Irreproducibility is a well-recognized problem in biomedical animal experimentation. Phenotypic variation in animal models is one of the many challenging causes of irreproducibility. How to deal with phenotypic variation in experimental designs is a topic of debate. Both reducing and embracing variation are highlighted as strategies for reproducibility. In this theoretical review, we use variation in mouse microbiome composition as an example to analyze this ongoing discussion, drawing on both animal research and philosophy of science. We provide a conceptual explanation of reproducibility and analyze how the microbiome affects mouse phenotypes to demonstrate that the role of the microbiome in irreproducibility can be understood in two ways: (i) the microbiome can act as a confounding factor, and (ii) the result may not be generalizable to mice harboring a different microbiome composition. We elucidate that reducing variation minimizes confounding, whereas embracing variation ensures generalizability. These contrasting strategies make dealing with variation in experimental designs extremely complex. Here, we conclude that the most effective strategy depends on the specific research aim and question. The field of biomedical animal experimentation is too broad to identify a single optimal strategy. Thus, dealing with variation should be considered on a case-by-case basis, and awareness amongst researchers is essential.

Probability of finding germline BRCA1/2 PVs varies widely among histological subtypes of ovarian carcinoma (OC).• Germline BRCA1/2 PVs are most frequently detected in high-grade serous OC patients.• Limiting testing to high-grade serous histology will be insufficient to identify all OC patients with germline BRCA1/2 PVs.

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Universal tumor DNA testing in epithelial ovarian cancer patients can function not only as an efficient prescreen for hereditary cancer testing, but may also guide treatment choices. This innovation, introduced as Tumor-First workflow, offers great opportunities, but ensuring optimal multidisciplinary collaboration is a challenge. We investigated factors that were relevant and important for large-scale implementation. In three multidisciplinary online focus groups, healthcare professionals (gynecologic oncologists, pathologists, clinical geneticists, and clinical laboratory specialists) were interviewed on factors critical for the implementation of the Tumor-First workflow. Recordings were transcribed for analysis in Atlas.ti according to the framework of Flottorp that categorizes seven implementation domains. Healthcare professionals from all disciplines endorse implementation of the Tumor-First workflow, but more detailed standardization and advice regarding the logistics of the workflow were needed. Healthcare professionals explored ways to stay informed about the different phases of the workflow and the results. They emphasized the importance of including all epithelial ovarian cancer patients in the workflow and monitoring this inclusion. Overall, healthcare professionals would appreciate supporting material for the implementation of the Tumor-First workflow in the daily work routine. Focus group discussions have revealed factors for developing a tailored implementation strategy for the Tumor-First workflow in order to optimize care for epithelial ovarian cancer patients. Future innovations affecting multidisciplinary oncology teams including clinical geneticists can benefit from the lessons learned.

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