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Interplanetary human missions to Mars and beyond will suppose a very demanding physical and psychological environment for future astronauts. Isolation, confinement, hypoxia or hypercapnia in a less pressurized atmosphere, darkness and other factors are expected to endanger a mission's success, directly influencing human performance. In order to study the effects of such environmental conditions on human beings, the SIMSKILL Experiment aims to investigate how spacecraft piloting performance decays over time by deploying a Soyuz flight simulator on the Antarctic research stations Halley VI and Concordia, which feature similar living conditions as those of a space mission, leading eventually to muscular atrophy, loss of cognitive capacities, and reduction of psycho-motor skills. This paper offers an analysis on the recorded data from the scientific campaigns in Antarctica, compared to those of the subjects in a control group in Stuttgart, Germany. An overall total of 69 subjects and more than one thousand approach and docking flights to the ISS performed in a Soyuz-TMA simulator have been analysed using a performance assessment methodology. The post-processed simulation dataset allows to recognize collective trends and find which are the essential parameters that affect the pilot's skill evolution. The results obtained from this analysis show how the influence of isolation, confinement and hypoxia in Antarctica is crucial to understand how differences in performance appear between subjects. The significance of the obtained results has been proven by means of statistical models, which show that a one-month training refreshing delivers satisfactory performance for a docking simulation, whereas a frequency of 3 months follows to a loss of piloting reliability. Moreover, the effect of isolation and hypoxia aggravates the loss of flight performance. • Use of a Soyuz space flight simulator for the analysis of flight performance. • International Space Station approach and docking procedures prove to be an optimal testbed for human performance analysis. • Antarctic isolation and confinement conditions cause a degradation on spacecraft piloting performance. • Training intervals of three months show a decrease on flight performance and reliability. • The hypoxic environment at the Concordia Station exacerbates the decay of piloting skills. [ABSTRACT FROM AUTHOR]