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Purpose: Cost of novel medications has increased worldwide, causing financial toxicity to heart failure patients. Patients can discuss medication costs with clinicians to manage financial burden, but such discussion can be uncommon. This study seeked to investigate the experiences and preferences of heart failure patients in Singapore regarding medication cost discussions to develop effective strategies to encourage such conversations., Patients and Methods: Participants were recruited from a hospital outpatient heart failure clinic in 2022 to participate in a qualitative survey containing open-ended questions. Inclusion criteria were patients aged 21 years and above, diagnosed with heart failure, and capable of comprehending English. There were no exclusion criteria. Conventional content analysis was performed on collected responses., Results: Among forty-eight heart failure patients (median age: 63.5 years, 43.8% male, 72.9% Chinese) who participated, most (93.8%) wanted to discuss medication costs with clinicians for reasons such as concern over affordability, taking ownership of health, making informed decisions, minimizing inconvenience, and obtaining tailored cost information. Affordability of medications was a concern for patients but only 8.3% of patients actually had regular cost discussions with clinicians in the past year. Patients mentioned a lack of initiative from the clinicians, limited cost awareness, and time constraints as reasons why cost conversations did not happen., Conclusion: Outpatient heart failure patients in Singapore desire to discuss medication costs with clinicians but few participants reported having such conversations. Barriers hindering cost discussions have to be addressed to ensure patients make an informed medication decision with minimal financial burden., Competing Interests: The authors declare that they have no competing interests., (© 2025 Shen et al.)

Introduction: The study sought to assess the cost-effectiveness of silver diamine fluoride (SDF) relative to sodium fluoride varnish (NaF), and direct restorations placed chairside or under general anaesthesia (GA), accounting for caries activity., Methods: An analytical decision tree model was developed with clinical data from multiple centres to evaluate the four treatment options among all children aged 1 to 6 years in Singapore (N=231,880) over a 12-month time horizon. Base-case scenarios consisted of children with low- (1 carious tooth) and high- (7 carious teeth) caries activity. Incremental cost-effectiveness ratios (ICER) and net monetary benefits (NMB) were tabulated with the outcomes set to be the control of active caries and avoidance of tooth extractions. Deterministic and probabilistic sensitivity analyses were conducted., Results: Overall, SDF was less effective than direct restorations placed chairside but was less costly. For children with low-caries activity, the ICER for SDF was $9 per caries-controlled tooth, and $68 per extraction avoided. For children with high-caries activity, the ICERs were $267 and $1 909 respectively. At a willingness-to-pay threshold of $30, the NMB was negative (favours restorations) for caries control in children with low-caries activity and positive (favours SDF) for all other situations. In the low-caries activity group, SDF had a 41.5% probability of being cost-effective for caries control and 49.2% probability of being cost-effective for the avoidance of extraction. The corresponding probabilities for the high-caries activity group were 99.8% and 100%. The NMB of SDF increases proportionally with caries activity, suggesting utilisation of SDF should depend on caries activity. Results were most sensitive to changes in relative cost, and effectiveness of SDF/direct restorations., Conclusion: SDF was cost-effective in most situations except for caries control in children with low-caries activity. Direct restorations were more effective and should be considered in low-caries activity children., (The Author(s). Published by S. Karger AG, Basel.)

Background: Atopic dermatitis (AD) affects both adults and children, impacting their quality of life and productivity; however, traditional systemic treatments such as cyclosporine have limitations. Emerging novel systemic interventions, including monoclonal antibodies and Janus kinase (JAK) inhibitors, have been shown to improve patient outcomes., Objective: This study evaluates the cost-effectiveness of novel systemic interventions for moderate-to-severe AD in adults compared with the best supportive care (BSC) in Singapore., Methods: The economic evaluation used a hybrid model consisting of a decision tree and Markov model. Treatment responses at 16 weeks were based on a network meta-analysis that was developed specifically for this study. Long-term response, discontinuation rates, episodes of flares and treatment-emergent adverse events were obtained from key dupilumab, abrocitinib, baricitinib and upadacitinib trials. The study had a 5-year time horizon and considered the healthcare payer's perspective. Sensitivity and scenario analyses were performed as well., Results: Baricitinib 4 mg and 2 mg have the lowest incremental cost-effectiveness ratios, at Singapore dollars (S$) 60,730/quality-adjusted life-year (QALY) and S$66,842/QALY, respectively. Upadacitinib 30 mg offers the highest incremental QALY gain, while baricitinib 2 mg offers the least. The cost of the intervention drugs accounted for the highest proportion of the overall expenses (68-93%) for those in the maintenance state. Other influential factors within the model included (1) the incremental utility derived from intervention response; (2) the probability of achieving Eczema Area and Severity Index 75 (EASI-75) with BSC; and (3) the relative risk of achieving EASI-75 with the interventions. In a scenario where the cost of all drugs is matched to the lowest-priced drug, the top three cost-effectiveness interventions are dupilumab, upadacitinib 30 mg and abrocitinib 200 mg, respectively., Conclusion: The interventions are not found to be cost-effective at their existing prices when compared with BSC. Ideally, a composite score of treatment success and quality-of-life scores ought to be included, but such data were unavailable. Future research should consider conditional discontinuation data and long-term outcomes when such data become accessible., (© 2024. The Author(s).)

Objective: This study presents the development process of a heart failure (HF) medication decision aid (DA) specific to Singapore context, with the objective of promoting cost conversations., Methods: Phase 1 was to create a DA prototype, where two HF clinicians were consulted on their input and needs. Phase 2 was pilot testing where the prototype was tested on HF patients and revised based on their feedback., Results: The DA is a one-page poster that compares only two classes of HF medications. It encompasses seven attributes for comparison, including route of administration, treatment duration, frequency of use, hospitalization rate, survival rate, low blood pressure probability with personalized subsidized cost being the key attribute. A total of 48 patients participated in the pilot testing with only 2 patients (4.2 %) finding the DA difficult to understand. Almost all patients agreed that the DA provided greater clarity in the medication options., Conclusion: By integrating the needs of both clinicians and patients and conducting user testing, we developed a novel HF medication DA. Patients found the tool easy to understand and acceptable., Innovation: This innovative DA aims to improve cost conversations by providing tailored, concise, and locally relevant information for efficient use., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Background and Objective: This study aimed to assess the cost-effectiveness of two regimens regarded as the standard of care for the treatment of newly diagnosed, transplant-ineligible multiple myeloma in Singapore: (1) daratumumab, lenalidomide, and dexamethasone and (2) bortezomib, lenalidomide, and dexamethasone. Additionally, it aimed to explore potential strategies to manage decision uncertainty and mitigate financial risk., Methods: A cost-effectiveness analysis from the healthcare system perspective was conducted using a partitioned survival model to estimate lifetime costs and quality-adjusted life years (QALYs) associated with daratumumab-based treatment and the bortezomib-based regimen. The analysis used data from the MAIA and SWOG S0777 trials and incorporated local real-world data where available. Sensitivity analyses were performed to evaluate the robustness of the findings, and a risk analysis was conducted to analyze various payer strategies in terms of their payer strategy and uncertainty burden (P-SUB), which account for the decision uncertainty and the additional cost of choosing a suboptimal intervention., Results: The incremental cost-effectiveness ratio (ICER) for daratumumab, lenalidomide, and dexamethasone (DRd) compared with bortezomib, lenalidomide, and dexamethasone (VRd) was US $90,364 per QALY gained. The results were sensitive to variations in survival for DRd, postprogression treatment costs, cost of hospice care, and hazard ratio for progression-free survival. The scenarios explored indicated that structural assumptions, such as the time horizon of the analysis, significantly influenced the results due to uncertainties arising from immature trial data and treatment efficacy over time. Among the various payer strategies compared, an upfront price discount for daratumumab emerged as the best approach with the lowest P-SUB at US $14,708., Conclusion: In conclusion, this study finds that daratumumab as a first-line treatment for myeloma exceeds the cost-effectiveness threshold considered in this evaluation. An upfront price reduction is the recommended strategy to manage uncertainties and mitigate financial risks. These findings highlight the importance of targeted payer strategies to address specific types and sources of uncertainty., (© 2024. The Author(s).)

Objectives: The rising costs of drugs have necessitated the exploration of innovative payment methods in healthcare systems. Risk-sharing agreements (RSAs) have been implemented in many countries as a value-based payment mechanism to manage the uncertainty associated with expensive technologies. This study aimed to investigate stakeholder perspectives on value-based payment in the Singaporean context, providing insights for future directions in health technology assessment and financing., Methods: This descriptive qualitative inquiry involved participant interviews conducted between October 2021 and April 2022. Thematic analysis was conducted in two phases to analyze the interview transcripts., Results: Seventeen respondents participated in the study, and five key themes emerged from the analysis. Stakeholders viewed RSAs as moderately positive, despite limited experience with them. They emphasized the importance of clearly defining objectives and establishing transparent criteria for implementing these schemes. The current data infrastructure was identified as both a barrier and facilitator, as RSAs impose administrative burdens. To successfully implement these payment mechanisms, capacity building, and effective stakeholder engagement that fosters mutual trust and cocreation are crucial., Conclusion: This study confirms previously identified barriers and facilitators to successful RSA implementation while contextualizing them within the Singaporean setting. The findings suggest that value-based payment has the potential to address uncertainty and improve access to healthcare technologies, but these barriers must be addressed for the schemes to be effective.

Objectives: To compare the level of acceptance of silver diamine fluoride (SDF) treatment between different functional groups of older adults aged 65-years-old and above., Methods: Three groups were recruited representing functionally-independent ("Community dwelling"), frail ("Nursing home"), and functionally-dependent older adults ("Caregiver": proxy respondent involved in caring for an older adult of all functional levels). Participants viewed a video on SDF and an interviewer-led questionnaire collected demographics, dental experience and perception on SDF use., Results: The study recruited 201 participants (100 "Community dwelling", 51 "Nursing home", 50 "Caregiver"). Overall, 73 % of participants were accepting of SDF treatment. Those in the "Community dwelling" group were most accepting (85 %), followed by the "Nursing home" group (61 %) and "Caregiver" group (60 %) (p<0.001). Participants were more accepting of SDF use on posterior (73 %) compared to anterior teeth (46 %). They were more accepting when SDF was presented as a treatment to avoid infection and pain (87 %), and general anesthesia (78 %). In a regression analysis, "Nursing home" and "Caregiver" participants were three times less likely to accept SDF (OR 0.27 [95 % CI: 0.13 to 0.60], and OR 0.27 [95 % CI: 0.12 to 0.58] respectively) compared to "Community dwelling" participants. After adjusting for other factors, only the "Caregiver" group remained significant (Adjusted OR 0.32 [95 % CI: 0.13 to 0.78])., Conclusions: Older adults were accepting of SDF and this treatment modality has the potential to be a routine treatment option in dental caries management in this population. However, this was less certain among frail and functionally dependent older adults., Clinical Significance: An SDF program to manage caries is likely to be well-received by functionally-independent older adults. However, the acceptance among frail and functionally-dependent older adults were lower even though SDF is mostly likely to benefit these populations. There is a need to investigate this relatively lower levels of acceptance., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: The burden of cancer can be altered by screening. The field of cancer screening is constantly evolving; from the initiation of program for new cancer types as well as exploring innovative screening strategies (e.g. new screening tests). The aim of this study was to perform a landscape analysis of existing cancer screening programs in South-East Asia and the Western Pacific., Methods: We conducted an overview of cancer screening in the region with the goal of summarizing current designs of cancer screening programs. First, a selective narrative literature review was used as an exploration to identify countries with organized screening programs. Second, representatives of each country with an organized program were approached and asked to provide relevant information on the organizations of their national or regional cancer screening program., Results: There was wide variation in the screening strategies offered in the considered region with only eight programs identified as having an organized design. The majority of these programs did not meet all the essential criteria for being organized screening. The greatest variation was observed in the starting and stopping ages., Conclusions: Essential criteria of organized screening are missed. Improving organization is crucial to ensure that the beneficial effects of screening are achieved in the long-term. It is strongly recommended to consider a regional cancer screening network., (© 2024. The Author(s).)

Background: Promoting active, balanced lifestyles among children may be an important approach to optimising their health-related quality of life (HRQoL). However, the relationships between children's movement behaviours and HRQoL remain unclear., Methods: We examined the associations between movement behaviours (sleep, inactivity, light and moderate-to-vigorous intensity physical activity) assessed using accelerometers at ages 8 and 10 years and self-reported HRQoL scores (overall, and physical and emotional well-being, self-esteem, relationship with family and friends, and school functioning domains) at age 10 years among 370 children in a local birth cohort using compositional isotemporal substitution techniques., Findings: Cross-sectionally, light and moderate-to-vigorous intensity physical activities were associated with better self-esteem (β = 15.94 [2.71, 29.18]) and relationship with friends (β = 10.28 [3.81, 16.74]) scores respectively. Prospectively, inactivity was associated with lower overall HRQoL (β = -10.00 [-19.13, -0.87]), relationship with friends (β = -16.41 [-31.60, -1.23]) and school functioning (β = -15.30 [-29.16, -1.44]) scores, while sleep showed a positive trend with overall HRQoL (β = 10.76 [-1.09, 22.61]) and school functioning (β = 17.12 [-0.87, 35.10]) scores. Children's movement behaviours were not associated with their physical and emotional well-being, or relationship with family scores. The isotemporal substitution analyses suggest that increasing time spent in physical activity and/or sleep at the expense of inactivity may benefit children's HRQoL., Interpretation: Our findings suggest that sleep and physical activity may be associated with better HRQoL, with the inverse for inactivity. However, the relationship between children's movement behaviours and HRQoL is complex and warrants further research., Funding: Singapore National Research Foundation, Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research., Competing Interests: KMG reports being part of an academic consortium that has received research funding from Nestle Research, unrelated to the present manuscript. JYB is supported by a grant from the Agence Nationale de la Recherche (ANR) (iSCAN project, ANR-20-CE36-0001)., (© 2023 The Author(s).)

Multiple myeloma, a hematological malignancy, imposes a significant financial burden on healthcare systems. Health technology assessments (HTA) and economic evaluations play vital roles in reimbursement decisions and cost containment. This study aimed to explore healthcare utilization patterns and costs among myeloma patients in Singapore through a retrospective analysis of 605 patients treated at two cancer centers. Data encompassing demographics, treatment utilization, and billing were extracted from electronic records, and a cost analysis was performed from the perspective of the Singapore healthcare system. The results revealed common usage of immunomodulatory agents (52%) and proteasome inhibitors (37%), with bortezomib being the most frequently used targeted treatment. Treatment costs increased with disease progression, displaying variations depending on the therapeutic agent used. Notably, hospitalization costs due to adverse events were substantial, with pneumonia as the leading cause. This study highlights the high cost of myeloma therapy in Singapore, posing a financial burden for households. Findings may inform economic evaluations, evidence generation, reimbursement, and subsidy decisions. Leveraging real-world data from electronic records provides valuable insights into local healthcare utilization patterns. Future studies may explore integrating billing databases with clinical repositories for a more comprehensive analysis, and consider limitations such as incomplete clinical information and potential selection bias., Competing Interests: The authors declare no conflict of interest., (© 2023 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Introduction: Several non-pharmaceutical infection control measures have been implemented at community-based hemodialysis centers to reduce the risk of Coronavirus Disease of 2019 (COVID-19) transmission, caused by the SARS-CoV-2 virus. However, there have been concerns that such measures may disrupt the routine and timely care required by patients, with adverse effects on their health outcomes. This cross-sectional study aims to determine the unintended consequences of COVID-19 infection control measures on hemodialysis patients., Methods:  Electronic medical records were extracted from patients enrolled in community-based hemodialysis centers in Singapore. A baseline group prior of patients consisted of those enrolled in 2017, which was three years prior to the SARS-CoV-2-related pandemic (n = 548). This was compared with the study group of patients enrolled in 2019 (n = 426), just before the COVID-19 pandemic started. Medical records for these two groups were extracted from January to July 2018 for the baseline group and from January to July 2020, respectively. Three regression models were built to study dialysis adherence, kidney disease biomarkers, and hospitalization episodes., Results:  There was no statistically significant difference in hospitalization and mortality outcomes, adherence to dialysis management, laboratory results for dialysis-related clearance, and anemia outcomes. There was a higher proportion of patients hospitalized for vascular access-related reasons in the study group as compared to the baseline group (OR 1.6, 95% CI: 1.10 to 2.29, P = 0.014). Patients in the study group had albumin levels 2.13% higher (95% CI: 0.88 to 3.39, P < 0.001) and alkaline phosphatase levels 7.3% lower (95% CI: 1.17 to 13.02, P = 0.020) than those in the baseline group., Conclusions:  From this community-based hemodialysis study in Singapore, it was shown that the COVID-19 pandemic did not disrupt regular healthcare services for these patients. With strategies instituted for a coordinated health delivery workflow, ensuring sufficient capacity in the various healthcare delivery sites and overall pandemic preparedness, the patient clinical outcomes measures continued to be met with no adverse consequences noted. Some improvements in dialysis-related laboratory values and quality of care targets may be due to more stringent measures instituted to protect these vulnerable patients in the community., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Khan et al.)

Introduction: Outcomes-based risk-sharing agreements (OBRSA) have been increasingly used worldwide to manage uncertainty in value assessments. This review aimed to summarize motivations, barriers, and facilitators to implementing OBRSAs with a specific focus on therapies for hematological cancer., Areas Covered: An integrative review was conducted based on a scoping of existing reviews on the topic and reports published by UK NICE. Findings from 16 articles and 10 reports were summarized and categorized into three themes: applications in blood cancer drugs, motivations for adoption, and barriers and facilitators to implementation., Expert Opinion: There was a dissociation between the theoretical basis for opting for OBRSAs, and reasons stated or inferred from practice. The administrative burden was considered a notable barrier to implementation, which affects not only payers and manufacturers but also healthcare providers. Effective stakeholder engagement and building mutual trust among key groups were identified as factors enabling successful implementation. The review raises essential considerations in implementing OBRSAs and implications for their future role, particularly for blood cancer drugs where uncertainty is rife. Carefully designed and managed schemes may remain an option for health systems to manage risks involved when funding high-cost treatments.

Human papillomavirus (HPV) partial genotyping (PGT) identifies HPV16 and HPV18 individually, alongside 12 other high-risk HPV genotypes (hrHPV) collectively. HPV extended genotyping (XGT) identifies four additional hrHPV individually (HPV31, 45, 51, and 52), and reports the remaining eight in three groups (HPV33|58; 56|59|66; 35|39|68). Quality-adjusted life years (QALY), health care resource use, and costs of XGT were compared to PGT for cervical cancer screening in Singapore using DICE simulation. Women with one of the three hrHPV identified by XGT (HPV35|39|68; 56|59|66; 51), and atypical squamous cells of undetermined significance (ASCUS) on cytology, are recalled for a repeat screening in one year, instead of undergoing an immediate colposcopy with PGT. At the repeat screening, the colposcopy is performed only for persistent same-genotype infections in XGT, while with PGT, all the women with persistent HPV have a colposcopy. Screening 500,122 women, aged 30-69, with XGT, provided an incremental cost-effectiveness ratio (ICER) versus PGT of SGD 16,370/QALY, with 7130 (19.4%) fewer colposcopies, 6027 (7.0%) fewer cytology tests, 9787 (1.6%) fewer clinic consultations, yet 2446 (0.5%) more HPV tests. The XGT ICER remains well below SGD 100,000 in sensitivity analyses, (-SGD 17,736/QALY to SGD 50,474/QALY). XGT is cost-effective compared to PGT, utilizes fewer resources, and provides a risk-based approach as the primary cervical cancer screening method.

Background: Border control mitigates local infections but bears a heavy economic cost, especially for tourism-reliant countries. While studies have supported the efficacy of border control in suppressing cross-border transmission, the trade-off between costs from imported and secondary cases and from lost economic activities has not been studied. This case study of Singapore during the COVID-19 pandemic aims to understand the impacts of varying quarantine length and testing strategies on the economy and health system. Additionally, we explored the impact of permitting unvaccinated travelers to address emerging equity concerns. We assumed that community transmission is stable and vaccination rates are high enough that inbound travelers are not dissuaded from traveling., Methods: The number of travelers was predicted considering that longer quarantine reduces willingness to travel. A micro-simulation model predicted the number of COVID-19 cases among travelers, the resultant secondary cases, and the probability of being symptomatic in each group. The incremental net monetary benefit (INB) of Singapore was quantified under each border-opening policy compared to pre-opening status, based on tourism receipts, cost/profit from testing and quarantine, and cost and health loss due to COVID-19 cases., Results: Compared to polymerase chain reaction (PCR), rapid antigen test (ART) detects fewer imported cases but results in fewer secondary cases. Longer quarantine results in fewer cases but lower INB due to reduced tourism receipts. Assuming the proportion of unvaccinated travelers is small (8% locally and 24% globally), allowing unvaccinated travelers will accrue higher INB without exceeding the intensive care unit (ICU) capacity. The highest monthly INB from all travelers is $2,236.24 m, with 46.69 ICU cases per month, achieved with ARTs at pre-departure and on arrival without quarantine. The optimal policy in terms of highest INB is robust under changes to various model assumptions. Among all cost-benefit components, the top driver for INB is tourism receipts., Conclusions: With high vaccination rates locally and globally alongside stable community transmission, opening borders to travelers regardless of vaccination status will increase economic growth in the destination country. The caseloads remain manageable without exceeding ICU capacity, and costs of cases are offset by the economic value generated from travelers., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Lou, Lim, Cai, Dickens, Huynh and Wee.)

With countries progressing towards high COVID-19 vaccination rates, strategies for border reopening are required. This study focuses on Thailand and Singapore, two countries that share significant tourism visitation, to illustrate a framework for optimizing COVID-19 testing and quarantine policies for bilateral travel with a focus on economic recovery. The timeframe is the month of October 2021, when Thailand and Singapore were preparing to reopen borders for bilateral travel. This study was conducted to provide evidence for the border reopening policy decisions. Incremental net benefit (INB) compared to the pre-opening period was quantified through a willingness-to-travel model, a micro-simulation COVID-19 transmission model and an economic model accounting for medical and non-medical costs/benefits. Multiple testing and quarantine policies were examined, and Pareto optimal (PO) policies and the most influential components were identified. The highest possible INB for Thailand is US $125.94 million, under a PO policy with no quarantine but with antigen rapid tests (ARTs) pre-departure and upon arrival to enter both countries. The highest possible INB for Singapore is US $29.78 million, under another PO policy with no quarantine on both sides, no testing to enter Thailand, and ARTs pre-departure and upon arrival to enter Singapore. Tourism receipts and costs/profits of testing and quarantine have greater economic impacts than that from COVID-19 transmission. Provided healthcare systems have sufficient capacity, great economic benefits can be gained for both countries by relaxing border control measures.

Background: Globally, there is increasing interest in the use of real-world data (RWD) and real-world evidence (RWE) to inform health technology assessment (HTA) and reimbursement decision-making. Using current practices and case studies shared by eleven health systems in Asia, a non-binding guidance that seeks to align practices for generating and using RWD/RWE for decision-making in Asia was developed by the REAL World Data I n A S ia for H E alth Technology Assessment in Reimbursement (REALISE) Working Group, addressing a current gap and needs among HTA users and generators., Methods: The guidance document was developed over two face-to-face workshops, in addition to an online survey, a face-to-face interview and pragmatic search of literature. The specific focus was on what, where and how to collect RWD/ RWE., Results: All 11 REALISE member jurisdictions participated in the online survey and the first in-person workshop, 10 participated in the second in-person workshop, and 8 participated in the in-depth face-to-face interviews. The guidance document was iteratively reviewed by all working group members and the International Advisory Panel. There was substantial variation in: ( a ) sources and types of RWD being used in HTA, and ( b ) the relative importance and prioritization of RWE being used for policy-making. A list of national-level databases and other sources of RWD available in each country was compiled. A list of useful guidance on data collection, quality assurance and study design were also compiled., Conclusion: The REALISE guidance document serves to align the collection of better quality RWD and generation of reliable RWE to ultimately inform HTA in Asia., (© 2023 The Author(s); Published by Kerman University of Medical Sciences This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.)

Background: Economic evaluations have been widely used to inform and guide policy-making process in healthcare resources allocation as a part of an evidence package. An intervention is considered cost-effective if an ICER is less than a cost-effectiveness threshold (CET), where a CET represents the acceptable price for a unit of additional health gain which a decision-maker is willing to pay. There has been discussion to increase a CET in many settings such as the United Kingdom and Thailand. To the best of our knowledge, Thailand is the only country that has an explicit CET and has revised their CET, not once but twice. Hence, the situation in Thailand provides a unique opportunity for evaluating the impact of changing CET on healthcare expenditure and manufacturers' behaviours in the real-world setting. Before we decide whether a CET should be increased, information on what happened after the CET was increased in the past could be informative and helpful., Objectives: This study protocol describes a proposed plan to investigate the impact of increased cost-effectiveness threshold using Thailand as a case study. Specifically, we will examine the impact of increasing CET on the drug prices submitted by pharmaceutical companies to the National List of Essential Medicine (NLEM), the decision to include or exclude medications in the NLEM, and the overall budget impact., Materials and Designs: Retrospective data analysis of the impact of increased CET on national drug committee decisions in Thailand (an upper middle-income country) will be conducted and included data from various sources such as literature, local organizations (e.g. Thai Food and Drug Administration), and inputs from stakeholder consultation meetings. The outcomes include: (1) drug price submitted by the manufacturers and final drug price included in the NLEM if available; (2) decisions about whether the drug was included in the NLEM for reimbursement; and (3) budget impact. The independent variables include a CET, the variable of interest, which can take values of THB100,000, THB120,000, or THB160,000, and potential confounders such as whether this drug was for a chronic disease, market size, and primary endpoint. We will conduct separate multivariable regression analysis for each outcome specified above., Discussion: Understanding the impact of increasing the CET would be helpful in assisting the decision to use and develop an appropriate threshold for one's own setting. Due to the nature of the study design, the findings will be prone to confounding effect and biases; therefore, the analyses will be adjusted for potential confounders and statistical methods will be explored to minimize biases. Knowledge gained from the study will be conveyed to the public through various disseminations such as reports, policy briefs, academic journals, and presentations., Competing Interests: This work is funded by the Health Systems Research Institute (HSRI) of Thailand (https://www.hsri.or.th), Grant number HSRI. 64-159. The funders have no contribution to the study such as the study design, data collection, and data analysis. HITAP is funded by national and international public funding agencies. iDSI is funded by the Bill & Melinda Gates Foundation (OPP1202541), the UK’s Department for International Development, and the Rockefeller Foundation. HITAP is also supported by the Access and Delivery Partnership, which is hosted by the United Nations Development Programme and funded by the Government of Japan.

Introduction: Breast cancer is a leading cause of cancer death among women, and its age-standardised incidence rate is one of the highest in Asia. We aimed to review studies on barriers to breast cancer screening to inform future policies in Singapore., Method: This was a literature review of both quantitative and qualitative studies published between 2012 and 2020 using PubMed, Google Scholar and Cochrane databases, which analysed the perceptions and behaviours of women towards breast cancer screening in Singapore., Results: Through a thematic analysis based on the Health Belief Model, significant themes associated with low breast cancer screening uptake in Singapore were identified. The themes are: (1) high perceived barriers versus benefits, including fear of the breast cancer screening procedure and its possible outcomes, (2) personal challenges that impede screening attendance and paying for screening and treatment, and (3) low perceived susceptibility to breast cancer., Conclusion: Perceived costs/barriers vs benefits of screening appear to be the most common barriers to breast cancer screening in Singapore. Based on the barriers identified, increasing convenience to get screened, reducing mammogram and treatment costs, and improving engagement with support groups are recommended to improve the screening uptake rate in Singapore.

Background: In Singapore, the current cervical cancer screening (CCS) coverage rate of 48% falls below the national target of 70%. Health care providers (HCPs) play a critical role in promoting CCS uptake. However, there is limited understanding of the perspectives of HCPs regarding CCS. Hence, we aimed to understand the challenges encountered by HCPs delivering CCS in different care settings in the Singapore health system. We also aimed to explore perspectives on newer features of CCS such as self-sampling and HPV genotyping., Methods: Physicians, nurses, program administrators and laboratory technicians involved with CCS were invited for a one-on-one semi-structured interview conducted over Zoom between May to August 2021. The interviews were transcribed and analyzed using thematic analysis., Results: Eighteen HCPs from 12 institutions were interviewed. Most participants were women (61.1%) and worked in public health institutions (72.2%). For factors influencing CCS, nine key themes were identified and organized into four categories: (1) patient factors, (2) HCP factors, (3) health system factors and (4) health promotion factors. Key themes commonly highlighted by study participants were related to patients' preferences and acceptance for screening, the processes of delivering CCS, the national priority for cervical cancer and the effectiveness of existing health promotion efforts. Five key themes were identified for CCS innovations. Self-sampling was viewed favorably to increase CCS uptake, while primary HPV screening with HPV partial genotyping had higher sensitivities to detect pre-cancers and cancers compared to cytology. Extended HPV genotyping beyond HPV16/18 could play an important role in CCS with increasing HPV vaccination coverage, as well as in the management of persistent HPV infection., Conclusion: In Singapore, HCPs face multiple challenges for CCS in practice. Insights from this study are directly relevant to, and useful for developing policies around national CCS programs and treatment guidelines., Competing Interests: The authors declare that the research was conducted by a PhD student (BWBC) who is a staff of a medical device company. The participants were informed of the interviewer's (BWBC) work background prior to providing consent to participate., (Copyright © 2022 Chua, Neo, Ma, Lim, Ng and Wee.)

Objectives: This study aims to assess the trade-offs between vulnerability and efficiency attributes of contact tracing programmes based on preferences of COVID-19 contact tracing practitioners, researchers and other relevant stakeholders at the global level. Methods: We conducted an online discrete choice experiment (DCE). Respondents were recruited globally to explore preferences according to country income level and the prevailing epidemiology of COVID-19 in the local setting. The DCE attributes represented efficiency (timeliness, completeness, number of contacts), vulnerability (vulnerable population), cooperation and privacy. A mixed-logit model and latent class analysis were used. Results: The number of respondents was 181. Timeliness was the most important attribute regardless of country income level and COVID-19 epidemiological condition. Vulnerability of contacts was the second most important attribute for low-to-lower-middle-income countries and third for upper-middle-to-high income countries. When normalised against conditional relative importance of timeliness, conditional relative importance of vulnerability ranged from 0.38 to 0.42. Conclusion: Vulnerability and efficiency criteria were both considered to be important attributes of contact tracing programmes. However, the relative values placed on these criteria varied significantly between epidemiological and economic context., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Wang, Faradiba, Del Rio Vilas, Asaria, Chen, Babigumira, Dabak and Wee.)

Objective: To estimate the economic impact of border closure and social distancing by estimating the decline of gross domestic product (GDP) in Kenya, Singapore and Thailand. Methods: We analysed secondary data retrospectively. To calculate impact of NPIs on GDP, the relationship between GDP and stock market index was examined using ordinary least squares (OLS). Then, autoregressive and moving averages (ARMA) model was used to examine the impact of NPI on stock market index. The change in GDP due to NPIs was derived by multiplying coefficients of OLS and ARMA models. Results: An increase in stock market index correlated with an increase in GDP, while both social distancing and border closure negatively correlated with stock market index. Implementation of NPIs correlated with the decline in GDP. Thai border closure had a greater decline in GDP than social distancing; Kenya exhibited the same trends; Singapore had the opposite trend. Conclusion: We quantified the magnitude of economic impact of NPIs in terms of GDP decline by linking stock market index and GDP. This approach may be applicable in other settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Briones, Wang, Prawjaeng, Wee, Kairu, Orangi, Barasa and Teerawattananon.)

High degrees of uncertainty and a lack of effective therapeutic treatments have characterized the COVID-19 pandemic and the provision of drug products outside research settings has been controversial. International guidelines for providing patients with experimental interventions to treat infectious diseases outside of clinical trials exist but it is unclear if or how they should apply in settings where clinical trials and research are strongly regulated. We propose the Professional Oversight of Emergency-Use Interventions and Monitoring System (POEIMS) as an alternative pathway based on guidance developed for the ethical provision of experimental interventions to treat COVID-19 in Singapore. We support our proposal with justifications that establish moral duties for physicians to record outcomes data and for institutions to establish monitoring systems for reporting information on safety and effectiveness to the relevant authorities. Institutions also have a duty to support generation of evidence for what constitutes good clinical practice and so should ensure the unproven intervention is made the subject of research studies that can contribute to generalizable knowledge as soon as practical and that physicians remain committed to supporting learning health systems. We outline key differences between POEIMS and other pathways for the provision of experimental interventions in public health emergencies., (© 2022. The Author(s).)

Routine mammography screening is currently the standard tool for finding cancers at an early stage, when treatment is most successful. Current breast screening programmes are one-size-fits-all which all women above a certain age threshold are encouraged to participate. However, breast cancer risk varies by individual. The BREAst screening Tailored for HEr (BREATHE) study aims to assess acceptability of a comprehensive risk-based personalised breast screening in Singapore. Advancing beyond the current age-based screening paradigm, BREATHE integrates both genetic and non-genetic breast cancer risk prediction tools to personalise screening recommendations. BREATHE is a cohort study targeting to recruit ~3,500 women. The first recruitment visit will include questionnaires and a buccal cheek swab. After receiving a tailored breast cancer risk report, participants will attend an in-person risk review, followed by a final session assessing the acceptability of our risk stratification programme. Risk prediction is based on: a) Gail model (non-genetic), b) mammographic density and recall, c) BOADICEA predictions (breast cancer predisposition genes), and d) breast cancer polygenic risk score. For national implementation of personalised risk-based breast screening, exploration of the acceptability within the target populace is critical, in addition to validated predication tools. To our knowledge, this is the first study to implement a comprehensive risk-based mammography screening programme in Asia. The BREATHE study will provide essential data for policy implementation which will transform the health system to deliver a better health and healthcare outcomes., Competing Interests: The authors have declared that no competing interests exist.

Background: The COVID-19 pandemic has resulted in the closure or partial closure of international borders in almost all countries. Here, we investigate the efficacy of imported case detection considering quarantine length and different testing measures for travellers on arrival., Methods: We examine eight broad border control strategies from utilizing quarantine alone, pre-testing, entry and exit testing, and testing during quarantine. In comparing the efficacy of these strategies, we calculate the probability of detecting travellers who have been infected up to 2 weeks pre-departure according to their estimated incubation and infectious period. We estimate the number of undetected infected travellers permitted entry for these strategies across a prevalence range of 0.1-2% per million travellers., Results: At 14-day quarantine, on average 2.2% (range: 0.5-8.2%) of imported infections are missed across the strategies, leading to 22 (5-82) imported cases at 0.1% prevalence per million travellers, increasing up to 430 (106-1641) at 2%. The strategy utilizing exit testing results in 3.9% (3.1-4.9%) of imported cases being missed at 7-day quarantine, down to 0.4% (0.3-0.7%) at 21-day quarantine, and the introduction of daily testing, as the most risk averse strategy, reduces the proportion further to 2.5-4.2% at day 7 and 0.1-0.2% at day 21 dependent on the tests used. Rapid antigen testing every 3 days in quarantine leads to 3% being missed at 7 days and 0.7% at 14 days, which is comparable to PCR testing with a 24-hour turnaround., Conclusions: Mandatory testing, at a minimal of pre-testing and on arrival, is strongly recommended where the length of quarantining should then be determined by the destination country's level of risk averseness, pandemic preparedness and origin of travellers. Repeated testing during quarantining should also be utilized to mitigate case importation risk and reduce the quarantining duration required., (© International Society of Travel Medicine 2021. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

During the coronavirus disease 2019 (COVID-19) pandemic, social service agencies (SSAs) play a crucial role in supporting renal patients, who are particularly vulnerable to infections. Social media platforms such as Facebook, serves as an effective medium for these SSAs to disseminate information. Content analysis of the SSAs' Facebook posts can provide insights on whether Facebook has been adequately utilized during the COVID-19 pandemic and enable SSAs to improve their social media use in future pandemics. This study aimed to compare renal-related SSAs' Facebook post content before and during the COVID-19 pandemic. Facebook posts of three SSAs National Kidney Foundation (NKF), Kidney Dialysis Foundation (KDF), and Muslim Kidney Action Association (MKAC), posted during the pre-COVID-19 period (January 23, 2019 to June 2, 2019) and the peri-COVID-19 period (January 23, 2020 to June 1, 2020) were extracted. A classification scheme was developed by two coders with themes derived inductively and deductively. Each Facebook post was assigned with a theme. Quantitative analyses indicate that the number of Facebook posts increased from 115 in the pre-COVID-19 period to 293 in the peri-COVID-19 period. During peri-COVID-19, posts regarding lifestyle changes, donations and infectious disease surfaced. While the proportion of posts about encouraging kindness increased from one to 77 posts, the proportion of posts about community-based events and psychosocial support decreased from 44 to 15 posts and 17 to 10 posts respectively during the two periods. Facebook was found to be well-utilized by two of the three renal SSAs in engaging their beneficiaries during the pandemic. During future pandemics, renal SSAs should place emphasis on posts related to psychosocial support and encouraging kindness. Further studies are required to ascertain the impact of COVID-19 from the perspective of renal patients and also to validate the classification scheme which was developed in this study. The study's methodology and classification scheme can be used to guide future studies for evaluating the social media outreach performance of renal health support groups., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Tan, Sesagiri Raamkumar and Wee.)

Introduction: Several treatment options are available for COVID-19 to date. However, the use of a combination of non-pharmaceutical interventions (NPIs) is necessary for jurisdictions to contain its spread. Although the implementation cost of NPIs may be low from the healthcare system perspective, it can be costly when considering the indirect costs from the societal perspective. COVID-19 vaccination campaigns have begun in several countries worldwide. Nonetheless, the quantity of vaccines available remain limited over the next 1 to 2 years. A tool for informing vaccine prioritisation that considers both cost and effectiveness will be highly useful. This study aims to identify the most cost-effective combination of COVID-19 response policies, using Singapore as an example., Methods and Analysis: An age-stratified Susceptible-Exposed-Infectious-Recovered model will be used to generate the number of infections stratified by disease severity under different intervention scenarios. Polices of interest include test-trace-isolate, travel restriction, compulsory face mask and hygiene practices, social distancing, dexamethasone/remdesivir therapy and vaccination. The latest phase 3 trial results and the WHO Target Product Profiles for COVID-19 vaccines will be used to model vaccine characteristics. A cost (expected resource utilisation and productivity losses) and quality-adjusted life years (QALYs) will be attached to these outputs for a cost-utility analysis. The primary outcome measure will be the incremental cost-effectiveness ratio generated from the incremental cost of policy alternatives expressed as a ratio of the incremental benefits (QALYs gained). Efficacy of policy options will be gathered from literature review and from its observed impacts in Singapore. Cost data will be gathered from healthcare institutions, Ministry of Health and published data. Sensitivity analysis such as threshold analysis and scenario analysis will be conducted., Ethics and Dissemination: Ethics approval was not required for this study. The study findings will be disseminated through peer-reviewed journals., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Background: The impact of lockdown measures can be widespread, affecting both clinical and psychosocial aspects of health. This study aims to assess changes in health services access, self-care, behavioural, and psychological impact of COVID-19 and partial lockdown amongst diabetes patients in Singapore., Methods: We conducted a cross-sectional online survey amongst people with diabetes with the Diabetes Health Profile-18 (DHP-18). Hierarchical regression analyses were performed for each DHP-18 subscale (Psychological Distress, Disinhibited Eating and Barriers to Activity) as dependent variables in separate models., Results: Among 301 respondents, 45.2% were women, 67.1% of Chinese ethnicity, 24.2% were aged 40 to 49 years, 68.4% have Type 2 diabetes and 42.2% on oral medications alone. During the pandemic and the lockdown, nearly all respondents were able to receive care safely from the clinics they attend (94%) and obtain their medications and diabetes equipment and supplies (97%) when needed. Respondents reported less frequent engagement in physical activity (38%), checking of blood pressure (29%) and blood glucose (22%). Previous diagnosis of mental health conditions (β = 9.33, P = .043), Type 1 diabetes (β = 12.92, P = .023), number of diabetes-related comorbidities (β = 3.16, P = .007) and Indian ethnicity (β = 6.65, P = .034) were associated with higher psychological distress. Comorbidities were associated with higher disinhibited eating (β = 2.49, P = .014) while ability to reach their doctor despite not going to the clinic is negatively associated with psychological distress (β = -9.50 P = .002) and barriers to activity (β = -7.53, P = .007)., Conclusion: Health services access were minimally affected, but COVID-19 and lockdown had mixed impacts on self-care and management behaviours. Greater clinical care and attention should be provided to people with diabetes with multiple comorbidities and previous mental health disorders during the pandemic and lockdown., (© 2021 John Wiley & Sons Ltd.)

This study aims to describe Facebook users' beliefs toward physical distancing measures implemented during the Coronavirus disease (COVID-19) pandemic using the key constructs of the health belief model. A combination of rule-based filtering and manual classification methods was used to classify user comments on COVID-19 Facebook posts of three public health authorities: Centers for Disease Control and Prevention of the United States, Public Health England, and Ministry of Health, Singapore. A total of 104,304 comments were analyzed for posts published between 1 January, 2020, and 31 March, 2020, along with COVID-19 cases and deaths count data from the three countries. Findings indicate that the perceived benefits of physical distancing measures ( n = 3,463; 3.3%) was three times higher than perceived barriers ( n = 1,062; 1.0%). Perceived susceptibility to COVID-19 ( n = 2,934; 2.8%) was higher compared with perceived severity ( n = 2,081; 2.0%). Although susceptibility aspects of physical distancing were discussed more often at the start of the year, mentions on the benefits of intervention emerged stronger toward the end of the analysis period, highlighting the shift in beliefs. The health belief model is useful for understanding Facebook users' beliefs at a basic level, and it provides a scope for further improvement.

Objectives: WHO recommends that low burden countries consider systematic screening and treatment of latent tuberculosis infection (LTBI) in migrants from high incidence countries. We aimed to determine LTBI prevalence and risk factors and evaluate cost-effectiveness of screening and treating LTBI in migrants to Singapore from a government payer perspective., Design: Cross-sectional study and cost-effectiveness analysis., Setting: Migrants in Singapore., Participants: 3618 migrants who were between 20 and 50 years old, have not worked in Singapore previously and stayed in Singapore for less than a year were recruited., Primary and Secondary Outcome Measures: Costs, quality-adjusted life-years (QALYs), threshold length of stay, incremental cost-effectiveness ratios (ICERs), cost per active TB case averted., Results: Of 3584 migrants surveyed, 20.4% had positive interferon-gamma release assay (IGRA) results, with the highest positivity in Filipinos (33.2%). Higher LTBI prevalence was significantly associated with age, marital status and past TB exposure. The cost-effectiveness model projected an ICER of S$57 116 per QALY and S$12 422 per active TB case averted for screening and treating LTBI with 3 months once weekly isoniazid and rifapentine combination regimen treatment compared with no screening over a 50-year time horizon. ICER was most sensitive to the cohort's length of stay in Singapore, yearly disease progression rates from LTBI to active TB, followed by the cost of IGRA testing., Conclusions: For LTBI screening and treatment of migrants to be cost-effective, migrants from high burden countries would have to stay in Singapore for ~50 years. Risk-stratified approaches based on projected length of stay and country of origin and/or age group can be considered., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

With vaccines for coronavirus disease 2019 (COVID-19) being introduced in countries across the world, policy makers are facing many practical considerations about how best to implement a vaccination programme. The supply of vaccines is insufficient for the global population, so decisions must be made as to which groups are prioritised for any vaccination and when. Furthermore, the aims of vaccination programmes will differ between countries, with some prioritising economic benefits that could stem from the relaxation of non-pharmaceutical interventions and others seeking simply to reduce the number of COVID-19 cases or deaths. This paper aims to share the experiences and lessons learned from conducting economic evaluations in Singapore and Thailand on hypothetical COVID-19 vaccines to provide a basis for other countries to develop their own contextualised economic evaluations, with particular focus on the key uncertainties, technical challenges, and characteristics that modellers should consider in partnership with key stakeholders. Which vaccines, vaccination strategies, and policy responses are most economically beneficial remains uncertain. It is therefore important for all governments to conduct their own analyses to inform local policy responses to COVID-19, including the implementation of COVID-19 vaccines in both the short and the long run. It is essential that such studies are designed, and ideally conducted, before vaccines are introduced so that policy decisions and implementation procedures are not delayed., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The Singapore government implemented multiple restrictive measures as the novel coronavirus infection (COVID-19) spread through the community, thereby affecting the support service of cancer-related social service agencies (cancer-SSAs). We are interested to understand how Singapore's cancer-SSAs utilized the social media platform Facebook to overcome the restrictions which were introduced due to COVID-19. Facebook posts from two prominent cancer-SSAs 365 Cancer Prevention Society (365CPS) and Singapore Cancer Society (SCS) between comparable periods in 2019 and 2020 were extracted. These posts were categorized using a classification scheme which was specifically developed by two coders with adequate intercoder reliability. Statistical analyses were performed to determine if there was a significant difference in the frequency of posts between 2019 and 2020, and across three specific periods in 2020. Results indicate that 365CPS appears to have adapted to the pandemic by increasing their posting frequency on Facebook in 2020, but the same was not evident for SCS. However, both SSAs tweaked their social media outreach strategy in line with social distancing measures, publishing posts detailing activities that beneficiaries can participate from home such as healthy recipes and virtual events. SSAs can scale up their efforts to achieve a higher level of health promotion and support for their beneficiaries. Further qualitative studies are required to ascertain the impact of COVID-19 from the perspective of beneficiaries and validate the classification scheme which was developed in this study. The classification scheme could be used in ascertaining the quality of social media communication between public/private support groups and patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

In Southeast Asia, cervical cancer is the second most common cancer in women. Low coverage for cervical cancer screening (CCS) becomes a roadblock to disease detection and treatment. Existing reviews on CCS have limited insights into the barriers and facilitators for SEA. Hence, this study aims to identify key barriers and facilitators among women living in SEA. A systematic literature review was conducted on Pubmed, Embase, PsycINFO, CINAHL, and SCOPUS. Primary qualitative and quantitative studies published in English that reported barriers and facilitators to CCS were included. The Mix Methods Appraisal Tool was used for the quality assessment of the included studies. Among the 93 included studies, pap smears (73.1%) were the most common screening modality. A majority of the studies were from Malaysia (35.5%). No studies were from Timor-Leste and the Philippines. The most common barriers were embarrassment (number of articles, n = 33), time constraints ( n = 27), and poor knowledge of screening ( n = 27). The most common facilitators were related to age ( n = 21), receiving advice from healthcare workers ( n = 17), and education status ( n = 11). Findings from this review may inform health policy makers in developing effective cervical cancer screening programs in SEA countries.

Background: This study aimed to evaluate the cost-effectiveness of a breast cancer screening programme that incorporates genetic testing using breast cancer associated single nucleotide polymorphisms (SNPs), against the current biennial mammogram-only screening programme to aid in its implementation into the current programme in Singapore., Methods: A Markov model was used to compare the costs and health outcomes of the current screening programme, against a polygenic risk-tailored screening programme, which can advise a long-term screening strategy depending on the individual's polygenic risk. The model took the perspective of the healthcare system, with a time horizon of 40 years, following women from the age of 35 to 74. Epidemiological and cost data were taken from Asian studies, and an annual discount rate of 3% was used. The model outcome was the incremental cost-effectiveness ratio (ICER), calculated from the difference in costs per quality-adjusted life year (QALY). Scenarios with varying risk thresholds for each polygenic risk group were examined. One-way and probabilistic sensitivity analyses were performed to assess parameter uncertainty., Results: The ICER for a polygenic risk-tailored breast cancer screening programme, compared with the current biennial mammogram-only screening programme, was - 3713.80 SGD/QALY, with incremental costs < 0 and incremental effects > 0. The scenario analysis of different polygenic risk cutoffs showed that the ICERs remain negative, with all ICERs falling within the south-east quadrant of the cost-effectiveness plane, indicating that tailored screening is more cost effective than mammogram-only screening, with lower costs and higher QALYs to be gained. This suggests that a polygenic risk-tailored breast cancer screening programme is cost effective, entailing lower cost than the current mammogram-only programme, while causing no additional harm to women., Conclusion: Results from this cost-effectiveness analysis show that polygenic risk-tailored screening is cost effective with an ICER of - 3713.80 SGD/QALY. Tailored screening remains cost effective even across varying percentile cutoffs for each risk group. While the results look promising for incorporating polygenic risk into the current breast cancer screening programme, further studies should be conducted to address various limitations.

Background: Limited research is available on the cost-effectiveness of breast cancer screening programs in Asian countries. We evaluated the cost-effectiveness of Singapore's national mammography screening program, implemented in 2002, recommending annual screening between ages 40 and 49 and biennial screening between ages 50 and 69, and alternative screening scenarios taking into account important country-specific factors., Methods: We used national data from Singapore in the MIcrosimulation SCreening ANalysis-Fatal diameter (MISCAN-Fadia) model to simulate 302 screening scenarios for 10 million women born between 1910 and 1969. Screening scenarios varied by starting and ending age, screening interval, and attendance. Outcome measures included life-years gained (LYG), breast cancer deaths averted, false positives, overdiagnosis, quality-adjusted life years (QALY), costs (in 2002 Singapore dollars; S$), and incremental cost-effectiveness ratios (ICER). Costs and effects were calculated and discounted with 3% using a health care provider's perspective., Results: Singapore's current screening program at observed attendance levels required 54,158 mammograms per 100,000 women, yielded 1,054 LYG, and averted 57 breast cancer deaths. At attendance rates ≥50%, the current program was near the efficiency frontier. Most scenarios on the efficiency frontier started screening at age 40. The ICERs of the scenarios on the efficiency frontiers ranged between S$10,186 and S$56,306/QALY, which is considered cost-effective at a willingness-to-pay threshold of S$70,000/QALY gained., Conclusions: Singapore's current screening program lies near the efficiency frontier, and starting screening at age 40 or 45 is cost-effective. Furthermore, enhancing screening attendance rates would increase benefits while maintaining cost-effectiveness., Impact: Screening all women at age 40 or 45 is cost-efficient in Singapore, and a policy change may be considered., (©2021 American Association for Cancer Research.)

Purpose: Assessing the clinical importance of an exposure effect on a quality of life (QoL) score often requires quantifying the effect in terms of a difference in scores. Using the linear regression model (LRM) for this purpose assumes the ordinal score is a proxy for an underlying continuous variable, but the analysis offers no assessment for the validity of the assumption. We propose an approach that assesses the proxy assumption and estimates the exposure effect by using the cumulative link model (CLM)., Patients and Methods: CLM is a well-established regression model that assumes an ordinal score is an ordered category generated from applying thresholds to a latent continuous variable. Our approach assesses the proxy assumption by testing whether these thresholds are equidistant. We compared the performance of CLM and LRM using simulated ordinal data and illustrated their application to the effect of time since diagnosis on five subscales of fatigue among breast cancer survivors measured using the Multidimensional Fatigue Inventory., Results: CLM had good performance in estimating the difference in means with simulated ordinal data satisfying the proxy assumption, even when the outcome had only a few categories. When the proxy assumption was inadequate, both the CLM and LRM had biased estimates with poor coverage. The proxy assumption was appropriate for four of the five subscales in our real data application to fatigue scores, which highlighted the importance of assessing the proxy assumption to avoid reporting invalid estimates in terms of the difference in scores., Conclusion: The proxy assumption is critical to the interpretation of the exposure effect on the difference in mean QoL scores. CLM offers a valid test for the presence of an association, a method for assessing the proxy assumption, and when the assumption is adequate, an assessment for clinical significance using the difference in means., Competing Interests: Hwee-Lin Wee reports grants from Johnson and Johnson (Singapore), Novartis (Singapore), Roche (Singapore), and Pfizer (Singapore), outside the submitted work. The authors report no other potential conflicts of interest in this work., (© 2021 Ning et al.)

Purpose: The 15- and 10-item short forms of the Singapore Caregiver Quality of Life Scale (SCQOLS-15 and SCQOLS-10) were recently developed as a quick assessment of caregiver quality of life. Reference values describing the distribution of the total and domain scores are available for the full-length version, but they are not yet available for the short forms. This study aimed to estimate the reference values for the short forms., Methods: Data from a cross-sectional survey of 612 family caregivers of patients with advanced cancer in Singapore were fitted in quantile regression models. Percentiles were estimated by regressing the short forms' scores on caregiver characteristics. Classification by the reference values for the short forms and the full-length version were compared and agreement was evaluated., Results: The caregiver's role in caring for the patient and the patient's performance status were associated with the percentiles of the total scores and most domain scores (each Bonferroni-adjusted p-value, P B , < 0.05). Higher-educated caregivers were categorized into higher percentiles according to the SCQOLS-15 and SCQOLS-10 total scores and the SCQOLS-15 Mental Well-being and Financial Well-being domain scores (each P B < 0.05). Ethnicity was associated with the SCQOLS-15 Physical Well-being and Experience & Meaning domains (each P B < 0.05). The percentiles for the short forms showed moderate to substantial agreement with those for the full-length version in terms of classifying caregivers into percentile intervals (quadratic-weighted Kappa = 0.72 to 0.92)., Conclusion: Reference values for the SCQOLS-15 and SCQOLS-10 were estimated in relation to caregiver characteristics to facilitate interpretation of the short form scores.

Background: Little is known about the effect of the coronavirus disease 2019 (COVID-19) pandemic and the outbreak response measures on door-to-balloon time (D2B). This study examined both D2B and clinical outcomes of patients with STEMI undergoing primary percutaneous coronary intervention (PPCI)., Methods and results: This was a retrospective study of 303 STEMI patients who presented directly or were transferred to a tertiary hospital in Singapore for PPCI from October 2019 to March 2020. We compared the clinical outcomes of patients admitted before (BOR) and during (DOR) the COVID-19 outbreak response. The study outcomes were in-hospital death, D2B, cardiogenic shock and 30-day readmission. For direct presentations, fewer patients in the DOR group achieved D2B time <90 min compared with the BOR group (71.4% vs. 80.9%, P=0.042). This was more apparent after exclusion of non-system delay cases (DOR 81.6% vs. BOR 95.9%, P=0.006). Prevalence of both out-of-hospital cardiac arrest (9.5% vs. 1.9%, P=0.003) and acute mitral regurgitation (31.6% vs. 17.5%, P=0.006) was higher in the DOR group. Mortality was similar between groups. Multivariable regression showed that longer D2B time was an independent predictor of death (odds ratio 1.005, 95% confidence interval 1.000-1.011, P=0.029)., Conclusions: The COVID-19 pandemic and the outbreak response have had an adverse effect on PPCI service efficiency. The study reinforces the need to focus efforts on shortening D2B time, while maintaining infection control measures.

Psychological and social factors are known to influence blood pressure (BP) and risk of hypertension and associated cardiovascular diseases. To identify novel BP loci, we carried out genome-wide association meta-analyses of systolic, diastolic, pulse, and mean arterial BP taking into account the interaction effects of genetic variants with three psychosocial factors: depressive symptoms, anxiety symptoms, and social support. Analyses were performed using a two-stage design in a sample of up to 128,894 adults from 5 ancestry groups. In the combined meta-analyses of Stages 1 and 2, we identified 59 loci (p value <5e-8), including nine novel BP loci. The novel associations were observed mostly with pulse pressure, with fewer observed with mean arterial pressure. Five novel loci were identified in African ancestry, and all but one showed patterns of interaction with at least one psychosocial factor. Functional annotation of the novel loci supports a major role for genes implicated in the immune response ( PLCL2 ), synaptic function and neurotransmission ( LIN7A, PFIA2 ), as well as genes previously implicated in neuropsychiatric or stress-related disorders ( FSTL5, CHODL ). These findings underscore the importance of considering psychological and social factors in gene discovery for BP, especially in non-European populations., Competing Interests: Declaration of interest The authors declare no conflict of interests.

Aims: To examine whether the excess risks of coronary heart disease (CHD), stroke, dialysis, and lower extremity amputation (LEA) associated with type 2 diabetes mellitus (T2DM) differ across age, sex, and ethnicity in Singapore., Methods: Using a 10-year administrative data, we matched individuals with T2DM using nearest neighbour matching, to those without, in 1:2 ratio. To examine whether the excess risks were heterogeneous across age, sex, and ethnicity, we generated interaction terms of age, sex, and ethnicity with T2DM status in Cox proportional hazard (PH) models., Results: The main analyses included ~1 million person years, comprising 66,099 and 120,485 individuals with and without T2DM, respectively. The associations of T2DM with CHD and dialysis, split into two time periods to address violation of PH assumption, were higher with older age in short-term but lower with older age in long-term. The association of T2DM with stroke and LEA were lower with older age. The associations of T2DM with CHD and stroke were also consistently higher in women than men. The associations of T2DM with LEA were higher in ethnic Malays than ethnic Chinese., Conclusions: The excess risks of CHD, stroke, dialysis, and LEA associated with T2DM were heterogeneous across some demographic subgroups., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Aim: To evaluate the relative importance of CYP2C19 genotype-guided treatment attributes to patients. Patients & methods: A discrete choice experiment questionnaire was administered to 63 patients with acute coronary syndrome. Attributes examined in the discrete choice experiment questionnaire were: cost of genetic testing (S$50, S$100, S$200); cost of antiplatelet medication (S$100, S$500, S$1000); heart attack or stroke risk (5 in 100, 15 in 100, 25 in 100); bleeding risk (5 in 100, 15 in 100, 25 in 100); doctor's recommendation (yes, neutral). Mixed logit model was used for analysis. Results & conclusion: All attributes were important in patients' decision-making. Most displayed strong preference for doctor's recommendation and reduced heart attack or stroke risk. Genotyping was chosen by 63.5% of the patients.

Objective: Ras wild-type metastatic colorectal cancers (mCRC) may be treated with anti-vascular endothelial growth factor (VEGF) or anti-epidermal growth factor receptor (EGFR) agents. We aim to estimate patients' preferences for mCRC treatment and relative importance of cost, efficacy improvement, avoidance of side effects and therapy convenience, and relative uptake between profiles that resemble Bevacizumab (anti-VEGF) and Cetuximab (anti-EGFR), two commonly prescribed mCRC targeted therapies., Methods: Discrete choice experiment (DCE) was administered to English- or Chinese-speaking Stage 2 or 3 colon cancer patients at the National Cancer Centre Singapore. DCE attributes comprise progression-free survival (PFS), severity of acne-like skin rashes, severity of bleeding, out-of-pocket cost per month and frequency of drug administration. Mixed logit model was used to calculate preference weights for all attribute levels. Subgroup analyses were conducted by interacting attribute levels with selected respondent characteristics. Relative uptake rates for various medication scenarios were studied., Results: 169 respondents aged 61.5 ± 10.5 years completed the survey. They placed the greatest weight on cost, followed by bleeding and skin rashes, then PFS and finally frequency of drug administration. This was similarly observed in the subgroup analyses. A scenario with shorter PFS but less severe side effects has a slightly higher relative uptake at 55%. One quarter of respondents reported that they would not take the treatment they preferred in the choice task., Conclusion: Patients were willing to trade off some degree of efficacy to avoid certain severity of side effects. It is therefore crucial for patients and physicians to discuss patients' preferences and circumstances to understand which attributes are more important, as well as patients' views on the trade-offs between treatment benefits and risks.

There is growing interest globally in using real-world data (RWD) and real-world evidence (RWE) for health technology assessment (HTA). Optimal collection, analysis, and use of RWD/RWE to inform HTA requires a conceptual framework to standardize processes and ensure consistency. However, such framework is currently lacking in Asia, a region that is likely to benefit from RWD/RWE for at least two reasons. First, there is often limited Asian representation in clinical trials unless specifically conducted in Asian populations, and RWD may help to fill the evidence gap. Second, in a few Asian health systems, reimbursement decisions are not made at market entry; thus, allowing RWD/RWE to be collected to give more certainty about the effectiveness of technologies in the local setting and inform their appropriate use. Furthermore, an alignment of RWD/RWE policies across Asia would equip decision makers with context-relevant evidence, and improve timely patient access to new technologies. Using data collected from eleven health systems in Asia, this paper provides a review of the current landscape of RWD/RWE in Asia to inform HTA and explores a way forward to align policies within the region. This paper concludes with a proposal to establish an international collaboration among academics and HTA agencies in the region: the REAL World Data In ASia for HEalth Technology Assessment in Reimbursement (REALISE) working group, which seeks to develop a non-binding guidance document on the use of RWD/RWE to inform HTA for decision making in Asia.

Aim: Early-onset dementia (EOD) (defined as dementia onset before age 65) presents specific challenges and issues, adding to the negative impact of dementia on the health-related quality of life (HRQOL) of both patients and their caregivers. However, very few published studies have specifically compared the HRQOL of caregivers of people with EOD and late-onset dementia (LOD). This information is critical in allocating and prioritizing scarce health-care resources. We aimed to assess the HRQOL of primary informal caregivers of community-dwelling individuals with EOD in Singapore and compare it with that of caregivers of individuals with LOD., Methods: This was a cross-sectional study of consecutive patient-caregiver dyads from a tertiary dementia clinic., Results: No significant differences in disease severity were found between the 111 EOD and 235 LOD patient-caregiver dyads. The mean Mental Component Summary score of the 36-item Short-Form Health Survey version 2 was significantly worse in caregivers of EOD patients than in LOD caregivers (mean: 41.42 vs 45.12, P = 0.001), although the mean Physical Component Summary scores were comparable (49.71 vs 49.53, P = 0.934). However, the impact of dementia early onset on caregivers' mental health diminished immediately after adjustment for the disease severity indicators, of which the Neuropsychiatric Inventory Questionnaire distress score was the only significant clinical factor (regression coefficient β = -0.29, P < 0.001). The amount of variability in the HRQOL of the caregivers explained by patient and caregiver factors across all the models was rather small (adjusted R 2 = 19.3% for the Mental Composite Score, 5.2% for Physical Composite Score)., Conclusion: Caregivers of EOD patients had worse mental health than LOD caregivers probably because individual with EOD have more behavioural disturbances. This reinforces the indispensable role of managing behavioural problems when caring for a family member with dementia, especially for EOD. HRQOL ideally needs to be assessed based on self-report rather than inferences from indirect data such as the subjective caregiver burden., (© 2020 Japanese Psychogeriatric Society.)

Background: Public health authorities have been recommending interventions such as physical distancing and face masks, to curtail the transmission of coronavirus disease (COVID-19) within the community. Public perceptions toward such interventions should be identified to enable public health authorities to effectively address valid concerns. The Health Belief Model (HBM) has been used to characterize user-generated content from social media during previous outbreaks, with the aim of understanding the health behaviors of the public., Objective: This study is aimed at developing and evaluating deep learning-based text classification models for classifying social media content posted during the COVID-19 outbreak, using the four key constructs of the HBM. We will specifically focus on content related to the physical distancing interventions put forth by public health authorities. We intend to test the model with a real-world case study., Methods: The data set for this study was prepared by analyzing Facebook comments that were posted by the public in response to the COVID-19-related posts of three public health authorities: the Ministry of Health of Singapore (MOH), the Centers for Disease Control and Prevention, and Public Health England. The comments made in the context of physical distancing were manually classified with a Yes/No flag for each of the four HBM constructs: perceived severity, perceived susceptibility, perceived barriers, and perceived benefits. Using a curated data set of 16,752 comments, gated recurrent unit-based recurrent neural network models were trained and validated for text classification. Accuracy and binary cross-entropy loss were used to evaluate the model. Specificity, sensitivity, and balanced accuracy were used to evaluate the classification results in the MOH case study., Results: The HBM text classification models achieved mean accuracy rates of 0.92, 0.95, 0.91, and 0.94 for the constructs of perceived susceptibility, perceived severity, perceived benefits, and perceived barriers, respectively. In the case study with MOH Facebook comments, specificity was above 96% for all HBM constructs. Sensitivity was 94.3% and 90.9% for perceived severity and perceived benefits, respectively. In addition, sensitivity was 79.6% and 81.5% for perceived susceptibility and perceived barriers, respectively. The classification models were able to accurately predict trends in the prevalence of the constructs for the time period examined in the case study., Conclusions: The deep learning-based text classifiers developed in this study help to determine public perceptions toward physical distancing, using the four key constructs of HBM. Health officials can make use of the classification model to characterize the health behaviors of the public through the lens of social media. In future studies, we intend to extend the model to study public perceptions of other important interventions by public health authorities., (©Aravind Sesagiri Raamkumar, Soon Guan Tan, Hwee Lin Wee. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 14.07.2020.)

Background: The coronavirus disease (COVID-19) pandemic presents one of the most challenging global crises at the dawn of a new decade. Public health authorities (PHAs) are increasingly adopting the use of social media such as Facebook to rapidly communicate and disseminate pandemic response measures to the public. Understanding of communication strategies across different PHAs and examining the public response on the social media landscapes can help improve practices for disseminating information to the public., Objective: This study aims to examine COVID-19-related outreach efforts of PHAs in Singapore, the United States, and England, and the corresponding public response to these outreach efforts on Facebook., Methods: Posts and comments from the Facebook pages of the Ministry of Health (MOH) in Singapore, the Centers for Disease Control and Prevention (CDC) in the United States, and Public Health England (PHE) in England were extracted from January 1, 2019, to March 18, 2020. Posts published before January 1, 2020, were categorized as pre-COVID-19, while the remaining posts were categorized as peri-COVID-19 posts. COVID-19-related posts were identified and classified into themes. Metrics used for measuring outreach and engagement were frequency, mean posts per day (PPD), mean reactions per post, mean shares per post, and mean comments per post. Responses to the COVID-19 posts were measured using frequency, mean sentiment polarity, positive to negative sentiments ratio (PNSR), and positive to negative emotions ratio (PNER). Toxicity in comments were identified and analyzed using frequency, mean likes per toxic comment, and mean replies per toxic comment. Trend analysis was performed to examine how the metrics varied with key events such as when COVID-19 was declared a pandemic., Results: The MOH published more COVID-19 posts (n=271; mean PPD 5.0) compared to the CDC (n=94; mean PPD 2.2) and PHE (n=45; mean PPD 1.4). The mean number of comments per COVID-19 post was highest for the CDC (mean CPP 255.3) compared to the MOH (mean CPP 15.6) and PHE (mean CPP 12.5). Six major themes were identified, with posts about prevention and safety measures and situation updates being prevalent across the three PHAs. The themes of the MOH's posts were diverse, while the CDC and PHE posts focused on a few themes. Overall, response sentiments for the MOH posts (PNSR 0.94) were more favorable compared to response sentiments for the CDC (PNSR 0.57) and PHE (PNSR 0.55) posts. Toxic comments were rare (0.01%) across all PHAs., Conclusions: PHAs' extent of Facebook use for outreach purposes during the COVID-19 pandemic varied among the three PHAs, highlighting the strategies and approaches that other PHAs can potentially adopt. Our study showed that social media analysis was capable of providing insights about the communication strategies of PHAs during disease outbreaks., (©Aravind Sesagiri Raamkumar, Soon Guan Tan, Hwee Lin Wee. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 19.05.2020.)

Purpose: The Singapore Caregiver Quality of Life Scale (SCQOLS) was recently developed and validated in two languages - English and Chinese. The total and domain scores are scaled to range from 0 to 100. However, the scale is not at the interval-ratio level of measurement. To facilitate interpretation, we established the percentiles of the scale's total and domain scores among family caregivers of patients with advanced cancers and demonstrate the effect size in terms of differences in relation to caregiver and patient characteristics., Methods: Data were drawn from a cross-sectional survey of family caregivers of patients with stage III or IV solid cancers in Singapore. Quantile regression was used to estimate the percentiles in relation to caregiver and patient characteristics., Results: Participants in adjacent categories of patient's performance status and caregiver's having other family members to share caregiving duties differed by 3 to 5 points in median quality of life total score and most domain scores (each Bonferroni-adjusted P, P[B], < 0.05). Ethnicity was associated with the Physical Well-being and Experience & Meaning domain scores (each P[B] < 0.05), with variable direction and magnitude. Education was associated with Mental Well-being and Financial Well-being (each P[B] < 0.05). Equations and examples for calculation of the percentiles are provided., Conclusion: Percentiles and effect size estimates are provided to facilitate interpretation of the SCQOLS.

There has been continuous development in the field of health technology assessment (HTA) owing to the added value of HTA in supporting healthcare reimbursement decisions. Collaboration and engagement among countries in Asia has been carried out to share experiences and learning on the barriers and factors facilitating the implementation and use of HTA in policy making. A symposium on the topic of Health Technology Assessment (HTA): Selecting the Highest Value Care was held on January 10, 2019 at the National University of Singapore, during which 3 major challenges confronting HTA development in Asia were identified. The symposium also offered possible ways to overcome the challenges., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)