Diagnostic thresholds

Diagnostic thresholds

Published January 10, 2026

Diagnostic thresholds

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Diagnostic Thresholds - The Cutoff Conflict

  • The cutoff value determines a test's sensitivity (Sn) & specificity (Sp).
  • An inverse relationship exists: ↑Sn = ↓Sp, and vice-versa.
  • Receiver Operating Characteristic (ROC) curve: Plots Sn (true positive rate) vs. 1-Sp (false positive rate) for various cutoffs.
    • Area Under the Curve (AUC) measures accuracy.
    • AUC = 0.5: Chance (useless test).
    • AUC = 1.0: Perfect test.

ROC curve showing sensitivity vs 1-specificity trade-off

⭐ For severe diseases with effective treatment (e.g., cancer screening), a lower cutoff is used to maximize sensitivity and not miss cases (ruling out disease, SNOUT).

ROC Curves - Accuracy at a Glance

  • A Receiver Operating Characteristic (ROC) curve graphically plots a test's diagnostic performance across all possible cut-off thresholds.
  • It plots Sensitivity (True Positive Rate) vs. 1-Specificity (False Positive Rate).
    • Y-axis: Sensitivity = $TP / (TP + FN)$
    • X-axis: 1 - Specificity = $FP / (FP + TN)$

ROC curves comparing diagnostic accuracy of different tests

  • Interpretation:
    • The curve shows the trade-off between sensitivity and specificity.
    • A more accurate test has a curve that "bows" closer to the top-left corner.
  • Area Under the Curve (AUC):
    • Represents the test's overall accuracy; its ability to correctly distinguish between diseased and non-diseased individuals.
    • AUC = 1.0: Perfect test.
    • AUC = 0.5: No discrimination (the diagonal line).

⭐ The ideal cut-off point on the ROC curve is often the point closest to the top-left corner (0,1), as it maximizes the Youden Index (Sensitivity + Specificity - 1).

Clinical Strategy - Screen or Confirm?

  • Screening Tests: Prioritize high sensitivity (Sn).
    • Goal: Rule-out disease (📌 SNOUT: SeNsitivity rules OUT).
    • Use when missing a case is unacceptable (e.g., serious but treatable conditions).
    • Accepts higher false positives (FP).
  • Confirmatory Tests: Prioritize high specificity (Sp).
    • Goal: Rule-in disease (📌 SPIN: SPecificity rules IN).
    • Use after a positive screen to confirm diagnosis.

⭐ In low prevalence settings, a test's Negative Predictive Value (NPV) is maximized, making a negative result highly reliable for ruling out disease.

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Predictive Values - The Prevalence Effect

  • Positive Predictive Value (PPV) is directly proportional to prevalence.
    • As disease prevalence ↑, PPV ↑.
  • Negative Predictive Value (NPV) is inversely proportional to prevalence.
    • As disease prevalence ↑, NPV ↓.
  • Sensitivity and Specificity are intrinsic to the test and are not affected by prevalence.

⭐ High-prevalence populations yield higher PPVs, making screening tests most useful when targeted at high-risk groups.

High-Yield Points - ⚡ Biggest Takeaways

  • Altering the diagnostic threshold creates a trade-off between sensitivity and specificity.
  • ↓ threshold: ↑ sensitivity (more true positives), ↓ specificity (more false positives). Good for screening tests.
  • ↑ threshold: ↑ specificity (more true negatives), ↓ sensitivity (more false negatives). Good for confirmatory tests.
  • ROC curves plot sensitivity (y-axis) vs. 1-specificity (x-axis) for various thresholds.
  • The Area Under the Curve (AUC) measures a test's overall diagnostic accuracy.

Practice Questions: Diagnostic thresholds

Test your understanding with these related questions

A 36-year-old female presents to clinic inquiring about the meaning of a previous negative test result from a new HIV screening test. The efficacy of this new screening test for HIV has been assessed by comparison against existing gold standard detection of HIV RNA via PCR. The study includes 1000 patients, with 850 HIV-negative patients (by PCR) receiving a negative test result, 30 HIV-negative patients receiving a positive test result, 100 HIV positive patients receiving a positive test result, and 20 HIV positive patients receiving a negative test result. Which of the following is most likely to increase the negative predictive value for this test?

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Flashcards: Diagnostic thresholds

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