Development of innovative statistical approaches to biol

摘要：该项目的目标是通过提供科学合理的标准来促进FDA保护消费者的使命，以确保疫苗和免疫球蛋白的安全性和有效性，防止病毒通过血液传播，并评估与传染性海绵状脑病和受监管产品相关的风险。该项目旨在为CBER和FDA的其他中心提供有效的方法和统计途径，架起生物统计学和实验室实验微生物学和免疫学领域的桥梁。对疫苗试验发展的早期研究导致制定了被世卫组织工作组和世卫组织生物标准专家委员会接受的统计试验有效性标准和决定(批次发布)标准，用于脊髓灰质炎病毒活口服疫苗(OPV)安全性的两种替代试验：1)通过聚合酶链式反应和限制性内切酶裂解进行突变分析(MAPREC-参见参考文献)；2)转基因小鼠神经毒力试验(VI.)。此外，在保护易受脊髓灰质炎病毒感染的转基因小鼠免受野生型病毒致命攻击的基础上，开发了一种针对灭活脊髓灰质炎病毒疫苗效力的创新测试。OBRR、OTRR和OVRR的9个CBER实验室最近参与的其他合作努力包括： 1.为预测流行性腮腺炎疫苗神经毒力的测试制定统计基础； 2.评估联合疫苗的其他成分对灭活脊髓灰质炎病毒免疫反应的抑制作用； 3.巨噬细胞对HIV感染易感性的调节及感染单核细胞和细胞系的凋亡； 4.开发可靠的统计模型，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，并改进免疫分析方法，以便对感染人类T细胞淋巴病毒的献血者进行更灵敏的筛查； 5.为制定新的Rho(D)免疫球蛋白国家参比标准提供指导； 6.根据最新的统计合理原则(根据哈佛公共卫生学院提供的关于定量风险评估技术的高级培训)，为准备对传染性海绵状脑病进行定量风险分析提供了指导； 7.在CBER调节的移植组织中建立克雅病(CJD)模型并进行敏感性分析； 8.与CDRH的科学家一起，开发了一种分析方法，适用于解决食品和药物管理局管制的手术器械和植入设备传播CJD的风险。

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.