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: 9014479
• 负责人: Susan E Dorman
• 金额: $ 15.75万
• 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/9014479
• 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; Pharmacotherapy; Phase; Physician Executives; Physicians; Pragmatic clinical trial; 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; novel therapeutics; patient oriented; patient oriented research; pragmatic trial; professor; programs; 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（由申请人提供）：细菌耐药性和艾滋病毒继续威胁结核病的控制，结核病是一种传染病，每年造成100多万人死亡[41]。然而，经过几十年的停滞，最近对结核病基础科学研究的投资导致了新药物和诊断方法的出现。关键的挑战和机遇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;历史上结核病领域在这方面一直进展缓慢，令人烦恼。实用的临床试验是解决这一挑战的一种有前途的机制[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，并传播给从业人员和方案的经验，这些干预措施。实用的临床试验可能特别适合结核病，其中集中的临床数据收集和结果报告是程序规范--这类似于电子病历系统如何促进糖尿病、心血管疾病和其他健康领域的实用试验的进行。虽然务实试验的想法 结核病并不是一个全新的问题，迄今为止，还没有对结核病实用试验的设计、结核病实用试验的监管方面、在各种环境中实施实用试验的策略和研究问题进行集中、系统的探索。这个K24提案的职业发展目标是扩大我的实用试验的知识，系统地探索结核病实用试验的设计和实施方面，并设计和获得一个或多个结核病治疗或诊断的大型实用试验的资金。 我们团队的以患者为导向的结核病研究将成为K24指导的背景，重点是结核病治疗和诊断的解释性临床试验-即新药和测试是否在理想条件下工作。大部分工作都是在我担任领导职务的研究联盟中完成的。我担任NIH/NIAID结核病临床诊断研究联盟（TB-CDRC）的PI，并在CDC结核病试验联盟（TBTC）内领导2期和3期治疗试验。我们在这些联盟中的工作一直处于实施高质量监测、严格实施的临床研究（包括实验室组成部分）的前沿，旨在产生具有最高内部有效性的结果。对结核病临床试验的详细了解，沿着结核病公共卫生项目工作的知识和经验，为开展旨在了解新的结核病干预措施的外部有效性（可推广性）的实用性试验的新研究提供了非常坚实的基础。 关于辅导，青年保健专业人员对结核病、艾滋病毒和全球卫生事业的兴趣大增，这带来了前所未有的机会。我在指导方面有很好的记录，包括通过成功的NIH K23项目指导一名传染病医生，并获得独立的R 01资金。K24资金将为扩大辅导活动提供保护时间。 这K24建议在于将结核病研究转化为实践和培训下一代结核病研究人员的需求和机会的联系。具体目标是： 目的1：直接指导初级研究人员在结核病患者为导向的研究。导师将主要是在研究财团的背景下，我在其中担任领导角色（NIH结核病临床诊断研究财团和CDC结核病试验财团）。初级研究人员将接受指导，因为他们在主要联合体研究中发挥作用和/或领导利用正在进行的联合体活动的小型附加项目。 目标2：开发和实施临床研究联盟内的指导模式。初步工作将集中在结核病临床诊断研究联盟和结核病试验联盟内制定和实施一项指导计划。将开发一个工具包，然后用于将该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艾滋病临床试验联盟。 目标三：建立我在结核病实用试验中的技能和知识，以便进行未来的实用试验，以评估新的结核病治疗和/或诊断是否以及在常规实践中是否有效。这将通过与实用试验领域的专家（Andrew纳恩教授和Jeremy Sugarman博士）的互动，在约翰霍普金斯彭博公共卫生学院进行的课程，参与NIH医疗保健系统研究合作实验室，以及与结核病领域的主要利益相关者的访谈来实现。