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Gene drive technologies (GDTs) bias the inheritance of a genetic element within a population of non-human organisms, promoting its progressive spread across this population. If successful, GDTs may be used to counter intractable problems such as vector-borne diseases. A key issue in the debate on GDTs relates to what governance is appropriate for these technologies. While governance mechanisms for GDTs are to a significant extent proposed and shaped by professional experts, the perspectives of these experts have not been explored in depth. A total of 33 GDT experts from different professional disciplines were interviewed to identify, better understand, and juxtapose their perspectives on GDT governance. The pseudonymized transcripts were analyzed thematically. Three main themes were identified: (1) engagement of communities, stakeholders, and publics; (2) power dynamics, and (3) decision-making. There was broad consensus amongst respondents that it is important to engage communities, stakeholders, and publics. Nonetheless, respondents had diverging views on the reasons for doing so and the timing and design of engagement. Respondents also outlined complexities and challenges related to engagement. Moreover, they brought up the power dynamics that are present in GDT research. Respondents stressed the importance of preventing the recurrence of historical injustices and reflected on dilemmas regarding whether and to what extent (foreign) researchers can legitimately make demands regarding local governance. Finally, respondents had diverging views on whether decisions about GDTs should be made in the same way as decisions about other environmental interventions, and on the decision-making model that should be used to decide about GDT deployment. The insights obtained in this interview study give rise to recommendations for the design and evaluation of GDT governance. Moreover, these insights point to unresolved normative questions that need to be addressed to move from general commitments to concrete obligations. [ABSTRACT FROM AUTHOR]

Recent developments in gene transfer and gene editing provide promising avenues for the treatment of monogenetic paediatric diseases. First-in-human (FIH) trials are a crucial step towards market authorization. Such trials involve notable uncertainties and risks, and for diseases that manifest in early childhood adult data are often lacking. In research involving minors, an important requirement to allow exposure to more than minimal risks is that there must be a prospect of direct benefit for the minors involved. However, in FIH pediatric gene therapy trials it can be questioned whether a certain therapy meets this requirement for a prospect of direct benefit and when such trials should be allowed, due to the uncertainty that accompanies them. To aid the review of these trials, we investigated definitions of the prospect of direct benefit in the ethical literature and important regulatory documents, such as the European Clinical Trial Regulation, FDA Common Rule and CIOMS guidelines. Additionally, we explored if and how preclinical research can substantiate evidence for the prospect of direct benefit. We found that "benefit" is inconsistently defined in regulatory documents, allowing different types of benefit to influence risk-benefit analysis. In some regulatory documents, direct benefit solely refers to clinical benefits that result from an intervention, whereas other regulations also include other, indirect, benefits in their definition of direct benefit. In addition, we found that what is meant with "prospect" is ill-defined in many regulatory documents. This raises questions on how this requirement for a "prospect" of direct benefit needs to be interpreted. We provide recommendations how this prospect could be understood. To do so, we look at different types of evidence - mechanical and statistical - that are used to substantiate claims of effectiveness, and thus potential direct benefit. Clearly defining and accurately interpreting the requirement for a prospect of direct benefit is crucial for effectively reviewing FIH pediatric gene therapy trials. A failure to do so could lead to mislabeling trials as providing a prospect of direct benefit, fostering therapeutic misconception and accepting trials with an unfavourable risk-benefit ratio. [ABSTRACT FROM AUTHOR]