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The Lung Image Database Consortium (LIDC) has provided a publicly available collection of CT images with nodule markings from four radiologists. The LIDC protocol does not require radiologists to reach a consensus during the reading process, and as a result, there are varying levels of reader agreement for each potential nodule with no explicit reference standard for nodules. The purpose of this work was to investigate the effects of the level of reader agreement on the development of a reference standard and the subsequent impact on CAD performance. Ninety series were downloaded from the LIDC database. Four different reference standards were created based on the markings of the LIDC radiologists, reflecting four different levels of reader agreement. All series were analyzed with a research CAD system and its performance was measured against each of the four standards. Between the standards with …