Systematic reviews or health technology assessments (HTAs) that examine the body of evidence on diagnostic procedures can - and should - transparently assess and report the overall certainty of evidence as part of their findings. In the two-part, 21st installment of the GRADE guidance series published in the Journal of Clinical Epidemiology, Schünemann and colleagues provide methods for approaching the first two major domains of the GRADE approach: risk of bias and indirectness.
While there are certainly differences between methods for assessing the certainty of evidence of diagnostic tests as opposed to interventions, the fundamental parts of GRADE remain unchanged:
Make Clinical Questions Clear via PICOs
It is paramount to clearly define the purpose or role of a diagnostic test and to see the test in light of its potential downstream consequences for making subsequent treatment decisions. As with a review of an intervention, a review of a diagnostic test should be built upon questions that define the Population, Intervention (the “index test” being assessed), Comparator (the “reference” test representing the current standard of care), and Outcomes (PICOs).
Prioritize Patient-Important Outcomes
Outcomes should be relevant to the population at hand. As such, the ideal study design to generate this evidence for outcomes related to test accuracy is a randomized controlled trial with a test-retest format that directly investigates the downstream effects of a testing strategy on outcomes in the population at hand, seen in Figure 1A below.
However, this is often not available. In this case, test accuracy would be used as a surrogate outcome, and test accuracy studies such as those in Figure 1B can be linked to additional evidence that examines the effect of downstream consequences of test results on patient-important outcomes. (More on that in a March 2020 blog post, here.)
Assessing Risk of Bias in Test Accuracy Studies
There are several important factors to consider when assessing a body of test accuracy studies for risk of bias. Potential issues with regard to risk of bias include:
· Populations that differ from those intended to receive the test (e.g., in terms of disease risk)
· Failure to compare the test in question to an independent reference/standard test in all enrolled patients (e.g., by using only a composite test)
· Lack of blinding when ascertaining test results
The QUADAS-2 tool can be used to guide assessment of bias in these studies.
Use PICO to Guide Assessment of Indirectness
Lastly, as when evaluating intervention studies, indirectness can be assessed by determining whether the Population, Index test, Comparator/reference test, and Outcomes match those in the clinical question.
Schünemann H, Mustafa RA, Brozek J, Steingart KR, Leeflang M, Murad MH, Bossuyt P, et al. GRADE guidelines 21 pt. 1: Study design, risk of bias, and indirectness in rating the certainty across a body of evidence for test accuracy. J Clin Epidemiol Feb 12. pii: S0895-4356(19)30673-0. doi: 10.1016/j.jclinepi.2019.12.020. [Epub ahead of print]
Manuscript available here on publisher’s site.