Cts-Clinical and Translational Science最新文献

{"title":"Enhancement of Statin Effects on Lipid Lowering and Reduction of Cardiovascular Risk Score by (−)-Epicatechin in Proof-of-Concept Pilot Study","authors":"Cameron K. Ormiston,&nbsp;Aryana Pazargadi,&nbsp;Ashley Rosander,&nbsp;Guillermo Ceballos,&nbsp;Francisco Villarreal,&nbsp;Pam R. Taub","doi":"10.1111/cts.70236","DOIUrl":"https://doi.org/10.1111/cts.70236","url":null,"abstract":"<p>Statins play an instrumental role in reducing and managing atherosclerotic cardiovascular disease (ASCVD) but can be difficult to tolerate due to muscle-associated side effects. There remains an unmet need for strategies that improve statin tolerance and synergize their effect on atherogenic lipids. (−)-Epicatechin (Epi) is a natural flavonoid that can improve lipid biomarkers and mitochondrial function. This study explored the capacity of Epi to augment statin's beneficial effects on lipid profile and ASCVD risk parameters. In total, 19 patients completed a randomized, double-blind placebo-controlled trial. The study consisted of two cohorts. Cohort 1 consisted of healthy patients with elevated low-density lipoprotein (LDL) &gt; 100 mg/dL and was used to determine appropriate Epi dosing. Cohort 2 consisted of patients with metabolic syndrome. Patients were randomized into statin-only (<i>n</i> = 8; 5 in Cohort 2) or statin + Epi (<i>n</i> = 11; 8 in Cohort 2) for 3 months. VO₂ max and lipid biomarkers were assessed at baseline and at the end of 3 months. Final analysis included Cohort 2 only. The statin + Epi group saw significant beneficial changes in total cholesterol (<i>p</i> = 0.002) and non-HDL cholesterol (<i>p</i> = 0.007). There was a significantly larger increase in HDL (<i>p</i> = 0.037) and significantly greater decrease in LDL particle number (<i>p</i> = 0.0003) and small LDL particle number (<i>p</i> = 0.003) among the statin + Epi group compared to statin-only. Ten-year ASCVD risk was significantly lower at end-of-study for the statin + Epi arm compared to statin-only (<i>p</i> &lt; 0.05). No VO₂ max differences were found. This is the first proof-of-concept study to show combination therapy of a statin with Epi is safe and effective in augmenting statin-associated improvements in lipid biomarkers.</p><p><b>Trial Registration:</b> ClinicalTrials.gov: NCT02490527</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70236","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085506","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":"Physiologically Based and Population Pharmacokinetic Modeling of Midazolam in Children With Obesity Using Real-World Data","authors":"Sean McCann,&nbsp;Victória E. Helfer,&nbsp;Stephen J. Balevic,&nbsp;William J. Muller,&nbsp;John N. van den Anker,&nbsp;Amira Al-Uzri,&nbsp;Marisa L. Meyer,&nbsp;Sarah G. Anderson,&nbsp;Sitora Turdalieva,&nbsp;Andrea N. Edginton,&nbsp;Daniel Gonzalez,&nbsp;the Best Pharmaceuticals for Children Act Pediatric Trials Network Steering Committee","doi":"10.1111/cts.70247","DOIUrl":"https://doi.org/10.1111/cts.70247","url":null,"abstract":"<p>Children represent a highly complex and variable population for treatment, including interindividual differences in drug dose–exposure. Midazolam has been used as a sedative for hospitalized children on- and off-label; however, factors affecting interindividual variability (IIV) in observed clearance for this population are not fully understood and can result in extreme under- or overexposure. Obesity has been described as a significant influence on midazolam in adolescents, which could potentially alter drug exposure. The goal of this study was to use two modeling strategies to evaluate dose–exposure of midazolam in children with and without obesity. Population pharmacokinetic modeling assessed whether measures of obesity status would explain some of the observed IIV for midazolam clearance. In all, 164 plasma concentrations were collected from 93 participating children, many with obesity. Covariate modeling did not identify any factors influential to clearance beyond body weight. Model IIV was similar to that observed in previous models of critically ill children (coefficient of variation, 175%) along with considerable residual unexplained variability (50.4%). Then, a previously published virtual population of children with obesity was incorporated into an existing physiologically based pharmacokinetic model of midazolam in the open-source PK-Sim software. Dosing simulations for a subset of 46 participants demonstrated minor overpredictions in children with obesity compared to those without. Both models predicted a minor (&lt; 20%) increase in exposure for children with obesity given the same weight-based dose. This research demonstrates the use of population pharmacokinetics combined with physiologically based pharmacokinetic modeling to compare simulated exposures in children with and without obesity.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70247","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143944841","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 a 6-h N,N-Dimethyltryptamine (DMT) Infusion in Healthy Volunteers: A Randomized, Double-Blind, Placebo-Controlled Trial","authors":"Katelijne V. van der Heijden,&nbsp;Rob G. J. A. Zuiker,&nbsp;Marije E. Otto,&nbsp;Christopher S. Bryan,&nbsp;Nancy Stewart,&nbsp;Christopher Stillwell,&nbsp;Marieke L. De Kam,&nbsp;Marloes B. van Leuken,&nbsp;Joop M. A. van Gerven,&nbsp;Gabriel E. Jacobs","doi":"10.1111/cts.70234","DOIUrl":"https://doi.org/10.1111/cts.70234","url":null,"abstract":"<p>The serotonergic psychedelic <i>N</i>,<i>N</i>-dimethyltryptamine (DMT) presumably stimulates neuroplasticity in vitro and in vivo, by which it may exert neuroprotective effects during acute ischemic stroke. Since neuroplasticity has been implicated in the mechanism of action of rehabilitative therapy in stroke recovery, a pharmacological augmentation strategy facilitating neuroplasticity could be beneficial. To optimize this treatment strategy, a detailed understanding of the safety, pharmacokinetics, and pharmacodynamics of prolonged DMT administration is required. This randomized, double-blind, placebo-controlled, single ascending dose study administered three intravenous doses of DMT as a 30-s bolus followed by a 6-h infusion: 1.5 mg + 0.105 mg/min, 7.5 mg + 0.525 mg/min, and 5.0 mg + 0.7875 mg/min. Twelve female and seventeen male psychedelic-experienced and naïve healthy participants, with a mean age of 27.3 (SD 10.2, range 19–57) years, were included. No serious adverse events occurred, and all adverse events were mild in intensity and self-limiting. No significant abnormalities in vital signs or 12-lead electrocardiography, and no suicidality or treatment-emergent psychopathology occurred. Moderate interindividual pharmacokinetic variability was observed. Mild psychedelic effects were accompanied by decreases in sustained attention, postural stability, and occipital alpha electroencephalographic power at the highest dose, which peaked rapidly after bolus administration and remained relatively stable or decreased over time. Together, DMT administered intravenously as a 30-s bolus followed by a 6-h infusion and reaching maximal exposures of approximately 35 ng/mL in healthy volunteers was safe and demonstrated rapidly occurring but mild psychedelic effects, providing the basis for future proof-of-mechanism studies in patient populations.</p><p><b>Trial Registration:</b> ClinicalTrial.gov identifier: NCT05559931</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70234","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939565","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, Tolerability, and Pharmacokinetics of Single and Multiple Topical Applications of Sodium Taurodeoxycholate, a Treatment for Atopic Dermatitis","authors":"Heejae Won,&nbsp;Inseung Jeon,&nbsp;Joo-Youn Cho,&nbsp;Seung-Yong Seong,&nbsp;Kyung-Sang Yu","doi":"10.1111/cts.70242","DOIUrl":"https://doi.org/10.1111/cts.70242","url":null,"abstract":"<p>Sodium taurodeoxycholate (TDCA) gel is a novel candidate for the treatment of atopic dermatitis and is currently under clinical development. TDCA is a taurine-conjugated bile acid derivative that acts as a G protein-coupled bile acid receptor agonist and modulates immune responses. This phase 1 study aimed to investigate the safety, tolerability, and pharmacokinetic profile of sodium TDCA after single and multiple topical administrations of sodium TDCA gel in healthy male subjects. Subjects were randomized to receive a single topical administration of sodium TDCA 5, 10, 30, and 50 mg (0.05%, 0.1%, 0.3%, and 0.5% of 10 g) gel or placebo in the single-ascending dose (SAD) study (<i>N</i> = 32), and sodium TDCA 10, 30, and 50 mg (0.1%, 0.3%, and 0.5% of 10 g) gel or placebo for 28 days (<i>N</i> = 24) in the multiple-ascending dose (MAD) study. Safety profiles were assessed based on adverse events (AEs), global irritation score (GIS), and numerical pain rating scale (NPRS). Serial blood samples were collected for 24 h at baseline and up to 168 h post-dose in the SAD study and for 72 h at baseline and up to 240 h post-dose at steady state in the MAD study. No serious AEs were reported and all AEs were mild in severity for both SAD and MAD studies. The plasma concentrations of TDCA did not increase significantly after topical administrations. Changes in the plasma concentrations of TDCA likely reflected the circadian rhythm rather than the administration of sodium TDCA gel.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70242","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939100","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":"Frequency and Implications of High-Risk Pharmacogenomic Phenotypes Identified in a Diverse Australian Pediatric Oncology Cohort","authors":"Claire Moore,&nbsp;Andreas Halman,&nbsp;Tayla Stenta,&nbsp;Dhrita Khatri,&nbsp;Elizabeth Williams,&nbsp;Roxanne Dyas,&nbsp;Julian Stolper,&nbsp;David A. Elliott,&nbsp;Rachel Conyers","doi":"10.1111/cts.70246","DOIUrl":"https://doi.org/10.1111/cts.70246","url":null,"abstract":"<p>Pharmacogenomics remains underutilized in pediatric oncology, despite the existence of evidence-based guidelines. Implementation of pharmacogenomics-informed prescribing could improve medication safety and efficacy in pediatric oncology patients, who are at high risk of adverse drug reactions. This study examines the prevalence of high-risk pharmacogenomic phenotypes and the prescription of relevant medications in a diverse Australian pediatric oncology cohort, highlighting the potential impact of pharmacogenomic testing in this unique population. Whole genome sequencing data from 180 patients were analyzed to assess 14 genes with evidence-based pharmacogenomic guidelines relevant to pediatric oncology. Over 90% of patients had at least one high-risk phenotype, with 20% presenting four or more. Ondansetron, mercaptopurine, omeprazole, pantoprazole, and voriconazole were commonly prescribed medications that have pharmacogenomic prescribing recommendations, with the latter three showing the highest actionability rates. High-risk phenotypes were most frequently observed for <i>CYP2C19</i> and <i>CYP2D6</i>, with 30% of patients having a high-risk phenotype for both genes. This study underscores the potential utility of pharmacogenomics in pediatric oncology patients across a range of pharmacogenes and commonly prescribed medications. The findings support advocacy for implementing broad, pre-emptive pharmacogenomic testing in oncology patients to improve treatment safety and efficacy.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70246","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143932275","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":"Phase 1 Study Evaluating the Pharmacokinetics, Dose Proportionality, Bioavailability, and Tolerability of Subcutaneous Levothyroxine Sodium (XP-8121)","authors":"Richard Fitch,&nbsp;Diane R. Mould,&nbsp;Valentina Conoscenti,&nbsp;Robbie Huang,&nbsp;Dawn Harper","doi":"10.1111/cts.70244","DOIUrl":"https://doi.org/10.1111/cts.70244","url":null,"abstract":"<p>Levothyroxine sodium has been the cornerstone of hypothyroidism management worldwide, with daily oral administration (PO) recognized as standard of care. Oral administration of levothyroxine, however, poses challenges due to variability in pharmacokinetics (PK), influenced by factors such as gastrointestinal absorption, food/drug interactions, and patient adherence. XP-8121 (levothyroxine for subcutaneous administration) is a ready-to-use, subcutaneous (SC) injection formulation of levothyroxine in Phase 3 development. This Phase 1, single-center, 2-part study aimed to characterize the PK and dose proportionality of XP-8121 SC compared to 600 μg oral Ievothyroxine in healthy adults. Additionally, the study evaluated the safety and tolerability of XP-8121 and incorporated population pharmacokinetic (PPK) modeling to support future development. Part 1 was a randomized, open-label, crossover, fixed-sequence study (<i>n</i> = 30). Dose linearity was evaluated by escalating XP-8121 SC doses up to 1200 μg. Part 2 was an open-label, single-period study (<i>n</i> = 30) evaluating PK characteristics of a single dose of XP-8121 SC (1500 μg), potential clinical exposure range, and dose proportionality. After oral levothyroxine administration, baseline-adjusted levothyroxine concentration increased rapidly in plasma (<i>T</i>_max median: 3.1 h); absorption for all XP-8121 SC doses was slower compared to 600 μg oral levothyroxine, and levels remained elevated for 4–5 days before decreasing. Dose proportionality was confirmed, and safety results were similar between all groups. PPK analysis results suggested that weekly doses of XP-8121 SC at four times the daily oral levothyroxine dose provide similar exposure at steady state (AUC_ss). Overall, these data for XP-8121 provide adequate predictive performance to inform future phase 2 studies.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70244","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926158","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":"Elexacaftor/Tezacaftor/Ivacaftor Population Pharmacokinetics in Pediatric Patients With Cystic Fibrosis","authors":"Ngoc Hoa Truong,&nbsp;Sihem Benaboud,&nbsp;Naïm Bouazza,&nbsp;Mahassen Barboura,&nbsp;Emmanuelle Bardin,&nbsp;Michel Miralles,&nbsp;Gabrielle Lui,&nbsp;Léo Froelicher-Bournaud,&nbsp;Steeve Rouillon,&nbsp;Tiphaine Bihouee,&nbsp;Stéphanie Bui,&nbsp;Philippe Reix,&nbsp;Marie-Laure Dalphin,&nbsp;Muriel Laurans,&nbsp;Jeanne Languepin,&nbsp;Harriet Corvol,&nbsp;Françoise Troussier,&nbsp;Laurence Weiss,&nbsp;Rames Cinthia,&nbsp;Aurélie Tatopoulos,&nbsp;Eric Deneuville,&nbsp;Raphael Chiron,&nbsp;Nathalie Stremler,&nbsp;Cathy Llerena,&nbsp;Sophie Ramel,&nbsp;Caroline Perisson,&nbsp;Véronique Houdoin,&nbsp;Marie Mittaine,&nbsp;Jean-Marc Treluyer,&nbsp;Isabelle Sermet-Gaudelus,&nbsp;Frantz Foissac,&nbsp;MODUL-CF study group","doi":"10.1111/cts.70245","DOIUrl":"https://doi.org/10.1111/cts.70245","url":null,"abstract":"<p>Elexacaftor/tezacaftor/ivacaftor (ETI) significantly improves treatment outcomes for people with cystic fibrosis (pwCF) with at least one F508del allele. In 2023, the Food and Drug Administration approved ETI for children with CF aged 2–5 years. However, real-world pharmacokinetic-pharmacodynamic data for ETI in pediatric and adult populations are still limited. This study aimed to characterize the population PK of ETI in children with CF (chCF) and evaluate current dosing recommendations. Population PK modeling was conducted using Monolix software on 150 ETI concentrations obtained from therapeutic drug (TDM) monitoring in 96 children with CF aged 2–18 years, as part of the MODUL-CF study. Area under the curve was derived from individual Bayesian pharmacokinetic estimates. A one-compartment model with a lag time, first-order absorption, and elimination best described the PK of elexacaftor/ivacaftor, while the PK of tezacaftor followed a one-compartment model with first-order absorption and elimination. A large between-subject variability was observed. The effect of body weight was significant on apparent clearance and volume of distribution parameters using allometric scaling. Children weighing 30–40 kg who received the adult-recommended dose showed higher drug exposure compared to adults with cystic fibrosis. This is the first study to describe the population pharmacokinetics of ETI in chCF aged 2–18 years, revealing high between-subject variability for all three drugs. In this context, TDM is likely essential for managing ETI exposure levels and guiding dosing adjustments. The appropriateness of current dosing recommendations for children under 12 years old weighing 30–40 kg remains to be clarified.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70245","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926159","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":"Chemoprevention of Gastrointestinal Cancers: An Umbrella Review of Meta-Analyses of Randomized Controlled Trials and Cohort Studies","authors":"Jia En Chan,&nbsp;Suresh Shanmugham,&nbsp;Suresh Kumar,&nbsp;Yeong Yeh Lee,&nbsp;Siew Mooi Ching,&nbsp;Nathorn Chaiyakunapruk,&nbsp;Sajesh K. Veettil","doi":"10.1111/cts.70235","DOIUrl":"https://doi.org/10.1111/cts.70235","url":null,"abstract":"<p>Several meta-analyses have investigated the association between chemopreventive agents (CPAs) and the risk of gastrointestinal cancers, but syntheses of the quality of evidence in aggregate are lacking. This umbrella review aimed to assess the quality of evidence from meta-analyses of randomized controlled trials (RCTs) and cohort studies that examine inverse associations between CPAs and the risk of gastrointestinal cancers or any premalignant conditions. Summary effect sizes from random-effects models, between-study heterogeneity, 95% prediction interval, small-study effect, excess significance, and credibility ceilings were devised to classify the credibility of evidence from meta-analyses of cohort studies, whereas the GRADE approach was used for meta-analyses of RCTs. From 20,296 publications, 577 full-text articles were evaluated for eligibility, and 69 articles that provided 194 unique meta-analyses were included. Among meta-analyses of RCTs (<i>N</i> = 93), 26 reached statistical significance (<i>p</i> &lt; 0.05). Seven inverse associations were graded as either high quality (celecoxib and colorectal adenomas, (<i>N</i> = 4)) or moderate (aspirin and colorectal adenomas, (<i>N</i> = 2) and <i>H-pylori</i> eradication and gastric cancer (<i>N</i> = 1)). Among meta-analyses of cohort studies (<i>N</i> = 101), 60 reached statistical significance. Four inverse associations were graded as either convincing (antivirals with hepatocellular carcinoma (HCC); <i>N</i> = 1) or highly suggestive (aspirin with HCC (<i>N</i> = 2) and colorectal cancer (<i>N</i> = 1)). This review suggests that the associations with the most consistent empirical evidence were confined to those targeting the well-established risk factors of gastrointestinal cancer progression. Despite the limited established evidence, the inverse associations observed between metformin and colorectal, esophageal, and gastric cancers, as well as between statins and HCC and gastric cancer, merit further research.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70235","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143926102","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":"Integrating Sustainability Pillars Into Trial Design Decision-Making: Results of an International Survey","authors":"Pritibha Singh,&nbsp;Oleksandr Sverdlov,&nbsp;Robert A. Beckman,&nbsp;Andrea M. Burden","doi":"10.1111/cts.70241","DOIUrl":"https://doi.org/10.1111/cts.70241","url":null,"abstract":"<p>The pharmaceutical industry is increasingly shifting to decentralized clinical trials (DCTs) conducted at the patient's home, sometimes including trial material home delivery. The traditional clinical trial (CT) is conducted at the investigational site. Research suggests that centralized and decentralized trials have a large carbon footprint, with DCTs potentially providing patient-centric solutions. However, leaders must determine how to integrate environmental, economic, and social sustainability pillars into their portfolios and subsequent downstream trial-level decisions. An online survey was designed and deployed via Eidgenössische Technische Hochschule's (ETH, Swiss Federal Institute of Technology) SurveySelect software to capture perceptions of priorities and tradeoffs when deciding between a DCT and a traditional CT for each pillar. The survey closed on 31st January 2023. A total of 447 participants responded. The findings revealed that the overall cohort prioritized greenhouse gas emissions (22.4%) for environmental impact, trial probability of success (15%) for economic considerations, and patient convenience (23.3%) for social criteria. Overall, the DCT setting was perceived as more sustainable in all pillars. Participants reported tradeoffs centered on patient engagement and bringing new medicines to the market. The results from this survey provide initial insights into international multistakeholder perceptions of the priorities and tradeoffs when choosing between a traditional CT and DCT. The synthesized perceptions inform three key recommendations: the need (1) for simulation studies to guide holistic decision-making across all pillars as empirical data accumulates, (2) to protect the environment, and (3) to protect the supply chain. As empirical data accumulates, these recommendations provide directionality for further research.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143892861","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":"Protocol Development for Investigator-Sponsored Clinical Studies","authors":"Lyn Frumkin","doi":"10.1111/cts.70237","DOIUrl":"https://doi.org/10.1111/cts.70237","url":null,"abstract":"<p>Clinical trials with investigator sponsors at academic sites have increased, in part due to studies involving drug repurposing, the process of identifying new uses for existing drugs that are initially conducted in patients rather than healthy participants. In contrast to industry- or government-sponsored trials, investigator-sponsored clinical studies, also known as investigator-initiated trials, are typically conducted at one or several academic centers and are resource-limited by finances and patient numbers. These studies can serve as crucial pilot studies to inform the design of larger, more definitive clinical trials. Drawing from the experience of working with clinical researchers in academic settings, this tutorial presents guidelines for writing clinical protocols for resource-limited investigator-sponsored studies that meet international standards and optimize the detection of meaningful signals or outcomes that can lead to investigation in larger well-controlled trials.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"18 5","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70237","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143889018","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}