Statistical analysis
REGRESSION, SECONDARY
Analysis was conducted in the per-protocol population due to the physiological nature of this study and for reasons of feasibility.Mixed model linear regression with all available data was performed to analyze the effect of altitude and drug on DE and secondary outcomes such as laboratory values, vital parameters, or reaction time. If necessary, variable transformation was implemented to ensure normal distribution of residuals.Besides including location and drug as independent variables, the model for DE also controlled for age, sex, target direction, number of valid movements and consecutive movement*block interaction effects over a section. In a stepwise forward selection approach oxygen saturation and mean arterial pressure were added as further factors.To assess the overnight learning effect, a more complex model was developed including the 60° adaptation, immediate and post-sleep recall sections as independent variables.The effects of altitude and medication on the probability of performing a valid movement were studied with a mixed logistic regression model developed using a stepwise forward selection approach. As this model showed a significant influence of drug and altitude on movement validity, movements excluded from DE analysis were not assumed to be missing at random. Hence, inverse probability weighting using the predicted result from the logistic regression was incorporated in the linear regression model for DE described above (See Supporting Information, S1–S3 Tables in Data analysis was performed with Stata 14.2 (Stata Corp., College Station, Texas, USA). A p-value < 0.05 was considered as statistically significant.