ROC method for early detection of disease

• US 5,800,347 A
• Filed: 11/03/1995
• Issued: 09/01/1998
• Est. Priority Date: 11/03/1995
• Status: Expired due to Term

• Current Assignee: The General Hospital Corporation (Mass General Brigham, Inc.), Queen Mary And Westfield College
• Original Assignee: The General Hospital Corporation (Mass General Brigham, Inc.)
• Inventors: Jacobs, Ian, Skates, Steven J.
• Primary Examiner(s): JAWORSKI, FRANCIS J
• Application Number:
  US08/552,823
• Time in Patent Office: 1,033 Days
• Field of Search: 128/630, 128/660.04, 128/660.07, 128/923, 600/300, 600/340, 600/343
• US Class Current: 600/300
• CPC Class Codes: A61B 5/00 Measuring for diagnostic purposes radiation diagnosis A61B6/00; diagnosis by ultrasonic, sonic or infrasonic waves A61B8/00; Identification of persons
• CPC Class Codes: A61B 5/7275 Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor
• CPC Class Codes: G01N 33/57449 of ovaries
• CPC Class Codes: G16H 50/20 for computer-aided diagnosis, e.g. based on medical expert systems
• CPC Class Codes: G16H 50/30 for calculating health indices; for individual health risk assessment
• CPC Class Codes: Y10S 128/923 by comparison of patient data to other data

Abstract

A method of assessing risk of an individual for a disease is disclosed. A level of a marker for the disease is detected, and the risk of disease is computed from a statistical analysis of the marker level distributions for tested normal and diseased populations, using multivariate distributions. The computed risk is compared to thresholds to triage the individual into a normal, borderline, or elevated risk group, and a course of action based on the risk group is determined. Memory storing a program for execution on a data processing system, as well as a computer system comprising said memory is also disclosed, the memory comprising a receiver for signals representative of levels of a marker for the disease; a central procesing unit for computing risk of disease from one or more levels of the marker, and for comparing the computed risk to thresholds to triage the individual; and storage medium for the marker levels for subsequent computations of risk of disease.

Claims

1. A method of assessing the risk of an individual for a disease, comprising:

a) testing the individual to detect a level of a marker for the disease;

b) computing risk of disease from a detected level of the marker; and

c) comparing the computed risk to thresholds to triage the individual into one of normal, borderline and elevated risk groups,

wherein if the individual is triaged to a borderline risk group, the step of testing the individual to detect the level of the marker is repeated at a retest interval substantially less than a routine screening interval.

2. A method as claimed in claim 1, wherein if the individual is triaged to a normal risk group, the step of testing the individual to detect the level of the marker is repeated at a routine screening interval.

3. A method as claimed in claim 1, wherein if the individual is again triaged to a borderline risk group upon repeat testing, the step of testing the individual is again repeated to detect the level of the marker at a retest interval substantially less than a routine screening interval.

4. A method as claimed in claim 1 wherein the retest interval is inversely related to the computed risk.

5. A method as claimed in claim 1 wherein, if the individual is triaged into an elevated risk group, the individual is subjected to a secondary test to determine likelihood of presence of disease.

6. A method as claimed in claim 5 wherein the individual is a postmenopausal woman, the disease is ovarian cancer, the marker is CA125 and the secondary test is an ultrasonographic test.

7. A method as claimed in claim 5 wherein, if the individual is triaged into the elevated risk group, the level of the marker is again detected and the risk is again computed.

8. A method as claimed in claim 7 wherein, if results of the secondary test are equivocal, the secondary test is repeated and a course of action is determined based on results of the repeated test or recomputed risk.

9. A method as claimed in claim 7 wherein, if the results of the secondary test are normal, a course of action is determined based on a recomputed risk.

10. A method as claimed in claim 1 wherein the individual is a postmenopausal woman, the disease is ovarian cancer and the marker is CA125.

11. A method as claimed in claim 10 wherein, if the individual is triaged into an elevated risk group, the individual is subjected to a secondary test of ultrasound examination to determine a course of action.

12. A method as claimed in claim 10 wherein the individual is triaged to the borderline risk group if the risk of disease is computed to be in a range of 0.05 to 4%.

13. The method of claim 1 wherein the risk of the disease is computed from a statistical analysis of the marker level distributions for tested normal and diseased populations.

14. A method as claimed in claim 13 wherein the risk is determined from multivariate distributions.

15. A method as claimed in claim 14 wherein the marker level changes exponentially over time for diseased individuals and the multivariate distributions are determined from the slope and intercept of the log of detected marker levels over time for individuals within the normal and diseased populations.

16. The method of claim 14 wherein random draws are used to compute average densities from the normal and disease populations given the marker levels for the individual.

17. A method as claimed in claim 16 wherein the risk is computed as a product of an odds factor and an estimate of prior odds, wherein the odds factor is the ratio of the average density from the disease population to the average density from the normal population.

18. A method as claimed in claim 16 wherein the risk is determined through addition of a time correlation component to a linear regression model of marker levels.

19. A method as claimed in claim 14 wherein the multivariate distribution is obtained by detecting plural markers.

20. A method of assessing the risk of a woman for ovarian cancer, comprising:

a) testing the woman to detect a level of a marker for ovarian cancer;

b) computing risk of ovarian cancer from a detected level of the marker; and

c) comparing the computed risk to thresholds to triage the woman into one of normal, borderline and elevated risk groups,

wherein if the woman is triaged to a borderline risk group, the step of testing the woman to detect the level of the marker is repeated at a retest interval substantially less than a routine screening interval.

21. A method as claimed in claim 20 wherein the marker level changes exponentially over time for diseased individuals and the multivariate distributions are determined from the slope and intercept of the log of detected marker levels over time for individuals within the normal and diseased populations.

22. The method of claim 21 wherein random draws are used to compute average densities from the normal and disease populations given the marker levels for the individual.

23. A method as claimed in claim 22 wherein the risk is computed as a product of the odds factor and an estimate of prior odds, wherein the odds factor is the ratio of the average density from the disease population to the average density from the normal population.

24. A method as claimed in claim 21 wherein the risk is determined through addition of a time correlation component to a linear regression model of marker levels.

25. A method as claimed in claim 20 wherein the multivariate distribution is obtained by detecting plural markers.

26. A method of assessing the risk of an individual for a ovarian cancer comprising;

testing the individual at plural times to detect a level of a marker to the disease;

computing risk of ovarian cancer from a statistical analysis of detected marker levels relative to multivariate marker level distributions for tested normal and diseased populations; and

determining a course of action for the individual based on the computed risk factor.

27. A method as claimed in claim 26 wherein the marker level changes exponentially over time for diseased individuals and the multivariate distributions are determined from the slope and intercept of the log of detected marker levels over time for individuals within the normal and diseased populations.

28. The method of claim 27 wherein random draws are used to compute average densities from the normal and disease populations given the marker levels for the individual.

29. A method as claimed in claim 28 wherein the risk is computed as a product of the odds factor and an estimate of prior odds, wherein the odds factor is the ratio of the average density from the disease population to the average density from the normal population.

30. A method as claimed in claim 27 wherein the risk is determined through addition of a time correlation component to a linear regression model of marker levels.

31. A method as claimed in claim 26 wherein the multivariate distribution is obtained by detecting plural markers.