Administrative Resource

行政资源

• 批准号: 7997514
• 负责人: Reese T. Jones
• 金额: $ 7.25万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2015-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7997514
• 关键词: Accounting; Address; Adolescent; Analytical Chemistry; Area; Arts; Award; Biological Assay; Biological Availability; Biological Markers; Biometry; Clinical; Clinical Research; Clinical Trials; Cocaine; Committee Members; Communities; Consult; Consultations; Contracts; Core Facility; Cost Analysis; Cotinine; Data; Data Analyses; Data Base Management; Deuterium; Development; Doctor of Philosophy; Drug Addiction; Drug Controls; Drug Kinetics; Drug abuse; Drug effect disorder; Educational workshop; Elements; Ensure; Equipment; Equipment and Supplies; Ethanol; Ethics; Faculty; Gases; Goals; Grant; Hair; Health; Health Policy; Human; Hydrogen; Individual; Informatics; Infrastructure Activities; Institutes; Institution; Intake; Intravenous; Isotopes; Journals; Label; Laboratories; Laboratory Assistant; Light; Manuscripts; Mass Spectrum Analysis; Metabolism; Methamphetamine; Methodology; Nail plate; Nicotine; Opioid; Oral; Organic Chemistry; Outcomes Research; Paper; Patients; Pharmaceutical Preparations; Pharmacodynamics; Pharmacogenetics; Postdoctoral Fellow; Preparation; Progress Reports; Qualitative Research; Radioisotopes; Relative (related person); Reporting; Request for Applications; Research; Research Design; Research Ethics Committees; Research Methodology; Research Personnel; Research Support; Resources; Route; Services; Site; Smoke; Smokeless Tobacco; Smoker; Smoking; Solutions; Speed; Stable Isotope Labeling; Staging; Support System; Synthesis Chemistry; System; TNFRSF5 gene; Techniques; Time; Time Study; Tracer; Training; Translating; Translational Research; United States National Institutes of Health; addiction; benzoylecgonine; cocaethylene; cocaine use; computerized data processing; cost effective; data management; experience; human subject; human subject protection; hydroxycotinine; innovation; instrument; instrumentation; interest; member; metabolic abnormality assessment; nicotine replacement; programs; racial difference; ranpirnase; stable isotope; tool

Analytical and Synthetic Chemistry Laboratories The need for analytical chemistry support for clinical studies arose because of increased appreciation of the importance of pharmacokinetics in understanding drug action in the late 1970s. Neal Benowitz had initiated pharmacokinetic studies of nicotine and opioids and Reese Jones initiated studies of cocaine pharmacokinetics and pharmacodynamics, largely supported by a P50 award. At that time, our analytical laboratory consisted of a chemist, two technicians and two gas chromatographs. Since, many projects requiring analytical chemistry support were initiated and our laboratory staff has grown from three to 14: Two PhD Research Chemists, nine Staff Research Associates and three Laboratory Assistants. Major equipment includes two gas chromatographs, two desktop GC-MS systems, two HPLCs, three triple-stage quadrupole LC-MS/MS systems, and two triple-stage quadrupole GC-MS/MS systems. Support for the laboratories comes from the P30 Center, ROIs and contracts. In recent years, our group has made extensive, and we believe innovative, use of stable isotope methodology. Stable isotope-labeled drugs, unlike those labeled with radioisotopes, are no more hazardous than unlabeled drugs. A stable isotope, such as the hydrogen isotope deuterium, incorporated into a drug molecule allows the labeled drug to be used as a tracer. This is a powerful tool in studies of pharmacokinetics and metabolism, frequently used in bioavailability studies. While the natural drug is administered by its usual route, such as oral, transdermal, or by smoking, the labeled drug is simultaneously administered intravenously for pharmacokinetic characterization. We have used this technique to determine nicotine intake from smoking (Benowitz et al. 1991a) and from smokeless tobacco (Jacob et al. 1999), bioavailability of transdermal nicotine (Benowitz et al. 1991b) and bioavailability of cocaine administered by various routes. We have used stable isotope methodology to study the metabolic disposition of cocaine and ethanol, including determination of the fractional conversion of cocaine to cocaethylene (Jacob et al. 1997; Everhart et al. 1998). Stable isotope methodology was used to determine the bioavailablity of intranasal and smoked methamphetamine (Harris et al. 2003). Our use of stable isotopes is continuing and expanding. We will be utilizing labeled frans-3'-hydroxycotinine to further our understanding of nicotine pharmacogenetics and to better understand the mechanism of racial differences in nicotine metabolism.. Cotinine-d4 and the metabolite ratio will be used to study the association of the rate of metabolism and development of addiction in adolescent light smokers (Mark Rubinstein, MD, CA140216). We have used stable isotope methodology to address questions unique to the drug abuse area. One such question was to determine whether intravenous nicotine replacement would suppress nicotine intake from smoking (Benowitz and Jacob 1990). This led to the conclusion that nicotine replacement medications such as transdermal patches (at that time undergoing premarketing clinical trials) would suppress smoking even if subjects were unable to quit entirely. We have used deuterium-labeled cocaine administration to study the time course of distribution of cocaine and its metabolite benzoylecgonine into human hair. For ethical reasons, these studies had to be carried out in cocaine abusers, and the use of labeled drug guaranteed that subsequent street cocaine use would not invalidate the results (Henderson et al. 1996). We are also using labeled nicotine to study the time course of accumulation of nicotine into hair and nails, which appear to be good long term biomarkers of nicotine exposure. Such studies require laboratories with synthetic and analytical chemists, and modern analytical instruments. Extensive use of mass spectrometry is necessary when using stable isotopes. Suitably labeled drugs or metabolites may not be commercially available, and our capability in synthetic organic chemistry has been needed to prepare stable-isotope labeled drugs, metabolites, and internal standards for clinical studies and assays. In this application, we are requesting support for laboratory, and administrative staff, and for instrumentation to maintain and enhance our analytical chemistry capabilities. Administrative Core Element A modest administrative core facility has been an important and cost effective element to maintain a coordinated clinical research support program. The unifying influence of a single office that answers or efficiently redirects procedural questions, helps prepare and distribute documents and papers, facilitates purchase of specialized equipment and supplies, manages ordering of controlled drugs, gives advice on human subject protection regulatory and procedural issues, assists in progress reports and offers guidance for journal manuscripts preparation, and acts as an interface with the UCSF accounting, purchasing and research administration bureaucracy has proved valuable. Much of those functions will continue as part of the Administrative Core. However since the time of our last competing renewal submission there have been significant positive changes in resources for researchers at UCSF, particulariy the establishment of a Clinical & Translational Science Institute (CTSI) that make advisable some significant reordering of priorities and certain functions of the Administrative Core. UCSF was one of the first academic institutions to become part of the NIH's national clinical & translational science consortium. The consortium goal, that the UCSF CTSI shares is to transform and enhance clinical and translational research to ensure that the best health solutions get to patients as quickly as possible. At UCSF, CTSI is a cross-campus institute. As a part of the National Institute of Health's CTSA network, UCSF's CTSI offers to the UCSF research community activities and an infrastructure for all the major areas identified as necessary to support clinical & translational research including for example, a Clinical Research Center (formally known as GCRCs) with 9 different sites, Biostatistics, Research Design and Ethics and Data Management consulting service, and Health Policy and Community Engagement programs. Many of members of our participating projects (Guydish, McCance-Katz for example) are involved with the CTSI integrated through direct studies, members of committees, participation in workshops and courses and/or as consultants. The CTSI and associated UCSF campus wide resources offer clinical researchers biostatistical consulting, data management and analysis resources far more sophisticated and complete than could ever be offered by a P30 Center. The same is true for training and consultation on research design, for example current courses available to all UCSF faculty and trainees offer courses biostatistics, clinical trials, informatics and database management, decision/cost analysis, translating practice into evidence and qualitative research methods. Consultation available on those and other matters of interest to researcher. So, with such Campus resources what additional resources can the P30 Administrative Core offer? Consultation through the CTSI and Division of Biostatistics at UCSF provides a useful resource. However, as part of P30 core support, additional modest, relative rapid, but more focused biostatistical consulting or initial consultations will be provided from a consultant (Dr. Delucchi, also a member of the CTSI/Biostatistics Division) experienced in dealing with the types of data and research design issues most common in drug dependence research. This would provide to investigators in participating projects more efficient and targeted data analysis and data base management advice. This would supplement Division of Biostatistics campus biostatistical consultation and outcomes research resources that offers excellent service but sometimes necessitates tracking down just the right consultant and spending a fair effort in bringing them up to speed on some of the particular research questions.

分析和合成化学实验室 由于对1970年代后期药代动力学在理解药代作用中的重要性的增强，因此需要对临床研究的分析化学支持。尼尔·贝诺维茨（Neal Benowitz）启动了对尼古丁和阿片类药物和里斯·琼斯（Reese Jones）的药代动力学研究，开始了对可卡因药代动力学和药效学的研究，并在很大程度上得到了P50奖的支持。当时，我们的分析实验室由化学家，两名技术人员和两名气相色谱仪组成。由于，许多需要分析化学支持的项目开始了，我们的实验室工作人员已从三名增加到14个：两名博士学位研究化学家，九名员工研究助理和3名实验室助手。主要设备包括两种气相色谱仪，两个台式GC-MS系统，两个HPLC，三个三阶段四极杆LC-MS/MS系统和两个三个阶段四阶段四杆GC-MS/MS系统。 对实验室的支持来自P30中心，ROI和合同。 近年来，我们的小组已经广泛，我们认为创新的使用稳定的同位素方法。 稳定的同位素标记的药物与标记有放射性同位素的药物相比，危险不过 未标记的药物。合并到药物分子中的稳定的同位素，例如氢同位素氘，允许将标记的药物用作示踪剂。这是对药代动力学和代谢研究的强大工具，经常用于生物利用度研究。虽然天然药物是通过其通常的途径（例如口服，透皮或吸烟）给药的，但标记的药物同时静脉注射以进行药代动力学表征。我们已经使用了这种技术来确定吸烟（Benowitz等，1991a）和无烟烟草（Jacob等，1999），透皮尼古丁的生物利用度（Benowitz等，1991b）和各种途径施用可卡因的生物利用度。我们使用了稳定 研究可卡因和乙醇代谢处置的同位素方法，包括确定可卡因向可卡因的分数转化（Jacob等，1997; Everhart等，1998）。稳定的同位素方法用于确定鼻内和熏制甲基苯丙胺的生物宽敞性（Harris等，2003）。我们对稳定的同位素的使用正在持续和扩展。我们将利用标记为frans-3'-羟基霉素的标签，以进一步了解尼古丁药物遗传学，并更好地了解尼古丁代谢中种族差异的机制。Cotinine-D4和代谢物比率将用于研究研究的速度率青春期轻型吸烟者的代谢和成瘾的发展（Mark Rubinstein，MD，CA140216）。 我们已经使用稳定的同位素方法来解决药物滥用区域所特有的问题。一个这样的问题是确定静脉注射尼古丁的替代是否会抑制吸烟中的尼古丁摄入（Benowitz和Jacob 1990）。这导致了一个结论，即尼古丁替代药物（如透皮贴剂（当时正在进行临床试验），即使受试者无法完全退出，也会抑制吸烟。我们已经使用了氘标记的可卡因给药来研究可卡因及其代谢物苯甲酰链氨酸在人头发中的分布时间。出于道德原因，这些研究必须在可卡因施虐者中进行，并且使用标记的药物保证，随后的街道可卡因使用不会使结果无效（Henderson等，1996）。我们还使用标记的尼古丁来研究尼古丁在头发和指甲中积累的时间过程，这似乎是尼古丁暴露的长期生物标志物。 这样的研究要求实验室具有合成和分析化学家以及现代分析工具。 当使用稳定同位素时，需要广泛使用质谱法。可能无法获得适当标记的药物或代谢物，我们需要在合成有机化学方面的能力来准备稳定的同位素标记的药物，代谢产物以及临床研究和试验的内部标准。在此应用程序中，我们要求为实验室和行政人员提供支持，并要求仪器维护和增强我们的分析化学能力。 管理核心元素 适度的行政核心设施一直是维持一个重要且具有成本效益的因素 协调的临床研究支持计划。单个办公室的统一影响，该办公室回答或有效地重定向程序问题，帮助准备和分发文件和论文，促进购买专业设备和用品，管理受控药物的订购，对人类主题保护监管和程序性问题，协助，协助，协助进度报告并提供了期刊手稿准备的指南，并与UCSF会计，采购和研究管理官僚机构充当界面已被证明是有价值的。 这些功能中的许多功能将继续作为行政核心的一部分。但是，自从我们上次竞争更新提交的时间以来，UCSF的研究人员的资源已经发生了重大的积极变化，尤其是建立临床和转化科学研究所（CTSI），这些研究所（CTSI）使建议对行政行政的优先级和某些功能进行一些重大的重新订购核。 UCSF是最早成为NIH国家临床和转化科学联盟一部分的学术机构之一。联盟的目标是，UCSF CTSI股份是改造和增强临床和转化研究，以确保尽快获得最佳的健康解决方案。在UCSF，CTSI是一家跨校园研究所。作为美国国家卫生研究院CTSA网络的一部分，UCSF的CTSI向UCSF研究社区活动提供了为支持临床和转化研究所必需的所有主要领域提供的基础设施，包括临床研究中心（例如，正式称为临床研究中心） GCRC）具有9个不同的站点，生物统计学，研究设计和道德和数据管理咨询服务以及健康政策和社区参与计划。我们参与项目的许多成员（例如Guydish，McCance-Katz）与CTSI有关，通过直接研究，委员会成员，参加研讨会和/或作为顾问的CTSI涉及。 CTSI和相关的UCSF校园广泛资源为临床研究人员提供生物统计咨询，数据管理和分析资源比P30中心提供的更为复杂和完整。研究和咨询研究设计也是如此，例如，所有UCSF教师提供的当前课程提供了生物统计学，临床试验，信息学和数据库管理，决策/成本分析，将实践转化为证据和定性研究方法。 有关研究人员感兴趣的事项的咨询。 因此，借助这样的校园资源，P30行政核心可以提供哪些其他资源？ 通过UCSF的CTSI和生物统计学划分的咨询提供了有用的资源。但是，作为P30核心支持的一部分，将由顾问（DeLucchi博士，也是CTSI/Biostatistics部门的成员）提供额外的谦虚，相对快速的，但更为集中的生物统计咨询或初步咨询将提供。数据和研究设计问题在药物依赖研究中最常见。这将为参与项目的调查人员提供更高效，有针对性的数据分析和数据库管理建议。这将补充生物统计学校园生物统计学咨询和结果研究资源，这些研究资源提供出色的服务，但有时需要追踪合适的顾问，并花费公平的努力来使他们加快速度 一些特定的研究问题。