Real estate diagrams: A tool to quickly assess the utility of a new predictive technology

Introduction: Scientists are increasingly in a position to ask whether or not to adopt new technologies. We present a visualization tool to help scientists swiftly evaluate the worth of new assays. Methods: The parameters (prevalence, sensitivity and, specificity) relevant to use of a toxicity test have values between 0 and 1. The proper arrangement of the parameters can be used to define areas in a [0,1] x [0, 1] cross-space. Our analogy is a square plot of land subdivided into smaller lots. We call the resultant graphic a real estate diagram. Results: We use the well studied example of predicting prolongation of the QT interval of the electrocardiogram to illustrate the diagrams. The experience in human clinical Thorough QT (TQT) studies has been described (Park et al., 2013). Within the data we chose two chronological sets: 2 blocks of two years (2005-2006 and 2011-2012). In the first block 13 of 29 (45%) submitted compounds had positive TQT studies; in the second block the prevalence was 4 of 42 (10%). In other studies, the hERG channel patch-clamp assay used in predicting TQT outcome had an expected sensitivity of 0.70 and expected specificity of 0.72. Real estate diagrams were constructed to yield insight into the positive and negative predictive value (PPV and NPV, respectively) of the TQT prediction. The structure of the real estate diagrams revealed that increasing assay sensitivity in the face of declining prevalence would have a trivial effect on PPV and NPV. Discussion: Nonclinical safety scientists will be called upon to question whether a new technology has the potential to meaningfully increase the predictive value of testing regimens. The real-estate diagram is a useful tool in making that assessment.