Multidisciplinary Clinical Research and Mentoring in Tuberculosis Diagnostics

结核病诊断的多学科临床研究和指导

• 批准号: 8891560
• 负责人: Susan E Dorman
• 金额: $ 16.03万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-02-13 至 2020-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8891560
• 关键词: AIDS clinical trial group; Acquired Immunodeficiency Syndrome; Address; Area; Award; Bacterial Drug Resistance; Baltimore; Basic Science; Bioethics; Cardiovascular Diseases; Centers for Disease Control and Prevention (U.S.); Cessation of life; Cities; Clinical; Clinical Data; Clinical Management; Clinical Research; Clinical Trials; Collaborations; Communicable Diseases; Computerized Medical Record; Data Collection; Diabetes Mellitus; Diagnosis; Diagnostic; Diagnostics Research; Drug resistance in tuberculosis; Effectiveness; Epidemiologic Studies; Foundations; Funding; Future; Gap Junctions; Goals; HIV; Health; Health Professional; Health system; Healthcare Systems; Institutes; International; Intervention; Interview; Investments; Knowledge; Laboratories; Lead; Leadership; London; Medical Research; Mentors; Mentorship; Modeling; Monitor; National Institute of Allergy and Infectious Disease; Outcome; Pharmaceutical Preparations; Phase; Physician Executives; Physicians; Process; Public Health; Public Health Practice; Public Health Schools; Pulmonary Tuberculosis; Randomized; Randomized Clinical Trials; Regimen; Reporting; Research; Research Activity; Research Personnel; Role; Services; System; Therapeutic; Therapeutic Trials; Time; Training; Translating; Translational Research; Translations; Tuberculosis; Uncertainty; United States National Institutes of Health; Universities; Work; base; career; career development; clinical practice; collaboratory; college; design; diagnostic accuracy; drug efficacy; drug testing; experience; global health; health care delivery; interest; multidisciplinary; next generation; novel diagnostics; patient oriented; patient oriented research; pragmatic trial; professor; programs; public health relevance; research to practice; rifapentine; routine practice; skills; systems research; tool; treatment as usual; treatment duration; tuberculosis treatment; AIDS clinical trial group; Acquired Immunodeficiency Syndrome; Address; Area; Award; Bacterial Drug Resistance; Baltimore; Basic Science; Bioethics; Cardiovascular Diseases; Centers for Disease Control and Prevention (U.S.); Cessation of life; Cities; Clinical; Clinical Data; Clinical Management; Clinical Research; Clinical Trials; Collaborations; Communicable Diseases; Computerized Medical Record; Data Collection; Diabetes Mellitus; Diagnosis; Diagnostic; Diagnostics Research; Drug resistance in tuberculosis; Effectiveness; Epidemiologic Studies; Foundations; Funding; Future; Gap Junctions; Goals; HIV; Health; Health Professional; Health system; Healthcare Systems; Institutes; International; Intervention; Interview; Investments; Knowledge; Laboratories; Lead; Leadership; London; Medical Research; Mentors; Mentorship; Modeling; Monitor; National Institute of Allergy and Infectious Disease; Outcome; Pharmaceutical Preparations; Phase; Physician Executives; Physicians; Process; Public Health; Public Health Practice; Public Health Schools; Pulmonary Tuberculosis; Randomized; Randomized Clinical Trials; Regimen; Reporting; Research; Research Activity; Research Personnel; Role; Services; System; Therapeutic; Therapeutic Trials; Time; Training; Translating; Translational Research; Translations; Tuberculosis; Uncertainty; United States National Institutes of Health; Universities; Work; base; career; career development; clinical practice; collaboratory; college; design; diagnostic accuracy; drug efficacy; drug testing; experience; global health; health care delivery; interest; multidisciplinary; next generation; novel diagnostics; patient oriented; patient oriented research; pragmatic trial; professor; programs; public health relevance; research to practice; rifapentine; routine practice; skills; systems research; tool; treatment as usual; treatment duration; tuberculosis treatment

 DESCRIPTION (provided by applicant): Bacterial drug resistance and HIV continue to threaten control of tuberculosis, a communicable disease responsible for well over one million deaths annually [41]. However, after decades of stasis, recent investment in tuberculosis basic science research has resulted in the emergence of new drugs and diagnostics. Critical challenges and opportunities lie in translating recent research advances and new tools into tuberculosis public health practice; historically the tuberculosis field has been vexingly slow in this regard. Pragmatic clinical trials are a promising mechanism to address this challenge [3]. Specifically, pragmatic trials will help to understand the effectiveness of new interventions under usual-care conditions, and to disseminate to practitioners and programs experience with those interventions. Pragmatic clinical trials may be particularly well-suited to tuberculosis, in which centralized clinical data collection and outcome reporting are programmatic norms - this is analogous to how electronic medical record systems are facilitating conduct of pragmatic trials in diabetes, cardiovascular disease, and other health fields. While the idea of pragmatic trials in tuberculosis is not entirely new, to date there has been no focused, systematic exploration of the design of tuberculosis pragmatic trials, regulatory facets of tuberculosis pragmatic trials, an strategies for pragmatic trial implementation across a variety of settings and research questions. The career development goal of this K24 proposal is to expand my knowledge of pragmatic trials, to systematically explore facets of the design and implementation of tuberculosis pragmatic trials, and to design and obtain funding for one or more large pragmatic trials in tuberculosis treatment or diagnosis. Our team's patient-oriented tuberculosis research, which will be the context for mentoring under this K24, is focused on explanatory clinical trials of tuberculosis therapeutics and diagnostics - that is, whether new drugs and tests work under ideal conditions. Much of this work is done in the context of research consortia in which I have leadership roles. I serve as a PI of the NIH/NIAID Tuberculosis Clinical Diagnostics Research Consortium (TB-CDRC), and lead phase 2 and phase 3 therapeutics trials within the CDC Tuberculosis Trials Consortium (TBTC). Our work in these consortia has been at the vanguard of implementation of highly quality monitored, strictly implemented clinical studies (including laboratory components) intended to produce results with the highest possible internal validity. A detailed understanding of tuberculosis clinical trials, along with knowledge and experience in tuberculosis public health program work, provides a very strong foundation from which to undertake new research into pragmatic trials aimed at understanding external validity (generalizability) of new tuberculosis interventions. With respect to mentoring, there is unprecedented opportunity arising from the surge in interest among young health professionals in careers in tuberculosis, HIV, and global health. I have a strong track record in mentoring, including having mentored one infectious disease physician through a successful NIH K23 project and on to independent R01 funding. K24 funding will provide protected time for expansion of mentoring activities. This K24 proposal lies at the nexus of the needs and opportunities for translating tuberculosis research into practice and for training the next generation of investigators in patient-oriented research in tuberculosis. The specific aims are: Aim 1: To directly mentor junior investigators in patient-oriented research in tuberculosis. Mentorship will be principally in the context of research consortia in which I have leadership roles (NIH Tuberculosis Clinical Diagnostics Research Consortium and CDC Tuberculosis Trials Consortium). Junior investigators will be mentored as they take on roles within main consortium studies and/or lead smaller add-on projects that leverage ongoing consortium activities. Aim 2: To develop and implement a model for mentoring within clinical research consortia. Initial work will focus on developing and implementing a mentoring program within the Tuberculosis Clinical Diagnostics Research Consortium and Tuberculosis Trials Consortium. A toolkit will be developed, and then used to expand the model to other clinical research consortia, for example the CDC Tuberculosis Epidemiologic Studies Consortium and the NIH AIDS Clinical Trials Consortium. Aim 3: To build my skills and knowledge in the conduct of pragmatic trials in tuberculosis, in order to conduct future pragmatic trials to assess whether and which new tuberculosis treatments and/or diagnostics work in routine practice. This will be accomplished through interaction with experts in the field of pragmatic trials (Prof. Andrew Nunn and Dr. Jeremy Sugarman), coursework undertaken at Johns Hopkins Bloomberg School of Public Health, engagement in the NIH Health Care Systems Research Collaboratory, and interviews with key stakeholders in the tuberculosis field.

 描述（由适用提供）：细菌耐药性和艾滋病毒继续威胁控制结核病，该结核病是一种可传播的疾病，导致每年超过100万人死亡[41]。但是，经过数十年的停滞，最近对结核病基础科学研究的投资导致新药和诊断的出现。关键的挑战和机会在于将最新的研究进展和新工具转化为结核病公共卫生实践；从历史上看，在这方面，结核病领域一直令人难以置信。务实的临床试验是应对这一挑战的有前途的机制[3]。具体而言，务实的​​试验将有助于了解新干预措施的有效性 通常的护理条件，并传播到从业者和计划中经历这些干预措施。务实的临床试验可能特别适合结核病，其中集中式临床数据收集和结果报告是程序规范 - 这类似于电子医疗记录系统如何支持在糖尿病，心血管疾病和其他健康领域中进行实用试验的进行实用试验。而务实的考验想法 结核病并不全新，迄今为止，还没有针对结核病设计设计的专注，系统的探索，结核病实用试验的监管方面，这是一种实施各种环境和研究问题的实施务实试验的策略和研究问题。这项K24提案的职业发展目标是扩大我对务实试验的了解，系统地探索结核病的设计和实施方面，并在结核病治疗或诊断治疗中设计和获得一项或多项大型务实试验的设计和资金。 我们的团队以患者为导向的结核病研究将是在此K24下进行指导的背景，重点是诱发结核病治疗和诊断的临床试验，即在理想的条件下，新药物和测试是否起作用。这项工作的大部分是在我担任领导角色的研究财团的背景下完成的。我在CDC结核病试验（TBTC）中充当NIH/NIH/NIAID结核病临床诊断研究联盟（TB-CDRC）的PI，以及铅第2阶段和3期治疗试验。我们在这些联盟中的工作一直是实施高质量监测的，严格实施的临床研究（包括实验室组件）的先锋，旨在产生最高的内部有效性结果。对结核病临床试验的详细理解，以及结核病公共卫生计划工作的知识和经验，为旨在了解新的结核病干预措施的外部有效性（普遍性）的实用试验提供了非常强大的基础。 关于心理，在结核病，艾滋病毒和全球卫生中，年轻卫生专业人员对年轻卫生专业人员的兴趣激增，引起了前所未有的机会。我在心理方面有着良好的记录，包括通过成功的NIH K23项目和独立R01资金进行了脑力。 K24资金将为扩大心理活动提供受保护的时间。 这项K24提案是将结核病研究转化为实践的下一个需求和机会，并培训下一代研究人员从事结核病研究的研究。具体目的是： 目的1：直接指导初级研究人员的结核病研究。指导将主要是在我担任领导角色的研究联盟的背景下（NIH结核病临床诊断研究联盟和CDC结核病试验联盟）。初级调查人员将在主要财团研究中担任角色和/或领导较小的附加项目，以利用正在进行的财团活动。 目标2：在临床研究联盟内开发和实施一种心理模型。最初的工作将着重于制定和实施结核病临床诊断研究联盟和结核病试验联盟中的心理计划。将开发一个工具包，然后用来将模型扩展到其他临床研究联盟，例如CDC结核病流行病学研究联盟和NIH AIDS临床试验联盟。 目标3：在结核病进行务实试验中建立我的技能和知识，以进行未来的实用试验，以评估在常规实践中是否以及哪些新的结核病治疗和/或诊断工作。这将通过与务实试验领域的专家互动（Andrew Nunn教授和Jeremy Sugarman博士），在Johns Hopkins Bloomberg公共卫生学院进行的课程，参与NIH Health Care System Research Consergoration的课程，以及与Tuberculisosis Field Field Field Fielders的访谈者的参与。