Proposal for the revision of guidelines for clinical trials of vaccines to prevent infectious diseases in Japan

The development of vaccines against infectious diseases requires a different approach from that of ther-apeutics, because vaccines are inoculated into healthy individuals and have a preventive effect by activat-ing the immunity of the inoculated human. In Japan, The Guideline for Clinical Trials of Vaccines for the Prevention of Infectious Diseases was published in 2010 before changes occurred in the vaccine devel-opment environment in Japan, such as the introductions of foreign vaccines and simultaneous global development. This study aimed to identify current challenges in vaccine development through a questionnaire-based survey of pharmaceutical companies in Japan and by comparing the domestic and international guidelines and surveying review reports of 35 vaccines approved in Japan between April 2010 and December 2020. Identified challenges included the requirement for protective efficacy trials, efficacy evaluation of combination vaccines, development of multiregional and foreign clinical trials, and immunization of older adults and immunocompromised patients. We propose that new vaccines against infectious diseases should be evaluated for the protective efficacy, preferably through multire-gional clinical trials. Additionally, differences in the incidence of infectious diseases or in epidemic virus strains between regions may affect the trials, when multiregional clinical trials are conducted, but immunogenicity-based studies can be conducted if a correlation between protective efficacy and immunogenicity has been established. We suggest that licensed combination vaccines can be used as comparators when an antigen is added to a licensed combination vaccine. We also proposed that the effi-cacy of a vaccine in non-major subjects, such as older adults or immunocompromised patients could be evaluated by comparing immunogenicity in major subjects with the confirmed protective effects of the vaccine. It is expected that these revisions will lead to the rapid advancement of vaccine development, which should contribute to the improvement of public health.(c) 2022 Elsevier Ltd. All rights reserved.

Automated summary

The study identifies current challenges in vaccine development through a questionnaire-based survey and review of vaccine approval reports in Japan. The challenges include the requirement for protective efficacy trials, evaluation of combination vaccines, development of multiregional and foreign clinical trials, and immunization of specific populations. The study proposes the use of multiregional clinical trials for assessing protective efficacy and suggests strategies for evaluating vaccine efficacy in specific populations.