Christine Y. Lu

1. Global pharmaceutical expenditure continues to rise, with total medicine spending projected to grow by 3–6% annually [1]. Biologic disease-modifying antirheumatic drugs (bDMARDs) account for a d...

Background: Cancer can impose substantial financial strain on patients and their families, particularly through high out-of-pocket healthcare costs. This study aims to compare out-of-pocket and catastrophic healthcare expenditures among individuals with cancer, those with non-cancer chronic conditions, and healthy individuals, and to identify socio-demographic and health-related factors associated with higher financial burden. Methods: We analysed data from four waves of the Household, Income and Labour Dynamics in Australia (HILDA) survey. Two-part and random-effects logistic regression models were used to examine associations between cancer status and total out-of-pocket and catastrophic healthcare expenditures, adjusting for socio-demographic characteristics and health service utilisation. Results: Cancer patients had significantly higher financial burden than both healthy individuals and those with non-cancer chronic conditions. Compared to healthy individuals, cancer patients had 15% higher out-of-pocket healthcare expenditures (95% CI: 1.09–1.22) and 1.05 times higher odds of experiencing catastrophic health expenditure (95% CI: 1.03–1.06). When compared to individuals with non-cancer chronic conditions, cancer patients had 11% higher out-of-pocket healthcare expenditure (95% CI: 1.06–1.17) and 1.03 times higher odds of experiencing catastrophic spending (95% CI: 1.01–1.05). Key factors associated with higher odds of catastrophic healthcare expenditure included older age, long-term disability, lower household income, and higher education attainment. Conclusion: Cancer patients had higher out-of-pocket healthcare costs and higher odds of catastrophic healthcare expenditure than comparison groups. These findings highlight the need for targeted supportive care strategies and policy interventions to reduce the financial burden associated with cancer and promote equitable access to care.

Antipsychotics are often prescribed in the management of behaviors and psychological symptoms of dementia. While the potential harms of antipsychotic use in people with dementia have been established, little is known about the risk associated with antipsychotic drug–drug interactions (DDIs). This study aims to examine the patterns of antipsychotic DDIs and their association with 90‐day mortality among people with dementia using antipsychotics. This retrospective cohort study utilized Australian nationwide linked 2021 Census and Pharmaceutical Benefits Scheme data. People with dementia aged ≥ 65 years who initiated a single antipsychotic (risperidone, quetiapine, aripiprazole, haloperidol, or olanzapine) between August 2021 and July 2022 were included. Antipsychotic DDIs were defined by Micromedex® Drug‐Reax, and were stratified by number, severity, and pharmacological mechanism. Mortality risk was assessed using modified Poisson regression and confounding was addressed with overlapped weighting. Among 9064 incident antipsychotic users, 6913 (76.3%) were exposed to ≥ 1 DDI, with the majority of them classed as “major” severity ( n = 6709). Nervous system drugs were the most commonly interacting agents. When compared to those without antipsychotic interactions, those with ≥ 1 DDI had a 43% increased risk of 90‐day mortality (adjusted relative risk [aRR]: 1.43; 95% confidence interval [CI]: 1.22–1.69), while those with ≥ 2 DDIs had an 80% increased risk (aRR: 1.80; 95% CI: 1.49–2.17). Overall, antipsychotic DDIs are common among older adults with dementia and are associated with increased risk of 90‐day mortality. As such, medication review and regular monitoring is important when initiating antipsychotics in this vulnerable population.

Introduction: Pembrolizumab monotherapy improves survival in advanced non-small cell lung cancer (NSCLC) with programmed death ligand 1 (PD-L1) tumour proportion score (TPS) ≥ 50%. However, survival in randomised trials may not fully reflect outcomes in routine practice, with implications for economic evaluation. Aim: To evaluate the cost-effectiveness of pembrolizumab monotherapy compared with platinum-based chemotherapy from an Australian health-payer perspective, integrating both randomised controlled trial (RCT) and real-world evidence (RWE). Method: A semi-Markov model with three health states (progression-free, progressed disease, death) was developed over a 3-year horizon. Clinical inputs were derived from KEYNOTE-024 for the RCT scenario and from nationwide Australian real-world data for the RWE scenario, with chemotherapy outcomes retained from the pivotal trials in both scenarios. Direct medical costs (2024 AU$) and quality-adjusted life years (QALYs) were estimated. Incremental cost-effectiveness ratios (ICERs) were calculated, probabilistic and deterministic sensitivity analyses conducted. Results: Compared with chemotherapy, pembrolizumab monotherapy was associated with incremental costs of AU$87,399 (RCT-based) and AU$75,935 (RWE-based), and incremental QALY gains of 0.23 and 0.11, respectively. Corresponding ICERs were AU$385,561/QALY (RCT) and AU$705,729/QALY (RWE). At a AU$75,000/QALY willingness-to-pay (WTP) threshold, the probability of cost-effectiveness was < 1% in both scenarios. Differences in overall survival between trial and real-world cohorts likely contributed to the variation in ICERs. Conclusion: At current pricing and Australian WTP thresholds, pembrolizumab monotherapy is unlikely to be cost-effective, with RWE-informed scenarios yielding less favourable cost-effectiveness estimates than from trial data. These findings highlight that cost-effectiveness estimates may be sensitive to differences between trial-based and real-world effectiveness inputs.

Background: Romosozumab and denosumab are two highly effective, widely used osteoporosis treatments. There has been no study directly comparing the effectiveness of romosozumab and denosumab in a clinical setting using large-scale, real-world data. Objectives: To evaluate the association between romosozumab and cardiovascular outcomes compared to denosumab in patients with osteoporosis. Design: Retrospective propensity score-matched cohort study. Methods: Using the TriNetX global health research network, we identified 59,058 patients aged 60 years or older with osteoporosis who initiated romosozumab ( n = 5200) or denosumab ( n = 53,858) between January 2019 and December 2024. After 1:1 propensity score matching, 2 balanced cohorts of 5192 patients each were obtained. Cardiovascular outcomes, including three-point major adverse cardiac events (3P-MACE ), 4P-MACE, 5P-MACE, individual MACE components, and other cardiovascular diseases (CVDs), were assessed across three follow-up periods: short-term (1 year), mid-term (3 years), and long-term (5 years). Primary analyses were conducted among patients without a prior cardiovascular history, and sensitivity analyses were performed among those with a prior cardiovascular history. Results: Among patients without a prior cardiovascular history, romosozumab was associated with significantly lower risks of 3P-MACE at 3-year (hazard ratio (HR) 0.645, 95% confidence interval (CI) 0.438–0.950, p = 0.023) and 5-year follow-up (HR 0.755, 95% CI 0.512–0.873, p = 0.028), and lower mortality at 3-year (HR 0.554, 95% CI 0.316–0.972, p = 0.038) and 5-year follow-up (HR 0.533, 95% CI 0.312–0.913, p = 0.028). No significant differences were observed at 1-year follow-up. In contrast, among patients with a prior cardiovascular history, romosozumab was associated with significantly higher risks of 4P-MACE, 5P-MACE, stroke, mortality, and chronic ischemic heart disease across all three follow-up time horizons. Conclusion: Romosozumab was associated with lower risks of 3P-MACE and mortality compared to denosumab among patients without a prior cardiovascular history at mid-term and long-term follow-up. In contrast, romosozumab was associated with consistently higher cardiovascular risks in patients with preexisting CVD. These findings highlight the importance of careful cardiovascular risk assessment prior to initiating romosozumab, particularly in patients with preexisting CVD. The 3P-MACE finding in patients without prior cardiovascular history is the primary confirmatory result; all other outcomes should be considered exploratory and hypothesis-generating.

Immune checkpoint inhibitor (ICI)-based regimens are the standard first-line therapy for advanced renal cell carcinoma (RCC). However, their comparative effectiveness and safety in routine clinical practice remain incompletely characterised. The aim of this study was to systematically synthesise comparative real-world evidence on the efficacy and safety of ICI-based regimens in patients with advanced RCC. A systematic search of MEDLINE, Embase, and Scopus was conducted from database inception to 21 January 2026, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Observational cohort studies evaluating ICI-based regimens in advanced RCC with an active comparator were included. Primary efficacy outcomes were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). Safety outcomes included treatment-related adverse events. Study quality was assessed using the Newcastle-Ottawa Scale, with efficacy and safety evaluated separately. Owing to substantial clinical and methodological heterogeneity, findings were synthesised narratively. Overall, 58 retrospective cohort studies comprising 35,215 patients were included. Most studies evaluated first-line therapy and involved populations with mixed histology and heterogeneous prognostic risk profiles. Overall, ICI-tyrosine kinase inhibitor (TKI) combinations were generally associated with more favourable survival outcomes compared with dual ICI therapy or TKI monotherapy, with the most consistent benefit observed for PFS. Evidence comparing dual ICI therapy with TKI monotherapy was mixed, with most studies reporting no statistically significant differences in survival outcomes. Comparative safety data were limited, with the majority of studies relying on unadjusted descriptive analyses, limiting robust comparative interpretation of safety outcomes. Real-world evidence suggests that ICI-TKI combinations are associated with more favourable survival outcomes compared with other treatment options in advanced RCC, while the comparative effectiveness of dual ICI therapy versus TKI monotherapy remains inconclusive. Substantial heterogeneity and methodological limitations, particularly in safety reporting, limit definitive interpretation. High-quality real-world studies incorporating robust confounding adjustment and clinically relevant subgroup analyses are needed to better inform treatment selection in routine practice. International Prospective Register of Systematic Reviews (PROSPERO) registration number: CRD420251149614.

Biologic therapies are a major and growing driver of pharmaceutical expenditure globally, with tumor necrosis factor (TNF) inhibitors among the most widely used and costly biologics. In Australia, these therapies are funded through the Pharmaceutical Benefits Scheme (PBS), where biosimilars offer lower cost alternatives; however, the long‐term public expenditure impact of TNF inhibitor biosimilars under regulated pricing systems has not been comprehensively quantified. We conducted a retrospective, population‐level expenditure analysis using publicly available PBS Item Reports data from 2015 to 2025 to estimate PBS cost savings associated with the listing of adalimumab, etanercept, and infliximab biosimilars for inflammatory arthritis. Counterfactual scenarios were constructed to estimate expected expenditure in the absence of biosimilar entry, explicitly accounting for key PBS pricing mechanisms, including mandatory price reductions and price‐disclosure cycles. Biosimilar listing was associated with cumulative PBS savings of AU$562.3 million over the study period. Etanercept biosimilar generated the largest absolute savings (AU$341.5 million; 23.7% reduction), whereas adalimumab biosimilars generated smaller relative savings (AU$195.3 million; 9.4% reduction), reflecting delayed biosimilar entry despite high utilization. Most savings accrued in rheumatoid arthritis, followed by ankylosing spondylitis and psoriatic arthritis. In conclusion, TNF inhibitor biosimilars were associated with substantial and sustained reductions in public medicine expenditure in Australia. The magnitude of savings varied markedly by molecule and was jointly determined by the timing of biosimilar entry and statutory pricing mechanisms, illustrating how regulated reimbursement systems shape realized biosimilar value.

Purpose of Review: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy, producing durable responses across multiple malignancies. However, treatment outcomes may be influenced by immunological drug–drug interactions (DDIs) arising from commonly prescribed concomitant medications. Unlike classical pharmacokinetic or pharmacodynamic DDIs, these interactions operate through systemic mechanisms that modulate anti-tumour immunity, including alterations to the gut microbiome, immune signalling pathways, and the tumour microenvironment. This review proposes a conceptual framework for "immunological DDIs" (iDDIs), extending beyond metabolic interactions toward a system-level understanding of immune regulation. Recent Findings: We synthesise current evidence on commonly used medication classes—organised by their primary immunological mechanisms: (1) gut microbiome-mediated effects, (2) systemic immunosuppression, and (3) tumour microenvironment modulation—and their impact on ICI efficacy and safety. Meta-analyses suggest that certain medications, particularly antibiotics and proton pump inhibitors, are associated with poorer clinical outcomes, although confounding by indication and disease severity remain important limitations. Artificial intelligence (AI) is an emerging approach to detect and characterise complex DDIs using large-scale clinical and real-world data. Natural language processing, machine learning models, and large language models show potential for extracting medication exposure, predicting adverse events, and supporting clinical decision-making. Summary: Most AI applications remain at an early stage, with limited external validation and uncertain clinical utility. Future research should integrate mechanistic biology, prospective clinical studies, and explainable AI approaches to improve identification of iDDIs and optimise the safe and effective use of ICIs in oncology.

Background: Risperidone is widely used in people with dementia and has an approved indication for behaviours and psychological symptoms of dementia (BPSD) in some countries. However, its clinical use is challenging, as treatment effects are modest and heterogeneous, while risks remain substantial. We aimed to develop and evaluate clinical prediction models to estimate individual response to risperidone for BPSD.Methods: Individual participant data from four randomised trials of risperidone use in dementia were harmonised. Three trials (N=1,327) were used for model development and one (N=337) for external validation. Symptom improvement was assessed using the Behavioural Pathology in Alzheimer’s Disease (BEHAVE-AD) scale. Potential risperidone-associated adverse drug events (ADEs) included major cardiovascular events, extrapyramidal symptoms, and somnolence. Outcomes included improvement in BEHAVE-AD score (overall, psychosis, aggression) and composite benefit–risk categories (low ADE risk–high therapeutic benefit and high ADE risk–low therapeutic benefit). Predictors included risperidone use, demographic factors and clinical characteristics. Conditional inference forest, random forest, and XGBoost models were trained and evaluated in internal–external cross-validation and external validation. Individualised treatment effect (ITE) was assessed using the concordance-statistic for benefit.Outcomes: In the external dataset, our models can predict overall BPSD (c-statistic: 0·76; 95% CI: 0·70 to 0·83) and psychosis (c-statistic: 0·81; 95% CI: 0·75 to 0·87) improvement at week 8. Models distinguished patients benefiting from risperidone for overall BPSD (c-for-benefit: 0·74; 95%CI: 0·66 to 0·82) and psychosis (c-for-benefit: 0·71; 95%CI: 0·60 to 0·80) outcomes. They can identify those with low ADE risk-high therapeutic benefit for psychosis outcomes (c-statistic: 0·76; 95% CI: 0·69 to 0·83). Performance for aggression-related outcomes was limited.Interpretation: Clinical prediction models can predict the ITE of risperidone for overall BPSD and psychosis. This approach could support personalised treatment decisions in BPSD, although further real-world validation is required before clinical implementation.

Biomarker testing plays a critical role in precision oncology by guiding targeted therapy selection. In Australia, public reimbursement for somatic tumor biomarker tests has expanded over the past decade, yet national data on utilization patterns, equity of access, and public expenditure remain limited. We identified all cancer biomarker tests listed in the March 2025 Medicare Benefits Schedule (MBS), defined as tumor‐based assays and selected germline tests used to guide systemic cancer therapy. National claims and expenditure (2010–2024) were extracted from publicly available Medicare Item Statistics. Trends were analyzed by test type, sex, age group, and jurisdiction, and standardized to the 2020 cancer incidence as a proxy for population‐level testing coverage. We identified 21 reimbursed cancer biomarker test items, of which 19 had claims during the study period. Between 2010 and 2024, annual claims increased nearly fivefold, from 5130 to 25,374, representing 6% of all MBS‐funded genetic test volume and 10% of total expenditure. Median reimbursement per test rose from AU$339 in 2014 to AU$667 in 2024, reflecting increased use of multigene panel tests. Uptake tripled among adults aged 75–84 years, while remaining below 3% among individuals under 35 years. Women accounted for 67% of claims in 2024, down from 88% in 2014. Geographic disparities were marked, with test uptake highest in New South Wales (23.8% of incident cancers) and lowest in the Northern Territory (8.7%). Although national funding for cancer biomarker testing has increased, utilization in Australia remains uneven across demographic and geographic lines. These findings highlight the need to ensure equitable access to genomic diagnostics as part of routine cancer care.