Development of a rigorous design and analytical framework for the evaluation of transgenic insects for use in the control of insect-borne disease

害虫直接或作为疾病媒介危害人类健康、牲畜和作物。昆虫遗传学和基因工程为害虫的控制提供了相当大的希望。然而，转基因昆虫的田间表现仍不确定。如果发现转基因昆虫相对于野生昆虫表现得足够好，它们在改善人类健康方面的可能作用可能包括产生对病原体传播具有抗性的昆虫和/或改善不育昆虫的大规模释放以抑制昆虫数量。环境机构对释放转基因昆虫有监管利益，因为它们有可能成为野生动物，有可能逃脱控制，有可能流动，对生态系统有可能产生不可预见的影响。然而，显然需要让卫生机构参与关于使用转基因昆虫控制虫媒疾病的决策。因此，需要从设计良好的研究中获得结果，以评估转基因昆虫释放对健康的潜在影响。各机构对药品许可证的要求导致了严格和明确定义的协议，用于评估特定药物的益处、风险、副作用和安全性问题。然而，标准的临床试验不适用于评价涉及转基因昆虫的干预措施。该项目将制定一个框架，用于评价转基因昆虫用于控制虫媒疾病。它将独特地考虑实验设计问题和分析方法，从实验室评价新开发的昆虫品系的早期阶段，到实地释放，最后测量昆虫释放对人类健康的影响。在工业合作伙伴的监督下，学生将研究昆虫品系的生物学特性（及其测量的实用性），以将其性能与野生昆虫进行比较。这些将包括：蛹产量，羽化后死亡率，交配成功，传播和寿命。然后，学生将评估这些生物学特征的已发表研究（以及工业合作伙伴进行的任何未发表研究）的设计。将这些研究的设计和规模与特定等效性限值的非劣效性研究所需的设计和规模进行比较。这部分工作的监督将由学术主管领导。这项工作将根据BBSRC和合作伙伴的承诺进行，以减少研究中使用的动物数量，同时认识到估计精度和样本量之间的权衡。学生将学习转基因昆虫释放的健康影响研究的最佳设计和实施要求，并通过已发表的转基因昆虫疾病媒介特征数据进行了解。由于这些干预措施的影响并不特定于个人，学生将专注于社区随机研究。定义的“社区”的空间尺度将根据昆虫释放计划和昆虫的传播和寿命数据来选择。在整个项目过程中，将注意确保与所有估计数相关的不确定性得到明确描述，为决策者和其他科学家提供关键信息，例如那些使用数学模型来回答诸如“要达到特定的疾病减少水平，需要多大的蚊子密度？'.通过采取综合方法获取所需信息，以支持关于使用转基因昆虫释放来改善公众健康的成功决策，该项目将提供一个连贯的框架，最大限度地利用实验室和实地释放数据以及随机干预试验的数据。

Pest insects harm human health, livestock and crops, either directly or by acting as vectors of disease. Insect genetics and genetic engineering hold considerable promise for control of pest insects. However, uncertainty remains as to the field performance of transgenic insects. Were transgenic insects found to perform adequately relative to wild insects, their possible roles in improving human health could include generation of insects that are refractory to the transmission of pathogens and/or improvements in the large-scale release of sterile insects to suppress insect numbers. Environmental agencies have regulatory interests in the release of transgenic insects, based on the possibility of them becoming feral, their potential to escape containment, their mobility and the potential for unforeseen effects on ecosystems. However, there is clear need to engage health agencies in decision-making regarding the use of transgenic insects to control insect-borne disease. Thus, there is a need for results from well designed studies evaluating the potential health impacts of transgenic insect releases. The requirements of agencies to license medicinal products have led to rigorous and clearly defined protocols for evaluating the benefits, risks, side effects and safety issues for particular drugs. However, standard clinical trials do not apply to evaluation of interventions involving transgenic insects. This project will develop a framework for the evaluation of transgenic insects for use in the control of insect-borne disease. It will uniquely consider experimental design issues and analytical methods from the early stages of laboratory evaluation of a newly developed insect strain, through field releases and finally measurement of the impact of insect releases on the health of human populations. Under the supervision of the industrial partner, the student will study the biological characteristics (and the practicalities of the measurement thereof) of an insect strain required to compare its performance to wild insects. These will include: pupal yield, post-eclosion mortality, mating success, dispersal and longevity. The student will then evaluate the designs of published studies (as well as any unpublished studies undertaken by the industrial partner) of these biological characteristics. The design and the size of these studies will be compared with those required of non-inferiority studies for particular equivalence limits. The supervision of this component of the work will be led by the academic supervisor. This work will be conducted in light of the commitment by the BBSRC and the partners to reduce the number of animals used in research, while recognizing the trade-off between the estimate precision and sample size. The student will study requirements for the optimal design and implementation of studies of the health impacts of transgenic insect releases, informed by published data on characteristics of transgenic insect disease vectors. Because the impacts of such interventions are not specific to individuals, the student will concentrate on community randomised studies. The spatial scale of the defined 'community' will be chosen in light of both the insect release plan and data on the insect's dispersal and longevity. Throughout the project care will be taken to ensure that the uncertainties associated with all estimators are clearly characterised, providing crucial information to both policy makers and to fellow scientists, such as those using mathematical modelling to answer questions like 'What mosquito density is required to achieve a particular level of disease reduction?'. By taking an integrated approach to the information required to support successful decision making on the use of transgenic insect releases to improve public health, the project will provide a coherent framework making best use of lab and field release data in conjunction with data from randomised intervention trials.