Marisol Betensky, Manuela Albisetti, Tina Biss, Rukhmi V Bhat, Leonardo R Brandão, Thomas Diacovo, Paul Monagle, Leslie Raffini, Shoshana Revel-Vilk, C Heleen van Ommen, Hilary Whitworth, Neil A Goldenberg, Christoph Male
{"title":"儿童直接口服抗凝剂（DOAC）治疗静脉血栓栓塞试验的设计、方法和患者人群特征的系统分析。","authors":"Marisol Betensky, Manuela Albisetti, Tina Biss, Rukhmi V Bhat, Leonardo R Brandão, Thomas Diacovo, Paul Monagle, Leslie Raffini, Shoshana Revel-Vilk, C Heleen van Ommen, Hilary Whitworth, Neil A Goldenberg, Christoph Male","doi":"10.1016/j.jtha.2024.12.035","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>The pediatric direct oral anticoagulation (DOAC) trials provide an opportunity to evaluate and characterize challenges in their design and execution to inform future antithrombotic trials.</p><p><strong>Objective: </strong>To perform a systematic review of pediatric DOAC trials for the treatment of venous thromboembolism to critically appraise their methodology and understand the feasibility and challenges.</p><p><strong>Methods: </strong>Systematic search of MEDLINE, EMBASE, the Cochrane Library and ClinicalTrials.gov (January 2002 to December 2022). Studies reporting the results of interventional trials of a DOAC for the treatment of acute VTE in children, and their respective design papers were included. Trial registration information was reviewed in clinicaltrials.gov. Discrepancies in study design, targeted populations, sample size and analyses between planned and actual trial conduct were examined qualitatively.</p><p><strong>Results: </strong>Five published studies, and unpublished data for two additional trials were included. All trials had modifications to their design or methodology, and discrepancies between the trial's registration and the final published study, suggesting feasibility challenges. Modifications to the eligibility criteria, changes in sample size, challenges with recruitment of younger patients, and enrolled population not matching the clinical target population were identified for all trials. Discrepancies in outcome reporting, particularly for secondary endpoints, were also common.</p><p><strong>Conclusions: </strong>DOAC trials experienced feasibility challenges that led to design or methodology modifications. Future pediatric antithrombotic trials will need to be adaptive in their design, prioritize enrollment of younger children and input from clinicians providing care to target populations, ensure that enrolled populations match the clinical population, and select clinically meaningful endpoints.</p>","PeriodicalId":17326,"journal":{"name":"Journal of Thrombosis and Haemostasis","volume":" ","pages":""},"PeriodicalIF":5.5000,"publicationDate":"2025-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Systematic Analysis of the Design, Methodology and Patient Population Characteristics of the Pediatric Direct Oral Anticoagulant (DOAC) Trials of Venous Thromboembolism Treatment.\",\"authors\":\"Marisol Betensky, Manuela Albisetti, Tina Biss, Rukhmi V Bhat, Leonardo R Brandão, Thomas Diacovo, Paul Monagle, Leslie Raffini, Shoshana Revel-Vilk, C Heleen van Ommen, Hilary Whitworth, Neil A Goldenberg, Christoph Male\",\"doi\":\"10.1016/j.jtha.2024.12.035\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>The pediatric direct oral anticoagulation (DOAC) trials provide an opportunity to evaluate and characterize challenges in their design and execution to inform future antithrombotic trials.</p><p><strong>Objective: </strong>To perform a systematic review of pediatric DOAC trials for the treatment of venous thromboembolism to critically appraise their methodology and understand the feasibility and challenges.</p><p><strong>Methods: </strong>Systematic search of MEDLINE, EMBASE, the Cochrane Library and ClinicalTrials.gov (January 2002 to December 2022). Studies reporting the results of interventional trials of a DOAC for the treatment of acute VTE in children, and their respective design papers were included. Trial registration information was reviewed in clinicaltrials.gov. Discrepancies in study design, targeted populations, sample size and analyses between planned and actual trial conduct were examined qualitatively.</p><p><strong>Results: </strong>Five published studies, and unpublished data for two additional trials were included. All trials had modifications to their design or methodology, and discrepancies between the trial's registration and the final published study, suggesting feasibility challenges. Modifications to the eligibility criteria, changes in sample size, challenges with recruitment of younger patients, and enrolled population not matching the clinical target population were identified for all trials. Discrepancies in outcome reporting, particularly for secondary endpoints, were also common.</p><p><strong>Conclusions: </strong>DOAC trials experienced feasibility challenges that led to design or methodology modifications. Future pediatric antithrombotic trials will need to be adaptive in their design, prioritize enrollment of younger children and input from clinicians providing care to target populations, ensure that enrolled populations match the clinical population, and select clinically meaningful endpoints.</p>\",\"PeriodicalId\":17326,\"journal\":{\"name\":\"Journal of Thrombosis and Haemostasis\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.5000,\"publicationDate\":\"2025-01-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Thrombosis and Haemostasis\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.jtha.2024.12.035\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"HEMATOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Thrombosis and Haemostasis","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.jtha.2024.12.035","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"HEMATOLOGY","Score":null,"Total":0}
Systematic Analysis of the Design, Methodology and Patient Population Characteristics of the Pediatric Direct Oral Anticoagulant (DOAC) Trials of Venous Thromboembolism Treatment.
Introduction: The pediatric direct oral anticoagulation (DOAC) trials provide an opportunity to evaluate and characterize challenges in their design and execution to inform future antithrombotic trials.
Objective: To perform a systematic review of pediatric DOAC trials for the treatment of venous thromboembolism to critically appraise their methodology and understand the feasibility and challenges.
Methods: Systematic search of MEDLINE, EMBASE, the Cochrane Library and ClinicalTrials.gov (January 2002 to December 2022). Studies reporting the results of interventional trials of a DOAC for the treatment of acute VTE in children, and their respective design papers were included. Trial registration information was reviewed in clinicaltrials.gov. Discrepancies in study design, targeted populations, sample size and analyses between planned and actual trial conduct were examined qualitatively.
Results: Five published studies, and unpublished data for two additional trials were included. All trials had modifications to their design or methodology, and discrepancies between the trial's registration and the final published study, suggesting feasibility challenges. Modifications to the eligibility criteria, changes in sample size, challenges with recruitment of younger patients, and enrolled population not matching the clinical target population were identified for all trials. Discrepancies in outcome reporting, particularly for secondary endpoints, were also common.
Conclusions: DOAC trials experienced feasibility challenges that led to design or methodology modifications. Future pediatric antithrombotic trials will need to be adaptive in their design, prioritize enrollment of younger children and input from clinicians providing care to target populations, ensure that enrolled populations match the clinical population, and select clinically meaningful endpoints.
期刊介绍：
The Journal of Thrombosis and Haemostasis (JTH) serves as the official journal of the International Society on Thrombosis and Haemostasis. It is dedicated to advancing science related to thrombosis, bleeding disorders, and vascular biology through the dissemination and exchange of information and ideas within the global research community.
Types of Publications:
The journal publishes a variety of content, including:
Original research reports
State-of-the-art reviews
Brief reports
Case reports
Invited commentaries on publications in the Journal
Forum articles
Correspondence
Announcements
Scope of Contributions:
Editors invite contributions from both fundamental and clinical domains. These include:
Basic manuscripts on blood coagulation and fibrinolysis
Studies on proteins and reactions related to thrombosis and haemostasis
Research on blood platelets and their interactions with other biological systems, such as the vessel wall, blood cells, and invading organisms
Clinical manuscripts covering various topics including venous thrombosis, arterial disease, hemophilia, bleeding disorders, and platelet diseases
Clinical manuscripts may encompass etiology, diagnostics, prognosis, prevention, and treatment strategies.
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