To evaluate the cost-effectiveness of anti-vascular endothelial growth factor (VEGF) treatments for neovascular age-related macular degeneration (nAMD) using a value-based model that considers drug durability, dosing regimens and real-world administration strategies, including safe vial fractionation.

Model-based pharmacoeconomic analysis using data from randomised clinical trials and network meta-analyses. Analysis conducted from the payer perspective using cost data from the Spanish National Health System.

A model-based analysis compared five anti-VEGF agents—innovator and biosimilar ranibizumab, aflibercept 2 mg, brolucizumab and faricimab—across three dosing regimens: fixed, Pro Re Nata and Treat-and-Extend (TAE). Administration formats included single-use vials, prefilled syringes and vial fractionation (VF), with or without dead-space-free (DSF) syringes to minimise waste. The primary outcome was cost per optimal responder, defined as a patient gaining ≥15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters, with and without adverse events. Cost-effectiveness was evaluated using Number Needed to Treat (NNT), Net Efficacy Adjusted for Risk-NNT (adjusted for safety) and incremental cost-effectiveness ratios. Secondary outcomes included the number of treated patients and optimal responders achievable within a fixed 1 000 000 budget.

The most cost-effective strategy was aflibercept 2 mg under a TAE regimen using DSF VF, with a total cost of 6214 per patient and a cost per optimal responder of 27 155. Under a fixed budget of 1 000 000, this approach allowed treatment of 160 patients, yielding 36 optimal responders. Faricimab with DSF VF ranked second, with a total cost of 5847 and a cost per optimal responder of 28 652, treating 171 patients and achieving 34 responders. In contrast, single-use vials without VF led to substantially higher total costs (eg, 11 305 for aflibercept TAE) and lower treatment capacity (eg, 88 patients treated).

This model demonstrates that combining durable agents, extended dosing intervals and optimised delivery strategies (eg, prefilled syringes and DSF VF) can substantially improve the cost-effectiveness and sustainability of anti-VEGF therapy in public health systems.

There is evidence that talking about the end of life with patients facing a life-threatening disease is not upsetting, and in fact, it may even be beneficial. However, both patients and health professionals can find it difficult to engage in these conversations. The aim of this clinical trial is to explore whether proactively inviting people with advanced cancer to share their thoughts about death and dying is distressing for them, comparing the impact with usual clinical practice (ie, a reactive approach to these issues).

A stepped-wedge cluster randomised controlled trial involving six palliative care units in Spain will be conducted. Each unit will recruit participants for both the experimental and control groups. Units will be randomised to determine the order in which they will begin implementing the intervention: GO-TaD (Give the Opportunity to Talk about Death thoughts). The trial will involve six sequences and seven periods (steps), with four patients per period (patients in each period will be different). The primary outcome will be emotional distress, assessed with the Detecting Emotional Distress scale. The following secondary variables will also be analysed: hopelessness, using the Beck Hopelessness Scale; quality of the patient–professional relationship, with the Patient–Doctor Relationship Questionnaire (PDRQ-9); and quality of life, with the Palliative Outcome Scale . The trial will follow the CONSORT extension for stepped-wedge cluster randomised designs. The primary analysis will include all eligible patients, applying mixed-effects regression models for binary results and mixed linear models for continuous data. Results will be reported as risk differences and ORs, with 95% confidence intervals. Analyses by sub-groups of interest (eg, age, gender, type of palliative care unit) will also be conducted. All analyses will be performed using R.

Ethical approval has been obtained from the researchers' university and all participating centres. Results will be disseminated through peer-reviewed open access publications, academic conferences and presentations to clinical audiences.

NCT06420609.

A synthesis and appraisal of the recommendations for biomarkers in practice guidelines concerning sepsis is required to consolidate evidence-based practice. We generated an evidence gap map (EGM) on the use of biomarkers for managing adults with sepsis.

Scoping review.

MEDLINE, Guidelines International Network, Pan American Health Organization, Trip Database and UpToDate were searched from 2016 to March 2025.

Guidance documents (GD) that searched at least one literature source and provided clinical recommendations for the use of biomarkers for the management (diagnosis and prognosis, including treatment response) of adults with sepsis.

Two reviewers independently applied the eligibility criteria and extracted data. We used the AGREE-II (Appraisal of Guidelines for Research and Evaluation) tool to assess the GD quality. GDs that scored ≥50% on the AGREE-II 'Rigour of development' domain were considered robust. We also applied the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system to evaluate if the recommendations were strong or conditional.

We found 10 GDs, with only half (4/8) having a robust methodology. There were 31 recommendations concerning biomarkers. Among these, 24 (77.4%) recommendations were about single biomarkers, with lactate (23; 74.2%) and procalcitonin (8; 25.8%) most frequently recommended. Biomarker testing focused on prognosis in 28 (90.3%) recommendations. Overall, 16 (51.6%) recommendations were graded strong and 13 (42.0%) were conditional, which we displayed in an EGM.

The methodology of GDs concerning adult sepsis was poor. Our review calls for more prudent use of biomarkers in specific prognostic scenarios and in combination with standard clinical assessments. Enhancing the methodological quality of future GDs is essential to generate more valid and robust recommendations for optimising patient care.