Cost-Effectiveness of First-Line Pembrolizumab Monotherapy Versus Chemotherapy in High Programmed Death-Ligand 1 Advanced Non-Small Cell Lung Cancer in the Irish Healthcare Setting.

OBJECTIVES: This study aimed to assess the cost-effectiveness of pembrolizumab monotherapy in the first-line treatment of advanced non-small cell lung cancer (NSCLC) in adults whose tumors expressed programmed death-ligand 1 (PD-L1) with a tumor proportion score (TPS) ≥ 50% in the Irish healthcare setting. METHODS: Effectiveness inputs were derived from the 5-year analysis of KEYNOTE-024 phase III clinical trial. The intervention was pembrolizumab monotherapy; the comparator was a weighted average of the 5 chemotherapy regimens from the trial. The population included those with previously untreated advanced PD-L1 TPS ≥ 50% NSCLC. A de novo partitioned survival model was developed. Survival modeling was done using Bayesian model averaging on fitted parametric functions. Costs included drug acquisition, treatment initiation, administration and monitoring, adverse events, subsequent treatments, and terminal care. Costs and health state utilities were sourced from the literature and Irish sources. The model had a 20-year time horizon. The perspective taken was the Health Service Executive. A 4% discount rate was applied. Outcomes were expressed as an incremental cost-effectiveness ratio (ICER), measured in terms of incremental costs per quality-adjusted life-year (QALY). Probabilistic sensitivity analysis and 1-way sensitivity analyses were conducted. RESULTS: The model estimated a base case ICER of €54 237 per QALY. The probabilistic sensitivity analysis estimated an average ICER of €54 568 per QALY and a 11% probability of cost-effectiveness at the Irish cost-effectiveness threshold of €45 000 per QALY. CONCLUSION: At the current list price, first-line pembrolizumab monotherapy is not considered cost-effective for the treatment of advanced PD-L1 TPS ≥ 50% NSCLC in the Irish healthcare setting.

Coronavirus Disease 2019: Considerations for Health Technology Assessment From the National Centre for Pharmacoeconomics Review Group.

It is expected that the coronavirus disease 2019 (COVID-19) pandemic will leave large deficits in the budgets of many jurisdictions. Funding for other treatments, in particular new treatments, may become more constrained than previously expected. Therefore, a robust health technology assessment (HTA) system is vital. Many clinical trials carried out during the pandemic may have been temporarily halted, while others may have had to change their protocols. Even trials that continue as normal may experience external changes as other aspects of the healthcare service may not be available to the patients in the trial, or the patients themselves may contract COVID-19. Consequently, many limitations are likely to arise in the provision of robust HTAs, which could have profound consequences on the availability of new treatments. Therefore, the National Centre for Pharmacoeconomics Review Group wishes to discuss these issues and make recommendations for applicants submitting to HTA agencies, in ample time for these HTAs to be prepared and assessed. We discuss how the pandemic may affect the estimation of the treatment effect, costs, life-years, utilities, discontinuation rates, and methods of evidence synthesis and extrapolation. In particular, we note that trials conducted during the pandemic will be subject to a higher degree of uncertainty than before. It is vital that applicants clearly identify any parameters that may be affected by the pandemic. These parameters will require considerably more scenario and sensitivity analyses to account for this increase in uncertainty.

Global database of cement production assets and upstream suppliers.

Cement producers and their investors are navigating evolving risks and opportunities as the sector's climate and sustainability implications become more prominent. While many companies now disclose greenhouse gas emissions, the majority from carbon-intensive industries appear to delegate emissions to less efficient suppliers. Recognizing this, we underscore the necessity for a globally consolidated asset-level dataset, which acknowledges production inputs provenance. Our approach not only consolidates data from established sources like development banks and governments but innovatively integrates the age of plants and the sourcing patterns of raw materials as two foundational variables of the asset-level data. These variables are instrumental in modeling cement production utilization rates, which in turn, critically influence a company's greenhouse emissions. Our method successfully combines geospatial computer vision and Large Language Modelling techniques to ensure a comprehensive and holistic understanding of global cement production dynamics.

Bridging the gap between healthcare professions' regulation and practice: the "lived experience" of community pharmacists in Ireland following regulatory change.

BACKGROUND: Reforms to models of health and care regulation internationally have adapted to address the challenges associated with regulating healthcare professionals. Pharmacists in Ireland entered a new era of regulation with the enactment of the Pharmacy Act in 2007 which significantly updated the law regulating pharmacy in Ireland and expanded the regulatory scope considerably. An earlier study in 2017 examined the experiences of 20 community pharmacists of the Act. This follow-up study aimed to expand the scope of the original study to all community pharmacists in Ireland, to report their "lived experience" of the regulatory model introduced by the Act, assessing its impact on their professional practice using the principles of "better regulation". METHODS: Survey methodology was used to assess the perception of all community pharmacists registered with the Pharmaceutical Society of Ireland of the Act, as implemented, on their practice using an experimental design based on the seven principles of "Better Regulation". Descriptive statistics analyzed quantitative responses while answers from open-ended questions were analyzed using a combination of a modified framework analysis and a qualitative content analysis. RESULTS: Respondents agreed that the Act was necessary, although its implementation by the regulator was largely not viewed as fulfilling the remaining "Better Regulation" principles of being effective, proportional, consistent, agile, accountable and transparent. In particular, its proportionality was questioned. This resulted in pharmacists perceiving that their professional competency to act in the best interests of their patients was not appropriately acknowledged by the regulator, which in turn compromised their ability to provide optimal care for their patients. CONCLUSION: While healthcare professional regulation must primarily be concerned with public protection, it must also have regard to its impact on those delivering healthcare services. The findings highlight the challenge internationally of balancing rigidity and flexibility in professional health and care regulation, and the importance of a regulatory conversation occurring between those regulating and those regulated. This would serve to promote mutual learning and understanding to create a responsive approach to regulation, underpinned by mutual trust, effective risk assessment and adherence to the principles of "Better Regulation".

Understanding the Challenges and Uncertainties of Seroprevalence Studies for SARS-CoV-2.

SARS-CoV-2 continues to widely circulate in populations globally. Underdetection is acknowledged and is problematic when attempting to capture the true prevalence. Seroprevalence studies, where blood samples from a population sample are tested for SARS-CoV-2 antibodies that react to the SARS-CoV-2 virus, are a common method for estimating the proportion of people previously infected with the virus in a given population. However, obtaining reliable estimates from seroprevalence studies is challenging for a number of reasons, and the uncertainty in the results is often overlooked by scientists, policy makers, and the media. This paper reviews the methodological issues that arise in designing these studies, and the main sources of uncertainty that affect the results. We discuss the choice of study population, recruitment of subjects, uncertainty surrounding the accuracy of antibody tests, and the relationship between antibodies and infection over time. Understanding these issues can help the reader to interpret and critically evaluate the results of seroprevalence studies.