Identification of an Optimal COVID-19 Booster Allocation Strategy to Minimize Hospital Bed-Days with a Fixed Healthcare Budget.

Healthcare decision-makers face difficult decisions regarding COVID-19 booster selection given limited budgets and the need to maximize healthcare gain. A constrained optimization (CO) model was developed to identify booster allocation strategies that minimize bed-days by varying the proportion of the eligible population receiving different boosters, stratified by age, and given limited healthcare expenditure. Three booster options were included: B1, costing US $1 per dose, B2, costing US $2, and no booster (NB), costing US $0. B1 and B2 were assumed to be 55%/75% effective against mild/moderate COVID-19, respectively, and 90% effective against severe/critical COVID-19. Healthcare expenditure was limited to US$2.10 per person; the minimum expected expense using B1, B2, or NB for all. Brazil was the base-case country. The model demonstrated that B1 for those aged <70 years and B2 for those ≥70 years were optimal for minimizing bed-days. Compared with NB, bed-days were reduced by 75%, hospital admissions by 68%, and intensive care unit admissions by 90%. Total costs were reduced by 60% with medical resource use reduced by 81%. This illustrates that the CO model can be used by healthcare decision-makers to implement vaccine booster allocation strategies that provide the best healthcare outcomes in a broad range of contexts.

Development and validation of a serum microRNA biomarker panel for detecting gastric cancer in a high-risk population.

OBJECTIVE: An unmet need exists for a non-invasive biomarker assay to aid gastric cancer diagnosis. We aimed to develop a serum microRNA (miRNA) panel for identifying patients with all stages of gastric cancer from a high-risk population. DESIGN: We conducted a three-phase, multicentre study comprising 5248 subjects from Singapore and Korea. Biomarker discovery and verification phases were done through comprehensive serum miRNA profiling and multivariant analysis of 578 miRNA candidates in retrospective cohorts of 682 subjects. A clinical assay was developed and validated in a prospective cohort of 4566 symptomatic subjects who underwent endoscopy. Assay performance was confirmed with histological diagnosis and compared with Helicobacter pylori (HP) serology, serum pepsinogens (PGs), 'ABC' method, carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA19-9). Cost-effectiveness was analysed using a Markov decision model. RESULTS: We developed a clinical assay for detection of gastric cancer based on a 12-miRNA biomarker panel. The 12-miRNA panel had area under the curve (AUC)=0.93 (95% CI 0.90 to 0.95) and AUC=0.92 (95% CI 0.88 to 0.96) in the discovery and verification cohorts, respectively. In the prospective study, overall sensitivity was 87.0% (95% CI 79.4% to 92.5%) at specificity of 68.4% (95% CI 67.0% to 69.8%). AUC was 0.848 (95% CI 0.81 to 0.88), higher than HP serology (0.635), PG 1/2 ratio (0.641), PG index (0.576), ABC method (0.647), CEA (0.576) and CA19-9 (0.595). The number needed to screen is 489 annually. It is cost-effective for mass screening relative to current practice (incremental cost-effectiveness ratio=US$44 531/quality-of-life year). CONCLUSION: We developed and validated a serum 12-miRNA biomarker assay, which may be a cost-effective risk assessment for gastric cancer. TRIAL REGISTRATION NUMBER: This study is registered with ClinicalTrials.gov (Registration number: NCT04329299).

Evaluating the Use of microRNA Blood Tests for Gastric Cancer Screening in a Stratified Population-Level Screening Program: An Early Model-Based Cost-Effectiveness Analysis.

OBJECTIVES: To evaluate cost-effectiveness of a novel screening strategy using a microRNA (miRNA) blood test as a screen, followed by endoscopy for diagnosis confirmation in a 3-yearly population screening program for gastric cancer. METHODS: A Markov cohort model has been developed in Microsoft Excel 2016 for the population identified to be at intermediate risk (Singaporean men, aged 50-75 years with Chinese ethnicity). The interventions compared were (1) initial screening using miRNA test followed by endoscopy for test-positive individuals and a 3-yearly follow-up screening for test-negative individuals (proposed strategy), and (2) no screening with gastric cancer being diagnosed clinically (current practice). The model was evaluated for 25 years with a healthcare perspective and accounted for test characteristics, compliance, disease progression, cancer recurrence, costs, utilities, and mortality. The outcomes measured included incremental cost-effectiveness ratios, cancer stage at diagnosis, and thresholds for significant variables. RESULTS: The miRNA-based screening was found to be cost-effective with an incremental cost-effectiveness ratio of $40 971/quality-adjusted life-year. Key drivers included test costs, test accuracy, cancer incidence, and recurrence risk. Threshold analysis highlights the need for high accuracy of miRNA tests (threshold sensitivity: 68%; threshold specificity: 77%). A perfect compliance to screening would double the cancer diagnosis in early stages compared to the current practice. Probabilistic sensitivity analysis reported the miRNA-based screening to be cost-effective in >95% of iterations for a willingness to pay of $70 000/quality-adjusted life-year (approximately equivalent to 1 gross domestic product/capita) CONCLUSIONS: The miRNA-based screening intervention was found to be cost-effective and is expected to contribute immensely in early diagnosis of cancer by improving screening compliance.

Comparing 3 Approaches for Making Vaccine Adoption Decisions in Thailand.

BACKGROUND: The World Health Organization (WHO) has developed the Total System Effectiveness (TSE) framework to assist national policy-makers in prioritizing vaccines. The pilot was launched in Thailand to explore the potential use of TSE in a country with established governance structures and accountable decision-making processes for immunization policy. While the existing literature informs vaccine adoption decisions in GAVI-eligible countries, this study attempts to address a gap in the literature by examining the policy process of a non-GAVI eligible country. METHODS: A rotavirus vaccine (RVV) test case was used to compare the decision criteria made by the existing processes (Expanded Program on Immunization [EPI], and National List of Essential Medicines [NLEM]) for vaccine prioritization and the TSE-pilot model, using Thailand specific data. RESULTS: The existing decision-making processes in Thailand and TSE were found to offer similar recommendations on the selection of a RVV product. CONCLUSION: The authors believe that TSE can provide a well-reasoned and step by step approach for countries, especially low- and middle-income countries (LMICs), to develop a systematic and transparent decision-making process for immunization policy.

'It takes two to tango': Bridging the gap between country need and vaccine product innovation.

BACKGROUND: Despite a growing global commitment to universal health coverage, considerable vaccine coverage and uptake gaps persist in resource-constrained settings. One way of addressing the gaps is by ensuring product innovation is relevant and responsive to the needs of these contexts. Total Systems Effectiveness (TSE) framework has been developed to characterize preferred vaccine attributes from the perspective of country decision-makers to inform research and development (R&D) of products. A proof of concept pilot study took place in Thailand in 2018 to examine the feasibility and usefulness of the TSE approach using a rotavirus hypothetical test-case. METHODS: The excel-based model used multiple-criteria decision analysis (MCDA) to compare and evaluate five hypothetical rotavirus vaccine products. The model was populated with local data and products were ranked against decision criteria identified by Thai stakeholders. A one-way sensitivity analysis was performed to identify criteria that influenced vaccine ranking. Self-assessment forms were distributed to R&D stakeholders on the usability of the approach and were subsequently analysed. RESULTS: The model identified significant parameters that impacted on MCDA rankings. Self-assessment forms revealed that TSE was perceived as being able to encourage closer collaboration between country decision makers and vaccine developers. CONCLUSIONS: The pilot study demonstrates that it is feasible to use an MCDA approach to elicit stakeholder preferences and determine influential parameters to help identify the preferred product characteristics for R&D from the perspective of country decision-makers. It found that TSE can help steer manufacturers to develop products that are better aligned with country need. Findings will guide further development of the TSE concept.

Transient neonatal hyperinsulinaemic hypoglycaemia: perinatal predictors of length and cost of stay.

Admission to neonatal care causes separation of infants from their parents, can adversely affect breast-feeding and is associated with painful procedures. Our aim was to identify perinatal factors and cost of care associated with transient neonatal hyperinsulinaemic hypoglycaemia (HH). Infants born after 35 weeks of gestation admitted because of hypoglycaemia were studied. The neonates were divided into two groups (HH and non-HH), and their length and cost of care were compared and perinatal factors predicting those outcomes explored. Forty of the 474 infants admitted with hypoglycaemia were diagnosed with HH. The HH group had a lower median (IQR) glucose level on admission compared to the non-HH group (p < 0.001). The median (IQR) cost of stay was higher in the HH group (p < 0.001). In the HH group, the GIRmax was significantly correlated with cost of stay (p < 0.001). GIRmax predicted a cost of stay > £9140 with an area under the ROC curve of 0.956. GIRmax > 13.9 mg/kg/min predicted admission cost > £9140 with 86% sensitivity and 93% specificity.Conclusion: Transient neonatal HH was associated with a higher length and cost of stay in infants admitted for hypoglycaemia. The GIRmax can predict the length and cost of stay. What is Known: • Neonatal hypoglycaemia is the leading cause of term and late preterm neonatal admissions. • Hyperinsulinism (HH) is the commonest cause of persistent hypoglycaemia, and delay in the diagnosis and management can have a detrimental impact on long-term development. What is New: • We have demonstrated prior to NICU admission that blood glucose concentrations were lower in infants with HH compared to those without. • The maximum GIR had a stronger correlation with total length and cost of hospital stay compared to insulin levels in HH infants.

Role of pharmacogenetics in public health and clinical health care: a SWOT analysis.

Pharmacogenomics has been lauded as an important innovation in clinical medicine as a result of advances in genomic science. As one of the cornerstones in precision medicine, the vision to determine the right medication in the right dosage for the right treatment with the use of genetic information has not exactly materialised, and few genetic tests have been implemented as the standard of care in health systems worldwide. Here we review the findings from a SWOT analysis to examine the strengths, weaknesses, opportunities and threats around the role of pharmacogenetics in public health and clinical health care, at the micro, meso and macro levels corresponding to the perspectives of the individuals (scientists, patients and physicians), the health-care institutions and the health systems, respectively.

Reducing hypersensitivity reactions with HLA-B*5701 genotyping before abacavir prescription: clinically useful but is it cost-effective in Singapore?

AIM: Abacavir (ABC) is one of the more affordable antiretroviral drugs used for controlling HIV. Although with similar efficacy to current first-line drugs, its limited usage in Singapore can be attributed to its possible side effect of adverse hypersensitivity reactions (HSRs). HLA-B*5701 genotyping is a clinically relevant procedure for avoiding abacavir-induced HSRs. As patients who do not carry the risk allele are unlikely to develop HSRs, a simple rule can be developed to allow abacavir prescription for patients who are B*5701 negative. Here, we carry out a cost-effectiveness analysis of HLA-B*5701 genotyping before abacavir prescription in the context of the Singapore healthcare system, which caters predominantly to Han Chinese, Southeast-asian Malays, and South-asian Indians. In addition, we aim to identify the most cost-effective treatment regimen for HIV patients. METHODS: A decision tree model was developed in TreeAge. The model considers medical treatment and genotyping costs, genotyping test characteristics, the prevalence of the risk allele, reduction in the quality of life, and increased expenditure due to side effects and other factors, evaluating independently over early-stage and late-stage HIV patients segmented by drug contraindications. RESULTS: The study indicates that genotyping is not cost-effective for any ethnicity irrespective of the disease stage, except for Indian patients with early-stage HIV who are contraindicated to tenofovir. CONCLUSION: Abacavir (as first-line) without genotyping is the cheapest and most cost-effective treatment for all ethnicities except for early-stage Indian HIV patients contraindicated to tenofovir. The HLA-B*5701 frequency, the mortality rate from abacavir-induced HSRs, and genotyping costs are among the major factors influencing the cost-effectiveness.