Positive and Negative Predictive Value
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Predictive values answer the clinically relevant question: given a test result, what is the probability that the patient actually has (or does not have) the condition? Unlike sensitivity and specificity, predictive values depend on disease prevalence.
- Positive Predictive Value (PPV) = TP / (TP + FP) = probability of disease given a positive test
- Negative Predictive Value (NPV) = TN / (TN + FN) = probability of no disease given a negative test
- PPV increases as prevalence increases (more true positives relative to false positives)
- PPV decreases as prevalence decreases (false positives overwhelm true positives)
- NPV is generally high when prevalence is low (most negatives are true negatives)
This is why screening tests perform differently in high-risk vs low-risk populations.
Example 1: NIPT in high-risk vs low-risk
High-risk population (prevalence 1/100):
| T21+ (100) | T21- (9,900) | |
|---|---|---|
| Screen+ | 99 | 50 |
| Screen- | 1 | 9,850 |
PPV = 99/149 = 66%
Low-risk population (prevalence 1/1,000):
| T21+ (10) | T21- (9,990) | |
|---|---|---|
| Screen+ | 9.9 | 50 |
| Screen- | 0.1 | 9,940 |
PPV = 9.9/59.9 = 17%
Same test, same sensitivity/specificity, but PPV drops from 66% to 17% because prevalence is lower.
Example 2: Why confirmatory testing is needed
Problem: A 25-year-old with no risk factors has a positive NIPT for trisomy 18. Prevalence at her age is approximately 1/5,000. Test sensitivity is 96%, specificity is 99.5%. What is the PPV?
Solution:
- In 100,000 pregnancies: 20 with T18, 99,980 without
- True positives: 20 x 0.96 = 19.2
- False positives: 99,980 x 0.005 = 499.9
- PPV = 19.2 / (19.2 + 499.9) = 3.7%
- Over 96% of positive screens at this prevalence are false positives
- This is why diagnostic confirmation (amniocentesis/CVS) is essential after a positive screen
- A positive screening test in a low-prevalence population is more likely to be a false positive than a true positive
- Diagnostic tests (amnio, CVS) have near-100% sensitivity and specificity, so PPV approaches 100%
- When counseling a patient about a positive screen, always contextualize the PPV based on their prior risk
"Prevalence Powers PPV": PPV is driven by prevalence. Low prevalence = low PPV, even with an excellent test. Always consider the prior probability (age, family history, ultrasound findings) when interpreting a positive screen.