What information is required to calculate the specificity of a new blood test for prenatal diagnosis of cystic fibrosis?

Information Required to Calculate Specificity of a Prenatal Cystic Fibrosis Blood Test

To calculate the specificity of the new prenatal blood test for cystic fibrosis, the number of true negatives and false positives must be known.

Understanding Specificity in Diagnostic Testing

Specificity is defined as the proportion of negative test results among individuals who do not have the disease. In mathematical terms:

Specificity = True Negatives / (True Negatives + False Positives)

Data Available from the Study

• Total participants: 5000 pregnant women
• Positive test results: 29 women
• True positives: 26 women (confirmed by positive sweat chloride test in infants)
• False positives: 3 women (positive blood test but negative sweat chloride test in infants)

Missing Information

To calculate specificity, we need:

• True negatives: The number of women with negative blood tests whose babies had negative sweat chloride tests
• False positives: Already known (3)

Analysis of the Situation

According to the American College of Medical Genetics guidelines, clinical specificity is a critical parameter in evaluating prenatal diagnostic tests for cystic fibrosis 1. The specificity calculation requires knowing how many women without affected babies correctly tested negative.

In this case:

• We know there were 5000 total participants
• We know 29 had positive tests
• Therefore, 4971 women had negative tests
• But we don't know how many of these 4971 women had babies with negative sweat chloride tests (true negatives)

Clinical Implications

High specificity is particularly important in prenatal testing for cystic fibrosis to avoid unnecessary anxiety and interventions. The ACMG guidelines note that "analytic error or variable expressivity of certain mutations can reduce the clinical specificity of the test" 1.

Common Pitfalls in Test Evaluation

1. Confusing sensitivity and specificity: Sensitivity measures the test's ability to correctly identify those with the disease, while specificity measures the test's ability to correctly identify those without the disease.

2. Assuming all negative tests are true negatives: Without follow-up testing of all babies with negative prenatal tests, we cannot determine the true negative rate.

3. Overlooking the importance of the reference standard: The sweat chloride test is considered the gold standard for CF diagnosis, with values >60 mEq/L considered diagnostic 1.

Conclusion

To calculate the specificity of this new prenatal blood test for cystic fibrosis, we need to know the number of true negatives - specifically, how many of the 4971 women with negative blood tests had babies with negative sweat chloride tests.

Without this information, the specificity calculation cannot be completed.