Evolving partnership: A National Center for Global Health and Medicine Resilient Training Model for clinical research professionals during the COVID-19 pandemic.

The clinical trial industry has encountered challenging circumstances in which the increasing number of trials outpaces the number of trial specialists. For instance, there has been an unprecedented demand for clinical trials following the Covid-19 pandemic, which has worsened the global shortage of qualified personnel. It is therefore imperative to produce more qualified clinical trial professionals. An adaptive and collaborative training model was implemented by the National Center for Global Health and Medicine through the Department of International Trials. This aimed at building capacity among health workers in developing countries and providing them with the skills to be able to conduct all phases of the clinical trial from protocol design to publication of results. It also seeks to foster collaboration and partnership between local health workers and international experts. Since 2016, we have implemented a Japan-led training program, and since 2020, the COVID-19 pandemic has ushered in a shift from a single Train-the-trainer model (ToT) to a mixed model, the Evolving Partnership Training (ePT). In this model, we applied four different methods: train-the-trainer, needs-oriented training, open symposiums, and advanced learning. The total number of training participants increased exponentially from a total of 41 between 2016-2020 to 2,810 in 2021. Our experience has proven that despite the constraint of the pandemic, the ePT is a viable approach compared to a single method for providing quality training and increasing the number of participants.

Boosting multiregional clinical trials (MRCT) in Asia through the establishment of the Japan-led network for clinical research, the ARO alliance for ASEAN & East Asia (ARISE).

There is an increasing demand for clinical research, and this demand has particularly increased during the novel coronavirus infection (COVID-19) pandemic. In the light of these events, fostering international cooperation has become essential. The ARO Alliance for ASEAN & East Asia (ARISE) is a Japan-led international network for clinical research in Asia that was established to encourage and facilitate multiregional clinical trials. The Department of International Trials of the National Center for Global Health and Medicine (NCGM) launched ARISE in December 2021 to pursue efficacious, high-quality clinical research and ensure rapid responses to health emergencies, with the timely provision of new medicinal products to patients in Asia.

Knowledge, attitude, perception, and factors associated with the risk perception of COVID‐19 among nursing college students in Japanese universities: A cross‐sectional study

Background and Aim The spread of coronavirus disease 2019 (COVID‐19) in the world has brought different attitudes and perceptions among social strata. Nursing students being future first‐line healthcare workers are more at risk of being infected and exposed to various stressors from shared information. The objectives of this study were to evaluate the knowledge, attitude, and perception of COVID‐19 among nursing students and to estimate predictors of their risk perception. Methods We conducted an online survey among undergraduate nursing students at three selected Japanese Universities. Data on knowledge, attitude, and perception toward COVID‐19 were collected using a structured questionnaire. We performed multiple logistic regression analyses to identify factors associated with the risk perception toward COVID‐19 infection. Results Of the 414 nursing students who participated in the study, 368 (90.4%) reported that the media including radio, television, internet, and/or social media were the main source of knowledge. Fever (96.1%) and dry cough (89.6%) were reported as the main symptoms. Regarding the attitude toward the treatment and preventive measures, almost 92.8% of participants recommended the use of vaccines. Being female appeared to be three times associated with the fear of getting infected (adjusted odds ratio [aOR]:3.03;95% confidence interval [CI]: 1.21–7.58). Students who took part in extracurricular activities reported that they feared being infected with COVID‐19 (aOR:2.62;95% CI:1.33–5.16). Other factors did not show an association. Conclusion Knowledge and attitude of nursing students toward COVID‐19 were accurate for the majority of them, with the main source of information being the media. Practicing extracurricular activities and being female were associated with the fear of the disease. Efficient and controlled communication is needed during widespread disease outbreaks.

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 therapeutics, because vaccines are inoculated into healthy individuals and have a preventive effect by activating 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 development 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 multiregional 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 efficacy 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.

The efficacy and adverse effects of favipiravir on patients with COVID-19: A systematic review and meta-analysis of published clinical trials and observational studies.

OBJECTIVES: This study aimed to evaluate the efficacy and adverse events of favipiravir in patients with COVID-19. METHODS: Our protocol was registered on PROSPERO (CRD42020206305). Fourteen databases were searched until February 8th, 2021. An update search for new RCTs was done on March 2nd, 2022. Meta-analysis was done for randomized controlled trials (RCTs) and non-RCTs. RESULTS: Overall, 157 studies (24 RCTs, 1 non-RCT, 21 observational studies, 2 case series, and 106 case reports) were included. On hospitalized patients, in comparison to standard of care, favipiravir showed a higher rate of viral clearance at day 5 (RR = 1.60, p = 0.02), defervescence at day 3-4 (RR = 1.99, p <0.01), chest radiological improvement (RR = 1.33, p <0.01), hospital discharge at day 10-11 (RR = 1.19, p <0.01), and shorter clinical improvement time (MD = -1.18, p = 0.05). Regarding adverse events, favipiravir groups had higher rates of hyperuricemia (RR = 9.42, p <0.01), increased alanine aminotransferase (RR = 1.35, p <0.01) but lower rates of nausea (RR = 0.42, p <0.01) and vomiting (R R= 0.19, p=0.02). There were no differences regarding mortality (RR=1.19, p=0.32), and increased aspartate aminotransferase (RR = 1.11, p = 0.25). On nonhospitalized patients, no significant differences were reported. CONCLUSIONS: Adding favipiravir to the standard of care provides better outcomes for hospitalized patients with COVID-19. Pregnant, lactating women, and patients with a history of hyperuricemia should avoid using favipiravir.

Proposal for the revision of the guidelines for Non-clinical studies of vaccines for the prevention of infectious diseases in Japan.

The efficacy and safety of vaccines for the prevention of infectious diseases are mostly evaluated based on the induction of an immune response against antigens, and do not necessarily depend on the dose administered. Therefore, there are some specific aspects that need to be considered in the development of vaccines and have been described in "The Guidelines for the non-clinical studies of vaccines for the prevention of infectious disease" in Japan. Recent changes in the vaccine development field, such as the introduction of vaccines developed overseas in Japan and vaccine development on a global scale have increased the need for revision of these guidelines. In this study, we identified the current challenges in the development of vaccines through comparison of Japanese and international guidelines. We conducted a questionnaire-based survey of pharmaceutical industries in Japan, and found issues related to non-clinical studies, such as the necessity of safety pharmacology studies and repeated-dose toxicity studies for each route of administration. We examined international guidelines on these issues as well as review reports by regulatory authorities, and determined that the results of repeated-dose toxicity studies can be used to decide whether safety pharmacology studies are required, and that studies to evaluate toxicity due to systemic effects may not be necessary for both intramuscular and subcutaneous administration. We propose revision of the guidelines for the non-clinical studies of vaccines in Japan taking international harmonizaion into account. We expected that the revised guidelines will promote smooth and rational vaccine development.