Clinical therapeutics最新文献

{"title":"Clinical Study of Cardiac Electrophysiology Affected After Percutaneous Transluminal Septal Myocardial Ablation for Obstructive Cardiomyopathy.","authors":"Tianzhu Li, Jinzhao Li, Jun Zhang, Nimin Lu","doi":"10.1016/j.clinthera.2025.09.006","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.09.006","url":null,"abstract":"<p><strong>Purpose: </strong>Hypertrophic cardiomyopathy has an estimated prevalence of approximately 1/200, driven by advancements in genetic testing and high-sensitivity cardiac imaging. This study evaluates the efficacy of percutaneous transluminal septal myocardial ablation (PTSMA) in treating hypertrophic obstructive cardiomyopathy (HOCM) and its impact on cardiac electrophysiology.</p><p><strong>Methods: </strong>A cohort of 38 patients with HOCM, admitted between June 2022 and June 2023, underwent PTSMA. Cardiac function classifications, interventricular septal thickness, left ventricular end-diastolic diameter (LVEDD), left ventricular outflow tract (LVOT) diameter, mitral valve early diastolic velocity (E peak), mitral annular early diastolic velocity (e'), and cardiac electrophysiological parameters (Tp-Te interval and QTcd) were assessed before and 1 month postprocedure.</p><p><strong>Findings: </strong>One month post-PTSMA, significant reductions were observed in cardiac function classification, interventricular septal thickness, and E/e' ratio (P < 0.05), alongside increases in LVEDD and LVOT diameter (P < 0.05). The Tp-Te interval and QTcd were significantly shortened (P < 0.05).</p><p><strong>Implications: </strong>PTSMA shows potential to improve cardiac function and reduce LVOT obstruction in HOCM patients, with favorable effects on cardiac electrophysiology. However, further multi-center studies with long-term follow-up are required to validate these findings and establish its broader therapeutic role.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Effectiveness of Direct-Acting Antiviral Treatment for Hepatitis C Virus Infection on Depressive Symptoms in Patients With Posttraumatic Stress Disorder.","authors":"Brian Shiner, Bradley V Watts, Luke Rozema, Jaimie L Gradus","doi":"10.1016/j.clinthera.2025.09.008","DOIUrl":"10.1016/j.clinthera.2025.09.008","url":null,"abstract":"<p><strong>Purpose: </strong>Newer medications for Hepatitis C Virus Infection (HCV), called direct acting antivirals (DAAs), are less likely to cause depression than older interferon-containing treatments. However, the risk of exacerbating depression has not been examined in subgroups of patients with pre-existing mental illness. We investigated whether several DAAs for HCV, including glecaprevir/pibrentasvir (GLE/PIB), ledipasvir/sofosbuvir (LDV/SOF), and sofosbuvir/velpatasvir (SOF/VEL), impact depressive symptoms in a population of patients with post-traumatic stress disorder (PTSD).</p><p><strong>Methods: </strong>We developed a retrospective cohort of United States Department of Veterans Affairs (VA) patients with PTSD receiving DAAs for HCV. We measured depressive symptoms before and after DAA treatment using the Patient Health Questionare-9 (PHQ-9), a patient-reported outcome measure with a range of 0-27, a screening threshold of 10 or higher, and a minimal clinically important difference of 5 points. We measured pre/post changes in PHQ-9 score and compared adjusted differences between treatment groups.</p><p><strong>Findings: </strong>Our cohort included 873 patients (GLE/PIB n = 357, LDV/SOF n = 308, SOF/VEL n = 208). Adjusted baseline PHQ-9 scores were consistent with mild depression and similar across groups (10.5 ± 7.2 for GLE/PIB, 10.6 ± 7.2 for LDV/SOF, 10.9 ± 7.2 for SOF/VEL). Adjusted change in PHQ-9 score was minimal and did not differ across groups (-2.0 ± 5.8 for GLE/PIB, -1.1 ± 6.5 for LDV/SOF, -2.2 ± 6.1 for SOF/VEL). The adjusted frequency of 5-pont change was low and did not differ meaningfully across groups (Improvement: 22.4% for GLE/PIB, 18.9% for LDV/SOF, 26.6% for SOF/VEL; Worsening: 9.1% for GLE/PIB, 14.3% for LDV/SOF, 10.1% for SOF/VEL).</p><p><strong>Implications: </strong>DAAs had very little impact on depressive symptoms for VA patients with PTSD and HCV infection.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494158/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Rusfertide, a Hepcidin Mimetic, on Cardiac Repolarization: A Randomized, Placebo- and Positive-Controlled Crossover Thorough QT Study in Healthy Participants.","authors":"Nishit B Modi, Phillip Dinh, Hongqi Xue, Borje Darpo","doi":"10.1016/j.clinthera.2025.09.002","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.09.002","url":null,"abstract":"<p><strong>Purpose: </strong>Rusfertide, a hepcidin mimetic, is in clinical development for the treatment of polycythemia vera. This study evaluated the effect of rusfertide on cardiac repolarization.</p><p><strong>Methods: </strong>A positive-controlled, randomized, double-blind, crossover study was conducted in healthy adults. Subjects received subcutaneous rusfertide 90 mg, matching subcutaneous placebo, and oral moxifloxacin. Subjects underwent continuous 12-lead Holter recording during each period. A central laboratory extracted up to 10 replicate electrocardiograms (ECGs) at each time point prior to and following treatment, paired with pharmacokinetic sampling. The primary analysis for Fridericia corrected QT interval (QTcF) was a mixed model for repeated measures with change from baseline QTcF (ΔQTcF) as the dependent variable; period, sequence, time, treatment, and time-by-treatment interaction as fixed effects; and baseline QTcF as a covariate. The relationship between rusfertide and metabolite concentrations and change-from-baseline QTcF was quantified using linear mixed-effects modeling.</p><p><strong>Findings: </strong>Mean age and body mass index were 40.1 years and 25.4 mg/m², respectively, with a slight majority of female (57%) and White (60%) subjects. Mean rusfertide plasma concentrations increased rapidly, with median peak of 4 hours. The geometric mean rusfertide peak concentration (C_max) was 1100 ng/mL. Rusfertide did not have a clinically relevant effect on heart rate (HR) or cardiac conduction (PR and QRS interval). The least squares (LS) mean ΔQTcF on rusfertide closely followed the placebo pattern, and LS mean placebo-corrected ΔQTcF (ΔΔQTcF) varied from -2.0 to 1.8 ms. After 400 mg oral moxifloxacin, an increase of LS mean ΔΔQTcF was observed with a peak of 12.4, 12.4, and 11.2 ms at 2, 3, and 4 hours, respectively, with all three lower bounds of the 2-sided 90% confidence interval greater than 5 ms. Estimated population slope of the rusfertide concentration-QTc relationship was not statistically significant: 0.00042 ms per ng/mL (90% confidence interval [CI]: -0.001172 to 0.002013; P = 0.6624). Predicted ΔΔQTcF at the geometric mean C_max was 0.04 ms (90% CI: -1.21 to 1.29). Overall, 24 of 60 subjects (40.0%) experienced treatment-emergent adverse events (TEAEs). All TEAEs were mild. TEAEs noted in ≥5% subjects were headache, nausea, injection site erythema, injection site pain, and influenza-like illness. There were no clinically significant changes in clinical laboratory, vital signs, ECG, or physical examination findings.</p><p><strong>Implications: </strong>Rusfertide had no clinically relevant effect on HR, cardiac conduction, or QTc. Rusfertide was well tolerated. An effect on ΔΔQTcF exceeding 10 ms could be excluded within the observed rusfertide plasma concentrations up to approximately 2130 ng/mL.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145205698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Post Hoc Analyses of DKD Clinical Trials in Ethnic Minorities (Asian, Hispanic, Black) Narrative Review.","authors":"Li-Li Hsiao, Steven G Coca, Samuel H Fantaye, Francisca M Acosta, Carolina Solis-Herrera","doi":"10.1016/j.clinthera.2025.09.003","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.09.003","url":null,"abstract":"<p><strong>Purpose: </strong>The burden of Diabetic kidney disease (DKD) is escalating, with a particularly adverse impact on ethnic minority populations. Clinical trials of nonsteroidal mineralocorticoid receptor antagonist (nsMRA), such as finerenone, Sodium-Glucose Transport Protein 2 Inhibitors (SGLT2i), and Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have been conducted to minimize the DKD burden. The results and adequate representation of racial and ethnic minority groups in those clinical trials need special focus.</p><p><strong>Methods: </strong>A narrative review approach was utilized, using PubMed and Google Scholar Search tools for clinical trials of finerenone and different SGLT2i in patients with DKD. Subgroup analyses based on race, ethnicity, and geographic regions were extracted from the original manuscripts of each clinical trial and its supplement. Ethnic representation was also identified from published clinical trial results on ClinicalTrials.gov. The literature review also included Post hoc analysis of those clinical trials that study the effect of these medications on different races, ethnic minorities, and geographic regions.</p><p><strong>Findings: </strong>Post hoc analysis of clinical trials on finerenone and SGLT2i found no significant differences in the primary composite cardiorenal outcome by race/ethnicity, suggesting consistent efficacy of these medications across diverse populations. Furthermore, the overall incidence of serious adverse events or adverse events of interest in these analyses were similar by race/ethnicity, also supporting the general safety of current DKD therapies in these populations.</p><p><strong>Implications: </strong>Post hoc analyses of pivotal trials represent the best available evidence to guide clinical decision-making for DKD therapies in minority populations. Current guidelines do not yet recommend special considerations based on race or ethnicity. Instead, the community can gather contemporaneous real-world evidence of these agents in the minority and high-risk populations to provide valuable information about potential treatment and adverse effects by race/ethnicity.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145198562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Building Equitable Partnerships Between Industry Sponsors And Indigenous Communities to Enhance Engagement in Clinical Trials.","authors":"Lancer Stephens, Nicole Redvers, Maile Taualii, Angela Cimino, Kasey Boynton, Allison Kelliher, Heather Angel Mars-Martins, Dean S Seneca, Natalia Burgess, Jenny Garcia, Monique Adams","doi":"10.1016/j.clinthera.2025.08.013","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.08.013","url":null,"abstract":"<p><strong>Introduction: </strong>American Indians, Alaska Natives, and Native Hawaiians (AI/AN/NH) have among the lowest representation in clinical trial participation in the United States (US) compared with other racial/ethnic groups and experience many barriers to health care access. To promote equitable and justice-centered inclusion of Indigenous Peoples in clinical trials and improve health equity, industry sponsors need to be better attuned to community-based priorities. This article summarizes perspectives including strategies to build more effective and equitable partnerships with Indigenous communities in the US and to advance access to medical care.</p><p><strong>Methods: </strong>A panel of advisors on AI/AN/NH health care assembled for a virtual roundtable discussion in March 2024. A narrative review, supported by key publications, was conducted to summarize and contextualize the discussions.</p><p><strong>Results: </strong>AI/AN/NH face various health inequities and challenges in clinical trial enrollment, including justified distrust of medical research environments, inaccessible and unaffordable health care, and limited community engagement by the research community. Proposed methods for engagement based on advisor insights were developed to guide industry sponsors in building more effective partnerships with Indigenous communities. Engagement methods consist of several strategies such as investing in community priorities, building a long-term commitment, identifying trusted messengers, and co-developing engagement initiatives.</p><p><strong>Conclusions: </strong>Current challenges regarding clinical trial diversity are impacting health outcomes among Indigenous Peoples, furthering disparities. Based on advisor engagement, establishing effective, equitable, and justice-centered partnerships between industry sponsors and Indigenous Peoples has the potential to result in community-driven priorities being recognized in clinical trials, and thus expanding benefit of medical innovation.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacists' Knowledge and Perceptions of Buprenorphine at New York State Pharmacies: Identifying the Extent of Pharmacy-Level Barriers to Access Buprenorphine.","authors":"Mariana Buziashvili, Katarina Colón, Elizabeth M Boos, Piper Coalson, Tracy Berger, Sharon Stancliff, Shu-Yin John Leung","doi":"10.1016/j.clinthera.2025.08.015","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.08.015","url":null,"abstract":"<p><strong>Purpose: </strong>Despite initiatives to improve opioid treatment access by increasing availability of buprenorphine, substantial barriers persist, impacting treatment engagement across New York State (NYS). Pharmacists play a critical role in dispensing buprenorphine, yet their knowledge and perceptions significantly affect medication accessibility. We evaluated pharmacists' knowledge and perceptions about buprenorphine dispensing at pharmacies across NYS and assessed variations based on pharmacy characteristics.</p><p><strong>Methods: </strong>A 2019 NYS Department of Health survey collected data from pharmacists about their experiences and perspectives related to buprenorphine dispensing. Statistical analyses were conducted to describe the associations between pharmacies, region, and other characteristics.</p><p><strong>Findings: </strong>Of responding pharmacies (n = 620) 54.8% were in New York City, 22.7% of pharmacists had previously declined a buprenorphine prescription, with 65.5% declining prescriptions in the last 6 months alone. Key barriers included stocking issues on the supply side (19.9%) and lack of demand by patients (14.7%).</p><p><strong>Implications: </strong>Pharmacists play a critical role in providing access to buprenorphine. Addressing pharmacist knowledge gaps and stigma through education initiatives may improve opioid treatment access. Additional studies are required to evaluate the extent of the existing buprenorphine pharmacy accessibility barriers and to identify approaches to addressing and eliminating those barriers.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145174133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Direct Oral Anticoagulants in Patients After Heart Valve Replacement or Repair: A Systematic Review and Network Meta-Analysis.","authors":"Weiqi Gao, Zhijiao Zhang, Pengyan Jia, Lingjun Dong, Ruijuan Li, Juan Xu, Jingmin Zhang, Weihong Chen","doi":"10.1016/j.clinthera.2025.08.017","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.08.017","url":null,"abstract":"<p><strong>Purpose: </strong>The optimal anticoagulation strategy following bioprosthetic heart valve replacement or valve repair remains controversial. Therefore, we conducted a meta-analysis to compare the efficacy and safety of direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with heart valve disease.</p><p><strong>Methods: </strong>We searched PubMed, Cochrane Library, Embase, Web of Science, CNKI, and Wanfang for clinical studies comparing DOACs and VKAs in patients following bioprosthetic heart valve replacement or repair, up to November 1, 2023. The meta-analysis was conducted using RevMan 5.3 and Stata 17.0.</p><p><strong>Findings: </strong>Thirty-three studies involving 59,660 individuals were included in the meta-analysis. Compared with VKAs, DOACs may reduce the risk of stroke or systemic embolism (risk ratios [RR] = 0.83, 95% confidence interval [CI] 0.75-0.93, P = 0.0007) and major bleeding (RR = 0.76, 95% CI 0.62-0.94, P = 0.009), while the risks of all-cause death and intracranial bleeding were similar. DOACs may increase the risk of gastrointestinal bleeding (RR = 1.42, 95% CI 1.04-1.95, P = 0.03). Twelve studies (4,789 patients) were included in a network meta-analysis. Indirect comparisons suggested rivaroxaban appears most favorable in reducing stroke or systemic embolism and major bleeding, though based on indirect evidence.</p><p><strong>Implications: </strong>In patients following bioprosthetic heart valve replacement or repair, DOACs may reduce the risk of stroke or systemic embolism and major bleeding, but may increase gastrointestinal bleeding compared with VKAs. Among DOACs, rivaroxaban appears to be the optimal choice. These findings should be interpreted cautiously due to limited RCT evidence and incomplete drug-specific reporting.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145136755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anticancer Drugs Associated With Tumor Lysis Syndrome: Insights From the US Food and Drug Administration Adverse Event Reporting System.","authors":"Wei Wang, Zirui Dong, Qi Miao, Baoan Hong, Yuxuan Bo, Xuezhou Zhang, Xin Guan, Ning Zhang","doi":"10.1016/j.clinthera.2025.08.001","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.08.001","url":null,"abstract":"<p><strong>Purpose: </strong>Tumor lysis syndrome (TLS) is a life-threatening metabolic emergency caused by rapid tumor cell breakdown, either spontaneously or after therapy, leading to electrolyte imbalances that can result in acute kidney injury, arrhythmias, seizures, and multiorgan failure. Despite its clinical importance, the relationship between anticancer drugs and TLS, particularly newer targeted therapies, remains poorly understood.</p><p><strong>Methods: </strong>We analyzed the US Food and Drug Administration (FDA) Adverse Events Reporting System database, a repository of adverse events associated with medical products, to identify TLS cases reported from the first quarter of 2004 to the third quarter of 2024. For signal detection, we used disproportionality analysis with 4 algorithms-reported odds ratio, proportional reporting ratio, Bayesian confidence propagation neural network, and empirical Bayes geometric mean. These algorithms assessed statistical correlations between anticancer drugs and TLS, based on a 2 × 2 contingency table framework.</p><p><strong>Findings: </strong>From the first quarter of 2004 to the third quarter of 2024, a total of 7340 TLS cases were documented in the FDA Adverse Events Reporting System database. Clinical characteristics, including age, sex, and outcomes, were analyzed. Among all reported TLS cases, 53.0% were men, and the mean age across all individuals was 56.9 ± 21.5 years. The incidence of TLS peaked in 2022, with a 42% increase from 2016 to 2017. A total of 118 antineoplastic drugs were identified as highly associated with TLS, of which only 18 had FDA-labeled TLS-related adverse reactions. Chemotherapy drugs were the most frequently associated with TLS. Venetoclax emerged as the top drug associated with TLS, comprising 10.72% of all TLS reports.</p><p><strong>Implications: </strong>Our findings highlight critical drug-induced TLS associations, particularly with emerging targeted therapies such as venetoclax. The study underscores the need for clinicians to monitor TLS closely in patients receiving certain anticancer treatments and to refine therapeutic strategies to mitigate TLS risk, ensuring safer cancer care outcomes. Further longitudinal studies are warranted to validate these findings and enhance pharmacovigilance efforts.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091418","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers as Surrogate Endpoints in Drug Development: Finding Their Right Place.","authors":"Katarina Ilic","doi":"10.1016/j.clinthera.2025.07.026","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.07.026","url":null,"abstract":"<p><p>The use of biomarkers and surrogate endpoints has become increasingly important in drug development, regulatory decision-making, and clinical practice. This review provides an overview of the distinctions between clinical and surrogate endpoints, defines types of biomarkers, and outlines the criteria used to validate biomarkers as surrogate endpoints. Finally, selected examples in clinical trials in cardiovascular drug development, anticancer drug development and antidiabetic drugs drug development illustrate how these concepts are applied in real-world drug development.</p>","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Response to \"Letter to the Editor Regarding 'The Safety and Efficacy of Intravenous Ibuprofen in Older Patients: A Retrospective Subgroup Analysis'-Reframing Intravenous Ibuprofen Use in Geriatric Pain Management: Insights on Safety, Stratification, and Polypharmacy\" for Clinical Therapeutics.","authors":"Tong J Gan, Breanne Gibson, Emily Durr, Andrew Abad, Beth Zaborny, Sergio Bergese, Stephen Southworth","doi":"10.1016/j.clinthera.2025.08.018","DOIUrl":"https://doi.org/10.1016/j.clinthera.2025.08.018","url":null,"abstract":"","PeriodicalId":10699,"journal":{"name":"Clinical therapeutics","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145091155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}