HL7 Clinical Genomics Work Group
The Family History Standard –
Implementation Guide
(US Realm)
November 2627, 2012
Pedigree R1 Co-Editors:
Dr. Amnon Shabo (Shvo)[1]
Dr. Kevin S. Hughes[2]
US Realm IG Co-Editors:
Dr. Amnon Shabo (Shvo)
Mollie H. Ullman-Cullere
Yan Heras
Nnamdi Ihuegbu
Grant M. Wood
© 2011 Health Level Seven, Inc.
Ann Arbor, MI
All rights reserved.
Table of Contents
HL7 Clinical Genomics Work Group 1
The Family History Standard – Implementation Guide 1
DRAFT – November 26, 2012 1
Table of Contents 2
Table of Figures 4
Table of Tables 5
1 Introduction 6
2 storyboards 7
2.1 Cancer - BRCA 7
2.1.1 Storyboard Presentation 7
3 Sample Pedigrees 11
3.1 Breast / Ovarian Cancer – BRCA1/2 11
3.1.1 Annie Proband: 11
3.2 <PKU Disease> (PKU) - <gene> 12
3.2.1 Indiviual with PKU: 12
3.3 < Dominantly Inherited Hypertrophic Cardiomyopathy (HCM) - <genes> 12
3.3.1 Indiviual with Dominantly Inherited Hypertrophic Cardiomyopathy: 12
3.4 < X-linked Dialated Cardiomyopathy (DCM) - <genes> 13
3.4.1 Indiviual with an X-linked Dilated Cardiomyopathy: 13
4 The Family history model 15
4.1 Model Walkthrough 15
4.1.1 Entry Point - FamilyHistory 15
4.1.2 Patient & Person 16
4.1.3 Clinical Data 16
4.1.4 Genetic Data 16
4.1.5 Informant 17
4.1.6 Relative 17
4.1.7 subjectOf2 Shadow 18
4.1.8 Person and Relative 18
4.1.9 Relative’s Mother and Father Identifiers 19
5 vocabularies 21
5.1 Family Relationships 21
5.2 Age Attributes 21
5.2.1 Age at Death 21
5.2.2 Age of Onset of Disease 21
5.2.3 Age of Living Subject 21
5.3 Race 22
5.4 Ethnicity 22
6 Exchange of family health history 23
appendix a: The family history (Pedigree) model 26
appendix B: hierarchical vs. flat representation 28
appendix C: xml schema and samples 30
appendix D: HITSP specifications on personalized healthcare 31
Appendix E: Genetic Data Represenation 34
Table of Figures
Figure 1: Common Visualization of a Family Health History: Breast Ovarian Cancer Syndrome 11
Figure 2: Common Visualization of a Family Health History: PKU 12
Figure 3: Common Visualization of a Family Health HIstory: Dominantly Inherited Hypertrophic Cardiomyopathy 13
Figure 4: Common Visualization of a Family Health History: X-linked Dilated Cardiomyopathy 14
Figure 5: The Recursive Association of Person and Relative Which Enables a Hierarchical Representation of a Pedigree to Any Depth Needed 19
Figure 6: The Family History (Pedigree) Model 26
Figure 8: Construct Personal and Family Health History & Pedigree 31
Figure 9: Scenario 1: Clinical Assessment Component Data Flow Diagram 32
Table of Tables
Table 1: Outline for Family History of a Cancer Patient 7
Table 2: Age at Death 23
Table 3: Age of Onset of Disease 23
Table 4: Age of Living Object 23
Table 5: Race Value Set (excerpt) 24
Table 6: Ethnicity Value Set 24
Table 7: Personal Relationship Role Type Value Set (excerpt) 24
1 Introduction
A number of family history applications are in use by health care professionals (e.g., HughesRiskApps, CAGENE, Progeny) as well as by patients (e.g., the US Surgeon General’s My Family Health Portrait. Several of these have application-specific proprietary data formats for pedigree drawing and for the maintenance of family history health information; howeverwhile others are compliant with an international family history standard, for example, HughesRiskApps (available at: http://www.hughesriskapps.net/ ) and the US Surgeon General’s My Family Health Protrait (available at: https://familyhistory.hhs.gov/fhh-web/home.action) use an ANSI approved HL7 data standard. The benefits for using a proven data standard are many, including interoperability and an information model proven effective in clinical setting for patient care and clinical decision making.
Interoperability between applications had been essentially non-existent. In 2007, the HL7 Pedigree/Family History standard (codename “Pedigree R1”) was approved by ANSI as a normative specification, and thus disparate family history applications can now easily exchange patient information. The receiving application can understand the semantics of the incoming family history and enable the user to view and/or to edit that data using the receiving application’s interface.
In the United States, the Office of the National Coordination (ONC) of Health Information and Technology published Family History data requirements, developed by a multi-stakeholder workgroup which further defines the HL7 Pedigree/Family History standard. Additionally, the ONC Personalized Healthcare Use Case implementation includes recommendations illustrating the use of Family family History health history in the clinical workflow. These documents can be found at: http://healthit.hhs.gov/portal/server.pt/community/use_cases_and_requirements_documents/1202/personalized_healthcare/15671
This standard has been developed in parallel with clinical pilots and the ONC multi-stakeholder initiatives, providing a robust model for adoption. The HL7 Pedigree/Family History standard model proved effective in the identification of patients with increased familial risk of disease within multiple diverse settings (e.g. public use at home, genetic testing laboratory, clinican’s office, mammography center) and disease areas (e.g. cardiology, cancer and prenatal/ObGyn).
This US-Realm specific Family History Implementation Guide (IG) of is based on the Pedigree/Family History R1 standard and provides guidance on the use of the standard in the US by illustrating the preferred representation formats of key data elements such as genetic findings and clinical data. This guide also provides guidance on the exchange mechanism of family health data. Note that the HL7 Clinical Genomics Work Group works with the HHS in order for this guidance included in this IGto accommodates the US Meaningful Use requirements regarding family health history. In this first release of the US Guide, the guidance relates supportsto demographcdemographic and clinical data, as well as certain types of genetic data and risk assessment.
2 storyboards
This section describes scenarios where family health history is used and enables implementers to better understand the clinical workflow in which family history is integrated for patient care.
2.1 Cancer - BRCA
The objective of this storyboard is to illustrate the way a patient's pedigree/family health history is used for risk analysis of breast and ovarian cancers and other diseases. It extends the broader breast cancer story board and includes a sample outline for the patient's pedigree/family history.
2.1.1 Storyboard Presentation
1. Ms. Eve Everywoman has a family history of breast and ovarian cancer, and she is not of Ashkenazi Jewish descent.
2. She believes she is at high risk of developing breast cancer.
3. She goes to see her clinician (Medical oncologist, surgical oncologist, radiation oncologist, primary care provider) who takes a thorough family history. This history is recorded in the chart and the electronic medical record.
4. The clinician reviews the family history, decides what genetic syndrome her family might have, and categorizes the patient as to degree of risk (Perhaps high, medium, or low risk). The clinician thinks the patient is at high risk of having a BRCA1/2 mutation (i.e. sequence variant).
5. The clinician compares her Family History to tables of risk (Claus, Myriad) and runs computer models (algorithms such as BRCAPRO, see http://www.isds.duke.edu/~gp/brcapro.html). This gives a percentage risk of carrying a mutation (i.e. sequence variant) and/or a risk of developing breast and/or ovarian cancer. Her risk of a mutation is 25%, because her father's 4 sisters had ovarian caner.
6. The patient is considered to be at high risk of having a mutation (i.e. sequence variant), and this information is given to her.
7. She is referred to a High Risk Genetic Clinic.
8. She agrees to go to the High Risk Genetic Clinic.
9. Ms Eve Everywoman 's Family History details are sent to this clinic (the HL7 Interaction POCG_IN000001 is used), including her Family History, the syndrome suspected and her level of risk.
10. The counselor at the risk clinic (Nurse geneticist, genetic counselor, MD, etc.) reviews the family history information collected by the clinician (Medical oncologist, surgical oncologist, radiation oncologist, primary care provider), edits it and adds additional details.
11. The Counselor reviews the family history, decides what genetic syndrome the patient’s family might have, and categorizes her degree of risk (perhaps high, medium, or low risk). The Counselor thinks the patient is at high risk of having a BRCA1/2 mutation (i.e. sequence variant). <Do we have a coded answer list for result of risk assessment?>
12. The clinician compares the family history to tables of risk (Claus, Myriad) and runs computer models (algorithms such as BRCAPRO). This gives a percentage risk of carrying a mutation and/or a risk of developing breast and/or ovarian cancer. Her risk of a mutation is 25%, because her father's 4 sisters had ovarian caner.
13. The patient is considered to be at high risk, and she is told she is a candidate for genetic testing. This includes a thorough discussion of the pros and cons of testing. This discussion is recorded in the electronic medical record.
14. Ms. Eve Everywoman wants to have testing, but as she is not affected, it is the standard of care to test a living affected relative first (i.e. a living relative who has/or has had the disease for which the patient is at risk for).
15. The Counselor suggests that her Aunt, Ms. Jeanne Aunt, is the most appropriate candidate for testing. Ms. Jeanne Aunt had ovarian cancer, and is still living.
16. Ms. Eve Everywoman agrees to contact Ms. Jeanne Aunt.
17. Ms Eve Everywoman signs consent to release her own Family History details to Ms Jeanne Aunt and her Provider.
18. Ms. Jeanne Aunt is a 39-year-old woman who had been diagnosed with ovarian cancer at age 35.
19. Ms Jeanne Aunt agrees to discuss testing, and provides the name and address of the risk clinic she will attend.
20. Ms Eve Everywoman's family history details are sent to this clinic.
21. The counselor at the risk clinic (Nurse geneticist, genetic counselor, MD, etc.) reviews the family history information collected by the primary clinician through a pedigree drawing program, and changes the Proband[3] to Ms Jeanne Aunt, edits it and adds additional details (The family history message had Ms Eve Everywomanas the Proband (Self), and Ms Jeanne Aunt as the aunt. The pedigree from the point of view of Ms Jeanne Aunt must have Jeanne Aunt as the Proband (Self) and must show Ms Eve Everywoman as the niece).
22. The Counselor reviews the family history, decides what genetic syndrome her family might have, and categorizes the patient as to degree of risk (Perhaps high, medium, or low risk). The Counselor thinks the patient is at high risk of having a BRCA1/2 mutation, because the patient and one or more of her relatives have had breast/ovarian cancer.
23. The clinician compares the family history to tables of risk (Claus, Myriad) and runs computer models (algorithms such as BRCAPRO). This gives a percentage risk of carrying a mutation and/or a risk of developing breast and/or ovarian cancer. Ms. Jeanne Aunt is virtually at 100% risk of having a BRCA1/2 mutation (i.e. sequence variant).
24. The patient is considered to be at high risk, and she is told she is a candidate for genetic testing. This includes a thorough discussion of the pros and cons of testing. This discussion is reviewed in the electronic medical record.
25. Ms. Jeanne Aunt wants to have testing. She signs an informed consent document.
26. The order for testing is issued, and the informed consent, and the family history are included with the lab requisition. All are MESSEGED to the blood drawing facility.
27. The blood is drawn, and sent to the central testing facility along with the informed consent, the family history and the lab requisition.
28. At the central testing facility, the specimen is checked in (i.e. accessioned), and the DNA is extracted and prepared for DNA sequencing.
29. Full gene sequencing of BRCA1 and BRCA 2 are undertaken.
30. The sequence is assessed for mutations.
31. Identified mutations are assessed for clinical significance: associated with increased risk of developing breast and/or ovarian cancer(pathogenic/deleterious), do not increase the patient’s risk of disease (benign), or if the clinical implications of the mutation is unknown (unknown significance). The actual mutation, and the assessment of clinical significance are sent to the counselor.
32. In this case, a mutation is identified in BRCA1 and the mutation is Pathogenic/Deleterious.
33. The counselor discusses the result with the patient.
34. Patient care decisions (Screening, chemoprevention, prophylactic surgery) are beyond the scope of this storyboard.
35. Ms Jeanne Aunt agrees to share this information with Ms Eve Everywoman's Clinician.
36. This information is sent to Ms Eve Everywoman's Clinician.
37. Ms. Eve Everywoman wants to have testing. She signs an informed consent document.
38. The order for testing is issued, and the informed consent, and the family history are included with the requisition, as well as the results of Ms Jeanne Aunt’s test. All are messaged to the blood drawing facility.
39. The blood is drawn, and sent to the central testing facility along with the informed consent, the family history, the results of Ms Jeanne Aunt’s test, and the lab requisition.
40. At the central testing facility, the specimen is checked in, and the DNA is extracted and prepared for DNA sequencing.
41. Full gene sequencing is not needed. Testing only for the identified mutation is undertaken.
42. The DNA is assessed for that specific mutation (i.e. sequence variant).
43. The mutation is not found.
44. The normal result is sent to the counselor.
45. The counselor discusses the result with the patient.
46. Patient management/care decisions (Screening, chemoprevention, prophylactic surgery) are beyond the scope of this storyboard.
2.2 PKU – Phenylketonuria
This storyboard illustrates the use of family history as part of the follow-up for a newborn diagnosed with Neonatal Phenylketonuria (PKU), during newborn screening. Phenylketonuria is inherited in an autosomal recessive manner. More details can be found at: http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0002150/.
2.2.1 Storyboard Presentation
- Infant Ned Everynewborn is born.
- His heel is lightly pricked and a blood sample is blotted onto a card for newborn screening test.
- The ‘blood spot’ (card with sample from the newborn) is sent to the state’s newborn screening testing lab.
- Tests are performed and positive (or ambiguous) results are communicated to the hospital and infant’s clinician.
- The clinicain discusses these positve (or ambiguous) results with the newborn’s parents and refers them to a specialist.
- The clinical specialist collects the family history of the patient, to help guide patient care and follow-up. In addtion, the clinician educates the parents on risks for future children, as PKU is a inherited recessive condition and 25% of their offspring are at risk of inheriting the condition.
2.3 Familial Hypertrophic Cardiomyopathy(HCM)