The VICTRE Trial: Open-Source, In-Silico Clinical Trial For Evaluating Digital Breast Tomosynthesis

<p>Expensive and lengthy clinical trials delay regulatory evaluation of innovative medical technologies affecting patient access to high-quality medical products. Sophisticated simulation tools are increasingly being used in device development, but are rarely used in regulatory applications. We investigate a new paradigm for evaluating digital breast tomosynthesis (DBT) as a replacement for digital mammography (DM), using exclusively in-silico methods.</p><p>A total of 2986 subjects, with breast sizes and radiographic densities representative of a screening population and compressed thicknesses from 3.5 to 6 cm, were simulated and imaged on in-silico versions of DM and DBT systems using fast Monte Carlo x-ray transport. Images were interpreted by a computational reader detecting the presence of lesions. The in-silico trial (VICTRE) was designed to replicate a comparative trial from a previous regulatory submission. The endpoint was the difference in area under the receiver-operating-characteristic curve between modalities (delta-AUC) for lesion detection. Using a fully-crossed design, VICTRE was sized for a standard error (SE) of 0.01 in delta-AUC, half the uncertainty seen in the comparative trial. A 1-hour summary presentation of the project and findings was given at the FDA Grand Rounds on 3/14/2019 and can be found <a href="https://collaboration.fda.gov/p5wx8epckk7p/">here</a>.</p><p>A systematic exploration of the trial parameters including lesion types and sizes is also possible and greatly facilitated by the availability of open-source, free software tools available at <a href="https://github.com/DIDSR/VICTRE">https://github.com/DIDSR/VICTRE</a>.</p>

昂贵的长期临床试验延迟了创新医疗技术的监管评估，进而影响了患者获取高质量医疗产品。在设备开发中，高级仿真工具的使用日益增多，但在监管应用中却鲜有应用。本研究探讨了评估数字乳腺断层扫描（DBT）作为数字乳腺摄影（DM）替代品的新范式，该研究仅采用计算机模拟方法。共计2986名受试者，其乳腺大小和放射密度具有代表性，压缩厚度介于3.5至6厘米之间，在DM和DBT系统的计算机模拟版本上进行了模拟和成像，利用快速蒙特卡洛X射线传输进行。图像由检测病变存在的计算读者进行解读。计算机模拟试验（VICTRE）旨在复制先前监管提交的对比试验。终点是两种方法在接收者操作特征曲线下面积差异（delta-AUC）对于病变检测。采用完全交叉设计，VICTRE的规模设定为delta-AUC的标准误差（SE）为0.01，仅为对比试验中观察到的不确定性的二分之一。2019年3月14日在FDA大会系列讲座中进行了为期1小时的该项目及发现总结报告，可在以下链接中找到：[链接](https://collaboration.fda.gov/p5wx8epckk7p/)。此外，通过对试验参数进行系统探索，包括病变类型和大小，也是可能的，并且得益于开源、免费软件工具的可用性，这一过程得到了极大的简化，这些工具可在以下链接找到：[链接](https://github.com/DIDSR/VICTRE)。