Analytic validity of cystic fibrosis testing: A preliminary estimate

Purpose: Derive estimates of analytic sensitivity and specificity of DNA testing for cystic fibrosis in the United States. Methods: Analyze published results of the American College of Medical Genetics (ACMG)/College of American Pathologists (CAP) Molecular Genetics Survey between 1996 and 2001, taking into account difficult, simulated clinical samples included for educational purposes. Results: Analytic sensitivity is 97.9% [95% confidence interval (CI) 96.8-98.7%], and analytic specificity is 99.4% (95% CI 98.7-99.9%) after removing challenges involving dell507 and performing other adjustments. Analytic sensitivity is consistent over the 6 years. Specificity was lower in 1997. Conclusion: These preliminary estimates indicate that analytic validity of cystic fibrosis testing is very good and can likely be improved. To date, fewer than half of the mutations in the panel recommended for preconceptional or prenatal screening have been challenged. The present study highlights the value of performing confirmatory testing when a mutation is identified to reduce false-positive results.