2. HL7 Version 3 Laboratory Result-based Adverse Event Assessment Message Specifications RCRIM Technical Meeting September 18, 2007 Jennifer Neat Project Leader, City of Hope Abdul Malik Shakir HL7 Facilitator, Shakir Consulting

3. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification2 of 22 Introduction Project Scope Develop an HL7 v3 draft standard for trial use messaging specification that supports the unique data requirements for initial laboratory result-based adverse event (AE) assessment information. Objectives Met Evaluated existing message structures and identified the HL7 v3 CT Laboratory Message DSTU as an appropriate structure for laboratory result-based AE assessment messaging specifications Defined an AE Assessment CMET as an optional structure within the revised CT Laboratory Message Identified the AE Assessment CMET vocabulary requirements Identified the required messaging interactions

4. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification3 of 22 Regulated Studies Domain Summary of Clinical Trial Interactions in the Regulated Studies Domain

5. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification4 of 22 Project Scope in Context Revised Summary Clinical Trial Interactions to include: AE Assessment Request AE Assessment Response

6. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification5 of 22 Storyboard Overview Laboratory test results can indicate a patient has experienced/is experiencing an adverse event (AE). For clinical trials mandating use of a grading criteria for assessing laboratory result-based AEs, laboratory test results may be transmitted to an automated AE assessment service. The AE assessment service evaluates the laboratory results subject to quantitative AE assessment, based on the specified grading criteria, such as the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events v3.0 (CTCAE). An initial / first-level assessment is performed to determine the presence and severity of an AE(s). Upon completion, the laboratory test results and associated AE assessment outcomes are transmitted to a clinical information system within the clinical research environment. Subsequent investigation into the patients condition must be conducted within the clinical research environment in order to determine, in part, the AE reporting requirements.

7. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification6 of 22 Storyboard CT Laboratory Result-based Adverse Event Assessment (PORT_SN03000x) Narrative A laboratory facility has performed one or more tests on a patient specimen and the results of the testing are available electronically for review and further evaluation within the clinical research environment. A request is sent to an automated AE assessment service to evaluate the laboratory test results. Each test result that is subject to quantitative AE assessment is evaluated for the presence and severity of an adverse event, and the test result is appended with this AE assessment outcome data. The AE assessment service sends a response message containing the original and appended information.

8. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification7 of 22 Interaction Diagram Purpose The storyboard demonstrates an initial / first-level evaluation of clinical trial laboratory results subject to quantitative adverse event assessment.

9. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification8 of 22 Interaction Design Elements & Descriptions: Application Roles ClinicalTrial Observation Order Global Placer (PORT_AR03000x) An application that is capable of notifying another application about a significant clinical trial observation event and expects the receiver to take action. Adverse Event Assessment Observation Fulfiller (PORT_AR03000y) An application that is capable of receiving an adverse event (AE) assessment request from a Placer application. The Adverse Event Assessment Observation Fulfiller is responsible for evaluating clinical trial laboratory results and deriving AE assessment outcome data. The fulfiller is also responsible for initiating communication of this data to the Clinical Observation Event Global Tracker. ClinicalTrial Observation Event Global Tracker (PORT_AR010001UV01) The application role includes the behaviors needed to receive and appropriately manage notifications from another system about any change of a Clinical Trial Observation Event. This includes receiving information about status changes of that event and receipt of observation event information once that is available.

10. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification9 of 22 Interaction Design Elements & Descriptions: Trigger Event Agreed Transmission Criterion Attained – CT (PORT_TE010001UV01) An external event has occurred which marks a condition under which the sender and receiver have agreed that data is to be exchanged. Such events are often defined time points (e.g. end of business day/week/month). In a clinical trial, these may be significant milestones (e.g. subject enrolled; subject completes phase; all subjects complete phase; end of study). CT Laboratory Results Adverse Event Assessment Request (PORT_IN03000x) This interaction supports communication of clinical laboratory results to an AE assessment service. It is expected that the receiving application will initiate the CT Laboratory Results AE Assessment Response interaction (PORT_IN03000y) containing the original clinical laboratory results, in addition to the outcome of the initial / first-level quantitative adverse event assessment. CT Laboratory Results Adverse Event Assessment Response (PORT_IN03000y) This interaction supports communication of clinical laboratory results with the outcome of the initial / first-level quantitative adverse event assessment to a clinical information system within the clinical research environment / study site.

11. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification10 of 22 Interaction Design Elements & Descriptions: Interactions CT Laboratory Results Adverse Event Assessment Request (PORT_IN03000x) This interaction supports communication of clinical laboratory results to an AE assessment service. It is expected that the receiving application will initiate the CT Laboratory Results AE Assessment Response interaction (PORT_IN03000y) containing the original clinical laboratory results, in addition to the outcome of the initial / first-level quantitative adverse event assessment.

12. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification11 of 22 Interaction Design Elements: Interactions Contd CT Laboratory Results Adverse Event Assessment Response (PORT_IN03000y) This interaction supports communication of clinical laboratory results with the outcome of the initial / first-level quantitative adverse event assessment to a clinical information system within the clinical research environment / study site.

13. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification12 of 22 Lab-Based Adverse Event Assessment Domain Analysis Model Current CT-Lab Message Content Proposed New CMET Content

14. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification13 of 22 BRIDG-Derived Domain Analysis Model

15. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification14 of 22 Current CT Laboratory Message RMIM

16. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification15 of 22 CMET Addition to the CT-Laboratory Message

17. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification16 of 22 Proposed Changes to the CT-Laboratory Message 1.Change datatype of Range.value from PQ to IVL. 2.Add AdverseEventAssessment CMET with an ActRelationship to Base Unitary Result 1.Range.value datatype has been changed from PQ to IVL 2.Add AdverseEventAssessment CMET with an ActRelationship to Base Unitary Result

18. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification17 of 22 CMET RMIM

19. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification18 of 22 CMET RMIM Class Definitions AdverseEventAssessment The process of evaluating a clinical finding to detect the presence and severity of an abnormal condition, and assigning the corresponding adverse event category, term, and grade. AssessmentException This class represents one of two possible observation outcomes of an AdverseEventAssessment. It is a message provided to indicate that an adverse event assessment could not be executed or completed and to identify the reason for the failure. AdverseEventGrade This class represents one of two possible observation outcomes of the AdverseEventAssessment. It is the severity of an adverse event based on a specified assessment scale. GradeAnnotation Additional information provided about a grade that must be considered to determine the final grade.

20. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification19 of 22 Hierarchical Message Description

21. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification20 of 22 Vocabulary Requirements Vocabulary requirements have been identified in the following areas: External reference to a new code system Common Terminology Criteria for Adverse Events v3.0 (CTCAE): contains the adverse event category, adverse event term and adverse event short term that may be used to describe an adverse event. New value sets for existing domains Adverse Event Assessment Method: provides additional information about the means used to arrive at the assessment result. Adverse Event Assessment Exception: provides the reason an adverse event assessment could not be executed or completed Adverse Event Grade: indicates the level of severity for an adverse event, including the concept of Not Present. Adverse Event Grade Annotation: provides additional information about an adverse event assessment grade, which must be considered before determining the final grade. Focused discussion regarding these vocabulary requirements will be held during the working group meeting. The session is to be determined.

22. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification21 of 22 Motions RCRIM TC approval for the submission of the following items for RIM harmonization: New code system Common Terminology Criteria for Adverse Events v3.0 (CTCAE) New value sets AdverseEventAssessmentMethod AdverseEventAssessmentException AdverseEventGrade AdverseEventGradeAnnotation RCRIM TC approval for the submission of the following items for inclusion in the January 2008 ballot as a DSTU: Adverse Event Assessment CMET Revised HL7 v3 CT Laboratory Message New application roles ClinicalTrial Observation Order Global Placer Adverse Event Assessment Observation Fulfiller New interactions CT Laboratory Results Adverse Event Assessment Request CT Laboratory Results Adverse Event Assessment Response

23. September 18, 2007HL7 V3 Lab-Based Adverse Event Assessment Message Specification22 of 22 Next Steps