765 (0.08) from Models I-III, which overlapped with observed utilities 0.765 (0.18). Predicted utility using insomnia symptoms was higher (0.771(0.07)). Based on Model I, predicted utilities increased linearly with improving ISI (0.493 if ISI = 28 vs. 1.00 if ISI = 0, p < 0.01). From Model II, each unit decrease in ISI summary score was associated with a 0.022 (p < 0.001) increase in utility. Predicted utilities were 0.868, 0.809, 0.722, and 0.579, respectively, for the 4 clinical categories, suggesting that lower utility was related to greater insomnia severity. The symptom model (Model IV) indicated a concave sleep-duration function of the EQ-5D; thus, utilities diminished after an optimal amount of sleep. The MSEs/MAEs were substantially lower when predicting EQ-5D > 0.40, and results were comparable in all models. CONCLUSIONS: Findings suggest that mapping relationships between the EQ-5D and insomnia measures could be established. These relationships may be used to estimate insomnia-related treatment effects on health state utilities.

Cost effectiveness of axicabtagene ciloleucel versus tisagenlecleucel for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy in the United States.

AIMS: To assess from a US payer perspective the cost-effectiveness of the chimeric antigen receptor T (CAR T)-cell therapies axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) to treat relapsed or refractory (r/r) large B-cell lymphoma (LBCL) following ≥2 systemic therapy lines. METHODS: A three-state (i.e. pre-progression, post-progression, and death) partitioned survival model was used to estimate the quality-adjusted life-years (QALYs) and costs for patients on each treatment over a lifetime horizon. Progression-free survival (PFS) and overall survival (OS) were based on a matching-adjusted indirect treatment comparison (MAIC) that accounted for differences in trial population baseline characteristics. Mixture cure models (MCMs) were used to account for long-term survivors. Costs included drug acquisition and administration for the CAR T-cell therapies and conditioning chemotherapy, apheresis, CAR T-specific monitoring, transplant, hospitalization, adverse events, routine care, and terminal care. Health state utilities were derived from trial and published data. Sensitivity analyses included probabilistic sensitivity analyses (PSAs) and an analysis of extremes that assessed the results across a vast array of combinations of parametric OS and PFS curves across the two therapies. RESULTS: Compared to tisa-cel, axi-cel resulted in 2.31 QALYs gained and a cost reduction of $1,407 in the base case. In the PSA, the cost per QALY gained was ≤$31,500 in 95% of the 1,000 simulations. In the analysis of extremes, the cost per QALY gained was ≤$7,500 in 99% of the 1,296 combinations of MCMs and ≤$40,000 in 95% of the 1,296 combinations of standard models. LIMITATIONS: In absence of head-to-head comparative data, we relied on a MAIC, which cannot account for all possible confounders. Moreover, some outcomes (i.e. transplantations, hospitalizations, adverse events (AEs)) were not adjusted in the MAIC. CONCLUSIONS: In this simulation, axi-cel was a superior treatment option as it is predicted to achieve better outcomes at lower or minimal incremental costs versus tisa-cel.

Corneal cross-linking versus conventional management for keratoconus: a lifetime economic model.

AIMS: To assess the cost-effectiveness of corneal collagen cross-linking (CXL) versus no CXL for keratoconus in the United States (US). METHODS: A discrete-event microsimulation was developed to assess the cost-effectiveness of corneal cross-linking (CXL, Photrexa + KXL combination product) versus no CXL for patients with keratoconus. The lifetime model was conducted from a US payor perspective. The source for CXL efficacy and safety data was a 12-month randomized, open-label, sham-controlled, multi-center, pivotal trial comparing CXL versus no CXL. Other inputs were sourced from the literature. The primary outcome was the incremental cost per quality-adjusted life year gained. Costs (2019 USD) and effects were discounted 3% annually. The impacts of underlying uncertainty were evaluated by scenario, univariate, and probabilistic analyses. RESULTS: Starting at a mean baseline age of 31 years and considering a mixed population consisting of 80% slow-progressors and 20% fast-progressors, the CXL group was 25.9% less likely to undergo penetrating keratoplasty (PK) and spent 27.9 fewer years in advanced disease stages. CXL was dominant with lower total direct medical costs (-$8,677; $30,994 versus $39,671) and more QALYs (1.88; 21.80 versus 19.93) compared to no CXL. Considering the impact of reduced productivity loss in an exploratory scenario, CXL was associated with a lifetime cost-savings of $43,759 per patient. CXL was cost-effective within 2 years and cost-saving within 4.5 years. LIMITATIONS: Limitations include those that are common to similar pharmacoeconomic models that rely on disparate sources for inputs and extrapolation on short-term outcomes to a long-term analytical horizon. CONCLUSIONS: Keratoconus is a progressive and life-altering disease with substantial clinical, economic, and humanistic consequences. The economic value of cross-linking is maximized when applied earlier in the disease process and/or younger age, and extends to improved work productivity, out-of-pocket costs, and quality of life.

Economic outcomes of eszopiclone treatment in insomnia and comorbid major depressive disorder.

BACKGROUND: Eszopiclone is effective for the treatment of insomnia in patients with insomnia and comorbid major depressive disorder (MDD). Both conditions impose significant economic burden, with the US societal cost of depression estimated at USD 50 billion annually. AIMS OF THE STUDY: The purpose of this analysis was to examine the costs and benefits of eszopiclone co-administered with fluoxetine (ESZ+FLX) compared to placebo co-administered with fluoxetine (PBO+FLX) in adults meeting the DSM-IV criteria for insomnia and MDD. METHODS: Data from 434 patients enrolled in an 8-week clinical trial who met the economic-subanalysis criteria were examined. The costs of medical care (in 2007 USUSD ) and lost work time were estimated from the Hamilton Depression Scale (HAM-D17) scores using published algorithms. Cost of lost productivity while at work was based on responses to the Work Limitations Questionnaire. The impact of therapy on quality-adjusted life years (QALYs) was estimated by transforming HAM-D17 (base case analysis) or Short Form Health Survey (SF-12) (scenario analyses) responses into health utility scores using published algorithms. Drug costs were estimated based on average wholesale price. RESULTS: The mean 8-week increases in QALYs from baseline were 0.0392 and 0.0334 for the ESZ+FLX and PBO+FLX groups, respectively. Mean per-patient costs were USD 1,279 and USD 1,198 for the respective groups. Thus, co-treatment resulted in net increases of 0.0058 QALYs and USD 81, leading to an incremental cost per QALY gained of approximately USD 14,000. DISCUSSION AND LIMITATIONS: Co-administration of eszopiclone and fluoxetine improved patients' insomnia symptoms and appeared to be a cost-effective treatment strategy for patients with insomnia and comorbid MDD. One limitation of this study is that optimal utility estimation techniques were not available. Utilities were instead derived indirectly using the HAM-D17 (disease-specific, not generic) or SF-12 (generic, but potentially insensitive to important changes in some conditions) instruments. IMPLICATIONS FOR HEALTH CARE PROVISION: Sleep disturbance is predictive of depression relapse, and is the most common residual symptom in patients who have been successfully treated with fluoxetine for depression. Thus, identifying cost-effective strategies for the treatment of insomnia symptoms is important for this patient population. IMPLICATIONS FOR HEALTH POLICIES: Treatment guidelines and drug coverage decisions should be based on clinical evidence, effectiveness, and economic criteria (i.e., whether an effective drug therapy produces sufficient benefits given its costs). This information about the overall value of eszopiclone can be measured as the cost per QALY gained with the use of ESZ+FLX compared with FLX alone. In order to make decisions based on value, payers and policy makers must have access to reliable cost-effectiveness information. IMPLICATIONS FOR FURTHER RESEARCH: The residual efficacy observed in the clinical trial following the discontinuation of co-therapy should be explored further to determine whether intermittent treatment with ESZ+FLX is a cost-effective strategy.

Medical oncology referral and systemic therapy of patients with advanced stage urothelial carcinoma.

Aim: To understand physician visit patterns among patients with stage IV (including nonmetastatic [M0] and metastatic [M1] disease) urothelial carcinoma (UC) and understand factors associated with a timely referral to a medical oncologist and systemic treatment. Patients & methods: Retrospective analysis of Surveillance, Epidemiology and End Results-Medicare data. Results: First physician encounter was with a urologist (M0: 69%; M1: 53%) or primary care physician ([PCP]; M0: 19%, M1: 25%) for the majority of patients around UC diagnosis. After the index urologist encounter, most patients had a subsequent medical oncologist visit at a median of 52 days (M0: 69.5 days, M1: 33 days). In an adjusted model, older age, index PCP visit, higher comorbidities and M0 disease were negatively associated with a medical oncologist referral. Among those referred to a medical oncologist, older age, Hispanic or non-Hispanic Black race and not being married were negatively associated with subsequent chemotherapy receipt (p < 0.05). Conclusion: Many patients with advanced UC encounter multiple specialists during their disease course. Older patients or those with a first UC-related encounter with a PCP are less likely to be referred to medical oncology. Once referred to medical oncology, social determinants, including race and marital status, are relevant predictors of receiving chemotherapy.

Impact of Non-Cardiac Clinicopathologic Characteristics on Survival in Transthyretin Amyloid Polyneuropathy.

INTRODUCTION: Hereditary (variant) transthyretin amyloidosis (ATTRv) with polyneuropathy (ATTR-PN) is a rare genetic disorder that causes progressive autonomic and sensorimotor neuropathy, severe disability, and death within 10 years of onset. Previous studies have primarily focused on how baseline cardiac characteristics affect mortality, but the impact of non-cardiac baseline characteristics is less defined. METHODS: We systematically searched PubMed/Medline (1990-2019) to identify studies that assessed the impact of baseline ATTR-PN characteristics on survival. Outcomes were first summarized descriptively. Extracted survival data were then disaggregated, and parametric mixture models were used to assess survival differences among patient groups defined by factors known to affect survival. RESULTS: The search yielded 1193 records, of which 35 were retained for analysis. Median survival ranged from 0.5 to > 25 years. The largest survival differences were between cohorts who underwent liver transplantation (LTx) versus those who did not. Among LTx cohorts, pre-LTx ATTR-PN disease duration ≥ 7 years, poor nutritional status, and late disease onset reduced median survival by 13, 12, and 10 years, respectively. Other prognostic survival factors included non-Val30Met genotype and baseline presence of urinary incontinence, erectile dysfunction, or muscle weakness. CONCLUSION: Survival in patients with ATTR-PN is highly variable and affected by non-cardiac baseline characteristics, such as autonomic dysfunction, large fiber involvement, late-onset disease, and non-Val30Met mutation. Careful interpretation of these findings is warranted given that this synthesis did not control for differences between studies. Survival in patients with ATTR-PN remains poor among those who are untreated or with delayed diagnosis.

Survival, costs, and health care resource use by line of therapy in US Medicare patients with newly diagnosed glioblastoma: a retrospective observational study.

BACKGROUND: Glioblastoma (GBM) is associated with poor prognosis, large morbidity burden, and limited treatment options. This analysis evaluated real-world treatment patterns, overall survival, resource use, and costs among Medicare patients with GBM. METHODS: This retrospective observational study evaluated Medicare patients age 66 years or older with newly diagnosed GBM using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked data from 2007 through 2013. Patients were followed from diagnosis to death or end of follow-up. An algorithm defined treatment patterns as lines of therapy (LOTs). The Kaplan-Meier method was used to estimate overall survival for the full sample as well as by LOT, surgical resection, Charlson Comorbidity Index (CCI), tumor size, and age. Resource use and costs during the follow-up period were reported in terms of total and per-patient-per-month (PPPM) estimates. RESULTS: A total of 4308 patients with GBM were identified (median age, 74 years; CCI of 0, 52%). The most commonly used first LOT was temozolomide (82%), whereas chemotherapy + bevacizumab was most prevalent for second-line (42%) and third-line (58%) therapy. The median overall survival was 5.9 months for resected patients and 3 months for unresected patients, with considerable heterogeneity depending on patient characteristics. A great proportion of patients had claims for an ICU admission (86.2%), skilled nursing facility (76.9%), and home health (56.0%) in the postdiagnosis period. The cumulative mean cost was $95 377 per patient and $18 053 PPPM, mostly attributed to hospitalizations. CONCLUSIONS: Limited treatment options, poor survival, and economic burden emphasize the need for novel interventions to improve care for Medicare patients with GBM.

Landscape of Health-Related Quality of Life in Patients With Early-Stage Pancreatic Cancer Receiving Adjuvant or Neoadjuvant Chemotherapy: A Systematic Literature Review.

OBJECTIVES: Pancreatic resection is associated with postoperative morbidity and reduced quality of life (QoL). A systematic literature review was conducted to understand the patient-reported outcome measure (PROM) landscape in early-stage pancreatic cancer (PC). METHODS: Databases/registries (through January 24, 2019) and conference abstracts (2014-2017) were searched. Study quality was assessed using the Newcastle-Ottawa Scale/Cochrane risk-of-bias tool. Searches were for general (resectable PC, adjuvant/neoadjuvant, QoL) and supplemental studies (resectable PC, European Organisation for Research and Treatment of Cancer QoL Questionnaire [QLQ] - Pancreatic Cancer [PAN26]). RESULTS: Of 750 studies identified, 39 (general, 22; supplemental, 17) were eligible: 32 used QLQ Core 30 (C30) and/or QLQ-PAN26, and 15 used other PROMs. Baseline QLQ-C30 global health status/QoL scores in early-stage PC were similar to all-stage PC reference values but lower than all-stage-all-cancer values. The QoL declined after surgery, recovered to baseline in 3 to 6 months, and then generally stabilized. A minimally important difference (MID) of 10 was commonly used for QLQ-C30 but was not established for QLQ-PAN26. CONCLUSIONS: In early-stage PC, QLQ-C30 and QLQ-PAN26 are the most commonly used PROMs. Baseline QLQ-C30 global health status/QoL scores suggested a high humanistic burden. Immediately after surgery, QoL declined but seemed stable over the longer term. The QLQ-C30 MID may elucidate the clinical impact of treatment on QoL; MID for QLQ-PAN26 needs to be established.

Cost-effectiveness of eszopiclone for the treatment of adults with primary chronic insomnia.

STUDY OBJECTIVE: To assess the cost-effectiveness of treatment with eszopiclone for chronic primary insomnia in adults. METHODS: A model using patient-level data from a 6-month, double-blind, placebo-controlled, clinical trial (n = 824), combined with data from a claims database and published literature, was used to assess the quality-adjusted life years (QALYs) gained and costs associated with eszopiclone versus placebo in adults with primary insomnia. Quality of life data were collected during the trial via the SF-36, from which preference-based utility scores were derived using published algorithms. Medical and absenteeism costs, estimated via a retrospective analysis of a claims and absenteeism database, were assigned to patients based on the degree of severity of their insomnia, assessed via the Insomnia Severity Index collected in the clinical trial. Presenteeism costs (lost productivity while at work) were estimated from responses to the Work Limitation Questionnaire collected during the trial. Six-month gains in QALYs and costs for each treatment group were calculated to derive cost-effectiveness ratios. Uncertainty was addressed via univariate and multivariate sensitivity analyses. RESULTS: Over the 6-month period, eszopiclone use resulted in a net gain of 0.0137 QALYs over placebo at an additional cost of $67, resulting in an incremental cost per QALY gained of slightly less than $5,000. When absenteeism and presenteeism costs were excluded, the cost-effectiveness ratio increased to approximately $33,000 per QALY gained, which is below the commonly used threshold of $50,000 used to define cost-effectiveness. Extensive sensitivity analyses indicate the results are generally robust. CONCLUSION: Our model, based on efficacy data from a clinical trial, demonstrated eszopiclone was cost-effective for the treatment of primary insomnia in adults, especially when lost productivity costs were included.

Overall survival, costs, and healthcare resource use by line of therapy in Medicare patients with newly diagnosed metastatic urothelial carcinoma.

Aims: Medicare patients with metastatic or surgically unresectable urothelial carcinoma (mUC) often receive platinum-based chemotherapy as first line of therapy (LOT), but invariably progress, requiring additional LOTs and healthcare resource use (HCRU). To better understand the evolving mUC treatment landscape, the economic burden of chemotherapy-based mUC treatments among US Medicare patients was estimated. Methods: Newly diagnosed Medicare patients with mUC were identified from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Patients were followed from diagnosis to death, disenrollment, or end of study to characterize LOTs (first [LOT1], second [LOT2], and third or greater [LOT3+]). Kaplan-Meier methods were used to estimate overall survival (OS) by LOT. HCRU and mean costs were reported over the follow-up period, LOT duration, and maximum LOT received. Results: Among 1,873 eligible patients with mUC (median age = 77 years; median follow-up = 7.5 months), 1,035 (55%) received no chemotherapy. Among chemotherapy-treated patients, 61% had LOT1 only, 25% had LOT1 and LOT2 only, and 14% had LOT3+. Median OS was 8.1 months, range was 4.3 (untreated) to 29.8 (LOT3+) months. HCRU frequency increased with additional LOTs. Mean cumulative per-patient cost was $82,912 for all patients, increasing with additional LOTs (untreated = $57,207; LOT1 = $99,213; LOT2 = $125,190; LOT3+ = $163,884). Mean per patient per month cost was $18,827 for all patients, decreasing with increasing number of LOTs received (untreated = $27,211; LOT1 = $9,601; LOT2 = $7,325; LOT3+ = $6,017). Limitations: Potential for treatment misclassification when using the algorithm defining LOTs and non-generalizability of results to younger patients. Conclusions: Over 50% of Medicare patients with mUC received no chemotherapy. Among chemotherapy-treated patients, most received only one LOT. Additional LOTs led to higher mean costs and HCRU, but as patients were followed longer, monthly costs decreased. As treatments evolve to include immuno-oncology agents, these findings provide a clinically relevant economic benchmark for mUC treatment across different traditional LOTs.

Epidemiological and clinical characteristics of symptomatic hereditary transthyretin amyloid polyneuropathy: a global case series.

We describe 542 cases of symptomatic hereditary transthyretin amyloid polyneuropathy (ATTR-PN) identified through a review of the literature published between 2005 and 2016. Approximately 18% of the cases were from countries where ATTR-PN is traditionally considered to be endemic (i.e., Portugal, Japan, and Sweden). East Asia (Japan, China, Taiwan, and South Korea) contributed a sizeable combined proportion (37.0%, n = 200) with Japan (n = 92) and China (n = 71) being the primary contributors. The most common genotypes among the 65 genotypes represented in the sample were Val30Met (47.6%), Ser77Tyr (10%), Ala97Ser (6.5%), and Phe64Leu (4.4%). Cases with genotypes other than the aforementioned four had the lowest ages at onset (mean 49.2 [standard deviation {SD} 21.0; inter-quartile range {IQR}14.7]) and diagnosis (mean 53.4 [SD 21.0; IQR 14.7]). Conversely, Phe64Leu mean age of onset was 67.5 (SD 8.8; IQR 5.2) and mean age of diagnosis was 71.3 (SD 8.8; IQR 5.4). The prevalence of upper and lower limb involvement at the time of diagnosis (67 and 41%) observed across all cases is consistent with the typical presentation of ATTR-PN. Other notable findings at the time of diagnosis included a high rate of impotence among the Ala97Ser cases versus all others (67% vs. 21%) and a high rate of non-motor visual symptoms (i.e., visual opacities and glaucoma) in the Ser77Tyr cases versus all others (93% vs. 16%). Though comparisons were made descriptively and were hindered by inconsistency of reporting across the cases, these findings support the notion that ATTR-PN is a more phenotypically and geographically variable disease than is typically considered.

Understanding the Disease Course and Therapeutic Benefit of Tafamidis Across Real-World Studies of Hereditary Transthyretin Amyloidosis with Polyneuropathy: A Proof of Concept for Integrative Data Analytic Approaches.

INTRODUCTION: Hereditary transthyretin (TTR) amyloidosis with polyneuropathy (hATTR-PN) is a rare, autosomal dominant amyloidosis characterized primarily by progressive ascending sensorimotor neuropathy often associated with  autonomic involvement. hATTR-PN is caused by a mutation in the TTR gene leading to protein misfolding and amyloid accumulation in peripheral nerves and vital organs. The latest global prevalence estimates point to 10,000 cases worldwide, with an upper end of about 40,000. Tafamidis has been approved in over 40 countries for delaying neurologic disease progression in early-stage hATTR-PN. Multiple observational studies have examined clinical outcomes in hATTR-PN patients treated with tafamidis in the routine clinical setting. Integrative data analysis (IDA) is a technique for optimally constructing synthetic treatment and control cohorts from multiple independent studies, which allows meta-analysis of patient-level data. Herein, we provide a proof of concept for the application of IDA to real-world and natural history hATTR-PN data. IDA permits increased understanding of outcomes in tafamidis-treated and untreated persons with hATTR-PN by optimally pooling all available information. METHODS: Summary statistics corresponding to the Neuropathy Impairment Score-Lower Limb (NIS-LL) from five published studies were pooled, converted to change from baseline means and variances, and analyzed using IDA. IDA-based synthetic cohorts were generated by averaging across studies stratified on treatment versus control cohort. Trends in change from baseline in each study and the corresponding synthetic cohorts were plotted. Patient-level data were simulated from the synthetic cohort trends in a Monte Carlo simulation to highlight the ability to contrast synthetic cohort trends using the mixed model for repeated measures (MMRM). RESULTS: The average sample size among the five studies was 71 (37-128) patients. The average NIS-LL trends indicated that tafamidis-treated patients experienced slower progression in neuropathy compared to untreated patients. Synthetic cohort trends reflected the trends observed in the contributing studies, while simultaneously shrinking the width of corresponding confidence bands. Monte Carlo simulation results demonstrated precise recovery of the synthetic cohort and time-dependent simulated NIS-LL means by the MMRM. DISCUSSION: This proof of concept demonstrates the utility of IDA-based synthetic cohorts for increased precision in characterizing and testing hypotheses about treatment outcomes and prognosis in hATTR-PN. FUNDING: Pfizer. Plain language summary available for this article.