1. Assessing Risks for families with inherited cancers: an introduction to a new system Kevin Hughes, MD

2. OMIM: Online Mendelian Inheritance in Man 188 adult hereditary syndromes Syndromes with at least 1 adult chronic disease –Benign 153 –Cancer 32 –Cancer plus benign 3 Scheuner (Am J Med Gen, 2004)

3. Adult hereditary syndromes: 188 Scheuner (Am J Med Gen, 2004)

4. 13 years of genetic testing BRCA1/2 mutation carriers in the US –~1,000,000 Number identified to date –~50,000 (~5%) This is likely the best of any adult hereditary syndrome

5. Problems to solve Most high risk women are not being identified or referred for couseling Our Risk Clinics could not manage the volume if all high risk women were referred

6. Introduction and Concept In the age of the human genome project: –Our health care system must identify women at high risk of breast and ovarian cancer and manage them appropriately –This will decrease the morbidity and mortality of these diseases

7. Our solution We have developed a system that will –allow the patient to enter her own data into a database –decrease the labor intensive effort required of clinicians Automatic analysis Pedigree creation Thus –Decrease labor for staff –Decrease cost –Increase volume of patients cared for –Increase quality of care

8. HughesRiskApps modules follow a simple workflow Patient data entry Clinical Decision Support (CDS) Printout with suggested actions Clinician editing/enhancing Clinical Decision Support (CDS) Generate orders and documents

9. Large scale methods More high risk women identified –Integration of effective FH into workflow More women cared for by the Risk Clinic –Increased efficiency of risk counselor

10. Large scale methods More high risk women identified –Integration of effective FH into workflow More women cared for by the Risk Clinic –Increased efficiency of risk counselor

11. HughesRiskApps allows input to a central database from multiple sources Desktop Website iPad

12. iPad/Tablet PC Data Entry

13. Patient can enter her own data using a simple iPad/Tablet PC interface Requiring little or no help from the staff, patients enter their own data. ~5 th Grade Reading Level Available in English, Spanish and Italian Sample screenshots follow

15. Tablet questions available in Spanish

24. Data Entry via Website

25. Surgeon General Data Entry

26. My Family Health Portrait allows patients to enter family history data –Data saved as an HL7 message –Data saved to HealthVault via HL7

27. Data Entry via Website Web interface in development for patient data entry from home

28. Staff Data Entry Through Desktop Interface

29. The staff can enter or edit patient data using a simple Desktop interface

30. Clinical Decision Support Immediate actions –BRCAPRO Radiologist shown who is high risk –Patient receives written guidance Letter suggesting they make an appt Information sheet Weekly –Letter sent to patient and PCP

31. Large scale methods More high risk women identified –Integration of FH into normal clinic workflow More women cared for by the Risk Clinic –Increased efficiency of risk counselor

32. Next challenge: Minimize clinician work Minimize redundant data entry Minimize dictation and editing Improve efficiency in the Risk Clinic to manage the influx of patients

33. Newton Wellesley Hospital Breast Center 4/1/2007 to 12/01/2010 49,758 unique family histories Breast Center Breast Imaging 2,255 referred for counseling ≥10% risk of mutation

34. Current Approach

35. 70 to 150 minutes

36. RiskApps 45 to 75 minutes

37. Patient enters more detailed family history via a second level Tablet PC interface

38. Details about each family member are collected

42. Cancers are asked similar to the standard tablet

43. Desktop Application for the Risk Counselor

44. Data from Tablet available for review, editing and enhancement by the risk counselor: Table interface

45. Pedigree Interface

46. Additional risk factors are edited/enhanced

47. BRCA and other genetic test results can be easily recorded

48. Choose type of panel (Breast, colon, cardiac, etc.) and the available test can be selected

50. Testing of other genes (Cardiac shown here)by groups makes useful for any genetics clinic

51. Counselor can link families seen before to the current patient

52. Risk algorithms run Graphs show BRCAPRO run multiple times for the same family using different parameters

53. BRCAPRO has been run for each relevant family member, with the risk of mutation shown for each

55. Genetic Testing recommendations are made

57. Myriad and BRCAPRO results are shown with the ability to use the slider to set the clinician’s decision as to the risk of mutation

58. Right bottom side of the screen, family members are listed in order of likelihood of mutation. The willingness of each to be tested can be recorded.

59. Lifetime risk of breast cancer and the management suggestions are shown for multiple scenarios: without testing (Current synthesis), as if the patient tested positive, as if the patient tested negative and the population risk

60. Lifetime risk of ovarian cancer and the management suggestions are shown for multiple scenarios: without testing (Current synthesis), as if the patient tested positive, as if the patient tested negative and the population risk Lifetime risk of ovarian cancer

61. Switch perspective to consider the BRCA2 case

62. Gail model results are displayed

63. Claus model results are displayed

64. Myriad model results are displayed

65. Colorectal tab

69. PREMM Model

70. Clinical Decision support suggests alternative syndromes in order of liklihood

71. Clinical Decision support shows manifestations of selected syndrome

73. DoubleClick on syndrome opens specific OMIM Website and Genetests Website

74. RightClick on syndrome opens specific OMIM Website and Genetests Website

75. RightClick on syndrome opens both OMIM Website and Genetests Website

76. Find all mutation carriers Selective Testing Cascade Testing of family members Mutation Found

77. Cascade testing of relatives of mutation positive patients Help document the testing of family members Shows number tested vs number of living relatives age 18 or older with a mutation risk of 10% or greater

79. Generates multiple documents, saving time on dictation and cost of transcription Letter to referring doctor Letter to the patient Progress note for chart Letter to relatives who need testing Letter of Medical Necessity for insurance company –Justify gentic testing –Justify MRI

80. Letter to the patient

83. Letter for patient to give to her relative who needs testing

84. Letter to relative includes list of testing centers in her area

86. Letter to the referring doctor

90. Report generated at the click of a button

91. HughesRiskApps complies with the HL7 standard Data can be shared with any HL7 compliant software Data can be uploaded or downloaded to any EHR that has a complete family history section and that is HL7 compliant –None currently exist but EHR vendors are likely to improve their product to this level soon

92. HughesRiskApps can help move us into the Genomic Age on a population level More high risk women identified –Integration of FH into normal clinic workflow More women cared for by the Risk Clinic –Increased efficiency of risk counselor

93. References Scheuner 2004 AmJMedGenSeminars Contribution Of Mendelian Disorders To Common Chronic Disease Hughes KS, Roche CA, Campbell CT, Siegel N, Salisbury L, Chekos A, Katz MS, Edell E. Prevalence of Family History of Breast and Ovarian Cancer in a Single Primary Care Practice Using a Self-Administered Questionnaire. The Breast Journal 9: 19-25.Hughes KS, Roche CA, Campbell CT, Siegel N, Salisbury L, Chekos A, Katz MS, Edell E. Prevalence of Family History of Breast and Ovarian Cancer in a Single Primary Care Practice Using a Self-Administered Questionnaire. The Breast Journal 9: 19-25. Jones JL, Hughes KS, Howard-McNatt M, Kopans DB, Moore RH, Hughes SS, Lee NY, Roche CA, Siegel N, Gadd MA, Smith BL, Michaelson JS. Evaluation of Hereditary Risk in a Screening Mammography Population. Clinical Breast Cancer 6(1): 38-44.Jones JL, Hughes KS, Howard-McNatt M, Kopans DB, Moore RH, Hughes SS, Lee NY, Roche CA, Siegel N, Gadd MA, Smith BL, Michaelson JS. Evaluation of Hereditary Risk in a Screening Mammography Population. Clinical Breast Cancer 6(1): 38-44. Shabo A and Hughes, KS. Family History Information Exchange Services Using HL7 Clinical Genomics Standard Specifications. Int'l Journal on Semantic Web & Information Systems 1(4): 42-65Shabo A and Hughes, KS. Family History Information Exchange Services Using HL7 Clinical Genomics Standard Specifications. Int'l Journal on Semantic Web & Information Systems 1(4): 42-65 Dominguez FJ, Jones JL, Zabicki K, Smith BL, Gadd MA, Specht MC, Kopans DB, Moore RH, Michaelson JS, Hughes KS. Prevalence of Hereditary Breast/Ovarian Cancer Risk in Patients with a Personal History of Breast or Ovarian Cancer in a Mammography Population Cancer 2005; 104: 1849-53. Dominguez FJ, Jones JL, Zabicki K, Smith BL, Gadd MA, Specht MC, Kopans DB, Moore RH, Michaelson JS, Hughes KS. Prevalence of Hereditary Breast/Ovarian Cancer Risk in Patients with a Personal History of Breast or Ovarian Cancer in a Mammography Population Cancer 2005; 104: 1849-53. Dominguez FJ, Lawrence C, Halpern EF, Drohan B, Grinstein G, Black DM, Smith BL, Gadd MA, Specht MC, Kopans DB, Moore RH, Hughes SS, Roche CA, Hughes KS. Accuracy of Self- Reported Personal History of Cancer in an Outpatient Breast Center. J Gen Counseling, 2007Dominguez FJ, Lawrence C, Halpern EF, Drohan B, Grinstein G, Black DM, Smith BL, Gadd MA, Specht MC, Kopans DB, Moore RH, Hughes SS, Roche CA, Hughes KS. Accuracy of Self- Reported Personal History of Cancer in an Outpatient Breast Center. J Gen Counseling, 2007