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Patients with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL) have limited treatment options and poor prognoses. Tisagenlecleucel, a chimeric antigen receptor (CAR) T-cell therapy has shown early promise in improving survival outcomes, but at a high upfront cost. This study evaluated the cost-effectiveness of tisagenlecleucel versus salvage chemotherapy for treating patients with r/r DLBCL who have failed at least 2 lines of systemic therapies.A hybrid decision tree and three-state partitioned survival model (progression-free (PF), progressive disease and death) was developed from the Singapore healthcare payer perspective. Survival curves from JULIET trial and CORAL-1 extension study were extrapolated beyond trial period over a 15-year time horizon to estimate the underlying progression-free survival and overall survival parametric distributions for both arms. Health state utilities were retrieved from the literature, and direct costs were sourced from public healthcare institutions in Singapore. One-way probabilistic sensitivity analyses and scenario analyses were conducted to explore the impact of uncertainties and assumptions on cost-effectiveness results.Compared with salvage chemotherapy, tisagenlecleucel was associated with a base-case incremental cost-effectiveness ratio (ICER) US$508,530 (S$686,516) per quality adjusted life year (QALY) gained and US$320,200 (S$432,269) per life year (LY) gained. One-way sensitivity analysis showed the ICER was most sensitive to time horizon, PF utility and cost of tisagenlecleucel. Scenario analyses confirmed that the ICERs remained high under favorable assumptions and substantial price reduction was required to reduce the ICER.Our analysis showed tisagenlecleucel use in r/r DLBCL patients who failed at least 2 prior lines of systemic therapies was associated with exceedingly high ICER, which is unlikely to represent good use of healthcare resources. Comparative clinical evidence from the ongoing trials might provide more insight into future evaluations.

Background Klebsiella pneumoniae liver abscess (KLA) is emerging worldwide due to hypermucoviscous strains with a propensity for metastatic infection. Treatment includes drainage and prolonged intravenous antibiotics. We aimed to determine whether oral antibiotics were noninferior to continued intravenous antibiotics for KLA. Methods This noninferiority, parallel group, randomized, clinical trial recruited hospitalized adults with liver abscess and K. pneumoniae isolated from blood or abscess fluid who had received ≤7 days of effective antibiotics at 3 sites in Singapore. Patients were randomized 1:1 to oral (ciprofloxacin) or intravenous (ceftriaxone) antibiotics for 28 days. If day 28 clinical response criteria were not met, further oral antibiotics were prescribed until clinical response was met. The primary endpoint was clinical cure assessed at week 12 and included a composite of absence of fever in the preceding week, C-reactive protein Results Between November 2013 and October 2017, 152 patients (mean age, 58.7 years; 25.7% women) were recruited, following a median 5 days of effective intravenous antibiotics. A total of 106 (69.7%) underwent abscess drainage; 71/74 (95.9%) randomized to oral antibiotics met the primary endpoint compared with 72/78 (92.3%) randomized to intravenous antibiotics (risk difference, 3.6%; 2-sided 95% confidence interval, −4.9% to 12.8%). Effects were consistent in the per-protocol population. Nonfatal serious adverse events occurred in 12/72 (16.7%) in the oral group and 13/77 (16.9%) in the intravenous group. Conclusions Oral antibiotics were noninferior to intravenous antibiotics for the early treatment of KLA. Clinical Trials Registration NCT01723150.

Background Atrial fibrillation (AF) is the most common heart rhythm disorder and poses a growing disease burden worldwide because of an aging population. A multidisciplinary approach with an emphasis on patient education and self-management has been demonstrated to improve outcomes for AF through the engagement of patients in their own care. Although electronic tools (e-tools) such as apps have been proposed to provide patient education and facilitate self-management, there have been few studies to guide the development of these tools for patients with AF. Objective This study aims to explore the perceptions of patients and health care providers (HCPs) and their attitudes toward the use of e-tools for the self-management of AF. It also seeks to elicit the factors that contribute to these attitudes. Methods Semistructured qualitative interviews with HCPs and patients were conducted to understand the interpretations and expectations of an e-tool that would be used for the self-management of AF. Interview data were analyzed using an exploratory thematic analysis approach to uncover emergent themes and infer ideas of preferred features in a device. A modified technology acceptance model was developed as a framework to help interpret these findings. Data from the HCPs and patients were compared and contrasted. Results Both patients and HCPs thought that an e-tool would be useful in the self-management of AF. Although both groups favored educational content and monitoring of blood pressure, patients expressed more passivity toward self-care and an ambivalence toward the use of technology to monitor their medical condition. This appears to be related to factors such as a patient’s age, social support, and their attitudes toward technology. Instead, they favored using the app to contact their HCPs. Conclusions This study provides insights into significant differences in the attitudes of patients and HCPs toward the use of e-tools for self-care against their priorities. Understanding patients’ motivations and their needs are key to ensuring higher acceptance of such tools.

This paper explores the characteristics of health technology assessment (HTA) systems and practices in Asia. Representatives from nine countries were surveyed to understand each step of the HTA pathway. The analysis finds that although there are similarities in the processes of HTA and its application to inform decision making, there is variation in the number of topics assessed and the stakeholders involved in each step of the process. There is limited availability of resources and technical capacity and countries adopt different means to overcome these challenges by accepting industry submissions or adapting findings from other regions. Inclusion of stakeholders in the process of selecting topics, generating evidence, and making funding recommendations is critical to ensure relevance of HTA to country priorities. Lessons from this analysis may be instructive to other countries implementing HTA processes and inform future research on the feasibility of implementing a harmonized HTA system in the region.

Objective To estimate the cost of smoking in Singapore in 2014 from the societal perspective. Methods A prevalence-based, disease-specific approach was undertaken to estimate the smoking-attributable costs. These include direct and indirect costs of inpatient treatment, premature mortality, loss of productivity due to medical leaves and smoking breaks. Results In 2014, the social cost of smoking in Singapore was conservatively estimated to be at least US$479.8 million, ∼0.2% of the 2014 gross domestic product. Most of this cost was attributable to productivity losses (US$464.9 million) and largely concentrated in the male population (US$434.9 million). Direct healthcare costs amounted to US$14.9 million where ischaemic heart disease and lung cancer had the highest cost burden. Conclusions The social cost of smoking is smaller in Singapore than in other Asian countries. However, there is still cause for concern. A recently observed increase in smoking prevalence, particularly among adolescent men, is likely to result in rising total cost. Most significantly, our results suggest that a large share of the overall cost burden lies outside the healthcare system or may not be highly salient to the relevant decision makers. This is partly because of the nature of such costs (indirect or intangible costs such as productivity losses are often not salient) or data limitations (a potentially significant fraction of direct healthcare expenditure may be in private primary care where costs are not systematically captured and reported). The case of Singapore thus illustrates that even in countries perceived as success stories, strong multisectoral anti-tobacco strategies and a supporting research agenda continue to be needed.