Criteria for evaluation of novel markers of cardiovascular risk: a scientific statement from the American Heart Association

Abstract

There is increasing interest in utilizing novel markers of cardiovascular disease risk, and consequently, there is a need to assess the value of their use. This scientific statement reviews current concepts of risk evaluation and proposes standards for the critical appraisal of risk assessment methods. An adequate evaluation of a novel risk marker requires a sound research design, a representative at-risk population, and an adequate number of outcome events. Studies of a novel marker should report the degree to which it adds to the prognostic information provided by standard risk markers. No single statistical measure provides all the information needed to assess a novel marker, so measures of both discrimination and accuracy should be reported. The clinical value of a marker should be assessed by its effect on patient management and outcomes. In general, a novel risk marker should be evaluated in several phases, including initial proof of concept, prospective validation in independent populations, documentation of incremental information when added to standard risk markers, assessment of effects on patient management and outcomes, and ultimately, cost-effectiveness.

Figure 1

Predicted risk (horizontal axis) vs observed risk of events (vertical axis), based on patients grouped into deciles of predicted risk.

Figure 2

Clinical decisions vs predicted risk of disease (horizontal axis). A, The decision to treat is based solely on the estimated risk: Patients with risk levels below the treatment threshold are not treated, whereas patients with risk levels above the treatment threshold are given treatment. B, The possibility of testing leads to 2 thresholds. Patients with risk levels below threshold 1 are neither tested nor treated; patients with risk levels between thresholds 1 and 2 are tested, and treatment recommendations are based on test results; patients with risk levels above threshold 2 are treated without further testing.

Figure 3

Individual patient pretest risk levels (horizontal axis) and posttest risk levels (vertical axis) in relation to treatment thresholds (light lines). Solid circles indicate patients who subsequently developed an outcome event, and open circles indicate patients who did not develop an outcome event. For larger data sets, it may be preferable to display the data in 2 panels rather than 1: The first panel for the patients who developed an event (ie, the solid circles in Figure 3) and the second panel for patients who did not (ie, the open circles in Figure 3). Tx indicates treatment.