We agree with Dr. Razzak that cost-effectiveness is critical to selection of appropriate imaging, as is local availability of imaging technologies. Furthermore, different imaging strategies may be appropriate in different subsets of patients. These areas would benefit from further investigation.

We agree with Drs. Shiga, Wajima, and Inoue that summary ROC curves (1) and funnel plots may be useful in meta-analysis. We had performed similar analyses but did not include the results because of several concerns. Summary ROC curves may be affected by the assumptions used in curve calculation and are less useful at the bedside than likelihood ratios, which enable understanding of disease probabilities. Asymmetrical funnel plots are affected by both publication bias and other factors that cause heterogeneity, including small study effects (2).

The global sensitivity analysis that Dr. Goto used (3) can apply to studies with partial verification bias, where not all participants' diagnoses are confirmed by the single reference standard, but not to differential verification bias, as in the case of appendicitis. Under the global sensitivity analysis approach, the range of disease prevalence in patients with unverified diagnoses is applied to define the possible range of sensitivity and specificity for the test under consideration. This is appropriate if nothing is known about the patients who did not receive the reference standard (surgery). However, in the studies included in our review, most of the negative imaging results were verified by a secondary clinical reference standard (4). This differential verification bias will lead to some overestimation of overall accuracy, as we discussed in our paper. However, most patients with appendicitis should have developed worsening symptoms and therefore would have been identified through clinical follow-up. Dr. Goto's assumption that the prevalence of undiagnosed appendicitis is 0.10 to 0.50 in patients who do not have surgery and do not have appendicitis identified on clinical follow-up is almost certainly not clinically sensible. The use of clinical follow-up is a valuable if imperfect reference standard and is clearly superior to the global sensitivity analysis assumption that nothing is known about these patients.

In summary, on the basis of the data, although some differential verification bias leads to overestimation of diagnostic accuracy for both CT and ultrasonography, CT scanning is a more sensitive and specific imaging method to detect appendicitis in patients with indeterminate clinical suspicion.