Health care resource utilization in 3L + patients with chronic phase chronic myeloid leukemia receiving asciminib or bosutinib.

OBJECTIVES: To assess and compare health care resource utilization (HCRU) rates of asciminib and bosutinib at the Week 24, Week 48, and Week 96 cutoffs among 3 L + patients with chronic myeloid leukemia in chronic phase (CML-CP) in the randomized ASCEMBL trial. METHODS: Patients in the ASCEMBL trial (Clinicaltrials.gov: NCT03106779) were randomized to receive asciminib 40 mg twice daily (n = 157) or bosutinib 500 mg once daily (n = 76). At each scheduled visit, investigators conducted HCRU assessment on hospitalization, emergency room visit, general practitioner visit, specialist visit and urgent care visit; duration and type of hospitalization for the hospitalized patients; and reasons for HCRU. The number of patients with HCRU, rate of HCRU per patient-year, and length of hospital stay by ward type were compared at Week 24, Week 48, and Week 96 analyses. RESULTS: Lower proportions of patients receiving asciminib versus bosutinib used any resources including hospitalizations, emergency room visits, general practitioner visits, specialist visits, and urgent care visits (23.6% versus 36.8%, 26.1% versus 39.5%, and 28.6% versus 42.6% at Week 24, Week 48, and Week 96 analyses, respectively). After normalizing for treatment exposure, rates of HCRU for any resource per patient-year were significantly lower for asciminib versus bosutinib: 0.25 (95% CI: 0.18-0.34) versus 0.80 (95% CI: 0.55-1.16) at the Week 24 analysis, 0.20 (95% CI: 0.15-0.27) versus 0.47 (95% CI: 0.32-0.66) at the Week 48 analysis, and 0.17 (95% CI: 0.12-0.22) versus 0.40 (95% CI: 0.27-0.55) at the Week 96 analysis. Among the hospitalized patients, mean length of hospital stay was lower for asciminib than bosutinib for most wards at all three timepoints. CONCLUSIONS: In the ASCEMBL trial, asciminib-treated patients with CML-CP in 3 L + maintained lower resource utilization compared to bosutinib over the long-term.

Systematic literature review of evidence in amyloid light-chain amyloidosis.

Introduction: Treatment of amyloid light-chain (AL) amyloidosis, a rare disease with a <5-year lifespan, remains challenging. This systematic literature review (SLR) aimed to evaluate the current evidence base in AL amyloidosis. Methods: Literature searches on clinical, health-related quality of life, economic and resource use evidence were conducted using the Embase, MEDLINE and Cochrane databases as well as gray literature. Results: This SLR yielded 84 unique studies from: five randomized controlled trials; 54 observational studies; 12 health-related quality of life studies, none with utility values; no economic evaluation studies; and 16 resource use studies, none with indirect costs. Conclusion: This SLR highlights a paucity of published literature relating to randomized controlled trials, utility values, economic evaluations and indirect costs in AL amyloidosis.

Economic Model to Evaluate the Cost-Effectiveness of Second-Line Nilotinib Versus Dasatinib for the Treatment of Philadelphia Chromosome-Positive Chronic Myeloid Leukemia (CML-CP) in Italy.

OBJECTIVE: The aim of this study was to evaluate the cost effectiveness of second-line nilotinib versus dasatinib for the treatment of Philadelphia chromosome-positive chronic myeloid leukemia (CML-CP) patients who are intolerant or resistant to imatinib and can transition to treatment-free remission (TFR). METHODS: A partitioned survival model was developed to compare the cost effectiveness of nilotinib versus dasatinib. The model was developed from the Italian healthcare payer perspective and included the following health states: on second-line tyrosine kinase inhibitor (TKI), off second-line TKI, accelerated phase/blastic crisis, TFR, and death. Progression-free and overall survival curves were derived from patient-level data that compared nilotinib and dasatinib as second-line therapy in CML-CP patients who were resistant or intolerant to imatinib. Drug costs, healthcare costs, and adverse event costs were based on real-world evidence and publicly available databases. Cost effectiveness was estimated over a 40-year time horizon. Scenario analyses were performed by adjusting time horizon, TFR parameters, costs, and utilities. RESULTS: Second-line nilotinib resulted in greater time spent in TFR (0.91 life-years), increased quality-adjusted life-years (QALYs) (1.89), increased life-years (2.16), and decreased per-patient costs (- 38,760 €). Therefore, nilotinib was strongly dominant compared with dasatinib in the base-case analysis. Nilotinib remained strongly dominant in most scenario analyses including shorter time horizon, exclusion of TFR, and varying TKI drug costs. CONCLUSIONS: While the model showed that nilotinib treatment of imatinib-intolerant or resistant CML-CP patients was more effective and less costly than dasatinib treatment, there is considerable uncertainty in the findings.

Estimating the annual economic burden for the management of patients with transthyretin amyloid polyneuropathy in Spain.

Background: Transthyretin amyloid polyneuropathy (ATTR-PN) is a fatal disease associated with substantial burden of illness. Three therapies are approved by the European Medicines Agency for the management of this rare disease. The aim of this study was to compare the total annual treatment specific cost per-patient associated with ATTR-PN in Spain.Methods: An Excel-based patient burden and cost estimator tool was developed to itemize direct and indirect costs related to treatment with inotersen, patisiran, and tafamidis in the context of ATTR-PN. The product labels and feedback from five Spanish ATTR-PN experts were used to inform resource use and cost inputs.Results: Marked differences in costs were observed between the three therapies. The need for patisiran- and inotersen-treated patients to visit hospitals for pre-treatment, administration, and monitoring was associated with increased patient burden and costs compared to those treated with tafamidis. Drug acquisition costs per-patient per-year were 291,076€ (inotersen), 427,250€ (patisiran) and 129,737€ (tafamidis) and accounted for the majority of total costs. Overall, the total annual per-patient costs were lowest for patients treated with tafamidis (137,954€), followed by inotersen (308,358€), and patisiran (458,771€).Conclusions: Treating patients with tafamidis leads to substantially lower costs and patient burden than with inotersen or patisiran.

Development, validation and results from the impact of treatment evolution in non-small cell lung cancer (iTEN) model.

OBJECTIVES: Treatment of advanced NSCLC (aNSCLC) is rapidly evolving, as new targeted and immuno-oncology (I-O) treatments become available. The iTEN model was developed to predict the cost and survival benefits of changing aNSCLC treatment patterns from a Canadian healthcare system perspective. This report describes iTEN model development and validation. MATERIALS & METHODS: A discrete event patient simulation of aNSCLC was developed. A modified Delphi process using Canadian clinical experts informed the development of treatment sequences that included commonly used, Health Canada approved treatments of aNSCLC. Treatment efficacy and the timing of progression and death were estimated from published Kaplan-Meier progression free and overall survival data. Costs (2018 CDN$) included were: drug acquisition and administration, imaging, monitoring, adverse events, physician visits, best supportive care, and end-of-life. RESULTS AND CONCLUSION: Clinical validity of the iTEN model was assessed by comparing model survival predictions to published real-world evidence (RWE). Four RWE studies that reported the overall survival of patients treated with a broad sampling of common aNSCLC treatment patterns were used for validation. The validation coefficient of determination was R2 = 0.95, with the model generally producing estimates that were neither optimistic nor conservative. The model estimated that current Canadian practice patterns yield a median survival of almost 13 months, a five-year survival rate of 3% and a life-time per-treated-patient cost of $110,806. Cost and survival estimates are presented and were found to vary by aNSCLC subtype. In conclusion, the iTEN model is a reliable tool for forecasting the impact on cost and survival of new treatments for aNSCLC.

Clinical and Economic Benefits of Antimicrobial Stewardship Programs in Hemodialysis Facilities: A Decision Analytic Model.

BACKGROUND AND OBJECTIVES: Infections caused by multidrug-resistant organisms and Clostridium difficile are associated with substantial morbidity and mortality as well as excess costs. Antimicrobial exposure is the leading cause for these infections. Approximately 30% of antimicrobial doses administered in outpatient hemodialysis facilities are considered unnecessary. Implementing an antimicrobial stewardship program in outpatient hemodialysis facilities aimed at improving prescribing practices would have important clinical and economic benefits. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We developed a decision analytic model of antimicrobial use on the clinical and economic consequences of implementing a nationwide antimicrobial stewardship program in outpatient dialysis facilities. The main outcomes were total antimicrobial use, infections caused by multidrug-resistant organisms and C. difficile, infection-related mortality, and total costs. The analysis considered all patients on outpatient hemodialysis in the United States. The value of implementing antimicrobial stewardship programs, assuming a 20% decrease in unnecessary antimicrobial doses, was calculated as the incremental differences in clinical end points and cost outcomes. Event probabilities, antimicrobial regimens, and health care costs were informed by publicly available sources. RESULTS: On a national level, implementation of antimicrobial stewardship programs was predicted to result in 2182 fewer infections caused by multidrug-resistant organisms and C. difficile (4.8% reduction), 629 fewer infection-related deaths (4.6% reduction), and a cost savings of $106,893,517 (5.0% reduction) per year. The model was most sensitive to clinical parameters as opposed to antimicrobial costs. CONCLUSIONS: The model suggests that implementation of antimicrobial stewardship programs in outpatient dialysis facilities would result in substantial reductions in infections caused by multidrug-resistant organisms and C. difficile, infection-related deaths, and costs.

Spillover effects on health outcomes in low- and middle-income countries: a systematic review.

Background: Many interventions delivered to improve health may benefit not only direct recipients but also people in close physical or social proximity. Our objective was to review all published literature about the spillover effects of interventions on health outcomes in low-middle income countries and to identify methods used in estimating these effects. Methods: We searched 19 electronic databases for articles published before 2014 and hand-searched titles from 2010 to 2013 in five relevant journals. We adapted the Cochrane Collaboration's quality grading tool for spillover estimation and rated the quality of evidence. Results: A total of 54 studies met inclusion criteria. We found a wide range of terminology used to describe spillovers, a lack of standardization among spillover methods and poor reporting of spillovers in many studies. We identified three primary mechanisms of spillovers: reduced disease transmission, social proximity and substitution of resources within households. We found the strongest evidence for spillovers through reduced disease transmission, particularly vaccines and mass drug administration. In general, the proportion of a population receiving an intervention was associated with improved health. Most studies were of moderate or low quality. We found evidence of publication bias for certain spillover estimates but not for total or direct effects. To facilitate improved reporting and standardization in future studies, we developed a reporting checklist adapted from the CONSORT framework specific to reporting spillover effects. Conclusions: We found the strongest evidence for spillovers from vaccines and mass drug administration to control infectious disease. There was little high quality evidence of spillovers for other interventions.