Overcoming methodological barriers in electronic nose clinical studies, a simulation data-based approach

Analysis of volatile organic compounds by electronic nose (e-nose) may address gaps in non-invasive screening for neoplasia. Machine learning impacts study design and sample size requirements, but guidance on clinical study design is limited. This study evaluates how neoplasia prevalence, augmented data, and the number of e-nose devices impact sample size requirements. Simulated e-nose breath test data were created using real-world study data. We examined the effect of varying neoplasia prevalence (50%-5%) and data augmentation on model performance, as well as the impact of using multiple devices. Prediction models were developed using single value decomposition and random forest, and convolutional neural networks. Model performance was displayed as area under the receiver operating characteristics curve and F1-score. Stable model performance was defined as the phase where additional data no longer increases model performance. We found that lower neoplasia prevalence significantly increased sample size requirements, with low-prevalence settings (5%) requiring up to five times more data than high-prevalence settings (50%) for stable model performance. Model performance varied between devices, and integrating data from multiple devices required larger sample sizes. Approximately 400 data points per device at 50% prevalence, and 2100 data points at 5% prevalence, were necessary to reach stable model performance. Concluding, sample size requirements for e-nose studies are heavily influenced by disease prevalence and the number of devices used. Limiting device variability and ensuring sufficient case and control samples per device are crucial for achieving reliable predictive performance. Specific requirements will vary based on sensor and disease characteristics.<b>ClinicalTrials.gov Identifier:</b>Clinicaltrials.gov Identifier NCT03346005 (model study) and NCT04357158 (validation study).