- Question 4: Has work-up bias been avoided? (Greenhalgh, 1997)

This is easy to check. It simply means, "Did everyone who gotthe new diagnostic test also get the gold standard, and viceversa?" There is clearly a potential bias in studies where thegold standard test is performed only on people who have alreadytested positive for the test being validated.

- Question 5: Has expectation bias been avoided? (Greenhalgh, 1997)

Expectation bias occurs when pathologists and others who interpretdiagnostic specimens are subconsciously influenced by the knowledgeof the particular features of the case—for example, thepresence of chest pain when interpreting an electrocardiogram.In the context of validating diagnostic tests against a goldstandard, all such assessments should be "blind."

- Question 6: Was the test shown to be reproducible? (Greenhalgh, 1997)

If the same observer performs the same test on two occasionson a subject whose characteristics have not changed, they willget different results in a proportion of cases. Similarly, itis important to confirm that reproducibility between differentobservers is at an acceptable level.

- Question 7: What are the features of the test as derived from this validation study? (Greenhalgh, 1997)

All the above standards could have been met, but the test mightstill be worthless because the sensitivity, specificity, andother crucial features of the test are too low—that is,the test is not valid. What counts as acceptable depends onthe condition being screened for. Few of us would quibble abouta test for colour blindness that was 95% sensitive and 80% specific, but nobodyever died of colour blindness. The Guthrie heel-prick screeningtest for congenital hypothyroidism, performed on all babiesin Britain soon after birth, is over 99% sensitive but has apositive predictive value of only 6% (it picks up almost allbabies with the condition at the expense of a high false positiverate), and rightly so. It is more important to pick up everybaby with this treatable condition who would otherwise developsevere mental handicap than to save hundreds the minor stressof a repeat blood test.