Cts-Clinical and Translational Science最新文献

{"title":"A call for reporting of tumor-specific outcomes in studies of DPYD genotyping","authors":"Jean De Dieu Ndayishimiye,&nbsp;Mari Cayabyab,&nbsp;Glenda Hoffecker,&nbsp;Victoria Wittner,&nbsp;Penn Medicine Biobank,&nbsp;Sony Tuteja","doi":"10.1111/cts.70003","DOIUrl":"10.1111/cts.70003","url":null,"abstract":"<p>We read with great interest the findings published in your journal by Muldoon et al. of real-world implementation of DPYD and UGT1A1 pharmacogenetic testing in a community-based cancer center<span>¹</span> and would like to share some comments regarding the need for specifically reporting outcomes by tumor type.</p><p>Most existing studies focus on preemptive DPYD genotyping for fluoropyrimidines in gastrointestinal cancers, rarely are outcomes reported for breast cancer. Previous studies evaluating the impact of DPYD on outcomes enrolled a small proportion of patients with breast cancer, including Muldoon, at 6%,<span>¹</span> and another recent study at 12%.<span>²</span> Because of the small number of patients, the outcomes are not typically reported separately by tumor type, it is challenging to determine the true incidence of treatment-related toxicities experienced by DPYD variant carriers in this patient population.</p><p>Preemptive DPYD testing for patients treated with fluoropyrimidine is still controversial among US oncologists, and the hesitation is even greater in breast cancer clinicians due to limited data and a lack of endorsements from the NCCN and ASCO.<span>³</span> To fill this gap in knowledge, we evaluated capecitabine-related toxicities in 62 patients with breast cancer that were enrolled in an institutional biobank.<span>⁴</span> Serious treatment-related adverse events (TRAEs) were defined as chemotherapy-related events necessitating treatment in the hospital, emergency department, or oncology evaluation center (i.e., oncology urgent care).</p><p>One of the three variant carriers experienced severe diarrhea. This TRAE began during Week 1 of Cycle 1 of capecitabine initiation and resulted in 14 days of hospitalization. The patient was dose reduced from 2000 mg twice daily to 1000 mg in the morning and 1500 mg in the evening for cycle two. However, despite the dose reduction and loperamide administration, the patient still could not tolerate the treatment. The patient skipped several doses due to worsening diarrhea, which resulted in capecitabine being later discontinued.</p><p>Patients with breast cancer treated with capecitabine are classically monitored for reversible Hand-Foot Syndrome.<span>⁵</span> However, other side effects such as diarrhea and mucositis still occur and can result in hospitalization or treatment discontinuation as demonstrated in this case study. It is critical to focus on bridging the current knowledge and practice gap around the use of DPYD genotyping and preemptive dose reduction in patients on capecitabine for breast cancer, thereby optimizing efficacy and minimizing harm in this population.</p><p>No funding was received for this work.</p><p>The authors declared no competing interests for this work.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141989329","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":"MVP enhances FGF21-induced ferroptosis in hepatocellular carcinoma by increasing lipid peroxidation through regulation of NOX4","authors":"Jinkun Xia,&nbsp;Boqi Fu,&nbsp;Zhe Wang,&nbsp;Gaolin Wen,&nbsp;Quanshui Gu,&nbsp;Dayu Chen,&nbsp;Haozhen Ren","doi":"10.1111/cts.13910","DOIUrl":"10.1111/cts.13910","url":null,"abstract":"<p>Ferroptosis is a novel, iron-dependent regulatory cell death mainly caused by an imbalance between the production and degradation of intracellular reactive oxygen species (ROS). Recently, ferroptosis induction has been considered a potential therapeutic approach for hepatocellular carcinoma (HCC). Fibroblast growth factor 21 (FGF21) is a new modulator of ferroptosis; however, the regulatory role of FGF21 in HCC ferroptosis has not been investigated. In this study, we explored the role of FGF21 and its underlying molecular mechanism in the ferroptotic death of HCC cells. We identified Major vault protein (MVP) as a target of FGF21 and revealed that knockdown of MVP inhibited the lipid peroxidation levels of HCC cells by decreasing NADPH oxidase 4 (NOX4, a major source of ROS) transcription, thereby attenuating the effect of FGF21-mediated ferroptosis. On the other hand, MVP overexpression showed the opposite results. Mechanistically, MVP binds to IRF1 and thus interferes with the interaction between IRF1 and the YAP1 promoter, leading to an increase in NOX4 transcription. Importantly, forced expression of IRF1 or downregulation of YAP1 partially reversed the effect of MVP overexpression on HCC ferroptosis. Furthermore, the results in xenograft tumor models suggested that overexpression of MVP can efficiently increase the level of lipid peroxidation in vivo. Taken together, these results provide new insights into the regulatory mechanism of ferroptosis in HCC.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cts.13910","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141983810","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":"Benchmarking pharmacogenomics genotyping tools: Performance analysis on short-read sequencing samples and depth-dependent evaluation","authors":"Andreas Halman,&nbsp;Sebastian Lunke,&nbsp;Simon Sadedin,&nbsp;Claire Moore,&nbsp;Rachel Conyers","doi":"10.1111/cts.13911","DOIUrl":"10.1111/cts.13911","url":null,"abstract":"<p>Pharmacogenomics (PGx) investigates the influence of genetics on drug responses, enabling tailored treatments for personalized healthcare. This study assessed the accuracy of genotyping six genes using whole genome sequencing with four different computational tools and various sequencing depths. The effects of using different reference genomes (GRCh38 and GRCh37) and sequence aligners (BWA-MEM and Bowtie2) were also explored. The results showed generally minor variations in tool performance across most genes; however, more notable discrepancies were observed in the analysis of the complex <i>CYP2D6</i> gene. Cyrius, a <i>CYP2D6</i>-specific tool, demonstrated the most robust performance, achieving the highest concordance rates for <i>CYP2D6</i> in all instances, comparable to the consensus approach in most cases. There were rather small differences between the samples with 20× coverage depth and those with higher depth, but the decreased performance was more evident at lower depths, particularly at 5×. Additionally, variations in <i>CYP2D6</i> results were observed when samples were aligned to different reference genomes using the same method, or to the same genome using different aligners, which led to reporting incorrect rare star alleles in several cases. These findings inform the selection of optimal PGx tools and methodologies as well as suggest that employing a consensus approach with two or more tools might be preferable for certain genes and tool combinations, especially at lower sequencing depths, to ensure accurate results. Additionally, we show how the upstream alignment can affect the performance of tools, an important factor to take into account.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11315677/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914451","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":"Using exploratory pharmacokinetic and pharmacodynamic analyses to predict the probability of flu-like symptoms in healthy volunteers and patients with chronic hepatitis B treated with the toll-like receptor 7 agonist ruzotolimod","authors":"Qiudi Jiang,&nbsp;Yuchen Zhang,&nbsp;Dan Duan,&nbsp;Sylvie Retout,&nbsp;Ruchi Upmanyu,&nbsp;Katerina Glavini,&nbsp;Miriam Triyatni,&nbsp;Yonghong Zhu,&nbsp;Joseph F. Grippo,&nbsp;Yuyan Jin","doi":"10.1111/cts.13896","DOIUrl":"10.1111/cts.13896","url":null,"abstract":"<p>Ruzotolimod (Toll-like receptor 7 (TLR7) agonist, RG7854) is an oral, small molecule immuno-modulator activating the TLR 7 and is being evaluated in patients with CHB. As with other TLR7 agonists, the study drug-related adverse events of flu-like symptoms have been reported in some participants during phase I studies with ruzotolimod. An exploratory analysis of the relationship between pharmacokinetic (PK)/pharmacodynamic (PD) and flu-like symptoms was performed in participants from two phase I studies including both healthy volunteers and NUC-suppressed CHB patients who received either single or multiple ascending doses of orally administered ruzotolimod. Linear and logistic regression were used to explore potential relationships between dose, flu-like symptoms, PK, and PD. Generalized linear regression was performed to predict the probability of flu-like symptoms of all intensities at different RO7011785 (the active metabolite of the double prodrug ruzotolimod) PK exposure. This analysis showed that single or multiple doses of ruzotolimod at ⩾100 mg, the immune PD (IFN-α, neopterin, IP-10, and the transcriptional expression of ISG15, OAS-1, MX1, and TLR7) responses increase with the RO7011785 PK exposure, which increases linearly with the doses from 3 mg to 170 mg of ruzotolimod. The analysis also showed that the probability of flu-like symptoms occurrence increases with PD responses (IFN-α and IP-10). Dose reduction of ruzotolimod can be an effective way to reduce the magnitude of PD response, thus reducing the probability of study drug-related flu-like symptoms occurrence at all intensity in the participants who are highly sensitive to PD activation and intolerant to flu-like symptoms.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310849/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908210","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":"Functional differences in the mu opioid receptor SNP 118A>G are dependent on receptor splice-variant and agonist-specific recruitment of β-arrestin","authors":"Casey Patrick,&nbsp;Utibeabasi Ettah,&nbsp;Vu Nguyen,&nbsp;Caitlin Hart,&nbsp;Evan Atchley,&nbsp;Krishna Mallela,&nbsp;Robert I. Scheinman,&nbsp;Andrew A. Monte","doi":"10.1111/cts.13888","DOIUrl":"10.1111/cts.13888","url":null,"abstract":"<p>The <i>OPRM1</i> gene codes for the mu opioid receptor (MOR) and polymorphisms are associated with complex patient clinical responses. The most studied single nucleotide polymorphism (SNP) in <i>OPRM1</i> is adenine (A) substituted by guanine (G) at position 118 (118A&gt;G, rs1799971) leading to a substitution of asparagine (Asn) for aspartic acid (Asp) at position 40 in the N terminus of the resulting protein. To date, no structural explanation for the associated clinical responses resulting from the 118A&gt;G polymorphism has been proposed. We utilized computational modeling paired with functional cellular assays to predict unstructured N- and C-terminal regions of MOR-1. Using molecular docking and post-docking energy minimizations with morphine, we show that the extracellular substitution of Asn at position 40 alters the cytoplasmic C-terminal conformation, while leaving the G-protein binding interface unaffected. A real-time BRET assay measuring G-protein and β-arrestin association with MOR r generated data that tested this prediction. Consistent with this in silico prediction, we show changes in morphine-mediated β-arrestin association with receptor variants with little change in morphine-mediated G-protein association comparing MOR-1 wild type (WT) to MOR-1_118A&gt;G. We tested the system with different opioid agonists, the <i>OPRM1</i> 118A&gt;G SNP, and different MOR splice variants (MOR-1 and MOR-1O). These results are consistent with the observation that patients with the 118A&gt;G <i>OPRM1</i> allele respond more readily to fentanyl than to morphine. In conclusion, the 118A&gt;G substitution alters receptor responses to opioids through variable C-terminal domain movements that are agonist and splice variant dependent.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11310404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141908209","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":"Regulation of exosomes as biologic medicines: Regulatory challenges faced in exosome development and manufacturing processes","authors":"Chun-Kai Wang,&nbsp;Teng-Huang Tsai,&nbsp;Chung-Hsi Lee","doi":"10.1111/cts.13904","DOIUrl":"10.1111/cts.13904","url":null,"abstract":"<p>With advances in medical technology, extracellular vesicles, also known as exosomes, are gaining widespread attention because of their potential therapeutic applications. However, their regulatory landscape is complex and varies across countries because of their unique intracellular mechanisms of action. The diversity of manufacturing techniques renders their standardization challenging, leading to a fragmented regulatory landscape. The current global regulatory framework of exosomes can be broadly classified into two strategies: one involves elucidating constituent components within exosomes and the other involves examining the physiological repercussions of their secretion. When using exosomes as therapeutic agents, they should be governed similarly to biological medicinal products. Similar to biologics, exosomes have been analyzed to determine their particle size and protein composition. An exosome-based therapeutic agent should be clinically approved after understanding its molecular composition and structure and demonstrating its pharmacokinetics and therapeutic efficacy. However, demonstrating the pharmacokinetics and therapeutic efficacy of exosomes is challenging for regulatory agencies. This article reviews the technical characteristics of exosomes, analyzes the trends in regulatory laws in various countries, and discusses the chemistry, manufacturing, and control requirements of clinical applications.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11307316/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903484","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":"Exploring the discrepancies between clinical trials and real-world data: A small-cell lung cancer study","authors":"Luca Marzano,&nbsp;Adam S. Darwich,&nbsp;Asaf Dan,&nbsp;Salomon Tendler,&nbsp;Rolf Lewensohn,&nbsp;Luigi De Petris,&nbsp;Jayanth Raghothama,&nbsp;Sebastiaan Meijer","doi":"10.1111/cts.13909","DOIUrl":"10.1111/cts.13909","url":null,"abstract":"<p>The potential of real-world data to inform clinical trial design and supplement control arms has gained much interest in recent years. The most common approach relies on reproducing control arm outcomes by matching real-world patient cohorts to clinical trial baseline populations. However, recent studies pointed out that there is a lack of replicability, generalisability, and consensus. In this article, we propose a novel approach that aims to explore and examine these discrepancies by concomitantly investigating the impact of selection criteria and operations on the measurements of outcomes from the patient data. We tested the approach on a dataset consisting of small-cell lung cancer patients receiving platinum-based chemotherapy regimens from a real-world data cohort (<i>n</i> = 223) and six clinical trial control arms (<i>n</i> = 1224). The results showed that the discrepancy between real-world and clinical trial data potentially depends on differences in both patient populations and operational conditions (e.g., frequency of assessments, and censoring), for which further investigation is required. Discovering and accounting for confounders, including hidden effects of differences in operations related to the treatment process and clinical trial study protocol, would potentially allow for improved translation between clinical trials and real-world data. Continued development of the method presented here to systematically explore and account for these differences could pave the way for transferring learning across clinical studies and developing mutual translation between the real-world and clinical trials to inform clinical study design.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11306525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141903483","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":"Early administration of ketorolac after cardiac surgery and postoperative complications: Analysis of the MIMIC-IV database","authors":"Yi Liu,&nbsp;Bo Pan,&nbsp;Jie Liu,&nbsp;Jun Zhang","doi":"10.1111/cts.13907","DOIUrl":"10.1111/cts.13907","url":null,"abstract":"<p>Inflammation may contribute to postoperative cardiac complications and ketorolac, an anti-inflammatory agent inhibiting cyclooxygenase (COX), shows promise in enhancing cardiac graft patency by suppressing endothelial cell proliferation in animal studies. However, the safety of postoperative ketorolac use remains controversial. This study investigates the association between early ketorolac application and complications following cardiac surgery. Data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database fueled this retrospective cohort study. The primary outcome is a composite of mortality, pulmonary insufficiency, severe acute kidney injury (AKI), hemorrhage or hematoma, infection, cardiogenic shock, and cerebrovascular infarction postcardiac surgery. Propensity score matching (PSM; 1:1 match, caliper 0.2), multivariate logistic regression, interaction stratification analysis, pairwise algorithmic, and overlap weight model analyses were employed. Following inclusion and exclusion criteria, 7143 patients who underwent valvular surgery or coronary artery bypass grafting (CABG) were included. PSM created a balanced cohort of 3270 individuals (1635 in the ketorolac group). The matched cohort exhibited an 8.1% overall rate of postoperative complications, with a lower composite outcome rate in patients receiving ketorolac within 48 h of surgery compared with those without (PSM, OR 0.70 [95% CI, 0.54–0.90]). Consistent associations were observed in total cohort analyses, sensitivity, and subgroup analyses. Early ketorolac use within 48 h post-CABG or valvular procedures in adults is independently associated with a lower incidence of composite postoperative adverse events. Prospective trials are warranted to assess causality.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11299995/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141894807","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":"Real-world evidence to support regulatory submissions: A landscape review and assessment of use cases","authors":"Golnoosh Alipour-Haris,&nbsp;Xinyue Liu,&nbsp;Virginia Acha,&nbsp;Almut G. Winterstein,&nbsp;Mehmet Burcu","doi":"10.1111/cts.13903","DOIUrl":"10.1111/cts.13903","url":null,"abstract":"<p>Real-world evidence (RWE) has an increasing role in preapproval settings to support the approval of new medicines and indications. The main objectives of this study were to identify and characterize regulatory use cases that utilized RWE and other related observational approaches through targeted review of publications and regulatory review documents. After screening and inclusion/exclusion, the review characterized 85 regulatory applications with RWE. A total of 31 were in oncology and 54 were in non-oncology therapeutic areas. Most were for indications in adults only (<i>N</i> = 42, 49.4%), while 13 were in pediatrics only (15.3%), and 30 were in both (35.3%). In terms of regulatory context, 59 cases (69.4%) were for an original marketing application, 24 (28.2%) were for label expansion, and 2 (2.4%) were for label modification. Most also received special regulatory designations (e.g., orphan indication, breakthrough therapy, fast track, conditional, and accelerated approvals). There were 42 cases that utilized RWE to support single-arm trials. External data to support single-arm trials were utilized in various ways across use cases, including direct matching, benchmarking, natural history studies as well as literature or previous trials. A variety of data sources were utilized, including electronic health records, claims, registries, site-based charts. Endpoints in oncology use cases commonly included overall survival, progression-free survival. In 13 use cases, RWE was not considered supportive/definitive in regulatory decision-making due to design issues (e.g., small sample size, selection bias, missing data). Overall, RWE is utilized in regulatory approval processes for new indications/label expansion across various therapeutic areas with wide range of approaches. Multifaceted cross-sector efforts are needed to further improve the quality and utility of RWE in regulatory decision-making.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11295294/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876623","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 case study of inclusion of rural populations in research: Implications for science and health equity","authors":"Devon Noonan,&nbsp;Wendy K. K. Lam,&nbsp;James Goodrich,&nbsp;Sydney Sullivan,&nbsp;Keisha Bentley-Edwards,&nbsp;Dwight Koeberl,&nbsp;Anushka Palipana,&nbsp;F. Joseph McClernon","doi":"10.1111/cts.13885","DOIUrl":"10.1111/cts.13885","url":null,"abstract":"<p>Prior research highlights that rural populations have been historically underrepresented/excluded from clinical research. The primary objective of this study was to describe the inclusion of rural populations within our research enterprise using Clinical Research Management System demographic information at a large academic medical center in the Southeast. This was a cross-sectional study using participant demographic information for all protocols entered into our Clinical Research Management System between May 2018 and March 2021. Descriptive statistics were used to analyze the representation of rural and non-rural participants and demographic breakdown by age, sex, race, and ethnicity for our entire enterprise and at the state level. We also compared Material Community Deprivation Index levels between urban and rural participants. Results indicated that 19% of the research population was classified as rural and 81% as non-rural for our entire sample, and 17.5% rural and 82.5% urban for our state-level sample. There were significant differences in race, sex, and age between rural and non-rural participants and Material Community Deprivation Indices between rural and non-rural participants. Lessons learned and recommendations for increasing the inclusion of rural populations in research are discussed.</p>","PeriodicalId":50610,"journal":{"name":"Cts-Clinical and Translational Science","volume":"17 8","pages":""},"PeriodicalIF":3.1,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11294188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141876622","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}