Development of innovative statistical approaches to biol

开发创新的生物统计方法

• 批准号: 6546018
• 负责人: ROLF E TAFFS
• 金额: --
• 依托单位: BUREAU OF HEALTH PLANNING AND RESOURCES DEVELOPMENT
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6546018
• 关键词: HIV infections; apoptosis; biological products; blood bank /supply contamination; blood donor; cell line; communicable disease transmission; disease /disorder proneness /risk; human T cell lymphotropic virus type 1; human T cell lymphotropic virus type 2; immunoglobulins; immunologic assay /test; macrophage; mathematical model; microarray technology; model design /development; monocyte; mumps; poliovirus; spongiform encephalopathy; statistics /biometry; technology /technique development; vaccines; viral vaccines; virulence; virus infection mechanism

Summary: The goal of the project is to advance the FDA's mission to protect consumers by providing scientifically sound criteria to assure the safety and potency of vaccines and immune globulins, to prevent the transmission of viruses by blood, and to assess the risks associated with transmissible spongiform encephalopathies and regulated products. The project is intended to provide CBER and other Centers in the FDA with valid methods and statistical approaches that bridge the fields of biostatistics and laboratory-based experimental microbiology and immunology. Earlier research on vaccine test development resulted in development of statistical test-validity criteria and decision (lot release) criteria that were accepted by WHO Working Parties and the WHO Expert Committee on Biological Standards for two alternate tests for the safety of Poliovirus Vaccine Live Oral (OPV): 1) Mutant Analysis by PCR and Restriction Endonuclease Cleavage (MAPREC-see bibliography), and 2) the Transgenic Mouse Neurovirulence test (v.i.). In addition an innovative test was developed for the potency of inactivated poliovirus vaccine based on protection of transgenic mice susceptible to polioviruses against lethal challenge with wild-type viruses. Other more recent collaborative efforts involving nine CBER laboratories in OBRR, OTRR, and OVRR include the following: 1. development of the statistical basis for a test to predict the neurovirulence of mumps vaccines; 2. an assessment of inhibition of immune response to inactivated polioviruses by other components of combined vaccines; 3. research on the modulation of susceptibility of macrophages to infection with HIV and apoptosis in infected monocytes and cell lines; 4. development of accessible statistically sound models for validation and analysis of data generated by oligonucleotide microarrays to discriminate viral subtypes and for improved immunassays that may offer more sensitive screening of blood donors infected with human T-cell lymphotropic viruses; 5. provided guidance for development of a new national reference standard for Rho(D) immune globulin; 6. provided guidance on preparing quantitative risk analyses for transmissible spongiform encephalopathies based on the most current statistically sound principles (based on advanced training in quantitative risk assessment techniques received from the Harvard School of Public Health; 7. produced models and sensitivity analyses for Creutzfeldt-Jakob disease (CJD) in CBER-regulated transplanted tissues; 8. with CDRH scientists, development of an analytical approach suitable for addressing the risk of transmitting CJD by FDA-regulated surgical instruments and implanted devices.

摘要：该项目的目标是通过提供科学合理的标准来确保疫苗和免疫球蛋白的安全性和效力，防止病毒通过血液传播，并评估与传染性海绵状脑病和受管制产品相关的风险，从而推进 FDA 保护消费者的使命。该项目旨在为 CBER 和 FDA 的其他中心提供有效的方法和统计方法，以连接生物统计学和基于实验室的实验微生物学和免疫学领域。 关于疫苗测试开发的早期研究导致制定了统计测试有效性标准和决策（批签发）标准，这些标准被世卫组织工作组和世卫组织生物标准专家委员会接受，用于脊髓灰质炎病毒口服活疫苗（OPV）安全性的两种替代测试：1）通过PCR和限制性内切酶切割进行突变分析（MAPREC-参见参考文献），以及2）转基因小鼠 神经毒力测试（v.i.）。 此外，还针对灭活脊髓灰质炎病毒疫苗的效力开发了一项创新测试，其基础是保护易受脊髓灰质炎病毒影响的转基因小鼠免受野生型病毒的致命攻击。 最近涉及 OBRR、OTRR 和 OVRR 领域 9 个 CBER 实验室的其他合作项目包括： 1. 建立预测腮腺炎疫苗神经毒力测试的统计基础； 2. 联合疫苗其他成分对灭活脊髓灰质炎病毒免疫反应抑制作用的评估； 3. 巨噬细胞对HIV感染的易感性调节及感染单核细胞和细胞系凋亡的研究； 4. 开发可利用的统计合理模型，用于验证和分析寡核苷酸微阵列产生的数据，以区分病毒亚型，并改进免疫测定，从而可以对感染人类 T 细胞嗜淋巴细胞病毒的献血者进行更灵敏的筛查； 5. 为制定新的Rho(D)免疫球蛋白国家参考标准提供指导； 6. 根据最新的统计合理原则（基于哈佛大学公共卫生学院的定量风险评估技术高级培训），为准备传染性海绵状脑病的定量风险分析提供指导； 7. 在 CBER 调节的移植组织中制作克雅氏病 (CJD) 模型并进行敏感性分析； 8. 与 CDRH 科学家合作，开发一种适合解决通过 FDA 监管的手术器械和植入设备传播克雅氏病风险的分析方法。