Protocol for the development and validation of a driving simulator for evaluating the influence of drugs on driving performance

INTRODUCTION: Although automobile driving is often necessary in daily life, most package inserts for psychotropic drugs in Japan prohibit patients from driving under the influence of medication. This may be partially because no system to evaluate the influence of drugs on driving performance has been established. Standardized evaluation methods have been established in the Netherlands and the United States, but these cannot be implemented in Japan because of differences in road situations, traffic laws, and ethnicities. Therefore, to establish a method to evaluate the influence of drugs on driving performance in Japan, we planned a validation study using alcohol and a driving simulator (DS) and set a clinically meaningful threshold involving the standard deviation of lateral position (SDLP), which is a criterion standard evaluation item. METHODS: This study was designed as a double-blind, placebo-controlled, randomized, 4-way, fourth-order crossover trial (Williams design). Twenty-four healthy Japanese men aged 21 to 64 years will be recruited through advertisements. The participants will be required to drive daily for over 3 years and to carry the active-type aldehyde dehydrogenase (ALDH) gene polymorphism (ALDH 2∗1/∗1). Participants will be randomly assigned to 4 groups based on blood alcohol concentration (BAC): 0% (placebo), 0.025%, 0.05%, and 0.09%. The amount of alcohol intake will be calculated based on Widmark formula using a beverage that is a mixture of 40% vodka and orange juice. After a practice period, each examination period will be set with 6-day intervals. The primary outcome is SDLP in a 60-minute road-tracking test using the DS. The secondary outcomes are other evaluation items in the DS tasks and DS sickness and sleepiness according to questionnaire responses. The estimated difference in SDLP between BAC levels of 0.05% and 0% will be calculated using a linear model. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee at Hakata Clinic and the Nagoya University Medical School Hospital Bioethics Review Committee. The trial results will be disseminated through peer-reviewed publications and international conferences. TRIAL REGISTRATION: This study was registered at ClinicalTrials.gov NCT 03572985 on June 28, 2018.