A novel serum biomarker, UWRLD99, is being evaluated for early detection of pancreatic cancer. The concentration of UWRLD99 (measured in international units [IU] per dL) has been found to be elevated in patients with pancreatic adenocarcinoma. Test results in 200 volunteers ("healthy") and 190 patients with biopsy-proven pancreatic cancer ("diseased") are given in the figure below. The investigators determined the sensitivity and specificity of UWRLD99 for pancreatic cancer using a cutoff of 200 IU/dL (indicated by the solid vertical line). If they had instead used a lower cutoff as indicated by the dashed vertical line, which of the following would most likely be seen?

Question

A novel serum biomarker, UWRLD99, is being evaluated for early detection of pancreatic cancer.  The concentration of UWRLD99 (measured in international units [IU] per dL) has been found to be elevated in patients with pancreatic adenocarcinoma.  Test results in 200 volunteers ("healthy") and 190 patients with biopsy-proven pancreatic cancer ("diseased") are given in the figure below.  The investigators determined the sensitivity and specificity of UWRLD99 for pancreatic cancer using a cutoff of 200 IU/dL (indicated by the solid vertical line).  If they had instead used a lower cutoff as indicated by the dashed vertical line, which of the following would most likely be seen?

Quizplus · Accepted Answer

11ec160b_371a_897a_9249_175a997a68af_MD0001_00 Important parameters of diagnostic tests include the following: The cutoff value of a quantitative diagnostic test determines whether a given result is interpreted as positive or negative. Depending on the disease or condition being tested for, sensitivity or specificity may be preferred and the cutoff value adjusted accordingly. A cutoff value just outside the overlapping region of the curves can maximize the sensitivity or specificity at 100% by correctly classifying all diseased or healthy individuals, respectively. In the above example, changing the cutoff point to a lower value (shift to the left) would cause more patients with the disease to test positive (↑TP, ↓FN), increasing the sensitivity of the test. However, as a consequence, more patients without the disease would also test positive (↓TN, ↑FP), resulting in decreased specificity. (Choices A, D, and E) Raising the cutoff value (shift to the right) would cause fewer individuals with the disease to have a positive test result (↓TP, ↑FN), so sensitivity would decrease. Fewer individuals without the disease would also test positive (↑TN, ↓FP), so specificity would increase. (Choice B) Positive predictive value (PPV = TP / [TP + FP]) represents the probability that a patient with a positive test result actually has the disease. In this case, the lower cutoff value would increase both TP and FP; how this affects the PPV depends on disease prevalence, which is not provided. In a population with very low disease prevalence, the number of FP would be expected to increase proportionately more than the number of TP, which would lower the PPV. Educational objective: The cutoff value of a quantitative diagnostic test determines whether a given result is interpreted as positive or negative. Lowering the cutoff point typically causes more patients with the disease to test positive, decreasing the number of false negatives and increasing test sensitivity. Consequently, more patients without the disease will also test positive, resulting in an increased number of false positives and decreased specificity.

A Novel Serum Biomarker, UWRLD99, Is Being Evaluated for Early