Technical Information Research Resources for Cancer Preventive Agent Development

技术支持产品包括药物背景、原理、化学和测试文件，供DCP药物开发委员会、化学预防药物开发研究组和其他DCP研究组、快速获得预防干预开发（RAPID）计划用于决策和规划临床开发策略;与DCP签订合同的监管支持、临床试验监查和储存库获取、配制和分销人员;以及进行临床前研究和临床试验的研究者（如适用）;由DCP计划工作人员进行分析和规划;由NCI计划审查委员会根据NCI科学顾问委员会的建议建立;以及由其他NCI工作人员，其他政府机构的官员和其他科学家（例如，在大学、研究机构、医疗中心、制药和其他私营部门合作者站点等）。需要复杂，全面和多学科的技术资源，因为目前DCP高级科学家每年审查和优先考虑数百种候选药物进行初步临床前评价，在里程碑决策点持续评价临床开发跟踪中的数十种药物，以进一步开发，目的是使IND和早期临床试验的药物合格，并监督一系列潜在癌症预防药物的高级临床试验。此外，-omic？与用于临床试验的试剂鉴定、优化、开发和鉴定相关的技术、分子建模和生物信息学正在增加信息管理需求，以便做出明智的决策和战略规划。 DCP已经制定并实施了一个明确定义的化学预防剂评价综合计划。该计划包括：（1）从流行病学观察、实验致癌作用和药学文献、RAPID计划的应用、与私营工业和学术研究者的相互作用和/或理论考虑中鉴定潜在的癌症预防剂，（2）通过体外和体内筛选测定使试剂有资格用于潜在的进一步开发，（3）进行功效、药理学、中间终点，在动物模型中进行候选药物的毒性研究，以及（4）准备cGMP研究药物的供应，并进行最有希望的药物的1期药代动力学和安全性试验、2期疗效和中间终点试验以及3期疗效终点试验。详细的标准划定分类的数量和质量的信息，目前存在的任何化学预防剂，从而定义需要什么额外的信息和调查，以资格的实验使用的代理人在干预试验中的人类癌症。因此，本项目的主要目的是提供研究、技术支持和分析，以协助评价正在进行的和拟议的活动。

Technical support products include agent background, rationale, chemistry, and testing documents for use in decision making and in planning clinical development strategies by the DCP Agent Development Committee; by the Chemopreventive Agent Development Research Group and other DCP Research Groups; by the Rapid Access to Preventive Intervention Development (RAPID) Program; by regulatory support, clinical trial monitoring, and repository acquisition, formulation, and distribution personnel under contract to the DCP; and, as appropriate, by investigators conducting the preclinical studies and clinical trials; by DCP program staff for analysis and planning; by NCI program review committees established following recommendations of the NCI Board of Scientific Advisors; and by other NCI staff, officials of other government agencies, and other scientists (e.g., at universities, research institutes, medical centers, pharmaceutical and other private sector collaborator sites, etc.). Sophisticated, comprehensive and multi-disciplinary technical resources are required because currently the DCP senior scientists scrutinize and prioritize hundreds of candidate agents yearly for initial preclinical evaluation, continually evaluate dozens of agents in clinical development tracks at milestone decision points for further development with the objective of qualifying agents for INDs and early clinical trials, and oversee a portfolio of advanced clinical trials of potential cancer preventive agents. Additionally, advances in ¿-omic¿ technologies, molecular modeling, and bio-informatics related to agent identification, optimization, development, and qualification for clinical testing are increasing information management requirements in order to make informed decisions and strategic planning. The DCP has established and implemented a clearly defined integrated plan for evaluating chemopreventive agents. The plan includes: (1) identifying potential cancer preventive agents from epidemiological observations, experimental carcinogenesis and pharmaceutical literature, applications to the RAPID program, interactions with private industry and academic investigators, and/or theoretical considerations, (2) qualifying agents for potential further development through in vitro and in vivo screening assays, (3) conducting efficacy, pharmacology, intermediate endpoint, and toxicity studies of candidate agents in animal models, and (4) preparing supplies of cGMP investigational agents and conducting phase 1 pharmacokinetic and safety trials, phase 2 efficacy and intermediate endpoint trials, and phase 3 efficacy endpoint trials of the most promising agents. Detailed criteria are delineated for classifying the quantity and quality of information that currently exists on any chemopreventive agent and thus defining what additional information and investigations are required to qualify the experimental use of an agent in intervention trials of human cancer. Thus, the primary purpose of this project shall be to provide research, technical support, and analysis to assist in evaluating ongoing and proposed activities.