Sample size and power calculation The sample size needed in the GymNAST study is calculated using the method for one of the most cited recommendation for prognostic research: the ‘rule of ten events per variable (EPV)’.13 14 46 Based on our sample size calculation using the EPV-approach JQ1 structure approximately 150 patients will be recruited from the ICU of our long-term intensive care hospital in Germany.15 We anticipate reaching

this study size over the time course of 3 years. Our confidence results from a cross-sectional study. We found a point prevalence of 88 patients per month of people with ICU-acquired muscle weakness and defined diagnosis of CIM/CIP in our ICUs.16 Therefore, based on this pilot study it seems to be a realistically to reach the estimated sample size in our cohort

study within 3 years of recruitment. Ethics and dissemination Ethical considerations The GymNAST study will be conducted in accordance with the ‘Helsinki Declaration’. The study is non-invasive, imposes no risk on patients, seems to have enough power to detect meaningful determinants and our protocol has been approved by the medical ethical committees. Furthermore, written informed consent is obtained from all participants or if necessary from its legal guardian. The study will be registered before publication. Dissemination The results obtained will be disseminated to the scientific, medical and general public by publication in national and international peer-reviewed journals,

as well as by presentations in conferences and meetings with clinicians dealing with patients with ICU-acquired muscle weakness syndrome. Discussion The GymNAST study will be one of the first studies with rigorous repeated measures over the time course of 1 year with daily documentation of rehabilitation therapies of people with ICU-acquired muscle weakness. Also a wide range of functional variables to describe the pattern of regaining of walking is used. Until now many prognostic studies including people with ICU-acquired muscle weakness used rather a traditional prognostic design using a baseline test and compared with ICU discharge Entinostat and follow-ups5 28 29 and only some studies measures continuously over time.47 However, instead of comparing two or more measurements of the patient’s performance it seems to be more informative to analyse the dynamic recovery systematically using equal time intervals over an appropriate time period for example, with daily assessments of walking function and with daily description of physical rehabilitation over months. This might provide a more detailed understanding of the pattern and the dynamics of recovery of walking function, and allows a better understanding of changes in clinical characteristics and the applied rehabilitation therapies.