Introduction: Astronauts are exposed to a host of stressors that can affect their performance. Non-invasive and continuous monitoring of crew task performance as they work can identify performance decrements early so that countermeasures may be deployed in time- and safety-critical operations. A variety of non-invasive methods have been investigated, including for soldiers and officers in the field1. These performance detectors must be valid, reliable and detect subtle performance change. Here we provide a methodology for how to determine an optimal set of non-invasive performance measures that are cost-effective, specific for the population of interest and will lead to desired performance outcomes. Using astronauts as an example, we will provide a step-by-step approach to identify pragmatic performance metrics. Method & results: Fig. 1 presents the proposed process. First, define what you mean by performance by identifying critical tasks and skills in the target population. This is typically already done for training and procedures development. Next, identify the specific stressors your population will be exposed to; for astronauts this includes microgravity, high workload, fatigue, g forces, vision changes, isolation, atmospheric toxins, communication delay, etc. How performance may be compromised with exposure to each stressor alone and in concert is then determined2,3. The stressors leading to specific performance declines can define which non-invasive performance indicators to focus on. However, this relationship must either be confirmed or established. It is crucial that the cognitive tasks selected match operational task demands. It is likely that a combination of measures will be needed. Finally, degraded performance on the non-invasive measure can be used to make design decisions and to determine effective countermeasures. Discussions/conclusions: Safety critical operations cannot pause for a readiness-to-perform test to be administered. Many studies have explored methods for detecting and monitoring performance decrements. However, poor transferability of these methods from simulation to the field suggests that either different cognitive processes are being assessed or that the complexity of operations have not been captured. The dependent measures must align with the specific operational issues. We provide a methodology for identifying valid, non-invasive performance measures for the prediction of real-world task performance decline so that useful countermeasures may be proactively provided. References 1Vine CAJ, Myers SD, Coakley SL, et al. Transferability of military-specific cognitive research to military training and operations. Front Psychol 2021; 12:386-394. https://doi.org/10.3389/fpsyg.2021.604803 2Beard BL. Characterization of how CO2 level may impact crew performance related to the HSIA risk. NASA Technical Memorandum 20205011433. 2020; 1-54. Available at: https://ntrs.nasa.gov/citations/20205011433 accessed 31 Aug 2021. 3Beard BL. Characterization of international space station crew members’ workload contributing to fatigue, sleep disruption and circadian de-synchronization. NASA Technical Memorandum 20205006969. 2020; 1-46. Available at: https://ntrs.nasa.gov/citations/20205006969 accessed 31 Aug 2021.