Effect of verification bias on the sensitivity of fecal occult blood testing: a meta-analysis

Abstract

Objectives: There is controversy regarding the sensitivity of fecal occult blood tests (FOBT) for detecting colorectal cancer. Many of the published studies failed to correct for verification bias which may have increased the sensitivity.

Methods: A meta-analysis of published studies evaluating the sensitivity and specificity of chemical-based FOBT for colorectal cancer was performed. Studies were included if both cancer and control subjects underwent confirmatory testing. We also included studies that attempted to correct for verification bias by either performing colonoscopy on all subjects regardless of the FOBT result or by using longitudinal follow-up. We then compared the sensitivity, specificity, and other diagnostic characteristics of the studies that attempted to correct for verification (n=10) vs. those that did not correct for this bias (n=19).

Results: The pooled sensitivity of guaiac-based FOBT for colorectal cancer of studies without verification bias was significantly lower than those studies with this bias [0.36 (95% CI 0.25-0.47) vs. 0.70 (95% CI 0.60-0.80), p=0.001]. The pooled specificity of the studies without verification bias was higher [0.96 (95% CI 0.94-0.97) vs. 0.88 (95% CI 0.84-0.91), p<0.005]. There was no significant difference in the area under the summary receiver operating characteristic curves. More sensitive chemical-based FOBT methods (e.g., Hemoccult® SENSA®) had a higher sensitivity but a lower specificity than standard guaiac methods.

Conclusions: The sensitivity of guaiac-based FOBT for colorectal cancer has been overestimated as a result of verification bias. This test may not be sensitive enough to serve as an effective screening option for colorectal cancer.

Figure 1

Flow chart summarizing the process used to identify articles for inclusion in the meta-analysis.

Figure 2

A paired forest plot for the sensitivity and specificity of studies with verification bias. The boxes represent the sensitivities and specificities of the studies. The areas of the boxes are proportional to the “weights” of the study (calculated as the inverse of the variance). The horizontal bars illustrate the 95% confidence intervals and the diamonds represent the pooled estimate of the sensitivities and specificities. Abbreviations: TP=true positives, FP=false positives, FN=false negatives, TN=true negatives.

Figure 3

A paired forest plot for the sensitivity and specificity of studies without verification bias. The plot was constructed as described in the legend to Fig. 2. Abbreviations: TP=true positives, FP=false positives, FN=false negatives, TN=true negatives.

Figure 4

Panel A. The summary receiver operating characteristic (sROC) curve for studies of fecal occult blood test (FOBT) which did not correct for verification bias. Each point, shown as a “▼”, represents the true positivity and false positivity of each study. Panel B. The sROC curve for studies of FOBT which attempted to correct for verification bias. Each point, shown as a “●”, represents the true positivity and false positivity of each study. The exact area under the sROC curves were not significantly different (0.91 ± 0.01 vs. 0.69 ± 0.26, p = 0.37).