title: Voting for image scoring and assessment (VISA)--theory and application of a 2 + 1 reader algorithm to improve accuracy of imaging endpoints in clinical trials.
abstract: Independent central reading or off-site reading of imaging endpoints is increasingly used in clinical trials. Clinician-reported outcomes, such as endoscopic disease activity scores, have been shown to be subject to bias and random error. Central reading attempts to limit bias and improve accuracy of the assessment, two factors that are critical to trial success. Whether one central reader is sufficient and how to best integrate the input of more than one central reader into one output measure, is currently not known.In this concept paper we develop the theoretical foundations of a reading algorithm that can achieve both objectives without jeopardizing operational efficiency We examine the role of expert versus competent reader, frame scoring of imaging as a classification task, and propose a voting algorithm (VISA: Voting for Image Scoring and Assessment) as the most appropriate solution which could also be used to operationally define imaging gold standards. We propose two image readers plus an optional third reader in cases of disagreement (2 + 1) for ordinary scoring tasks. We argue that it is critical in trials with endoscopically determined endpoints to include the score determined by the site reader, at least in endoscopy clinical trials. Juries with more than 3 readers could define a reference standard that would allow a transition from measuring reader agreement to measuring reader accuracy. We support VISA by applying concepts from engineering (triple-modular redundancy) and voting theory (Condorcet's jury theorem) and illustrate our points with examples from inflammatory bowel disease trials, specifically, the endoscopy component of the Mayo Clinic Score of ulcerative colitis disease activity. Detailed flow-diagrams (pseudo-code) are provided that can inform program design.The VISA "2 + 1" reading algorithm, based on voting, can translate individual reader scores into a final score in a fashion that is both mathematically sound (by avoiding averaging of ordinal data) and in a manner that is consistent with the scoring task at hand (based on decisions about the presence or absence of features, a subjective classification task). While the VISA 2 + 1 algorithm is currently being used in clinical trials, empirical data of its performance have not yet been reported.
authors.affiliation: Quintiles, Immunology and Internal Medicine, Medical Strategy & Science, 1801 Rockville Pike Suite 300, Rockville, MD, 20852, USA. klaus.gottlieb@quintiles.com.
authors.forename: Klaus
authors.initials: K
authors.lastname: Gottlieb
authors.affiliation: Quintiles, Immunology and Internal Medicine, Medical Strategy & Science, 1801 Rockville Pike Suite 300, Rockville, MD, 20852, USA. fez.hussain@quintiles.com.
authors.forename: Fez
authors.initials: F
authors.lastname: Hussain
mesh_terms: D000465:Algorithms; D016099:Endoscopy, Gastrointestinal / Q000379:methods*; D023381:Endpoint Determination / Q000379:methods*; D006801:Humans; D007089:Image Enhancement / Q000379:methods*; D007090:Image Interpretation, Computer-Assisted / Q000379:methods; D015212:Inflammatory Bowel Diseases / Q000473:pathology* / Q000628:therapy*; D009045:Motor Endplate; D015588:Observer Variation; D011379:Prognosis; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome