Effect of Verification Bias on the Sensitivity of Fecal Occult Blood Testing: a Meta-Analysis
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
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.
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).
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.
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.
- Jemal A, Siegel R, Ward E, et al. Cancer statistics 2008. CA Cancer J Clin. 2008;58:71–96. CrossRef
- Allison JE. Review article: faecal occult blood testing for colorectal cancer. Aliment Pharmacol Ther. 1998;12:1–10. CrossRef
- Centers for Disease Control and Prevention. Use of colorectal cancer tests-United States, 2002, 2004, and 2006. MMWR Morb Mortal Wkly Rep. 2008;57:253–8.
- Greenwald B. From guaiac to immune fecal occult blood tests: the emergence of technology in colorectal cancer screening. Gastroenterol Nurs. 2005;28:90–6. CrossRef
- Ouyang DL, Chen JJ, Getzenberg RH, Schoen RE. Noninvasive testing for colorectal cancer: a review. Am J Gastroenterol. 2005;100:1393–403. CrossRef
- Crespi M, Lisi D. Is colorectal cancer screening by fecal occult blood feasible? Ann Oncol. 2002;13:47–50. CrossRef
- Bond JH. Fecal occult blood test screening for colorectal cancer. Gastrointest Endosc Clin N Am. 2002;12:11–21. CrossRef
- Burch JA, Soares-Weiser K, St John DJB, et al. Diagnostic accuracy of faecal occult blood tests used in screening for colorectal cancer: a systematic review. J Med Screen. 2007;14:132–7. CrossRef
- Mandel JS. Colorectal cancer screening. Cancer Metastasis Rev. 1997;16:263–79. CrossRef
- Simon JB. Fecal occult blood testing: clinical value and limitations. Gastroenterologist. 1998;6:66–78.
- Winawer SJ, Schottenfeld D, Flehinger BJ. Colorectal cancer screening. J Natl Cancer Inst. 1991;83:243–53. CrossRef
- Begg CB. Biases in the assessment of diagnostic tests. Stat Med. 1987;6:411–23. CrossRef
- Begg CB, Greenes RA. Assessment of diagnostic tests when disease verification is subject to selection bias. Biometrics. 1983;39:207–15. CrossRef
- Choi BC. Sensitivity and specificity of a single diagnostic test in the presence of work-up bias. J Clin Epidemiol. 1992;45:581–6. CrossRef
- Greenes RA, Begg CB. Assessment of diagnostic technologies. Methodology for unbiased estimation from samples of selectively verified patients. Invest Radiol. 1985;20:751–6. CrossRef
- Punglia RS, D'Amico AV, Catalona WJ, Roehl KA, Kuntz KM. Effect of verification bias on screening for prostate cancer by measurement of prostate-specific antigen. N Engl J Med. 2003;349:335–42. CrossRef
- Begg CB, McNeil BJ. Assessment of radiologic tests: control of bias and other design considerations. Radiology. 1988;167:565–9.
- Dinnes J, Deeks J, Kirby J, Roderick P. A methodological review of how heterogeneity has been examined in systematic reviews of diagnostic test accuracy. Health Technol Assess. 2005;9:1–113.
- Fleiss JL. The statistical basis of meta-analysis. Stat Methods Med Res. 1993;2:121–45. CrossRef
- DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials. 1986;7:177–88. CrossRef
- Takkouche B, Cadarso-Suarez C, Spiegelman D. Evaluation of old and new tests of heterogeneity in epidemiologic meta-analysis. Am J Epidemiol. 1999;150:206–15.
- Leeflang MMG, Deeks JJ, Gatsonis C, Bossuyt PMM, Cochrane Diagnostic Test Accuracy Working G. Systematic reviews of diagnostic test accuracy. Ann Intern Med. 2008;149:889–97.
- Hyde CJ, Stanworth SJ, Murphy MF. Can you see the wood for the trees? Making sense of forest plots in systematic reviews 2. Analysis of the combined results from the included studies. Transfusion. 2008;48:580–3. CrossRef
- Goodacre S, Sampson F, Thomas S, van Beek E, Sutton A. Systematic review and meta-analysis of the diagnostic accuracy of ultrasonography for deep vein thrombosis. BMC Med Imaging. 2005;5:6. CrossRef
- Lijmer JG, Bossuyt PMM, Heisterkamp SH. Exploring sources of heterogeneity in systematic reviews of diagnostic tests. Stat Med. 2002;21:1525–37. CrossRef
- Irwig L, Macaskill P, Glasziou P, Fahey M. Meta-analytic methods for diagnostic test accuracy. J Clin Epidemiol. 1995;48:119–30. CrossRef
- Irwig L, Tosteson AN, Gatsonis C, et al. Guidelines for meta-analyses evaluating diagnostic tests. Ann Intern Med. 1994;120:667–76.
- Moses LE, Shapiro D, Littenberg B. Combining independent studies of a diagnostic test into a summary ROC curve: data-analytic approaches and some additional considerations. Stat Med. 1993;12:1293–316.
- Rosman AS, Korsten MA. Application of summary receiver operating characteristics (sROC) analysis to diagnostic clinical testing. Adv Med Sci. 2007;52:76–82.
- Walter SD. Properties of the summary receiver operating characteristic (SROC) curve for diagnostic test data. Stat Med. 2002;21:1237–56. CrossRef
- Crowley ML, Freeman LD, Mottet MD, et al. Sensitivity of guaiac-impregnated cards for the detection of colorectal neoplasia. J Clin Gastroenterol. 1983;5:127–30. CrossRef
- Farrands PA, O'Regan D, Taylor I. An assessment of occult blood testing to determine which patients with large bowel symptoms require urgent investigation. Br J Surg. 1985;72:835–7. CrossRef
- Greenberg PD, Bertario L, Gnauck R, et al. A prospective multicenter evaluation of new fecal occult blood tests in patients undergoing colonoscopy. Am J Gastroenterol. 2000;95:1331–8. CrossRef
- Guittet L, Bouvier V, Mariotte N, et al. Comparison of a guaiac based and an immunochemical faecal occult blood test in screening for colorectal cancer in a general average risk population. Gut. 2007;56:210–4. CrossRef
- Hoepffner N, Shastri YM, Hanisch E, et al. Comparative evaluation of a new bedside faecal occult blood test in a prospective multicentre study. Aliment Pharmacol Ther. 2006;23:145–54. CrossRef
- Hope RL, Chu G, Hope AH, Newcombe RG, Gillespie PE, Williams SJ. Comparison of three faecal occult blood tests in the detection of colorectal neoplasia. Gut. 1996;39:722–5. CrossRef
- Jeanson A, Jamart J, Maisin JM, et al. Assessment of the new immunological test Hemoblot for detecting occult blood in faeces. Eur J Cancer Prev. 1994;3:407–12. CrossRef
- Kimmig JM, Strauch M, Hallen M. Negative Haemoccult test in malignant and premalignant lesions of the colon. Validation of the Haemoccult test with total colonoscopy. Endoscopy. 1989;21:136–40. CrossRef
- Leicester RJ, Lightfoot A, Millar J, Colin-Jones DG, Hunt RH. Accuracy and value of the Hemoccult test in symptomatic patients. Br Med J (Clin Res Ed). 1983;286:673–4. CrossRef
- Lenhard K, Bommer GT, Asutay S, et al. Analysis of promoter methylation in stool: a novel method for the detection of colorectal cancer. Clin Gastroenterol Hepatol. 2005;3:142–9. CrossRef
- Li S, Wang H, Hu J, et al. New immunochemical fecal occult blood test with two-consecutive stool sample testing is a cost-effective approach for colon cancer screening: results of a prospective multicenter study in Chinese patients. Int J Cancer. 2006;118:3078–83. CrossRef
- Miyoshi H, Oka M, Sugi K, Saitoh O, Katsu K, Uchida K. Accuracy of detection of colorectal neoplasia using an immunochemical occult blood test in symptomatic referred patients: comparison of retrospective and prospective studies. Intern Med. 2000;39:701–6. CrossRef
- Nakama H, Kamijo N. Accuracy of immunological fecal occult blood testing for colorectal cancer screening. Prev Med. 1994;23:309–13. CrossRef
- Niv Y, Sperber AD. Sensitivity, specificity, and predictive value of fecal occult blood testing (Hemoccult II) for colorectal neoplasia in symptomatic patients: a prospective study with total colonoscopy. Am J Gastroenterol. 1995;90:1974–7.
- Norfleet RG. Effect of diet on fecal occult blood testing in patients with colorectal polyps. Dig Dis Sci. 1986;31:498–501. CrossRef
- Pye G, Marks CG, Martin S, Marks V, Jackson J, Hardcastle JD. An evaluation of Fecatwin/Feca EIA; a faecal occult blood test for detecting colonic neoplasia. Eur J Surg Oncol. 1989;15:446–8.
- Thomas WM, Hardcastle JD, Jackson J, Pye G. Chemical and immunological testing for faecel occult blood: a comparison of two tests in symptomatic patients. Br J Cancer. 1992;65:618–20.
- Tibble J, Sigthorsson G, Foster R, Sherwood R, Fagerhol M, Bjarnason I. Faecal calprotectin and faecal occult blood tests in the diagnosis of colorectal carcinoma and adenoma. Gut. 2001;49:402–8. CrossRef
- Williams JA, Hunter R, Coles ME, Thomas DW, Huber TW. An assessment of an immunochemical test for human haemoglobin in the detection of colonic polyps. Aust N Z J Surg. 1985;55:485–8. CrossRef
- Williams JA, Hunter R, Smith M, Coles ME, Hubert TW, Thomas DW. Evaluation of an immunological test for occult bleeding from colorectal neoplasia. Aust N Z J Surg. 1982;52:617–21. CrossRef
- Ahlquist DA, Sargent DJ, Loprinzi CL, et al. Stool DNA and occult blood testing for screen detection of colorectal neoplasia. Ann Intern Med. 2008;149:441–50.
- Allison JE, Feldman R, Tekawa IS. Hemoccult screening in detecting colorectal neoplasm: sensitivity, specificity, and predictive value. Long-term follow-up in a large group practice setting. Ann Intern Med. 1990;112:328–33.
- Allison JE, Tekawa IS, Ransom LJ, Adrain AL. A comparison of fecal occult-blood tests for colorectal-cancer screening. N Engl J Med. 1996;334:155–9. CrossRef
- Imperiale TF, Ransohoff DF, Itzkowitz SH, Turnbull BA, Ross ME, Colorectal Cancer Study G. Fecal DNA versus fecal occult blood for colorectal-cancer screening in an average-risk population. N Engl J Med. 2004;351:2704–14. CrossRef
- Kristinsson J, Nygaard K, Aadland E, et al. Screening of first degree relatives of patients operated for colorectal cancer: evaluation of fecal calprotectin vs. hemoccult II. Digestion. 2001;64:104–10. CrossRef
- Lieberman DA, Weiss DG, Veterans Affairs Cooperative Study G. One-time screening for colorectal cancer with combined fecal occult-blood testing and examination of the distal colon. N Engl J Med. 2001;345:555–60. CrossRef
- Murakami R, Otani T, Nakanishi K, et al. Diagnostic validity of fecal occult blood tests for detecting gastroenterological cancers. Jpn J Cancer Res. 1992;83:141–5.
- Robinson MH, Kronborg O, Williams CB, et al. Faecal occult blood testing and colonoscopy in the surveillance of subjects at high risk of colorectal neoplasia. Br J Surg. 1995;82:318–20. CrossRef
- Sung JJY, Chan FKL, Leung WK, et al. Screening for colorectal cancer in Chinese: comparison of fecal occult blood test, flexible sigmoidoscopy, and colonoscopy. Gastroenterology. 2003;124:608–14. CrossRef
- Williams CB, Macrae FA, Bartram CI. A prospective study of diagnostic methods in adenoma follow-up. Endoscopy. 1982;14:74–8. CrossRef
- Levi Z, Hazazi R, Rozen P, Vilkin A, Waked A, Niv Y. A quantitative immunochemical faecal occult blood test is more efficient for detecting significant colorectal neoplasia than a sensitive guaiac test. Aliment Pharmacol Ther. 2006;23:1359–64. CrossRef
- Smith A, Young GP, Cole SR, Bampton P. Comparison of a brush-sampling fecal immunochemical test for hemoglobin with a sensitive guaiac-based fecal occult blood test in detection of colorectal neoplasia. Cancer. 2006;107:2152–9. CrossRef
- Wong BCY, Wong WM, Cheung KL, et al. A sensitive guaiac faecal occult blood test is less useful than an immunochemical test for colorectal cancer screening in a Chinese population. Aliment Pharmacol Ther. 2003;18:941–6. CrossRef
- Allison JE, Sakoda LC, Levin TR, et al. Screening for colorectal neoplasms with new fecal occult blood tests: update on performance characteristics. J Natl Cancer Inst. 2007;99:1462–70. CrossRef
- Cheng T-I, Wong J-M, Hong C-F, et al. Colorectal cancer screening in asymptomaic adults: comparison of colonoscopy, sigmoidoscopy and fecal occult blood tests. Taiwan Yi Xue Hui Za Zhi. 2002;101:685–90.
- Mandel JS, Bond JH, Bradley M, et al. Sensitivity, specificity, and positive predictivity of the Hemoccult test in screening for colorectal cancers. The University of Minnesota's Colon Cancer Control Study. Gastroenterology. 1989;97:597–600.
- Heijenbrok-Kal MH, Hunink MGM. Adjusting for bias in diagnostic reports. Am J Med. 2002;112:322–4. CrossRef
- Heresbach D, Manfredi S, D'Halluin PN, Bretagne J-F, Branger B. Review in depth and meta-analysis of controlled trials on colorectal cancer screening by faecal occult blood test. Eur J Gastroenterol Hepatol. 2006;18:427–33. CrossRef
- Towler B, Irwig L, Glasziou P, Kewenter J, Weller D, Silagy C. A systematic review of the effects of screening for colorectal cancer using the faecal occult blood test, hemoccult. Br Med J. 1998;317:559–65.
- Ransohoff DF, Lang CA. Screening for colorectal cancer with the fecal occult blood test: a background paper. Ann Intern Med. 1997;126:811–22.
- Screening for colorectal cancer: U.S.Preventive Services Task Force recommendation statement. Ann Intern Med 2008;149:627-37.
- Levin B, Lieberman DA, McFarland B, et al. Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. CA Cancer J Clin. 2008;58:130–60. CrossRef
- Davila RE, Rajan E, Baron TH, et al. ASGE guideline: colorectal cancer screening and surveillance. Gastrointest Endosc. 2006;63:546–57. CrossRef
- Rex DK, Johnson DA, Anderson JC, et al. American College of Gastroenterology guidelines for colorectal cancer screening 2008. Am J Gastroenterol. 2009;104:739–50. CrossRef
- Effect of Verification Bias on the Sensitivity of Fecal Occult Blood Testing: a Meta-Analysis
Journal of General Internal Medicine
Volume 25, Issue 11 , pp 1211-1221
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- fecal occult blood
- colorectal cancer
- summary receiver operating characteristic curve
- Industry Sectors