10. M-COU in light of ΔR (Table on the left) Consider M-COU in the context of differences between R-V and R-COU. 7. Is it appropriate to use the model aspects listed in Step 4 to make predictions about R-COU? Provide rationale, evidence, or discussion. Assume that these model aspects are appropriate for R-V (or refer to the validation results) and then consider each of the differences in DR (listed in Step 6). If the validation comparison is deemed adequate, can we be confident that the aspects that are the same in M-V and M-COU, as listed in Step 4, are appropriate for the COU? Differences between R-V and R-COU, listed in Step 6, might mean that this is not so. For each aspect listed in Step 4, provide rationale, evidence or discussion on whether the model aspect is appropriate for the COU, Use the Table on right, and for each entry, ask: “is it acceptable to use this model aspect (associated column) for making predictions about R-COU, given this difference (row)?” 5. Describe ∆M Describe the aspects of the model that are different between M-V and M-COU • Phantom → virtual human • Path of device lead • … 3. Describe primary validation evidence Provide details on both the validation setting and the model for the validation setting. R-V: A saline-filled phantom implanted with the new device was placed inside an RF coil; temperature changes were measured… M-V: A geometrical model of the phantom was used with the embedded device with one RF coil. The EM/thermal model was used to compute temperature change… 1.Describe COU Provide details on both the ‘reality’ to be modelled and the model that will simulate ‘reality’. For example: R-COU: Estimate the worst-case temperature change in the tissue around the implant that might occur during MRI across a wide-array of parameters… M-COU: Solve an electromagnetic model and a thermal model using a human body anatomical model containing the device, to determine the maximum temperature change under simulated MRI conditions for a range of parameters that closely represent the clinical setting… 2. Sources of validation evidence Describe the different types of validation results and sources of evidence. Denote one as the primary validation evidence 1. Primary validation evidence: Phantom validation experiments using the new device. 2. Animal validation experiments using a previous version of the device. 3. All historical validation evidence regarding similar models with different devices. 4. Literature regarding electromagnetic simulations using human anatomical models 6. Describe ∆R Describe the relevant differences between R-V and R-COU • Phantom → human (both sexes, range of ages and BMIs) • Path of device lead • MR system present in R-COU, only RF coil in R-V • … Applicability Analysis for Biomedical Computational Models Pras Pathmanathan, PhD, Richard Gray, PhD, Leonardo Angelone, PhD and Tina Morrison, PhD APPLICABILITY ANALYSIS • Computational modelling has the potential to revolutionise 21st Century healthcare • However, despite decades of research, progress in translating computational models to clinical care has been limited. • One major challenge is demonstrating the reliability of predictions from in silico approaches Excellence in Regulatory Science Office of Science and Engineering Laboratories Model as used in context-of-use M-COU Reality being modelled R-COU ? Model as used in validation simulations M-V Validation comparator R-V Directly comparable Primary validation results Other COU-based validation results General validation results Subject matter expertise Historical data Established theory M-COU R-COU R-V M-V ΔM ΔR 4. Describe model aspects common between M-V and M-COU The model that was ‘validated’ using the primary validation evidence will likely vary from the model that is used for the context of use. However, there will be many aspects of the model that remain the same. Therefore, describe the aspects of the model that are equivalent between M-COU and M-V: • Maxwell’s eq