OBJECTIVE: Given the persistent absence of direct head-to-head trials, this study aimed to evaluate the comparative efficacy, safety, and cost-effectiveness of rasagiline versus selegiline as early-stage monotherapy for Parkinson's disease (PD), informing clinical selection and healthcare policies in China. METHODS: A systematic search of PubMed, Embase, and the Cochrane Library identified randomized controlled trials (RCTs) up to April 2026. Focusing on short-term outcomes (10-16 weeks), an adjusted indirect treatment comparison (ITC) using placebo as a common anchor evaluated symptom improvement (UPDRS total scores) and adverse event (AE) incidence. For economic evaluation, a 2-year Markov model was constructed from a Chinese healthcare-system perspective. The incremental cost-effectiveness ratio (ICER) was calculated alongside robust sensitivity analyses. RESULTS: Ten RCTs (rasagiline: 6; selegiline: 4) were included. The ITC revealed no statistically significant differences between rasagiline and selegiline in short-term symptomatic relief (Mean Difference = -0.82, 95% CI [-2.08, 0.44], p = 0.203) or AE risk (Odds Ratio = 0.83, 95% CI [0.50, 1.38], p = 0.475). The overall evidence certainty was rated as moderate. Economically, the base-case simulation indicated rasagiline yielded a marginal benefit of 0.0088 QALYs over selegiline but incurred an additional 17,111.10 Yuan. This resulted in an ICER of 1,951,505.55 Yuan/QALY, substantially exceeding the conventional willingness-to-pay threshold. CONCLUSION: Supported by moderate-certainty evidence, rasagiline and selegiline provide comparable short-term efficacy and safety for early-stage PD monotherapy. However, at its current pricing, rasagiline is not cost-effective. Significant price reductions or definitive proof of long-term superiority are required to justify its economic value.
Pharmacoepidemiology and drug safetyPierre Marquet, Antoine Humeau, Sabrina Crépin, Clément Benoist, Sylvain Couderc, Caroline Monchaud, Marc Labriffe, Franck Saint-Marcoux
OBJECTIVES: The pharmaco-epidemiological research program in kidney transplantation (PERP-KT) aims to evaluate, for the principal maintenance immunosuppressive drugs (MISDs): the influence of model-informed precision dosing on graft and patient survival; long-term exposure-effects relationships; and the benefit-harm balance of their combinations and time sequences in patient groups or clinical settings not adequately evaluated in comparative randomized clinical trials. It also aims to develop a hybrid, dynamic, deep learning model capable of predicting the rate of renal graft function decline, thereby providing a platform for individualized prediction of the benefits and risks associated with MISDs. PATIENTS AND METHODS: After obtaining all regulatory andd ethical approvals, de-identified extracts of three national databases were linked to create the nationwide PERP-KT dataset, which is hosted within the highly secure environment of the French Health Data Hub. RESULTS: CRISTAL (the exhaustive registry of the French Agence de la Biomédecine) comprises data from 49 886 kidney donors and the corresponding 47 842 transplant recipients between 2005 and 2020. Following iterative deterministic matching and extensive quality control procedures, CRISTAL data were successfully linked to: the French national Health Data System (SNDS), which records reimbursed healthcare utilization, for 30 782 kidney transplant recipients; and to ISBA, a web-based platform for Bayesian dose adjustment of MISDs that contains pharmacological data, for 17 700 kidney grafts and 17 576 recipients. PERSPECTIVES: More than 20 pharmaco-epidemiological studies will leverage the database's extensive follow-up, large population size and richness of clinical, healtcare-utilization, and pharmacological data.
The Indian journal of medical researchBrijeshkumar Sojitra, Chetna Patel, Krishnakant Niranjanbhai Bhatt, Sajal Pandya, Paras Shah, Akash Shah, Jaykumar Patel, Chirag Adwani, Vaibhav Panchal
Background and objectives Dolutegravir (DTG)-based first line antiretroviral therapy (ART) is preferred globally due to its high efficacy, and tolerability. In India, data on evaluation of its pharmacoeconomic impact with effectiveness and safety remains limited. This study aimed to assess the pharmacoeconomic variables, effectiveness, and safety of the dolutegravir based first line ART regimen among people living with HIV (PLHIV) in south Gujarat. Methods This prospective, and observational study was conducted at an ART centre in a tertiary care hospital. Adults (≥18 yr) receiving first-line ART for ≥6 months were enrolled (n=204) following the informed consent. Pharmacoeconomic outcomes were evaluated using analysis of cost-effectiveness, cost minimisation, cost-utility, and cost-benefit. For effectiveness, CD4 count and plasma viral load (PVL) were recorded at baseline and 6 months. The safety was assessed using causality, severity, and preventability assessment of adverse drug reactions. Results Among 204 participants, 102 received TLD (tenofovir/lamivudine/dolutegravir) and 102 TLE (tenofovir/lamivudine/efavirenz). The TLD regimen demonstrated significantly better cost effectiveness (median CER 45.7 vs. 84.7; P<0.001) and lower mean annual treatment cost [INR (₹)17,074 vs. ₹19,283; P<0.001]. Quality-adjusted life years (QALY) and disability-adjusted life years (DALY) values were comparable between regimens. Both groups showed significant CD4 improvement over 6 months; inter-regimen differences were non-significant (P=0.386). Viral suppression at 6 months was higher with TLD (99% vs. 92.2%; P=0.019). Fourteen ADRs were reported for TLD group. Interpretation and conclusions Dolutegrevir-based regime demonstrated better cost effectiveness, lower annual cost, and more consistent viral load suppression, with comparable immunological recovery and a favourable safety profile, as compared to standard ART regime.
Pathogens (Basel, Switzerland)Andrea Marino, Emmanuele Venanzi Rullo, Giuseppe Pipitone, Alessandro Giorgio Geremia, Andrea De Vito, Antonio Albanese, Nicholas Geremia, Alessandro Franzò, F…
BACKGROUND: Long-acting lipoglycopeptides (LALs), including dalbavancin and oritavancin, may facilitate outpatient-oriented management of Gram-positive infections by reducing the need for prolonged hospitalization and daily intravenous therapy. However, real-world evidence on their use in day hospital pathways, particularly for complex off-label infections, remains limited. This study evaluated the clinical effectiveness, safety, and economic impact of LAL-based day hospital management, comparing in-label acute bacterial skin and skin-structure infections (ABSSSI) with complex off-label indications. METHODS: This retrospective, multicenter observational study included 160 adult patients treated with dalbavancin and/or oritavancin in a day hospital setting across nine Italian centers between January 2020 and December 2025. Indications were classified as in-label ABSSSI or off-label infections, including osteomyelitis, prosthetic joint infection, spondylodiscitis, endocarditis, septic arthritis, and prosthetic cardiac infection. The primary endpoint was clinical success at final follow-up. Secondary endpoints included adverse drug events, readmissions, inflammatory marker response, and a budget impact cost-offset analysis based on avoided inpatient bed-days. RESULTS: Overall, 54.4% of patients received LALs for off-label indications, mainly osteomyelitis, prosthetic joint infection, and spondylodiscitis. Clinical outcome was available for 159 patients, with an overall success rate of 86.8% (138/159). Success rates were 90.4% for in-label ABSSSI and 83.7% for off-label indications, with no statistically significant difference between groups (p = 0.247). In exploratory analyses, monotherapy was associated with lower failure odds; this most likely reflects confounding by indication and should not be interpreted as a treatment effect. Inflammatory markers significantly decreased from baseline to end of therapy. Adverse drug events were uncommon (3.3%), mild, and did not lead to treatment discontinuation. In a scenario-based cost-offset model (no matched inpatient comparator), the strategy corresponded to 1107-2214 avoided inpatient bed-days; estimated net savings ranged from approximate cost-neutrality under conservative assumptions (€11,976) to €676,176 under maximum assumptions, and one-way sensitivity analysis showed a possible net loss at low inpatient daily-cost values-underscoring that these are modeled rather than observed savings. CONCLUSIONS: In this uncontrolled, retrospective cohort, LAL-based day hospital management was feasible and associated with favorable observed clinical outcomes, an acceptable safety profile, and a potential for cost offset in selected patients with Gram-positive infections, including complex off-label indications. Because no matched inpatient or conventional OPAT comparator was included, these findings should be regarded as hypothesis-generating and cannot establish comparative efficacy, superiority, or actual cost savings.
BACKGROUND: Osimertinib has reshaped the treatment of EGFR-mutated non-small cell lung cancer (NSCLC), but its high cost raises persistent questions about value for money. OBJECTIVES: To review economic evaluations of osimertinib in EGFR-mutated NSCLC and identify the drivers of cost-effectiveness across first-line, second-line/sequential, and adjuvant settings in North America and Europe. METHODS: This review was registered with PROSPERO (CRD420251139947) and conducted in accordance with PRISMA 2020. We searched PubMed/MEDLINE, Embase, Web of Science Core Collection, and the Cochrane Library through August 2025 for peer-reviewed economic evaluations comparing osimertinib with chemotherapy or earlier-generation EGFR tyrosine kinase inhibitors from a payer perspective. Reporting quality was appraised with CHEERS 2022. Given heterogeneity in models, pricing, and survival extrapolation, results were synthesized narratively, each incremental cost-effectiveness ratio (ICER) interpreted against its own jurisdiction's willingness-to-pay (WTP) threshold. RESULTS: Nine studies published between 2018 and 2024 were included. First-line osimertinib improved outcomes but at ICERs of $151,922-$231,123/QALY (US) and €128,343-€273,895/QALY (Europe), exceeding local thresholds. Second-line T790M-positive estimates were favorable and context-dependent ($159,126/QALY US; £41,705/QALY UK under end-of-life criteria). Adjuvant results were most divergent: cost-effective under cure-fraction assumptions but unfavorable when benefit was modeled as delayed recurrence. Price, overall-survival (OS) extrapolation, sequencing, and local WTP thresholds were dominant. CONCLUSIONS: Osimertinib confers meaningful clinical benefit, but its value for money is context-specific and often uncertain at current list prices. These conclusions rest on few heterogeneous models and warrant caution; sustainable use will depend on price reductions, patient prioritization, maturation of OS data, and outcome-based reimbursement.
American journal of therapeuticsOana-Monica Leah, Florin G Leaşu, Mihaela Badea, Mihaela Constantinescu, Mihai Vârciu, Liliana M Rogozea
BACKGROUND: Cardiovascular disease remains the leading cause of global mortality (19.8 million deaths in 2022; 32% of all deaths worldwide). Drug repurposing-extending approved agents beyond their original indications-has emerged as a high-impact strategy in cardiovascular prevention, offering reduced development timelines, established safety profiles, and faster implementation than de novo molecular development. STUDY QUESTION: Which repurposed cardiovascular agents demonstrate the most favorable pharmacoeconomic profiles, and how does the convergence of clinical benefit, patient risk stratification, and economic sustainability define the optimal hierarchy for cardiovascular prevention? STUDY DESIGN: Narrative review synthesizing evidence from 19 pivotal cardiovascular outcomes trials and European and American guidelines. No formal meta-analysis was applied. MEASURES AND OUTCOMES: For 13 agents across 8 therapeutic classes, efficacy was quantified as relative and absolute risk reductions, and as the number needed to treat or to harm. Pharmacoeconomic value was assessed via incremental cost-effectiveness ratio in US dollars per quality-adjusted life year, integrating mortality in years of life lost and morbidity in years lived with disability. Primary outcomes included all-cause mortality, cardiovascular mortality, major adverse cardiovascular events, and heart failure hospitalizations. RESULTS: Three Incremental Cost-Effectiveness Ratio (ICER) tiers were identified: Low-cost (< $20,000/ Quality-Adjusted Life Year (QALY)): ramipril (Number Needed to Treat (NNT) 28), carvedilol (NNT 29), metformin ( NNT 9-15, highest Relative Risk Reduction (RRR) 38-42%), and generic statins - robust mortality benefits at negligible cost; Moderate-cost ($3,000-$50,000/QALY): empagliflozin (↓38% cardiovascular mortality, NNT 61), dapagliflozin (NNT 20 in Heart Failure with Reduced Ejection Fraction), liraglutide (NNT 51), semaglutide (NNT 43), colchicine (NNT 36, morbidity benefit only), and branded statins; High-cost ($80,000-$300,000/QALY): Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) inhibitors (evolocumab NNT 63; alirocumab NNT 64) - proven benefit compromised by unaffordable biologic pricing. CONCLUSIONS: Pharmacoeconomic stratification of repurposed cardiovascular agents identifies 3 distinct tiers. Generic agents-ramipril, carvedilol, metformin, and statins-demonstrate the most favorable cost-effectiveness profiles and should form the basis of any prevention protocol. SGLT2 inhibitors and GLP-1 receptor agonists offer clinically meaningful benefits in secondary prevention when applied to populations meeting pivotal trial eligibility criteria. PCSK9 inhibitors remain cost-effective only in patients with very high cardiovascular risk and inadequate LDL control on maximally tolerated statin therapy.
Expert review of pharmacoeconomics & outcomes researchMarta Trapero-Bertran
INTRODUCTION: Economic evaluation (EE) is a key input for pharmaceutical pricing and reimbursement (P&R), yet countries differ in how EE is specified, interpreted and integrated into decisions. Spain is a timely case: despite long-standing legal recognition of efficiency, EE has historically been weakly operationalized and difficult to trace in P&R. AREAS COVERED: This narrative review analyses Spain's reform trajectory through the lenses of specification, interpretation and integration, focusing on the work of the Advisory Committee for Pharmaceutical Financing (CAPF) (2019-2024). Evidence was identified through searches in PubMed, Scopus, Web of Science and Google Scholar (2000-2025), complemented by Spanish and EU legislative and policy documents. The review synthesizes CAPF recommendations to reorganize the evaluation pathway, including structured model linking clinical assessment, EE and budget impact analysis, and publication of national guideline and reference case. It also examines how these initiatives interact with draft national reforms and the EU HTA Regulation, highlighting a hybrid transitional context (late 2025) in which Joint Clinical Assessments are progressively incorporated while national procedural reform remains incomplete. EXPERT OPINION: Spain illustrates how EE standardization can strengthen deliberative, multi-criteria P&R by improving transparency and coherence, although impact depends on regulatory enactment, capacity and implementation.
The journal of headache and painSimona Guerzoni, Lanfranco Pellesi, Lisa Giannessi, Flavia Lo Castro, Maria Chiara Olivieri, Luca Degli Esposti, Francesca Gandolfi
BACKGROUND: Migraine is a leading cause of disability worldwide, impairing quality of life and productivity. Preventive therapies aim to reduce attack frequency, severity and the need for acute medications. Oral atogepant (60 mg), a calcitonin gene-related peptide (CGRP) receptor antagonist, has recently expanded migraine prevention options. This study evaluated changes in triptan use after atogepant initiation using real-world data. METHODS: This retrospective observational study used administrative healthcare databases from the Local Health Unit of Modena (Italy). Adults with chronic or high-frequency episodic migraine initiating atogepant between November 2023 and December 2024 were identified. Triptan use and related costs were assessed in the 6 months before and after treatment initiation (index date), measured as dispensed dosage units. RESULTS: Among 95 patients (86% female; mean age 53.5 years), 55 triptan users were included in the analysis. Triptan use decreased in 45 patients (82%), with ≥ 60% reduction in 27 (49%) and complete discontinuation in 10. Median consumption decreased from 76 to 24 dosage units, and mean consumption from 88.1 to 45.2. This reduction was statistically significant (Wilcoxon signed-rank test, p < 0.001). This reduction corresponded to a decrease of €2,591 in triptan-related pharmaceutical expenditure within the study cohort. CONCLUSION: Atogepant preventive treatment may substantially reduce acute migraine medication use in real-world practice, with potential clinical and economic benefits.
Frontiers in public healthYang Li, Yang Zou, Canhua Liang, Ziwei Feng, Shaohuan Lu, GuangZhao Wang, Guangyi Meng
OBJECTIVE: To evaluate the cost-effectiveness of first-line tislelizumab plus chemotherapy for extensive-stage small cell lung cancer (ES-SCLC) within the Chinese healthcare context. Furthermore, this study aims to comparatively validate the impact of traditional survival models vs. advanced machine learning models on the robustness of research findings, thereby providing refined empirical evidence for healthcare decision-making. METHODS: Based on data from the Phase III RATIONALE-312 clinical trial, a partitioned survival model (PSM) was constructed with a 10-year time horizon. From the perspective of the Chinese healthcare system, only direct medical costs were included. A willingness-to-pay (WTP) threshold was set at three times the 2025 per capita GDP of China (298,995 CNY/QALY). A dual-validation strategy was employed for survival extrapolation: a base-case analysis using the optimal parametric model (Log-logistic distribution) selected via Akaike Information Criterion/Bayesian Information Criterion (AIC/BIC) criteria, followed by a comparative validation using DeepSurv deep learning and random survival forest (RSF) models utilizing a simplified feature set. Uncertainty was assessed through one-way sensitivity analysis and probabilistic sensitivity analysis (PSA) using 1,000 Monte Carlo simulations. RESULTS: The base-case analysis (Log-logistic model) revealed that, compared with chemotherapy alone, the tislelizumab group yielded an incremental cost of 101,506.9 CNY and incremental quality-adjusted life years (QALYs) of 0.4044, resulting in an incremental cost-effectiveness ratio (ICER) of 251,030.5 CNY/QALY, which remains below the WTP threshold. Machine learning validation demonstrated exceptional consistency, with ICERs of 261,718.45 CNY/QALY for the DeepSurv model and 248,299.41 CNY/QALY for the RSF model. Sensitivity analysis identified the utility of progression-free survival (PFS) and the unit price of tislelizumab as the primary drivers of the model. PSA confirmed that the probability of tislelizumab being cost-effective exceeded 85% across all three survival-fitting logics, reaching a maximum of 94.90%. CONCLUSION: First-line tislelizumab plus chemotherapy demonstrates a significant cost-effectiveness advantage for ES-SCLC in China. The integration of machine learning survival models effectively reduced the inherent uncertainties of non-linear extrapolation in immunotherapy data, confirming the robustness of the conclusions. These findings provide a solid empirical basis for national health insurance negotiations and precision clinical applications.