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Objective: Only reproducible results are of significance to science. The lack of suitable standards and appropriate support of standards in software tools has led to numerous publications with irreproducible results. Our objectives are to identify the key challenges of reproducible research and to highlight existing solutions. Results: In this paper, we summarize problems concerning reproducibility in systems biology and systems medicine. We focus on initiatives, standards, and software tools that aim to improve the reproducibility of simulation studies. Conclusions: The long-term success of systems biology and systems medicine depends on trustworthy models and simulations. This requires openness to ensure reusability and transparency to enable reproducibility of results in these fields. [ABSTRACT FROM PUBLISHER]