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在控制害虫方面具有相当大的前景。然而，转基因昆虫的田间表现仍存在不确定性。如果发现转基因昆虫相对于野生昆虫有足够的表现，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难耐受的昆虫和/或改进大规模释放不育昆虫以抑制昆虫数量。环境机构对转基因昆虫的释放具有监管利益，因为它们有可能变成野生动物，它们有可能逃脱控制，它们的流动性以及它们可能对生态系统产生不可预见的影响。然而，显然有必要让卫生机构参与有关利用转基因昆虫控制虫媒疾病的决策。因此，有必要从设计良好的研究评估转基因昆虫释放的潜在健康影响的结果。各机构对药品颁发许可证的要求导致了严格和明确定义的方案，用于评估特定药物的益处、风险、副作用和安全问题。然而，标准的临床试验并不适用于评估涉及转基因昆虫的干预措施。该项目将制定一个框架，用于评价用于控制虫媒疾病的转基因昆虫。它将独特地考虑实验设计问题和分析方法，从实验室评估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，学生将研究一种昆虫的生物学特性（及其测量的实用性），并将其性能与野生昆虫进行比较。这些指标包括：蛹产量、羽化后死亡率、交配成功率、传播能力和寿命。然后，学生将评估这些生物特性的已发表研究（以及由工业合作伙伴进行的任何未发表的研究）的设计。这些研究的设计和规模将与非劣效性研究的特定等效限度进行比较。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，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。学生将学习优化设计和实施转基因昆虫释放对健康影响研究的要求，并根据已发表的转基因昆虫病媒特征数据进行研究。由于此类干预措施的影响并非针对个人，因此学生将专注于社区随机研究。所定义的“群落”的空间尺度将根据昆虫的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算器相关的不确定性得到明确表征，为决策者和同行科学家提供关键信息，例如那些使用数学模型来回答“需要多少蚊子密度才能达到特定的疾病减少水平？”等问题的科学家。通过对所需信息采取综合办法，以支持就利用转基因昆虫释放来改善公众健康作出成功决策，该项目将提供一个连贯的框架，充分利用实验室和田间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.