BACKGROUND:The evaluation of innovative oncology medicines presents significant challenges related to the selection of appropriate clinical endpoints and the sufficiency of evidence, particularly in therapeutic areas, such as immunotherapies, targeted treatments, single-arm trials, and tumor-agnostic therapies. In these contexts, the added value of new treatments is often not adequately captured by traditional clinical trial endpoints, such as overall survival (OS), which remains the gold standard in oncology assessment. This article aims to analyze the main sources of uncertainty in the value assessment of oncology therapies in Spain, with a focus on the limitations of current endpoints and evidence-generation processes, and to provide recommendations for enhancing the recognition and assessment of additional clinical benefit. METHODS:A multidisciplinary expert panel composed of twelve professionals, including medical oncologists, hospital pharmacists, health economists, and patient representatives, was convened to identify and discuss key sources of uncertainty in the value assessment of oncology treatments, particularly those related to clinical endpoint selection and evidence generation. The panel participated in three structured plenary sessions. Additional external experts were engaged to provide complementary input in areas, such as tumor-specific characteristics and statistical methodology. Consensus statements were developed through an iterative process of discussion, critical appraisal, and refinement across and between sessions. RESULTS:The expert panel issued twelve recommendations to improve value assessment in oncology. These include tailoring clinical endpoints to treatment type, tumor characteristics, and stage; complementing overall survival with milestone analysis and quality-of-life measures; and standardizing real-world evidence collection across the healthcare system. The panel advocated for a national portfolio of prioritized endpoints, appropriate statistical methods by context, and the conditional use of early-phase data for decision-making. Additional recommendations addressed the use of synthetic control arms, flexible reimbursement models, advanced analytics (e.g., AI and Big Data), evaluator expertise, and the promotion of stakeholder training and transparency. CONCLUSIONS:Addressing the challenges of clinical endpoint selection and evidence generation is essential to reduce uncertainty in the value assessment of innovative oncology treatments. The twelve expert recommendations outlined in this study provide a structured roadmap to improve methodological consistency, enhance the relevance and robustness of clinical and real-world data, and promote a more adaptive and transparent evaluation framework. These proposals aim to support more evidence-based, equitable, and sustainable decision-making within the Spanish healthcare system, while aligning with broader European initiatives in oncology drug assessment.
Hyperprolactinemia is classically linked to reproductive dysfunction, but emerging evidence suggests an association with metabolic and cardiovascular (CV) risk. This study evaluated sex differences in CV risk factors (CVRFs) and cardiovascular disease (CVD) in patients with hyperprolactinemia. A multicenter, retrospective cross-sectional study was conducted in 449 adult patients (199 men, 250 women) with confirmed hyperprolactinemia from 19 tertiary referral centers in Spain. Clinical, biochemical, and hormonal data were collected and analyzed. The prevalence of CVRFs and CVD was compared between sexes. Associations between serum prolactin levels and CVRFs/CVD were assessed using nonparametric tests, correlation analyses, and multivariable logistic regression. Men had significantly higher serum prolactin levels than women (median 796 [IQR 250–1499] vs. 114 [74.5–224] ng/mL; p < 0.001) and a greater crude prevalence of all major CVRFs (p < 0.001 for all). After adjustment for age, male sex remained independently associated with smoking (OR 2.16; p = 0.007) and hyperlipidemia (OR 1.97; p = 0.031). Serum prolactin levels positively correlated with age, BMI, systolic blood pressure, glucose, total cholesterol, and triglycerides (all p < 0.001). In sex-stratified analyses, prolactin was associated with BMI and lipid profile in men, and with hypertension and hyperlipidemia in women. Prolactin levels were significantly elevated in patients with any form of CVD (p = 0.007), particularly arrhythmias (p = 0.013), while a trend was noted for ischemic heart disease (p = 0.050). Men with hyperprolactinemia exhibit a more adverse cardiometabolic profile, characterized by higher serum prolactin levels and a greater burden of classical CVRFs and CVD. Prolactin concentrations are positively associated with multiple metabolic and CV parameters, with sex-specific patterns suggesting distinct mechanisms of susceptibility and regulation. These findings underscore the importance of incorporating sex and hormonal context into CV risk assessment in patients with hyperprolactinemia.
Background:Frailty assessment has emerged as a key component of pre-transplant evaluation. We aimed to validate, across international cohorts, the Hematopoietic Cell Transplantation Frailty Scale (HCT-FS) for the assessment of frailty in adult candidates for allogenic hematopoietic cell transplantation (allo-HCT). HCT-FS is designed for integration into routine workflows using existing resources. Methods:In this prospective, observational cohort study, we evaluated the performance of HCT-FS, a frailty scale that categorises patients as fit, pre-frail, or frail based on a cumulative weighted score derived from eight variables. We enrolled participants across 16 allo-HCT programmes (one in Canada, 15 in Spain). Eligible participants were all adult patients evaluated for frailty at the centres during the time frames: from the Hans Messner Allo-HCT Program at Princess Margaret Cancer Center (PMCC) in Toronto, Canada (2018-2024; where HCT-FS was developed) and from 15 Grupo Español de Trasplante Hematopoyético y Terapia Celular (GETH-TC) centres across Spain (2022-2023). Frailty was systematically assessed in all candidates for a median of 10 min at the first allo-HCT consultation by haematologists or trained nurses using the HCT-FS. The prognostic accuracy of the HCT-FS was assessed by evaluating its ability to discriminate clinical outcomes across frailty categories in the overall cohort and by testing the consistency of these associations within specific patient subgroups. Data were prospectively updated until February 2025. Findings:Overall, 1077 consecutive adult allo-HCT candidates were enrolled and evaluated across the PMCC (n = 734) and GETH-TC (n = 343) cohorts. The median age was 56 years (range 18-76); 411 patients (38.2%) were over 60, and 640 (59.4%) were male. Based on the HCT-FS, 33.4% patients were fit, 53.7% pre-frail, and 12.8% frail. Frailty was associated with longer hospital stays (23, 25, and 28 days for fit, pre-frail, and frail patients, respectively; p = 0.003) and higher ICU admission rates (Day +180: 7.0%, 10.8%, and 20.3% for fit, pre-frail, and frail patients, respectively; p = 0.002). 2-year OS decreased progressively with increasing frailty: 77.2% for fit, 65.7% for pre-frail, and 52.8% for frail (p < 0.001). Corresponding NRM rates were 11.7%, 19.5%, and 32.2%, respectively (p = 0.001). Multivariable analysis confirmed frailty as a predictor of inferior OS and increased NRM, when adjusting for age, comorbidities, performance status, DRI, and donor type. The HCT-FS maintained robust prognostic accuracy across subgroups stratified by age and comorbidity burden. Interpretation:The HCT-FS provided reliable measures of the frailty status of allo-HCT candidates that are informative for transplant outcomes, supporting its potential applicability in clinical practice. Notably, this tool was successfully integrated into clinical practice without additional resources. Future work is needed to further evaluate the applicability of the scale in transplant settings and whether targeted interventions based on can improve transplant outcomes. Funding:None.
OBJECTIVES:To evaluate the efficacy of intraoperative hemoadsorption (HA) during cardiopulmonary bypass (CPB) in reducing acute kidney injury (AKI) and other major postoperative complications in patients undergoing cardiac surgery. DESIGN:Systematic review and meta-analysis of randomized controlled trials (RCTs) conducted in accordance with PRISMA guidelines, with a protocol registered in PROSPERO (CRD42025638656). SETTING:Multicountry, multi-institutional hospital-based studies of patients undergoing cardiac surgery with CPB. PARTICIPANTS:A total of 1133 patients from 16 RCTs comparing CPB with versus without intraoperative HA. INTERVENTIONS:Intraoperative HA using sorbent-based devices (e.g., CytoSorb, oXiris, Jafron HA 380). MEASUREMENTS AND MAIN RESULT:Primary outcomes included AKI incidence, renal replacement therapy requirement, and mortality. Secondary outcomes included intensive care unit/hospital length of stay, postoperative delirium, stroke, sepsis, and reoperation. HA significantly reduced the incidence (RR 0.75; 95% CI 0.59-0.96; p = 0.020). No significant differences were observed for renal replacement therapy (RR 0.64; p = 0.58) or mortality (RR 0.96; p = 0.861). No significant effects were found for secondary outcomes. CONCLUSIONS:Intraoperative HA during CPB reduces the risk of AKI but does not significantly affect other major postoperative outcomes. Further studies are needed to determine its clinical relevance and optimal patient selection.
The increasing reliance on Deep Learning models, combined with their inherent lack of transparency, has spurred the development of a novel field of study known as eXplainable AI (XAI) methods. These methods aim to enhance end-users' trust in automated systems by providing insights into the rationale behind their decisions. This paper presents a novel trust measure in XAI systems, allowing their refinement. Our proposed metric combines both performance metrics and trust indicators from an objective perspective. To validate this novel methodology, we conducted three case studies showing an improvement with respect to the state-of-the-art, with an increased sensitivity to different scenarios.
