Cts-Clinical and Translational Science最新文献

{"title":"Safety and Pharmacokinetics of MK-8527 in Adults Without HIV","authors":"Gillian Gillespie,&nbsp;Russ P. Carstens,&nbsp;Xiaowei Zang,&nbsp;Ryan Vargo,&nbsp;Yash Kapoor,&nbsp;Arinjita Bhattacharyya,&nbsp;Jean-Francois Denef,&nbsp;Tom Reynders,&nbsp;Frédéric Vanhoutte,&nbsp;Sylvie Rottey,&nbsp;Randolph P. Matthews,&nbsp;S. Aubrey Stoch,&nbsp;Marian Iwamoto","doi":"10.1111/cts.70331","DOIUrl":"10.1111/cts.70331","url":null,"abstract":"<p>MK-8527 is a nucleoside reverse transcriptase translocation inhibitor (NRTTI) in clinical development. Two Phase 1 trials evaluated single (trial A) and multiple (trial B) ascending doses of MK-8527 in adults without HIV. In trial A, 34 participants were assigned to 1 of 4 panels and randomized to receive single oral doses of MK-8527 (0.5–200 mg) or placebo after fasting, over 3 dosing periods; 25 mg was assessed after a high-fat meal. In trial B, 32 participants were randomized to receive 3 once-weekly (QW) oral doses of MK-8527 (between 5 and 40 mg) or placebo. Safety and pharmacokinetics (PK) of MK-8527 and MK-8527-triphosphate (TP) were assessed. MK-8527 was generally well tolerated with no serious adverse events. Plasma exposure of MK-8527 increased approximately dose-proportionally, and intracellular exposure of MK-8527-TP was slightly less than dose-proportional over administered doses between 5 and 200 mg. Participants who received MK-8527 with a meal showed a 41% decrease in <i>C</i>_max with no effect on AUC_0–168, and a 20%, 22%, and 58% increase in intracellular MK-8527-TP <i>C</i>_max, <i>C</i>₁₆₈, and AUC_0–168, respectively. Across QW doses, plasma MK-8527 median <i>T</i>_max ranged from 0.5 to 1 h, and <i>t</i>_1/2 was 24–81 h; MK-8527-TP median <i>T</i>_max ranged from 10 to 24 h on Day 15, and geometric mean apparent <i>t</i>_1/2 was 216–291 h. Accumulation of intracellular MK-8527-TP was modest (accumulation ratios [Day 15/Day 1] for <i>C</i>_max and AUC_0–168 ranged from 1.1 to 1.6; <i>C</i>₁₆₈ from 1.2 to 2.4). Single and multiple QW doses of MK-8527 were generally well tolerated in adults without HIV. The safety and PK profiles of MK-8527 support continued clinical development.</p><p><b>Trial Registration:</b> EudraCT numbers: 2016-004647-36 (trial A); 2018-000846-20 (trial B)</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, Pharmacokinetics, and Pharmacodynamics of BI 1595043, a Selective Vanin Inhibitor, in Phase 1 Clinical Trials Involving Healthy Volunteers","authors":"Anjli Kukreja,&nbsp;Sascha Keller,&nbsp;Yury Shatillo,&nbsp;Andras Bauer,&nbsp;Ashish Sharma,&nbsp;Stephan Wojciekowski,&nbsp;Sudha Visvanathan,&nbsp;Stella Aslanyan","doi":"10.1111/cts.70285","DOIUrl":"10.1111/cts.70285","url":null,"abstract":"<p>BI 1595043 is an oral vanin-1 and vanin-2 inhibitor, which demonstrated promising effects on epithelial cell protection and reduction of inflammatory mediators in preclinical studies, as well as an acceptable safety profile in a previous single-rising-dose trial. Here, we report the results of a double-blind, randomized, placebo-controlled, multiple rising dose study, which investigated the safety, tolerability, pharmacokinetics, and pharmacodynamics of BI 1595043 in healthy male volunteers following oral administration of single and multiple rising doses over 18 days in total. Thirty subjects were treated (18–50 years of age; body mass index: 18.5–29.9 kg/m²); each dose group included 10 subjects, of which eight were administered BI 1595043 (15, 30, or 60 mg) and two were administered placebo after an overnight fast of ≥ 10 h. With multiple rising doses, BI 1595043 appeared to effectively inhibit the conversion of pantetheine to pantothenic acid. BI 1595043 achieved rapid absorption after administration (median time from dosing to maximum measured concentration of the analyte in plasma: ~1 h) and plasma concentrations generally increased in a dose-proportional manner, with the majority excreted in urine within the first 24 h after dosing. Most adverse events reported were of mild or moderate severity, e.g., headache, dizziness, and abdominal discomfort. However, this study was temporarily halted after ophthalmologic adverse events judged to be drug-related by the investigator were reported in six subjects treated with BI 1595043. The study was discontinued prematurely due to the sponsor's decision to terminate the development of BI 1595043 in all indications.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70285","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145062771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetics and Exposure–Response Analysis of Serplulimab in Small Cell Lung Cancer Patients","authors":"Kun Wang,&nbsp;Yuanyuan Shen,&nbsp;Chen Hu,&nbsp;Fengyan Xu,&nbsp;Qingyu Wang,&nbsp;Yuying Gao,&nbsp;Liang Zhou","doi":"10.1111/cts.70322","DOIUrl":"10.1111/cts.70322","url":null,"abstract":"<p>While PD-L1 antibodies have demonstrated efficacy in small cell lung cancer, the therapeutic benefits remain limited. To address this unmet medical need, serplulimab was developed as an innovative monoclonal antibody targeting PD-1. This study evaluated the pharmacokinetic (PK) properties of serplulimab and their relationship with efficacy and safety in patients with extensive-stage small cell lung cancer (ES-SCLC), using population pharmacokinetics (PopPK) and exposure–response (E–R) analysis to inform dose selection. Data from 1144 patients across eight Phase I–III clinical trials supported a two-compartment PopPK model with time-dependent clearance. Cox proportional hazards models were employed to analyze the correlation between exposure (<i>C</i>_avg1 and <i>C</i>_min1) and overall survival (OS)/progression-free survival (PFS), and adverse events (AEs) with exposure (<i>C</i>_avg1 and <i>C</i>_max1). Body weight, albumin (ALB), and gender significantly influenced the clearance and volume distribution of serplulimab; however, the observed differences in exposure ratio did not reach clinically relevant thresholds (0.8–1.25), thereby obviating the need for dose adjustments. Safety analysis revealed no monotonic increase in AE probability with increasing exposure (<i>p</i> &gt; 0.05). Efficacy analysis indicated no significant correlation between exposure and OS (<i>p</i> &gt; 0.05), whereas lactate dehydrogenase (LDH) and tumor burden emerged as significant predictors of OS (<i>p</i> &lt; 0.05). Results confirm favorable PK and safety of serplulimab at the recommended dose, requiring no adjustment for above covariates. These findings suggest that the current dose is on the plateau of the E–R curve, and dose escalation is unlikely to improve clinical outcomes.</p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT03952403, NCT04818359, NCT05246164, NCT04747236, NCT03973112, NCT04297995, NCT04778904, NCT04063163</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70322","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145034679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Japan's Perspective on Facilitating Drug Development Through Asian Cooperation in Multi-Regional Clinical Trials: Insights From Regulatory Research","authors":"Masahiro Tohkin,&nbsp;Yoshiro Saito,&nbsp;Yoshiaki Uyama","doi":"10.1111/cts.70347","DOIUrl":"10.1111/cts.70347","url":null,"abstract":"<p>Multi-regional clinical trials (MRCTs) have recently become a popular strategy for novel drug development, contributing to the early access to novel medicines in participating regions by enhancing development efficiency. To further facilitate MRCTs in Asia, the Japanese government has financially supported research activities in Japan for over 15 years that have studied the effect of ethnic factors on drug responses and identified practical challenges in conducting MRCTs in Asia. This mini-review highlights these research outcomes and related articles and presents our perspective on the current situation and future direction of MRCTs to explore opportunities for more collaboration between Japan and other East Asian/South-East Asian countries to facilitate drug development.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70347","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decentralized Clinical Trials in the Era of Real-World Evidence: A Critical Assessment of Recent Experiences","authors":"Hongwei Wang,&nbsp;Nadia Daizadeh,&nbsp;Yuan-Li Shen,&nbsp;Jie Chen,&nbsp;Frank W. Rockhold,&nbsp;Herbert Pang,&nbsp;Hana Lee","doi":"10.1111/cts.70328","DOIUrl":"10.1111/cts.70328","url":null,"abstract":"<p>Since the first decentralized clinical trial (DCT) was conducted in 2011, there has been an increased usage of DCT due to its benefits of patient-centricity and generalizability of findings. This trend was further expedited by the global COVID-19 pandemic. We identified 23 case studies across various therapeutic areas and grouped them into different categories according to their purposes—by necessity, for operational benefits, to address unique research questions, to validate innovative digital endpoints, or to validate decentralization as a clinical research platform. We leveraged the estimand framework from ICH E9(R1) including its five attributes (population, treatment, variable, intercurrent event, and summary measure) to critically assess their design and conduct. Common trends, opportunities, and challenges were reported along with recommendations for future DCT. Of note, intercurrent events and associated handling strategies are largely not present when reporting DCT. This is an area that can impact study conclusions and require more dedicated efforts when designing new DCTs.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70328","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Randomized Trial on the Combined Effect of Ponesimod and Propranolol on Heart Rate, Cardiac Safety, and Pharmacokinetics in Healthy Adults","authors":"Sivi Ouwerkerk-Mahadevan,&nbsp;Tessa Hosman,&nbsp;Italo Poggesi,&nbsp;Eva Vets,&nbsp;Freya Rasschaert,&nbsp;Jay Ariyawansa,&nbsp;Jaya Natarajan,&nbsp;Maroesja van Nimwegen-Velthuis,&nbsp;Andrea Vaclavkova,&nbsp;Juan Jose Perez-Ruixo,&nbsp;Tatiana Sidorenko","doi":"10.1111/cts.70341","DOIUrl":"10.1111/cts.70341","url":null,"abstract":"<p>The objective of this phase 1 study was to evaluate the pharmacokinetics (PK), pharmacodynamics, and cardiac effect following administration of ponesimod (a selective sphingosine-1-phosphate receptor modulator) and propranolol in healthy adults. In treatment period (TP) 1, participants received ponesimod (2 mg). In TP2, if resting heart rate (HR) was ≥ 55 bpm, the ponesimod up-titration regimen was initiated. Participants were randomized to TP2A (placebo plus ponesimod up-titration) or TP2B (80 mg propranolol plus ponesimod up-titration). Concomitant administration resulted in an increased bradyarrhythmic effect on HR versus ponesimod alone. The mean maximum difference in mean hourly HR from time-matched baseline for TP2B compared with TP2A during the first 12 h post-dose was −12.4 bpm. This was observed after the first dose of ponesimod, persisted for the first 4 doses, then decreased to −7.4 bpm post-up-titration. The lowest mean of the HR_nadir in TP2B was 48.9 bpm (95% CI: 46.4–51.3). There was no significant difference in the occurrence of 1st degree AV block between groups and no occurrences of 2nd or higher degree AV block. No clinically relevant changes were observed in the PK of ponesimod or propranolol. Overall, 88.5% of participants experienced ≥ 1 AE during the study. In TP2, the most reported TEAEs (≥ 5%) considered related to ponesimod were fatigue (12 [25.5%]) and dizziness (10 [21.3%]). No deaths were reported. Co-administration of ponesimod with propranolol resulted in a greater HR-lowering effect compared to ponesimod alone, without significant changes in PK parameters or serious cardiac adverse events in healthy adults.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70341","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population Pharmacokinetic Model-Based Optimization of Linezolid Dosing in Hematooncological Patients With Suspected or Proven Gram-Positive Sepsis","authors":"Alžběta Zavřelová,&nbsp;Sara Merdita,&nbsp;Pavel Žák,&nbsp;Jakub Radocha,&nbsp;Benjamin Víšek,&nbsp;Miriam Lánská,&nbsp;Jana Maláková,&nbsp;Pavel Michálek,&nbsp;Ondřej Slanař,&nbsp;Martin Šíma","doi":"10.1111/cts.70346","DOIUrl":"10.1111/cts.70346","url":null,"abstract":"<p>The objective of this study was to develop a population pharmacokinetic model for linezolid in hematooncological patients with sepsis, and to propose dosing optimization based on pharmacokinetic covariates that would lead to improved achievement of the PK/PD target. Therapeutic drug monitoring data from hematooncological patients treated with linezolid for suspected or proven sepsis were analyzed. A pharmacokinetic population model for linezolid was constructed using a nonlinear mixed-effects modeling approach. Monte Carlo simulations were then used to compare various dosing regimens in terms of PK/PD target attainment. A total of 197 linezolid serum concentrations obtained from 22 patients were included in the analysis. Patients' age was found to be the most predictive covariate for linezolid pharmacokinetics. In a patient with a median age of 59 years, the volume of distribution and clearance of linezolid were 46.2 L and 12.1 L/h, respectively. During the first 4 days of therapy, linezolid clearance decreased by 33%. The probability of PK/PD target attainment increased through the individualization of the dose according to the patient's age, administration of a loading dose, and administration of linezolid via continuous infusion. For this scenario, an easy-to-use nomogram was designed.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70346","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AI-NLME: A New Artificial Intelligence-Driven Nonlinear Mixed Effect Modeling Approach for Analyzing Longitudinal Data in Randomized Placebo-Controlled Clinical Trials","authors":"Roberto Gomeni,&nbsp;Françoise Bressolle-Gomeni","doi":"10.1111/cts.70345","DOIUrl":"10.1111/cts.70345","url":null,"abstract":"<p>A propensity weighted (PSW) methodology was recently proposed for assessing the treatment effect conditional to the probability of non-specific response to a treatment (prob-NSRT). Prob-NSRT was estimated using an artificial neural network (ANN) model applied to pre-randomization and study endpoint observations in a placebo arm of a placebo-controlled clinical trial. Placebo data were initially used to estimate prob-NSRT, then the ANN model was applied to the data of each individual in each treatment arm (placebo + active) for estimating the individual prob-NSRT, and finally all data in the trial enriched by the prob-NSRT values were used to assess the treatment effect. One of the major limitations of this methodology was that the ANN model was developed and applied to analyze data in the same dataset. To overcome this limitation, a new artificial intelligence driven nonlinear mixed effect modeling approach (AI-NLME) is proposed. This approach involves the development of the ANN model using a dataset that is independent from the dataset used to estimate the treatment effect. A case study is presented using data from a randomized, placebo-controlled trial in major depressive disorders. The AI-NLME approach provided an effective tool for controlling the confounding effect of treatment non-specific response, for increasing signal detection, for decreasing heterogeneity in the response, for increasing the effect size, for better assessing the responder rate, and for providing a reliable estimate of the “true” treatment effect. These findings provide convergent evidence on the potential role of AI-NLME to become the reference approach for analyzing placebo-controlled clinical trials.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70345","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methodology for Assessing Patient Centricity and Data Integrity in Clinical Trials With Decentralized Elements: A Pilot Trial on Mastic Gum","authors":"Jiyeon Park,&nbsp;Ki Young Huh,&nbsp;Jae-Yong Chung,&nbsp;Kyung-Sang Yu","doi":"10.1111/cts.70343","DOIUrl":"10.1111/cts.70343","url":null,"abstract":"<p>Decentralized elements enhanced patient centricity by shifting trial-related activities outside traditional trial sites. On the other hand, remote data collection poses potential risks to data integrity. Although these two are critical aspects of decentralized elements, methodologies for assessing them remain limited. We proposed a method to measure patient centricity by subtracting the participant's self-rated burden for trial-related procedures with decentralized elements from their estimated burden under the traditional approach. Additionally, we introduced an analytical framework to assess data integrity by considering the accurate performance rate, the sources of errors, and their cascading consequences. The feasibility and applicability of these methodologies were explored in a pilot clinical trial on mastic gum. Patient centricity was highest in wearable device-based drug adherence monitoring (4.30) and lowest in remote consent submission (1.80). For most trial-related procedures, patient centricity tended to be higher when participant engagement increased. However, blood sample collection recorded higher patient centricity when participants visited a nearby local hospital for nurse assistance (2.55) compared to the estimated burden of using a self-kit at home (2.35). Data integrity was lowest in wearable device-based drug adherence monitoring (88.6%), and the errors were attributable to the device being left behind, insufficient proficiency, broken WiFi connection, and depleted battery. Data integrity was second lowest in self-kit-based stool specimen collection (90.0%), and the errors led to successive delays in specimen delivery and microbiome analysis. The proposed methodologies will provide a foundation for assessing and predicting the impact of decentralized elements on clinical trials.</p><p><b>Trial Registration:</b> ClinicalTrials.gov identifier: NCT06005805</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70343","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144934952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Data Sharing Experience, Guidance, and Resources From the Rare Diseases Clinical Research Network (RDCRN)","authors":"Elaine Schwendeman,&nbsp;Henry J. Kaminski,&nbsp;Adeline Vanderver,&nbsp;Michael Wagner,&nbsp;Eileen King,&nbsp;The RDCRN Data Use & Data Sharing Committee,&nbsp;Maurizio Macaluso","doi":"10.1111/cts.70340","DOIUrl":"10.1111/cts.70340","url":null,"abstract":"<p>The Rare Diseases Clinical Research Network (RDCRN) comprises research consortia and other partners focused on the study of rare diseases. Its goals include sharing de-identified data with the scientific community and other stakeholders to advance rare disease research. The RDCRN Data Use &amp; Data Sharing Committee and RDCRN Data Management and Coordinating Center reviewed data sharing practices across established consortia and published literature to develop guidance documents. The Committee produced “RDCRN Suggestions for Establishing Data Sharing and Data Management Guidance for Individual Consortia”, which lays out the common elements of successful data sharing, and “Principles of Data Sharing Checklist,” which outlines the components of informed consent language, contractual language, and consortium policies that govern data sharing and use. Key principles of the guidance are: (1) informed consent language should allow data sharing while protecting participants' rights, (2) the research database should track participant's choices on how their data can be used and shared to ensure appropriate data use limitations are followed, (3) the research protocol and consortium agreements should include language stipulating that data will be shared with the consortium Administrative Core (Admin Core) for the purpose of further sharing according to NIH policies, and (4) consortia policies and agreements should emphasize the role of the Admin Core as the primary steward of the collective data and recognize its authority to further share consortium data. The RDCRN experience and learnings contribute to the advancement of Clinical and Translational Science and may help other research networks in designing data sharing policies.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ascpt.onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70340","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}