Development and evaluation of safety and effectiveness of novel cancer screening tests for routine clinical use with applications to multicancer detection technologies

Abstract

Multicancer screening is a promising approach to improving the detection of preclinical disease, but current technologies have limited ability to identify precursor or early stage lesions, and approaches for developing the evidentiary chain are unclear. Frameworks to enable development and evaluation from discovery through evidence of clinical effectiveness are discussed.

Keywords: cancer screening; clinical reference standard; clinical utility; diagnostic test accuracy; lead time bias; multicancer early detection; multicancer screening; standard of care screening test; test development framework; tumor of origin.

Figure 1.

Novel cancer test development and framework are illustrated. ^†Note that, for some tests, clinical utility may be inferred and thus enable implementation without obtaining primary evidence on effectiveness from prospective comparative studies with mortality outcome. Adapted from: Pepe et al, 2001; CanTest (Walter et al, 2019); and the analytic validity, clinical validity, clinical utility, and ethical (ACCE) frameworks (Centers for Disease Control and Prevention 2020).