Clinical Pharmacology & Therapeutics最新文献

{"title":"Exclusion of Participants for Substance Use in Clinical Trials.","authors":"Willyanne DeCormier Plosky, Benjamin C Silverman, David H Strauss, Barbara E Bierer","doi":"10.1002/cpt.70510","DOIUrl":"10.1002/cpt.70510","url":null,"abstract":"<p><p>Patterns of inclusion and exclusion of individuals who use illicit substances from clinical trials have not been well-studied. Given the widespread and increasing prevalence of drug use in the United States, this has significant implications for the generalizability of scientific findings and the validity of treatment recommendations for individuals with and without co-morbid substance use. Here, we analyzed study protocol eligibility and the rationale for excluding substance users using data from ClinicalTrials.gov. We found that 43% (110/254) of interventional and 7% (3/46) of observational study protocols excluded people who use substances. The description of substance use ranged widely across the study protocols, varying by the level of use, the time period of use, and the definition of which specific substances or substance categories were excluded. The majority (63%, 69/110) of studies that excluded substance use either did not offer any rationale for the exclusion or did not give a specific justification related to substance use. Additional guidance is needed to standardize the definitions and assessment of substance use applied to clinical trial eligibility determinations and to formalize the justification of inclusion and exclusion of substance use based on explicit scientific, clinical, ethical, and safety criteria.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639407/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dihydropyrimidine Dehydrogenase Genotype-Phenotype Correlations in Plasma and Peripheral Blood Mononuclear Cells.","authors":"Brianna M Bembenek, Seid Hamzic, Kelly J Bouchonville, Carlo R Largiadèr, Steven M Offer","doi":"10.1002/cpt.70511","DOIUrl":"10.1002/cpt.70511","url":null,"abstract":"<p><p>The chemotherapeutic 5-fluorouracil (5-FU) is commonly used to treat solid tumors, especially colorectal cancer. Deleterious variants in DPYD, which encodes dihydropyrimidine dehydrogenase (DPD), are strongly associated with severe and potentially lethal 5-FU toxicity. Phenotypic assays for DPD function have been proposed as alternative or complementary approaches to identify DPD deficiencies with the rationale that they may capture unrecognized causes. These assays include the direct measurement of DPD activity in peripheral blood mononuclear cell (PBMC) lysates and measuring plasma metabolites uracil (U), dihydrouracil (UH₂), and the dihydrouracil/uracil (UH₂:U) ratio. We evaluated correlations between PBMC DPD activity and plasma metabolite measures in matched samples from 203 patients with available DPYD exome sequencing data. We also compared the ability of phenotypic measures to identify carriers of deleterious DPYD variants. In addition to established high-risk variants, we identified three rare DPYD variants predicted to be deleterious: c.274C>G, c.966C>A, and c.1435G>A. Collectively, these variants were associated with impaired DPD function with effect sizes comparable to well-studied toxicity-associated variants. At the population level and within carriers of specific genotypes, weak but significant correlations were observed between PBMC DPD activity and either UH₂:U ratio or U level. These findings suggest that although phenotypic assays can detect severe DPD deficiency, high variability limits their utility as standalone diagnostic tools. Integration with genetic testing may provide a more robust pretreatment risk assessment strategy.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGLT2 Inhibitors and Asthma Exacerbation Risk Among Patients With Type 2 Diabetes and Asthma: A Target Trial Emulation.","authors":"Kevin Yi-Chen Liao, Daniel Hsiang-Te Tsai, Michael Chun-Yuan Cheng, Han-Wei Mu, Kuan-Wen Su, Shih-Chieh Shao, Edward Chia-Cheng Lai","doi":"10.1002/cpt.70514","DOIUrl":"10.1002/cpt.70514","url":null,"abstract":"<p><p>Emerging evidence suggests potential respiratory benefits from sodium-glucose cotransporter 2 (SGLT2) inhibitors, a glucose-lowering agent. However, the effects of these agents on asthma exacerbations remain unclear. A retrospective cohort study used Taiwan's National Health Insurance Research Database, covering 2016-2020, and included adults with type 2 diabetes and asthma. Exposure was defined as the initiation of SGLT2 or dipeptidyl peptidase 4 (DPP4) inhibitors, and the primary outcome was asthma exacerbation, defined as an asthma diagnosis accompanied by systemic corticosteroid use. Demographic characteristics, comorbidities, the Adapted Diabetes Complications Severity Index and concomitant medications were used to estimate propensity scores, and inverse probability of treatment weighting was applied. Altogether, 3,057 initiators of SGLT2 inhibitors and 15,050 initiators of DPP4 inhibitors were identified and followed from the index date until the occurrence of asthma exacerbation, death, or the end of the observation period (May 31, 2020). Over a mean follow-up of 2.06 years, initiation of SGLT2 inhibitors was associated with a lower risk of asthma exacerbation (HR: 0.87, 95% CI: 0.81-0.93), corresponding to incidence rates of 3.73 vs. 4.03 events per 100 person-years. The results were consistent across care settings, including outpatient- (HR: 0.88, 95% CI: 0.80-0.96), inpatient- (HR: 0.88, 95% CI: 0.78-1.00), and emergency department visits (HR: 0.72, 95% CI: 0.63-0.83), as also across subgroup and sensitivity analyses. Among adults with type 2 diabetes and asthma, initiation of SGLT2 inhibitors was associated with a reduced risk of asthma exacerbation, highlighting a potential respiratory benefit that warrants confirmation through future clinical trials.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643014/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acute Kidney Injury and Heart Failure Risk with Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitors: A Network Meta-Analysis.","authors":"Satoru Mitsuboshi, Makoto Morizumi, Shungo Imai, Satoko Hori, Kazumasa Kotake","doi":"10.1002/cpt.70516","DOIUrl":"10.1002/cpt.70516","url":null,"abstract":"<p><p>The aim of this systematic review and network meta-analysis was to clarify the risk of acute kidney injury (AKI) and acute heart failure associated with hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs) in patients with anemia of chronic kidney disease. The certainty of evidence for each outcome was assessed using the Confidence in Network Meta-Analysis approach. The primary outcomes were AKI and acute heart failure, while the secondary outcome was any kidney injury. Thirty-five studies, performed between 2009 and 2025, were included in the network meta-analysis. HIF-PHIs were associated with a higher risk of AKI compared with erythropoiesis-stimulating agents (ESAs) (risk ratio [RR] 1.23, 95% confidence interval [CI] 1.02-1.47, moderate certainty) and placebo (RR 1.40, 95% CI 1.11-1.75, high certainty). HIF-PHIs were also associated with an increased risk of any kidney injury compared with placebo (RR 1.13, 95% CI 1.01-1.26, moderate certainty). ESAs ranked lower in terms of acute heart failure risk than both HIF-PHIs and placebo, although the differences were not statistically significant. Vadadustat (RR 0.30, 95% CI 0.12-0.74, moderate certainty) and ESAs (RR 0.40, 95% CI 0.17-0.94, high certainty) were associated with a lower risk of acute heart failure compared with placebo. In conclusion, HIF-PHIs may be associated with an increased incidence of AKI compared with placebo and ESAs. In contrast, vadadustat and ESAs might be associated with a decreased incidence of acute heart failure compared with placebo. Further robust studies should be conducted to validate these findings.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating Static and Dynamic Models to Predict Cannabidiol-Mediated Metabolic Drug-Drug Interactions.","authors":"Sulafa Al Sahlawi, Bassma Eltanameli, Brian Cicali, Rodrigo Cristofoletti","doi":"10.1002/cpt.70509","DOIUrl":"10.1002/cpt.70509","url":null,"abstract":"<p><p>Cannabidiol (CBD) inhibits multiple cytochrome P450 (CYP450) enzymes in vitro via reversible and time-dependent mechanisms, raising concerns for metabolic drug-drug interactions (DDIs). Clinical DDI data for CBD are limited, and the translation of in vitro derived inhibition parameters into in vivo DDI predictions remains uncertain. We implemented a stepwise, model-informed framework to evaluate CBD-mediated metabolic DDIs using (i) basic, (ii) mechanistic static (MSM), and (iii) physiologically based pharmacokinetic (PBPK) models. The basic model and MSM incorporated in vitro inhibition parameters for CBD and its primary active metabolite, 7-hydroxycannabidiol (7-OH-CBD), to identify sensitive metabolic pathways. A PBPK model for CBD and 7-OH-CBD was developed and validated against clinical pharmacokinetic data, then used to simulate DDIs. Where necessary, inhibition parameters were refined using the PBPK model to capture clinical observations, and the optimized parameters were used to revisit the basic model and MSM, facilitating comparison across modeling approaches. The MSM predicted 3.6-, 4.1-, and 2.2-fold increases in exposure of sensitive CYP1A2, CYP2C9, and CYP3A4 substrates, respectively, and a strong CYP2C19-mediated interaction. In contrast, the PBPK model predicted lower DDI magnitudes consistent with clinical data, identifying CYP2C19 inhibition as the most clinically relevant liability, with a moderate interaction risk for sensitive substrates, while CYP1A2 inhibition increased sensitive substrate exposure twofold. The validated PBPK model was applied to evaluate exposure in special populations and DDI risk with commonly co-prescribed medications. Overall, this framework reconciles in vitro and clinical DDI data and supports population-specific assessment of CBD-mediated DDIs across diverse clinical scenarios.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Considerations for the Integration of Clinical Trials and Real-World Data.","authors":"Sky Qiu, Charles E Barr, Lauren Dang, Larry Han, Kajsa Kvist, Hana Lee, Andrew Mertens, Nerissa Nance, Lei Nie, Kara Rudolph, Xu Shi, Jens Tarp, Salina P Waddy, Kenneth Wiley, Andy Wilson, Margot Lisa Jing Yann, Zhiwei Zhang, Tianyue Zhou, Maya Petersen, Mark van der Laan","doi":"10.1002/cpt.70513","DOIUrl":"10.1002/cpt.70513","url":null,"abstract":"<p><p>As clinical decision-making increasingly moves toward individualized and context-specific treatment recommendations, reliance on any single evidence source, randomized or observational, may be insufficient. Principled integration of randomized controlled trials and real-world data, grounded in explicit causal frameworks, offers a path toward evidence that is both internally credible and externally relevant. In this article, we describe distinct objectives for the integration of randomized controlled trials and real-world data and discuss how these objectives shape key design and analytic considerations, illustrating the resulting choices through example estimands. We highlight practical issues that commonly arise in applied settings, including data relevance and curation, cross-source comparability, estimand specification, and sensitivity analysis. We aim for this article to help readers evaluate and implement principled approaches to integrating randomized controlled trials and real-world data in ways that can support more reliable treatment recommendations while maintaining regulatory-grade evidentiary standards.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13639411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Vaginal Microbiome Effects on Antiretroviral Exposure in the Female Genital Tract Using Pharmacometric and Machine Learning Approaches.","authors":"Diqin Yan, Lindsey B Collins, Christopher Staley, Flavia Kiweewa Matovu, Pamala Jacobson, Melanie Nicol, Shen Cheng","doi":"10.1002/cpt.70499","DOIUrl":"https://doi.org/10.1002/cpt.70499","url":null,"abstract":"<p><p>Antiretroviral pre-exposure prophylaxis (PrEP) is less effective in women than expected, partly because drug exposure within the female genital tract is variable and may be influenced by the vaginal microbiome. We developed an integrated pharmacometrics and machine learning framework to evaluate associations between vaginal microbiome composition and cervical antiretroviral exposure in women with human immunodeficiency virus (HIV) receiving tenofovir (TFV)-, lamivudine (3TC)-, or emtricitabine (FTC)-containing regimens. Pharmacokinetic and microbiome data were obtained from two single-center studies in Uganda and the United States. Published population pharmacokinetic models were used to estimate individual parameters by maximum a posteriori Bayesian estimation and to simulate plasma and cervical tissue exposure metrics under sexual-activity-driven dosing that were not studied in these trials. Microbiome diversity was assessed using alpha and beta diversity analyses. Associations between microbial genera and cervical drug exposure were evaluated using correlation analysis, differential abundance testing, and three machine learning approaches: LASSO, random forest, and XGBoost. Overall vaginal microbiome diversity was not associated with cervical exposure to TFV, 3TC, or FTC. In contrast, specific taxa-level associations with cervical drug exposure were identified. For TFV, Gemella was positively associated with cervical TFV-diphosphate exposure, whereas Megasphaera and Falsiporphyromonas were negatively associated across multiple models. For 3TC, Dialister, Prevotella, Atopobium, Streptobacillus, and Gardnerella were repeatedly identified. For FTC, Bifidobacteriaceae was consistently selected, with Lachnospiraceae and Prevotellaceae also implicated. This pharmacometrics-machine learning framework identified specific vaginal taxa associated with cervical antiretroviral exposure, supporting the future development of microbiome-based biomarkers and precision PrEP strategies for women.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633485/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measuring the Outcomes of International Oncology Regulatory Collaboration in Canada from 2019 to 2025: Project Orbis.","authors":"Jonathan Zaslavsky, David C Sealey","doi":"10.1002/cpt.70503","DOIUrl":"https://doi.org/10.1002/cpt.70503","url":null,"abstract":"<p><p>Project Orbis, launched by the US FDA in 2019, enables collaboration among international regulatory agencies on cancer drug reviews. We assessed the regulatory impact of Project Orbis in Canada by analyzing publicly available data on marketing authorization applications (MAAs). We analyzed US-Canada submission and approval gaps, time to regulatory decision, tumor areas, and sponsor involvement. From September 20, 2019 to the end of 2025, Health Canada approved 97 Orbis and 161 non-Orbis oncology MAAs. Orbis MAAs had a shorter median submission gap than non-Orbis MAAs, as well as a shorter median approval gap. Median time to decision was shorter for Orbis MAAs than non-Orbis MAAs and was related to accelerated or standard review pathways. The time to decision was consistent with Health Canada's performance standards, and notably, Orbis type A median time to decision was similar for standard and priority review MAAs. Health Canada has been a highly active Project Orbis partner. Further research is needed to determine whether Orbis accelerates the overall time from regulatory filing to patient access to treatment, inclusive of health technology assessment and reimbursement negotiation processes.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631845/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metformin Use Before Assisted Reproductive Technology and Pregnancy Outcomes in Women With Polycystic Ovary Syndrome: A Nationwide Cohort Study.","authors":"Yongtai Cho, Yeon Soo Park, Yubin Lee, HyunJoo Lim, Ju-Young Shin, Soo-Heon Kwak","doi":"10.1002/cpt.70512","DOIUrl":"https://doi.org/10.1002/cpt.70512","url":null,"abstract":"<p><p>Metformin has been hypothesized to improve ovulation and pregnancy rates in women with polycystic ovary syndrome (PCOS) undergoing assisted reproductive technology (ART). This population-based cohort study assessed pregnancy outcomes associated with metformin use prior to ART in women with PCOS. We included 10,178 women with PCOS undergoing their first fresh embryo transfer cycle under the national health insurance program of South Korea between 2017 and 2021. Women who received metformin for ovulation induction within 12 weeks prior to ovarian stimulation were compared with those who did not receive metformin. ART outcomes included successful oocyte retrieval, embryo transfer, and clinical pregnancy, while pregnancy outcomes included spontaneous abortion, preterm birth, and live birth. Overlap-weighted risk ratios (RR) were calculated for each outcome. Among the study population, 2,149 (21.1%) had used metformin prior to ovarian stimulation, and 8,029 (78.9%) had not. Metformin use did not improve or worsen ART outcomes, with comparable rates of oocyte retrieval (RR: 1.01, 95% confidence interval 1.00-1.02) and clinical pregnancy (RR: 1.05, 1.00-1.11), as well as no increased rates of spontaneous abortion (RR: 1.01, 0.84-1.21), preterm birth (RR: 0.99, 0.84-1.18), or live birth (RR: 1.05, 0.99-1.12). Subgroup analyses suggested modest benefits, including higher clinical pregnancy or live birth rates, among women aged ≥ 35 years, those undergoing a GnRH antagonist protocol, and those with ≥ 30 days of metformin use. In conclusion, metformin pretreatment before ART was not associated with any clinically meaningful benefits or harms in pregnancy outcomes among women with PCOS.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13633416/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101467","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toward the Use of Real-World Data for Regulatory and HTA Decision-Making: Experiences and Recommendations from Six EU-Funded Projects.","authors":"Martin Russek, Jonas Peltner, Kerstin Pfeifer, Theodoros N Arvanitis, Dirk De Valck, Sieta T de Vries, Michel Dumontier, Vera Ehrenstein, Omaima El Hakouni, Gregory Epiphaniou, Gokhan Ertaylan, Joana Fernandes, Scott Hansen, Stuart Harrison, Erzsébet Horváth-Puhó, Saif Ul Islam, Pekka Kahri, Julia K Mader, Carsten Maple, Nikolaos Matragkas, Shivani Misra, Peter G M Mol, Anne Paakinaho, Sami Pakarinen, Martina Radanović, Evy Reviers, Kathrine Kold Sørensen, Marco Spruit, Christina Tikka, Anna-Maija Tolppanen, Christian Torp-Pedersen, Mirna Vela, Thuan Vo, Puriya Daniel Würtz Yazdanfard, Britta Haenisch","doi":"10.1002/cpt.70502","DOIUrl":"https://doi.org/10.1002/cpt.70502","url":null,"abstract":"<p><p>Real-world data are increasingly important for regulatory and health technology assessment decision-making, yet their effective use across Europe remains limited by technical, methodological, regulatory, and societal challenges. Drawing on the experiences of six Horizon Europe projects in the MetReal cluster, this review summarizes common barriers and emerging solutions for the use of real-world data in regulatory decision-making. Key challenges include complex and lengthy data access procedures, fragmented governance frameworks, variable data quality and completeness, limited interoperability, methodological difficulties in analyzing heterogeneous datasets, and infrastructure constraints within secure data environments. The article highlights opportunities to address these barriers through improved metadata, harmonization, federated analytics, synthetic data sandboxes, sustainable funding, and stronger collaboration between researchers, regulators, health technology assessment bodies, data holders, and citizens. These recommendations aim to strengthen Europe's health data ecosystem and support more robust, efficient, and trusted evidence generation for public health and patient benefit.</p>","PeriodicalId":153,"journal":{"name":"Clinical Pharmacology & Therapeutics","volume":" ","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13631762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149101491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}