Central line-associated bloodstream infections (CLABSIs) result in morbidity and mortality among hospitalized patients. Hospital interventions to reduce the incidence of CLABSI are often broadly applied to all patients with central venous access. Identifying central lines at high risk for CLABSI at time of insertion will allow for a more focused delivery of preventative interventions.

This was an observational cohort study conducted at three hospitals including all patients who received central venous access. CLABSIs were identified using an institutional CLABSI database maintained by the hospital epidemiology team. Logistic regression (LASSO) and machine learning (random forest, XGboost) techniques were applied for the prediction of CLABSI occurrence, adjusting for selected patent and insertion-level characteristics.

A total of 40,008 central venous catheters were included, of which 409 (1.02%) were associated with CLABSI. The random forest and the XGBoost models had the highest discrimination (Area Under the Received Operating Curve [AUC] 0.79) followed by LASSO (0.73). High illness severity, receipt of total parenteral nutrition, receipt of hemodialysis, pre-insertion hospital length-of-stay, and low albumin levels were all predictive of CLABSI occurrence. Precision for all models was poor owing to a high false-positive rate.

CLABSI can be predicted based upon patient and insertion level factors in the electronic health record. In this study, random forest and gradient-boosted models had the highest AUC. Prediction cut-offs for the identification of CLABSI can be adjusted based upon the acceptable rate of false-positives for a given CLABSI preventative intervention.

Cerebral microbleeds are associated with an increased risk of hemorrhagic transformation (HT) following acute ischemic stroke. We investigated whether the effect of dabigatran (vs. aspirin) in patients with acute minor non-cardioembolic ischemic stroke/transient ischemic attack (TIA) is modified by baseline microbleeds on MRI.

The Dabigatran Treatment of Acute Stroke II trial randomized 305 patients with acute minor non-cardioembolic ischemic stroke/TIA to dabigatran (150/110 mg twice daily) or aspirin (81 mg daily) for 30 days. Microbleeds were centrally adjudicated in patients with an interpretable blood-sensitive sequence on baseline MRI. In this post hoc analysis, we used multivariable regression models to determine the association between microbleeds and any incident HT on day-30 MRI and excellent functional outcome (modified Rankin scale = 0–1) at 90 days.

A total of 251 (82.3%) participants (mean age = 66 ± 13 years, 36% women, median [IQR] onset-to-randomization time = 40[27–55] hours; median [IQR] NIHSS = 1 [0–2]) were included, of whom 82 (33%) had microbleeds. On day-30 MRI, 6% (n = 14) developed HT, and 80% (n = 191) achieved 90-day mRS of 0–1. We found no association between microbleed presence and HT (adjusted OR = 0.84; 95%CI:0.21–3.25) or excellent functional outcome (adjusted RR = 1.09; 95%CI:0.94–1.26). The rate of HT in patients with microbleeds was 3% with dabigatran and 4% with aspirin (OR = 0.85; 95%CI:0.11–6.75). Excellent functional outcome occurred in 74% and 84% of dabigatran and aspirin-treated patients, respectively (RR = 0.88; 95%CI:0.69–1.12). The presence, severity or location of microbleeds did not modify the effect of dabigatran on these outcomes (p-interaction > 0.05).

Early dabigatran treatment appears safe in patients with acute minor non-cardioembolic ischemic stroke/TIA and hemorrhage-prone cerebral small vessel disease marked by microbleeds on MRI.

Public healthcare institutions (PHIs) experience rising and discordant implant costs. Implementing subsidies for implants without concurrent price harmonization through national procurement contracts impedes equitable patient access. This abstract describes the collaboration between the Agency for Care Effectiveness (ACE), Singapore’s national health technology assessment (HTA) agency, and the public healthcare supply chain agency (ALPS) to establish the Implant Subsidy List (ISL).

The alignment between ISL and concurrent national procurement contracts for implants required close coordination and co-development of streamlined and scalable processes. To achieve this, ACE and ALPS collaborated to understand the complex implant landscape by leveraging on known vendors and products and pre-empting upcoming ones, identifying key opinion leaders, and sharing technical expertise. Both agencies also developed common-use templates and streamlined vendor submission processes. Of note, joint request-for-proposal (RFP) exercises for national subsidy and procurement listings combined negotiation efforts to achieve lower implant prices. Regular cross-agency discussions enabled continuous knowledge sharing and process refinement in an evolving implants landscape.

For phase one rollout of ISL, 15 implant topics across eight clinical functions were evaluated, supported by concurrent establishment of 15 national procurement contracts. As of December 2023, ACE listed 22,689 ISL implants for implementation, with more topics onboarded on a rolling basis. ACE and ALPS streamlined process flows, standardized communications channels and information, and utilized contractual tools. Vendors could submit for both subsidy and procurement through the secure ALPS portal, reducing duplication of work and errors while allowing procurement and subsidy consideration processes to proceed concurrently. Combined negotiation efforts have resulted in an average price reduction of 19 percent.

The alignment between national HTA and procurement agencies is important for successful scaling. The ACE–ALPS collaboration has synergized both agencies’ understanding of the complex implant landscape and established streamlined workplans and processes to support initial establishment of ISL and its maintenance. Challenges include navigating strict procurement rules and continuous cross-agency improvement efforts to ensure applicability in an evolving landscape.

In Singapore, a horizon scanning (HS) system was established in 2020 by the Agency for Care Effectiveness (ACE) to provide early alerts of new and emerging medical technologies (medtechs) for service planning and to warn against the diffusion of low value technologies. This study compared the medtechs identified and assessed by ACE with health technology trends identified by our reference agency.

Medtechs identified and assessed by ACE between 2020 and 2023 were analyzed to examine their distribution. Most of the identified medtechs were classified as digital health technologies, precision medicine, robotics, or implants. The prioritized technologies with a completed in-depth assessment were compared with the top 10 health technology trends identified in 2022 by our reference health technology assessment (HTA) agency, the Canadian Agency for Drugs and Technologies in Health (CADTH). Additionally, feedback from key stakeholders such as clinicians and policymakers on the HS reports was summarized to understand the relevance and value of the HS reports.

From 2020 to 2023, there were 1,703 medtechs identified from various databases and manufacturer submissions. Digital health technologies were the largest proportion of technologies identified during this period, increasing from 26 percent in 2020 to 31 percent in 2023. Of the 20 evaluated technologies, 70 percent belonged to the top trending medtech fields identified by CADTH. These included artificial intelligence for diagnostics (n=5), point-of-care testing (n=4), companion diagnostics (n=2), wearables (n=2), and remote monitoring (n=1). Initial stakeholder feedback was positive, citing HS reports as being relevant for clinical practice. Some HS reports were also referenced by other policymakers to support regulatory decisions.

In summary, similarities were observed between medtechs identified and assessed by the ACE HS system and the top trending medtech fields identified by CADTH. Additionally, digital health technologies were the largest proportion of technologies identified by the ACE HS system in 2023. This was substantiated by feedback from our key stakeholders, indicating the relevance and value of the ACE HS work.

The Agency for Care Effectiveness (ACE) conducts health technology assessments (HTAs) to inform funding decisions by the Ministry of Health (MOH) Drug Advisory Committee (DAC) in Singapore. In 2021 ACE introduced the company-led submission (CLS) process for cancer medicines, which allows pharmaceutical companies to request evaluations alongside regulatory reviews. This review reports key findings from the first year of its implementation.

A total of 10 CLS topics from the first year of implementation were included. We reviewed the status and outcomes of the DAC recommendations. We also used descriptive statistical methods to evaluate the time from HTA submission to first HTA recommendation and from regulatory approval to first HTA recommendation. The timelines were further analyzed by whether submissions were parallel submissions (i.e., HTA submission in tandem with regulatory review) or sequential submissions (i.e., HTA submission after regulatory approval). These statistics were compared with overseas reference jurisdictions (Australia, Canada, and the UK).

At the time of review, three topics were pending discussion. Of the remaining seven topics, three (43%) received positive recommendations for inclusion on the MOH Cancer Drug List and three (43%) received negative recommendations. The DAC was unable to make a recommendation on one topic. The median time from HTA submission or regulatory approval to first HTA recommendation was 172 days (range 169 to 263 days) and 279 days (range 53 to 374 days), respectively. Notably, parallel submissions (75 days; n=2) had considerably shorter timelines from regulatory approval to first HTA recommendation than sequential submissions (328 days; n=4). These timelines were within the range of the overseas reference countries.

Parallel CLS allows HTA processes to be conducted in tandem with regulatory reviews, moving HTA recommendations upstream and expediting patient access to clinically effective and cost-effective medicines. Efforts will be made to further evolve the CLS process to achieve timely reimbursement reviews from regulatory approval and to expand this process to noncancer medicines.

Human tissue biobanks provide vital infrastructure to support both basic science and clinical research, but their economic value in terms of attributable population health gains is unclear. We evaluated the population health returns from investment in the Victorian Cancer Biobank (VCB). The VCB comprises five hospital-integrated sample repositories and a central lead agency located in Melbourne, Australia.

This evaluation assigned monetary values to the health gains attributable to VCB-supported public-funded research. These were then compared to the total investment in VCB infrastructure since inception (2006 to 2022) to determine the return on investment (ROI). A time lag of 40 years was incorporated, recognizing the delay from investment to impact in scientific research. Health gains were therefore measured for the years 2046 to 2066, with a three percent discount rate applied. Health gains were measured in terms of disability-adjusted life years (DALYs) attributable to VCB-associated research, with monetary cost assigned via the standardized value of a statistical life year (AUD227,000 [USD149,883]).

The age-standardized DALY rate attributable to cancer was modeled for two standpoints: (i) extrapolating the current decreasing trajectory and (ii) assuming nil future improvement from current rates, with 33 percent of the difference attributed to scientific innovation. The proportion of the aggregate health gain attributable to VCB-supported research was estimated from the number of VCB-credited scientific publications as a proportion of total oncology publications over the same period. The AUD32,628,016 [USD21,554,571] of public funding invested in VCB activities over the years 2006 to 2022 generated AUD84,561,373 [USD55,868,539] total savings. Return on investment was AUD1.59 [USD1.05] for each AUD1 [USD0.66] invested.

The VCB offers a strong return on investment in terms of population health impacts, justifying the use of public funds and supporting the use of biobanks to advance scientific research. Future health technology assessments could capture the total impact of research on the role of the biobanks attributed to research outputs.

Long-acting muscarinic antagonist (LAMA) monotherapy and LAMA in combination with a long-acting beta2 agonist are preferred over inhaled corticosteroid/long-acting beta2-agonist (ICS/LABA) therapy for Global Initiative for Chronic Obstructive Lung Disease (COPD) Group B and C patients. This study assesses impact of the subsidy decision of umeclidinium (umec) and umeclidinium/vilanterol (umec/vil) on Singapore’s healthcare system.

A retrospective cohort study was conducted using national health record databases. Maintenance-naive COPD patients, with no concurrent asthma, initiated on umec, umec/vil, or ICS/LABA from 2016 to 2020, were included. Patient demographics, comorbidities, and clinical characteristics were balanced using propensity score matching. Primary outcomes measured were the rate of severe or moderate COPD exacerbation and pneumonia hospitalization within one-year follow-up. Effect size was estimated using incidence rate ratio (IRR) with 95% confidence intervals (CIs) from Poisson regression. Markov model extrapolated the number of exacerbations and pneumonia hospitalizations avoided arising from the initiation of umec or umec/vil over ICS/LABA.

Patients initiated on umec (n=1,019) were less likely to experience severe (IRR 0.649; 95% CI: 0.438, 0.961) and moderate exacerbations (IRR 0.713; 95% CI: 0.569, 0.892) than ICS/LABA. Similarly, umec/vil-treated patients (n=1,206) had lower rates of severe (IRR 0.713; 95% CI: 0.517, 0.985) and moderate exacerbation (IRR 0.778; 95% CI: 0.642, 0.942). Both therapies were safer than ICS/LABA, with fewer pneumonia hospitalizations for umec (IRR 0.719; 95% CI: 0.532, 0.973) and umec/vil (IRR 0.781; 95% CI: 0.623, 0.980). Coupled with reduced drug cost from value-based pricing, subsidy potentially resulted in SGD53 million (USD39 million) cost savings over 10 years.

As the largest real-world study conducted among COPD patients in Singapore, our findings contribute to the limited real-world evidence in the region. Compared to ICS/LABA, umec or umec/vil were associated with better COPD control and reduced rates of pneumonia hospitalization. This confirms the importance of appropriate prescribing of COPD therapies and validates the subsidy decision.

The Agency for Care Effectiveness (ACE) in Singapore has established a horizon scanning (HS) system to provide advance notice of new and emerging medical technologies (MedTechs) to inform service planning since 2020. To remain fit for purpose, HS needs to evolve over time to better serve its stakeholders. This abstract aims to share ACE’s early HS experience and future opportunities.

To gather insights into ACE’s HS successes and potential gaps, a mixed-methods approach was used. A review of key HS activities was conducted, including different HS outputs produced, stakeholder engagements conducted, and dissemination strategies employed. Feedback from key stakeholders was gathered to understand the potential utility of our outputs. Lastly, potential gaps and opportunities were identified to inform future initiatives.

As of July 2023, 20 HS reports were developed, comprising three high-level overviews and 17 in-depth briefs. Output of briefs increased five-fold from 2021 (n=2) to 2023 (n=10). Efforts to drive impact included industry submission of pipeline MedTechs to supplement identification sources; report dissemination to over 100 policymakers and healthcare professionals for early service planning; and participation in network activities and conferences to share knowledge. Initial stakeholder feedback was positive, citing the reports’ relevance for clinical practice. The review recommended diversifying HS outputs to include environmental scan and trends reports, strengthening patient involvement and formal impact assessment through stakeholder surveys.

ACE’s HS has made significant progress in achieving its intended objectives to enable service planning for new and emerging MedTechs. However, this remains an iterative process with new opportunities for growth. Future initiatives were identified, such as impact assessment, enhancing stakeholder engagement to include patients, and broadening outputs to meet stakeholder demands.

The diverse implant landscape, the rising and disparate costs of implants in public healthcare institutions (PHIs), and the limited application of health technology assessment (HTA) impede fair and sustainable implant subsidies in Singapore. This study described the Agency for Care Effectiveness (ACE) Implant Subsidy List (ISL) methodology and the key enablers for supporting government subsidy of clinically effective and cost-effective implants in Singapore.

A multi-tiered implant grouping scheme on the ISL was established by adapting overseas implant classifications, consulting clinicians, and conducting HTA evaluations, with subsidy extensions at the product group tier. Implants within a product group share similar biomechanical actions and patient outcomes and are subject to the same clinical criteria and pricing requirement. Implants on the ISL must be approved by the regulatory authority. Patients who meet the clinical criteria for ISL implants are eligible for subsidy. ACE conducted value-based pricing (VBP) and partnered with the public healthcare supply chain agency to harmonize PHI implant prices. The ISL is updated three times per year.

Implants listed on the ISL were deemed clinically and cost effective. Underpinned by HTA principles, the implant grouping scheme promoted parsimonious classification, while allowing the creation of new product groups for implants offering superior benefits for patients. Reasonable prices set for the product groups aided affordability and cost sustainability. The ISL clinical criteria and standardized implant identifiers encouraged the appropriate use of subsidized implants and facilitated implementation. By ISL implementation in December 2023, ACE assessed 42,165 implants and listed 22,689 ISL implants spanning 143 product groups. Industry can apply for ISL listing three times per year, which keeps the ISL updated and relevant.

The ISL adopts a fit-for-purpose methodology to standardize implant classifications, enable scalable application of HTA, drive appropriate use of subsidized implants, and bring cost sustainability to the government subsidy of implants in Singapore. A strategic partnership with the public healthcare supply chain agency to concurrently establish national procurement contracts reduced disparate implant prices in PHIs and provided greater leverage for better implant prices.

The growing use of real-world evidence (RWE) in pharmaceutical decision-making has prompted various guidelines, including REALISE (REAL World Data In ASia for HEalth Technology Assessment in Reimbursement). We compared RWE guidance from Asian, European, and North American health technology assessment (HTA) and regulatory bodies against the REALISE guidance.

Following a previous search for China/Japan guidelines in 2022, websites of the U.S. Food and Drug Administration (FDA), the National Institute for Health and Care Excellence (NICE), the European Medicines Agency (EMA), and the Canadian Agency for Drugs and Technologies in Health (CADTH) were searched for RWE guidance in May 2023. Sections from each guidance were mapped onto REALISE and categorized as “agree,” “mixed,” “disagree,” or “missing” based on coverage/consistency.

Eleven guidelines were identified: four from Japan, three from China, and one each from FDA, NICE, EMA, and CADTH. No disagreements were found (all mapped sections were tagged “agree”/”mixed”); divergences were in coverage only. Most regulatory guidance had narrower scopes: EMA covered registry-based studies, the FDA’s framework mainly referenced other documents, while Japan had guidance for database and registry data. Conversely, HTA guidelines (CADTH, NICE) were more comprehensive and provided specific recommendations on preferred methods (e.g., transparent reporting) that were “missing” (45 to 46%) from REALISE’s more conceptual discussions. Chinese regulatory guidance was the exception, with similar coverage as REALISE (77% “agree”/“mixed”).

Guidelines varied in scope, but there was overall concordance where recommendations could be mapped across documents. While regulatory bodies could focus on specific types of RWE, reflecting the specific role of RWE in regulatory evaluations (for example demonstrating safety), guidance for HTA was broader to account for different possible use cases in demonstrating comparative effectiveness and value.