Development of innovative statistical approaches to biol

总结：该项目的目标是推进FDA的使命，即通过提供科学合理的标准来保护消费者，以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。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，这些方法和统计方法将生物统计学和实验室实验微生物学和免疫学领域联系起来。 早期对疫苗测试开发的研究导致了统计测试有效性标准和决策的发展世卫组织工作组和世卫组织生物标准专家委员会接受的关于口服脊髓灰质炎病毒活疫苗（OPV）安全性的两种替代检测的（批放行）标准：1）通过PCR和限制性内切酶切割（MAPREC-参见参考书目）的突变体分析，和2）转基因小鼠神经毒力试验（v.i.）。 此外，基于对脊髓灰质炎病毒易感的转基因小鼠对野生型病毒致死性攻击的保护，开发了一种用于灭活脊髓灰质炎病毒疫苗效力的创新试验。 其他最近的合作努力涉及CBER在OBRR，OTRR和OVRR的九个实验室，包括： 1.为预测腮腺炎疫苗的神经毒力试验建立统计学基础; 2.评估联合疫苗的其他成分对灭活脊髓灰质炎病毒免疫应答的抑制作用; 3.研究巨噬细胞对HIV感染的易感性的调节以及受感染单核细胞和细胞系的凋亡; 4.开发可获得的统计学上合理的模型，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，并用于改进免疫测定，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.为开发新的Rho（D）免疫球蛋白国家参考标准提供了指导; 6.根据最新的统计学合理原则（根据从哈佛公共卫生学院和Palisades Corp.接受的定量风险评估技术高级培训），为编写传染性海绵状脑病定量风险分析提供指导; 7.在CBER调节的移植组织中产生克雅氏病（CJD）的风险模型和敏感性分析; 8.与CDRH科学家合作，开发一种分析方法，适用于解决FDA监管的手术器械和植入器械传播CJD的风险。 9.开发了基于报告基因表达的新型牛痘中和试验的统计学评价方法; 10.为牛痘天花疫苗临床前毒性试验的开发和验证提供了统计方法指南。

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 immunoassays 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 and Palisades Corp.); 7. produced risk 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. 9. developed statistical methods for evaluation of a novel vaccinia neutralization assay based on a reporter gene expression; 10. provided guidance on statistical approaches for the development and validation of pre-clinical toxicity assays for vaccinia-based smallpox vaccines.