Hariharan Prasanna, D'Souza Gavin A, Horner Marc, Morrison Tina M, Malinauskas Richard A, Myers Matthew R
US Food and Drug Administration, Silver Spring, Maryland, United States of America.
ANSYS, Inc., Evanston, Illinois, United States of America.
PLoS One. 2017 Jun 8;12(6):e0178749. doi: 10.1371/journal.pone.0178749. eCollection 2017.
A "credible" computational fluid dynamics (CFD) model has the potential to provide a meaningful evaluation of safety in medical devices. One major challenge in establishing "model credibility" is to determine the required degree of similarity between the model and experimental results for the model to be considered sufficiently validated. This study proposes a "threshold-based" validation approach that provides a well-defined acceptance criteria, which is a function of how close the simulation and experimental results are to the safety threshold, for establishing the model validity. The validation criteria developed following the threshold approach is not only a function of Comparison Error, E (which is the difference between experiments and simulations) but also takes in to account the risk to patient safety because of E. The method is applicable for scenarios in which a safety threshold can be clearly defined (e.g., the viscous shear-stress threshold for hemolysis in blood contacting devices). The applicability of the new validation approach was tested on the FDA nozzle geometry. The context of use (COU) was to evaluate if the instantaneous viscous shear stress in the nozzle geometry at Reynolds numbers (Re) of 3500 and 6500 was below the commonly accepted threshold for hemolysis. The CFD results ("S") of velocity and viscous shear stress were compared with inter-laboratory experimental measurements ("D"). The uncertainties in the CFD and experimental results due to input parameter uncertainties were quantified following the ASME V&V 20 standard. The CFD models for both Re = 3500 and 6500 could not be sufficiently validated by performing a direct comparison between CFD and experimental results using the Student's t-test. However, following the threshold-based approach, a Student's t-test comparing |S-D| and |Threshold-S| showed that relative to the threshold, the CFD and experimental datasets for Re = 3500 were statistically similar and the model could be considered sufficiently validated for the COU. However, for Re = 6500, at certain locations where the shear stress is close the hemolysis threshold, the CFD model could not be considered sufficiently validated for the COU. Our analysis showed that the model could be sufficiently validated either by reducing the uncertainties in experiments, simulations, and the threshold or by increasing the sample size for the experiments and simulations. The threshold approach can be applied to all types of computational models and provides an objective way of determining model credibility and for evaluating medical devices.
一个“可信的”计算流体动力学(CFD)模型有潜力对医疗设备的安全性进行有意义的评估。建立“模型可信度”的一个主要挑战是确定模型与实验结果之间所需的相似程度,以便模型被认为得到了充分验证。本研究提出了一种“基于阈值”的验证方法,该方法提供了明确的验收标准,这是模拟结果和实验结果与安全阈值接近程度的函数,用于确定模型的有效性。按照阈值方法制定的验证标准不仅是比较误差E(即实验和模拟之间的差异)的函数,还考虑了由于E对患者安全造成的风险。该方法适用于可以明确界定安全阈值的场景(例如,血液接触设备中溶血的粘性剪切应力阈值)。在FDA喷嘴几何形状上测试了新验证方法的适用性。使用背景(COU)是评估在雷诺数(Re)为3500和6500时喷嘴几何形状中的瞬时粘性剪切应力是否低于普遍接受的溶血阈值。将CFD得到的速度和粘性剪切应力结果(“S”)与实验室间实验测量结果(“D”)进行比较。根据ASME V&V 20标准对由于输入参数不确定性导致的CFD和实验结果中的不确定性进行了量化。对于Re = 3500和6500的CFD模型,使用学生t检验对CFD和实验结果进行直接比较时,无法得到充分验证。然而,按照基于阈值的方法,比较|S - D|和|阈值 - S|的学生t检验表明,相对于阈值,Re = 3500的CFD和实验数据集在统计上相似,并且该模型对于COU可被认为得到了充分验证。然而,对于Re = 6500,在某些剪切应力接近溶血阈值的位置,CFD模型对于COU不能被认为得到了充分验证。我们的分析表明,通过减少实验、模拟和阈值中的不确定性,或者通过增加实验和模拟的样本量,可以充分验证该模型。阈值方法可应用于所有类型的计算模型,并提供了一种确定模型可信度和评估医疗设备的客观方法。