1. 1 Does Fecal Occult Blood Testing Really Reduce Mortality? A Reanalysis of Systematic Review Data Am J Gastroenterol 2006;101:380–384

2. 2 CRC Screening The choices available for CRC screening are:  FOBT  flexible sigmoidoscopy every 5 yr  colonoscopy every 10 yr  CT colography The choices available for CRC screening are:  FOBT  flexible sigmoidoscopy every 5 yr  colonoscopy every 10 yr  CT colography

3. 3 CRC Screening FOBT has the most RCT evidence to support a reduction in CRC mortality FOBT is also less expensive than the other alternatives and is the only strategy that many health-care systems can afford. Is the endpoint of CRC death an ideal endpoint? Maybe “all cause” mortality should be the most appropriate outcome to evaluate. FOBT has the most RCT evidence to support a reduction in CRC mortality FOBT is also less expensive than the other alternatives and is the only strategy that many health-care systems can afford. Is the endpoint of CRC death an ideal endpoint? Maybe “all cause” mortality should be the most appropriate outcome to evaluate.

4. 4 CRC Screening The value of FOBT in preventing CRC mortality is accepted. This study evaluates whether FOBT reduces all cause mortality as an outcome. The value of FOBT in preventing CRC mortality is accepted. This study evaluates whether FOBT reduces all cause mortality as an outcome.

5. 5 CRC Screening שימוש ב -FOBT ל -screening מביא ירידה של 16% בתמותה מ -CRC.

6. 6 במטה - אנליזה נכללו שלושה מחקרים רקע Mandel et al. N Engl J Med 1993;328;1365–71. Scholefield et al. Gut 2002;50:840–4. Jorgensen et al. Gut 2002;50:29–32.

7. 7 CRC mortality in FOBT arm compared with no screening arm תוצאות שימוש ב -FOBT ל -screening מביא ירידה של 13% בתמותה מ -CRC.

8. 8 mortality not due to colorectal cancer in FOBT arm compared with no screening arm. תוצאות שימוש ב -FOBT ל -screening מעלה את שיעור התמותה מסיבות שאינן קשורות ל - !!CRC

9. 9 all cause mortality in FOBT arm compared with no screening arm. תוצאות שימוש ב -FOBT ל -screening לא משפיע על שיעור התמותה מסיבה כלשהי.

10. 10 דיון Concern with using all cause mortality as an outcome is that the power to detect clinically meaningful differences is diminished. The analysis of the data suggests that FOBT has no impact in overall mortality as there is an excess of deaths from non-CRC causes. Concern with using all cause mortality as an outcome is that the power to detect clinically meaningful differences is diminished. The analysis of the data suggests that FOBT has no impact in overall mortality as there is an excess of deaths from non-CRC causes. This seems counterintuitive as FOBT is an innocuous test and it is hard to conceive that this would result in death. Assuming that this is not a chance finding, there are three explanations for this unexpected result. This seems counterintuitive as FOBT is an innocuous test and it is hard to conceive that this would result in death. Assuming that this is not a chance finding, there are three explanations for this unexpected result.

11. 11 הסבר I If a screening program reduces CRC deaths and subjects are followed up for long enough they will die from something else and there will be an apparent excess mortality from other causes. The problem with this explanation is that the follow- up in these trials has been for less than 13 yr in most cases with only 26% of subjects dying so far. If a screening program reduces CRC deaths and subjects are followed up for long enough they will die from something else and there will be an apparent excess mortality from other causes. The problem with this explanation is that the follow- up in these trials has been for less than 13 yr in most cases with only 26% of subjects dying so far.

12. 12 הסבר II These trials were all open label. The behavior of both the subjects and the clinicians looking after them may be affected by the knowledge that FOBT has taken place. This bias would be particularly important when assessing the cause of death. These trials were all open label. The behavior of both the subjects and the clinicians looking after them may be affected by the knowledge that FOBT has taken place. This bias would be particularly important when assessing the cause of death.

13. 13 הסבר III FOBT screening results in a real increase in deaths from other causes. It is not conceivable that this is due to the test directly but there are biologically plausible reasons why the psychological effects of screening may increase mortality. Subjects taking part in screening may feel that this protects them from harm and conduct a lifestyle that increases their risk of mortality. FOBT screening results in a real increase in deaths from other causes. It is not conceivable that this is due to the test directly but there are biologically plausible reasons why the psychological effects of screening may increase mortality. Subjects taking part in screening may feel that this protects them from harm and conduct a lifestyle that increases their risk of mortality.

14. 14 קיים הסבר נוסף שאינו מופיע במאמר

15. 15 הסבר IV ההסבר האולטימטיבי יש טעות בחישובים של המאמר. אין הבדל בשיעור התמותה מסיבה שלא קשורה ל - CRC. לפי המאמר ה - RR בעבודה של Schoiefield הוא 1.03, אך בפועל ה - RR הוא 1.007 !! לפי המאמר ה - Pooled RR לתמותה שלא קשורה ל - CRC הוא 1.02, אך בחישוב שעשינו קבלנו RR=1.007 עם CI=(0.993,1.021)! אין תקפות למאמר !!!! יש טעות בחישובים של המאמר. אין הבדל בשיעור התמותה מסיבה שלא קשורה ל - CRC. לפי המאמר ה - RR בעבודה של Schoiefield הוא 1.03, אך בפועל ה - RR הוא 1.007 !! לפי המאמר ה - Pooled RR לתמותה שלא קשורה ל - CRC הוא 1.02, אך בחישוב שעשינו קבלנו RR=1.007 עם CI=(0.993,1.021)! אין תקפות למאמר !!!!