Mapping time use in clinical trials for vaccines against emerging infectious diseases.

ABSTRACT

BACKGROUND: Vaccines are potent tools to prevent outbreaks of emerging infectious diseases from becoming epidemics and need to be developed at an accelerated pace to have any impact on the course of an ongoing epidemic. The aim of this study was to describe time use in the execution of vaccine trials, to identify steps that could be accelerated to improve preparedness and planning for future emerging infectious diseases vaccine trials. METHODS: We used a mixed-methods approach to map time use and process steps that could be accelerated during vaccine trials. Trials for vaccines against infectious diseases registered in three global trial databases reported in the period 2011-2017 were eligible to join the survey. We invited sponsors to contribute data through a predefined structured questionnaire for clinical trial process metrics. Data were stratified by trial phase, disease type (i.e. emerging infectious diseases or not emerging infectious diseases), sponsor type, and continent. Qualitative interviews were conducted with purposively selected sponsors, and thematic analysis of the interview transcripts was performed. RESULTS: Based on data from 155 vaccine trials including 29,071 subjects, 52% were phase I, 23% phase II, and 25% phase III. We found that the regulatory approval, subject enrollment, study execution, and study close-out accounted for most of the cycle time of the vaccine trial process. Cycle times for the regulatory and ethical approvals, contract agreement, site initiation, and study execution were shorter in trials conducted during outbreaks. Qualitative interviews indicated that early engagement of the regulatory and independent ethical committee authorities in planning the vaccine trials was critical for saving time in trial approval. Furthermore, adapting the trial implementation to the reality of the study sites and active involvement of the local investigators during the planning of the trial and protocol writing were stated to be of paramount importance to successful completion of trials at an accelerated pace. CONCLUSION: The regulatory approval, subject recruitment, study execution, and close-out cycle times accounted for most of the vaccine trial time use and are activities that could be accelerated during a vaccine trial planning and implementation. We encourage tracking of key cycle time metrics and facilitating sharing of knowledge across industry and academia, as this may serve to reduce the time from index case detection to access of a vaccine during emerging infectious diseases epidemics.