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

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 The student will then evaluate the designs of published studies (as well as any unpublished studies undertaken by the industrial partner) of these biological characteristics.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.