ITEM 16.  Report the number of participants satisfying the criteria for inclusion that did or did not undergo the index tests and/or the reference standard; describe why participants failed to receive either test (a flow diagram is strongly recommended).

 

 

Example 1

During the course of the study, 272 patients with suspected deep vein thrombosis (DVT) were referred to the participating centers. Of these, 28 were excluded from the study for the following reasons: previous DVT (21), contrast allergy (1), renal failure (1), and unwillingness to provide consent (5). Of the remaining 244 patients, 25 were excluded from the analysis because of inadequate or failed venography and 5 were excluded because of inadequate or failed impedance plethysmography.[1]

 

 

Example 2

Example of a flow diagram of a diagnostic accuracy study (see figure).[2]

 

 

Figure – Example of a flow diagram of a diagnostic accuracy study.[2]

 

 

The study report should present the number of participants that were assessed for eligibility, if available. This number is a useful indicator of how closely the targeted study population resembles the patient population.

The flow diagram provides the exact number of patients at each stage of the study and thus the correct denominator for calculating rates and proportions. It also shows the number of subjects who failed to receive either the index test, or the reference standard, or both.

Measures of diagnostic accuracy will be biased if the result of the index test influences the decision to order the reference standard test.[3-10] The terms used to describe this effect include (partial) verification bias, work-up bias, (primary) selection bias, sequential ordering bias, and verification bias (the most general term). Verification bias occurs in up to 26% of diagnostic studies and is especially common when the reference standard is an invasive procedure.[7]
We strongly recommend the use of a flow diagram to illustrate the design of the study and provide the exact number of participants at each stage of the study. A flow diagram can communicate transparently the key elements of a study design. A flow diagram has been a helpful addition to reports of randomized clinical trials.[11]

 

 

References 

1. Wells PS, Brill-Edwards P, Stevens P, et al. A novel and rapid whole-blood assay for D-dimer in patients with clinically suspected deep vein thrombosis. Circulation 1995; 91:2184-7.
2. Garcia Pena BM, Mandl KD, Kraus SJ, et al. Ultrasonography and limited computed tomography in the diagnosis and management of appendicitis in children. JAMA 1999; 282:1041-6.
3. Ransohoff DF, Feinstein AR. Problems of spectrum and bias in evaluating the efficacy of diagnostic tests. N Engl J Med 1978; 299:926-30.
4. Choi BC. Sensitivity and specificity of a single diagnostic test in the presence of work-up bias. J Clin Epidemiol 1992; 45:581-6.
5. Zhou XH. Effect of verification bias on positive and negative predictive values. Stat Med 1994; 13:1737-45.
6. Begg CB, Greenes RA. Assessment of diagnostic tests when disease verification is subject to selection bias. Biometrics 1983; 39:207-15.
7. Greenes RA, Begg CB. Assessment of diagnostic technologies. Methodology for unbiased estimation from samples of selectively verified patients. Invest Radiol 1985; 20:751-6.
8. Cecil MP, Kosinski AS, Jones MT, et al. The importance of work-up (verification) bias correction in assessing the accuracy of SPECT thallium-201 testing for the diagnosis of coronary artery disease. J Clin Epidemiol 1996; 49:735-42.
9. Diamond GA, Rozanski A, Forrester JS, et al. A model for assessing the sensitivity and specificity of tests subject to selection bias. Application to exercise radionuclide ventriculography for diagnosis of coronary artery disease. J Chronic Dis 1986; 39:343-55.
10. Diamond GA. Off Bayes: effect of verification bias on posterior probabilities calculated using Bayes' theorem. Med Decis Making 1992;12:22-31.
11. Egger M, Juni P, Bartlett C. Value of flow diagrams in reports of randomized controlled trials. JAMA 2001; 285:1996-9.