Sensitivity/Specificity

Sensitivity/Specificity US Medical PG Question 1: A group of investigators who are studying individuals infected with Trypanosoma cruzi is evaluating the ELISA absorbance cutoff value of serum samples for diagnosis of infection. The previous cutoff point is found to be too high, and the researchers decide to lower the threshold by 15%. Which of the following outcomes is most likely to result from this decision?

• A. Increased negative predictive value (Correct Answer)
• B. Unchanged true positive results
• C. Decreased sensitivity
• D. Increased specificity
• E. Increased positive predictive value

Sensitivity/Specificity Explanation: ***Increased negative predictive value*** - Lowering the absorbance cutoff for the ELISA test makes it **easier to test positive**, which increases **sensitivity** (more true positives are detected, fewer false negatives occur). - **Negative predictive value (NPV)** is the probability that a person who tests negative truly does not have the disease: NPV = TN / (TN + FN). - When the cutoff is lowered, **fewer infected individuals will be missed** (false negatives decrease). This reduction in false negatives improves the NPV because there are fewer disease-positive individuals in the "test-negative" group. - Therefore, a negative test result becomes **more reliable at ruling out infection**, increasing the NPV. *Unchanged true positive results* - Lowering the cutoff means that samples with lower absorbance values (previously below threshold) from truly infected individuals will now be classified as positive. - This directly **increases the number of true positive results**, not keeps them unchanged. - The whole purpose of lowering the threshold is to capture more infected cases. *Decreased sensitivity* - **Sensitivity** = TP / (TP + FN), the ability to correctly identify those with disease. - Lowering the cutoff **increases sensitivity** by making it easier to test positive, thereby capturing more true positives and reducing false negatives. - A lower threshold would never decrease sensitivity—it does the opposite. *Increased specificity* - **Specificity** = TN / (TN + FP), the ability to correctly identify those without disease. - Lowering the cutoff causes some uninfected individuals to now test positive (false positives increase). - This **decreases specificity**, not increases it, as fewer true negatives remain. *Increased positive predictive value* - **PPV** = TP / (TP + FP), the probability that a positive test indicates true disease. - While lowering the cutoff increases true positives, it also **increases false positives more substantially**. - The increased false positives dilute the proportion of true positives among all positive results, thereby **decreasing the PPV**.

Sensitivity/Specificity US Medical PG Question 2: A 23-year-old woman with no significant past medical history currently on oral contraceptive pills presents to the emergency department with pleuritic chest pain. She states that it started today. Yesterday she had a trip and returned via plane. Her temperature is 98°F (36.7°C), blood pressure is 117/66 mmHg, pulse is 105/min, respirations are 14/min, and oxygen saturation is 98% on room air. Physical exam reveals tachycardia, a normal S1 and S2, and clear breath sounds. The patient’s lower extremities are non-tender and symmetric. Chest pain is not reproducible with position changes or palpation but is worsened with deep breaths. Which of the following is the most appropriate next test for this patient?

• A. D-dimer
• B. Ultrasound of the lower extremities
• C. Ventilation-perfusion scan
• D. CT angiogram (Correct Answer)
• E. Chest radiograph

Sensitivity/Specificity Explanation: ***CT angiogram*** - This patient has **HIGH probability for pulmonary embolism (PE)** based on **Wells criteria**: oral contraceptive use (hypercoagulable state), recent long-haul flight (immobilization), pleuritic chest pain, and tachycardia (pulse 105/min). - With a **Wells score ≥4**, the appropriate next step is **definitive imaging with CT pulmonary angiography (CTPA)**, which is the **gold standard** for diagnosing PE. - **D-dimer should be bypassed** in high-probability cases, as a negative result would not adequately rule out PE, and a positive result (expected in high-probability patients) would require CTPA anyway. - CTPA provides direct visualization of pulmonary arterial thrombi and can also identify alternative diagnoses. *D-dimer* - D-dimer is appropriate for **low to moderate probability PE** (Wells score <4) where a negative result can safely rule out PE and avoid unnecessary imaging. - In this **high-probability case**, D-dimer is likely to be positive regardless, making it an unnecessary intermediate step that delays definitive diagnosis. - Using D-dimer in high-probability patients can lead to false reassurance if negative or simply confirms the need for CTPA if positive. *Ultrasound of the lower extremities* - Lower extremity ultrasound diagnoses **deep vein thrombosis (DVT)**, not PE directly. - While finding DVT in a patient with suspected PE would support anticoagulation, **absence of DVT does not rule out PE**, as thrombi may have already embolized. - This would delay appropriate diagnosis and is not the most direct test for suspected PE. *Ventilation-perfusion scan* - V/Q scan is reserved for patients with **contraindications to CT contrast** (severe renal insufficiency, contrast allergy) or pregnant patients where radiation exposure should be minimized. - This young patient has no mentioned contraindications to contrast-enhanced CT. - V/Q scanning is less specific than CTPA and often yields indeterminate results. *Chest radiograph* - Chest X-ray is often **normal in PE** or shows non-specific findings (Westermark sign, Hampton's hump are rare). - While it may help exclude alternative diagnoses like pneumothorax or pneumonia, it cannot definitively diagnose or rule out PE. - In a patient with high clinical suspicion for PE, delaying CTPA to obtain a chest X-ray is not optimal management.

Sensitivity/Specificity US Medical PG Question 3: A scientist in Boston is studying a new blood test to detect Ab to the parainfluenza virus with increased sensitivity and specificity. So far, her best attempt at creating such an exam reached 82% sensitivity and 88% specificity. She is hoping to increase these numbers by at least 2 percent for each value. After several years of work, she believes that she has actually managed to reach a sensitivity and specificity even greater than what she had originally hoped for. She travels to South America to begin testing her newest blood test. She finds 2,000 patients who are willing to participate in her study. Of the 2,000 patients, 1,200 of them are known to be infected with the parainfluenza virus. The scientist tests these 1,200 patients’ blood and finds that only 120 of them tested negative with her new test. Of the following options, which describes the sensitivity of the test?

• A. 82%
• B. 86%
• C. 98%
• D. 90% (Correct Answer)
• E. 84%

Sensitivity/Specificity Explanation: ***90%*** - **Sensitivity** is calculated as the number of **true positives** divided by the total number of individuals with the disease (true positives + false negatives). - In this scenario, there were 1200 infected patients (total diseased), and 120 of them tested negative (false negatives). Therefore, 1200 - 120 = 1080 patients tested positive (true positives). The sensitivity is 1080 / 1200 = 0.90, or **90%**. *82%* - This value was the **original sensitivity** of the test before the scientist improved it. - The question states that the scientist believes she has achieved a sensitivity "even greater than what she had originally hoped for." *86%* - This value is not directly derivable from the given data for the new test's sensitivity. - It might represent an intermediate calculation or an incorrect interpretation of the provided numbers. *98%* - This would imply only 24 false negatives out of 1200 true disease cases, which is not the case (120 false negatives). - A sensitivity of 98% would be significantly higher than the calculated 90% and the initial stated values. *84%* - This value is not derived from the presented data regarding the new test's performance. - It could be mistaken for an attempt to add 2% to the original 82% sensitivity, but the actual data from the new test should be used.

Sensitivity/Specificity US Medical PG Question 4: A geriatric investigator is evaluating the consistency of Alzheimer dementia diagnoses based on clinical symptoms. Patients with known chart diagnoses of Alzheimer dementia were evaluated by multiple physicians during a fixed time interval. Each evaluator was blinded to the others' assessments. The extent to which the diagnosis by one physician was replicated by another clinician examining the same patient is best described by which of the following terms?

• A. Validity
• B. Specificity
• C. Predictive value
• D. Sensitivity
• E. Precision (Correct Answer)

Sensitivity/Specificity Explanation: ***Precision*** - **Precision** refers to the consistency or reproducibility of a measurement or diagnosis. When multiple physicians reach the same diagnosis for the same patient, it indicates high precision. - In this context, it specifically assesses **inter-rater reliability**, which is the extent to which different observers agree on the same assessment. *Validity* - **Validity** refers to the extent to which a test or measure accurately assesses what it is intended to measure. It is about the "truthfulness" of the diagnosis. - While important for diagnosis, validity is about accuracy against a gold standard, not consistency among different observers. *Specificity* - **Specificity** is the ability of a test to correctly identify individuals who do *not* have the disease (true negatives). - It measures the proportion of healthy individuals who are correctly identified as healthy by the test, which is not what is being evaluated here. *Predictive value* - **Predictive value** assesses the probability that a person *actually has* (positive predictive value) or *does not have* (negative predictive value) a disease given their test result. - This concept relates to the diagnostic utility of a test in a population, not the consistency of different clinician diagnoses. *Sensitivity* - **Sensitivity** is the ability of a test to correctly identify individuals who *do* have the disease (true positives). - It measures the proportion of diseased individuals who are correctly identified as diseased by the test, which is distinct from inter-rater agreement.

Sensitivity/Specificity US Medical PG Question 5: A research group wants to assess the safety and toxicity profile of a new drug. A clinical trial is conducted with 20 volunteers to estimate the maximum tolerated dose and monitor the apparent toxicity of the drug. The study design is best described as which of the following phases of a clinical trial?

• A. Phase 0
• B. Phase III
• C. Phase V
• D. Phase II
• E. Phase I (Correct Answer)

Sensitivity/Specificity Explanation: ***Phase I*** - **Phase I clinical trials** involve a small group of healthy volunteers (typically 20-100) to primarily assess **drug safety**, determine a safe dosage range, and identify side effects. - The main goal is to establish the **maximum tolerated dose (MTD)** and evaluate the drug's pharmacokinetic and pharmacodynamic profiles. *Phase 0* - **Phase 0 trials** are exploratory studies conducted in a very small number of subjects (10-15) to gather preliminary data on a drug's **pharmacodynamics and pharmacokinetics** in humans. - They involve microdoses, not intended to have therapeutic effects, and thus cannot determine toxicity or MTD. *Phase III* - **Phase III trials** are large-scale studies involving hundreds to thousands of patients to confirm the drug's **efficacy**, monitor side effects, compare it to standard treatments, and collect information that will allow the drug to be used safely. - These trials are conducted after safety and initial efficacy have been established in earlier phases. *Phase V* - "Phase V" is not a standard, recognized phase in the traditional clinical trial classification (Phase 0, I, II, III, IV). - This term might be used in some non-standard research contexts or for post-marketing studies that go beyond Phase IV surveillance, but it is not a formal phase for initial drug development. *Phase II* - **Phase II trials** involve several hundred patients with the condition the drug is intended to treat, focusing on **drug efficacy** and further evaluating safety. - While safety is still monitored, the primary objective shifts to determining if the drug works for its intended purpose and at what dose.

Sensitivity/Specificity Flashcard 1 of 5

Question: A high _____ test is useful for confirmation after a positive screening test

Answer: specificity

Sensitivity/Specificity Flashcard 2 of 5

Question: _____ is the probability that when the test is positive, the disease is present

Answer: Positive predictive value

Sensitivity/Specificity Flashcard 3 of 5

Question: _____ is the probability that when the test is negative, the disease is absent

Answer: Negative predictive value

Sensitivity/Specificity Flashcard 4 of 5

Question: Under Hardy-Weinberg conditions, what is the expected frequency of an X-linked recessive disease in males? Females?

Answer: males - q females - q2 (if condition is survivable)

Sensitivity/Specificity Flashcard 5 of 5

Question: coefficient of determination (r2) (biostatistics)

Answer: measure of correlation 0 indicates no relationship 1 indicates perfect concordance