A Philosophical Approach to Diagnostic Test Evaluation

IN RESPONSE:

We agree with Dr. Sonke and colleagues that one purpose of test accuracy studies is to determine whether the test provides accurate information about long-term clinical outcomes, that is, what is the prognostic value of the test information? We also agree that an ideal study to achieve this purpose is one in which the reference standard is a good proxy for patient outcome. In the absence of effective treatment, this information would be all that is required. However, if treatment is available, we also need to ask whether the test identifies patients whose outcomes would be improved by using this treatment, that is, what is the therapeutic value of testing? This is the issue we addressed in our article. Assessing the therapeutic value of a test does not just involve asking whether it provides accurate prognostic information. We also need to consider whether it identifies patients whose prognosis will improve with treatment (1).

In some cases, accuracy studies suffice because we already have evidence about effective treatments for the cases detected. In other situations, we require new randomized, controlled trials to assess the effect of test and treatment on patient outcomes.

To illustrate the difference between these 2 questions, let's consider a new test, such as a more detailed ultrasonographic study for detecting acute deep venous thrombosis. As Dr. Sonke and colleagues suggest, an accuracy study would suffice for conclusions about the prognostic value of the test if the relationship between the spectrum of disease detected by an abnormal venogram (the reference standard) and subsequent patient morbidity and mortality has been adequately established. If not, we would need a patient outcome study to assess the new test. However, to assess the therapeutic value of the test, we still need to consider whether detection improves patient outcomes. If evidence suggests that anticoagulant therapy is effective treatment for the spectrum of disease detected by the new test, a comparison of the accuracy and safety of the new test versus those of a standard test will suffice for conclusions about the new test's therapeutic value. Consider the use of d-dimer testing to identify patients at high risk for recurrence of deep venous thrombosis who may benefit from a longer course of anticoagulant therapy: Patient outcome studies have shown the test is prognostic for recurrence of deep venous thrombosis, but does this evidence suffice for conclusions about its therapeutic value? Neither simple prognostic studies nor existing treatment trials allow conclusions about whether using the test and subsequent treatment in this population would improve patient outcomes, and therefore, a new randomized, controlled trial is required. Such a trial has been done and provides evidence about both the prognostic value of testing and the effectiveness of treatment in patients with positive test results (2). Hence, sometimes new trials are required to determine the therapeutic value of testing, whereas in other circumstances, linking of accuracy studies to existing treatment trials may suffice.