FDA Annotated ECG Standard

1
FDA Annotated ECG Submission Standard Explained
Barry D. Brown February 26, 2003
FDA Annotated ECG Standard
2
Background

• Regulatory submission sponsors collect biological
  data to study the safety and effectiveness of
  candidate drugs.
• Collected data are oftentimes waveforms.
• Measurements (findings) are derived from the
  original waveforms and/or other algorithmic
  representations of them.
• Sponsors submit derived findings in SAS datasets.

3
Problem

• The FDA can not easily verify the accuracy and
  consistent usage of the derivation methods.
• Derivations are oftentimes from paper thats
  archived with the sponsor and/or contractor.
• FDA wants the opportunity to review accuracy and
  consistency of ECG derivation methods.
• FDA is interested in leveraging ECG standards
  work for other submission data.

4
Solution

• Develop an ECG standard that supports annotated
  waveforms analyzed in the context of a clinical
  trial.
• FDA will advise industry when annotated ECG
  waveforms are expected, and what annotations are
  expected.
• Refer to FDA concept paper The Clinical
  Evaluation of QT/QTc Interval Prolongation and
  Proarrhythmic Potential for Non-Antiarrhythmic
  Drugs http//www.fda.gov/cder/calendar/meeting/qt
  4jam.pdf
• FDA will probably update the submission guidance.
• FDA will advise sponsors on trial-specific
  submission requirements during review of trial
  protocols.

5
Standard Development Timeline

• November, 2001 FDA held public meeting in
  Rockville, Maryland to discuss Electronic
  Interchange Standard for Digital ECG and Similar
  Data.
• April, 2002 Ad-hoc group creates custom XML
  grammar for annotated plots.
• June, 2002 Work starts within HL7 to develop
  submission standard.
• September, 2002 Proposal made to HL7 for
  representing multi-dimensional data.
• February, 2003 Annotated ECG message ready for
  HL7 ballot.

6
Current Status

• HL7 Annotated ECG message will go to HL7
  membership ballot March 10, 2003 for a 30-day
  comment period.
• Around the same time, the FDA plans to issue a
  federal registry notice pointing the public to
  the HL7 materials for a public 30-day comment
  period.
• Feedback will be discussed and acted upon at the
  next HL7 working group meeting, April 28 May 2,
  2003.
• Depending on nature of feedback, FDA could start
  requesting ECG submissions for new trials
  starting Q3 2003.

7
HL7 Organization

• ANSI-accredited Standards Developing
  Organizations (SDO) in the healthcare arena.
• Domain is clinical and administrative data.
• Not-for-profit volunteer organization.
• Its members develop the standards providers,
  vendors, payers, consultants, government groups,
  pharmaceutical and others.
• Adheres to a strict and well-defined set of
  operating procedures that ensure consensus,
  openness and balance of interest.
• The most widely used HL7 messaging standard
  enables disparate healthcare applications to
  exchange key sets of clinical and administrative
  data.

8
Why HL7?

• The FDA is not interested in developing and
  maintaining its own submission standards.
• The FDA wanted to work with industry within a
  well-established, open, SDO.
• HL7 is a good fit for defining information
  exchange standards for clinical trials.
• The FDA participates in the HL7 process via the
  Regulated Clinical Research Information
  Management technical committee (RCRIM TC).
• The FDA is also migrating other submission
  standards (besides ECG waveforms) to HL7.
• Department of Health and Human Services has a
  commitment to use HL7 whenever possible.

9
HL7 V3 Standard Development Method

• Object Oriented (OO) approach using Unified
  Modeling Language (UML) principals.
• Message development starts with a storyboard.
• Storyboard gives a narrative that describes a set
  of actions giving the message context.

10
HL7 Message Development Framework
Analysis
Design
Application
Messaging Message Types for use with
XML (MT)
Requirements Analysis Use
Case Model (UCM)
Domain Analysis Information Model
Vocabulary (RIM)
Interaction Design Interaction Model (IM
)
Message Design HierarchicalMessageDescr
iptions (HMD)
TYPE MPSLOC CONTAINS idid.TYPE
IID nmname.TYPE ST adaddr.TYPE
XAD phphon.TYPE XTN email_address
emlAdr.TYPE XTN
2-nd Order 1 choice of 0-n Drug
0-1 Nursing
Reference Model Repository
11
Simplified MDF Process
12
Storyboards

• A storyboard depicts a story using a series of
  "snapshots" or events in chronological sequence.
• Each snapshot represents a recognizable,
  meaningful moment in the sequence of events that
  the reader must know about to understand the
  overall sequence and result.
• Each snapshot illustrates the key participants in
  the storyboard and their interaction with other
  players.
• The whole series of snapshots provides a coherent
  description of a complete process or activity.

13
Annotated ECG Storyboard
14
Annotated ECG Storyboard Narrative 1/5

• The story starts when the Sponsor decides to
  study the effects of a new drug on a populations
  cardiac electrophysiology. The sponsor decides
  the effects to be studied can be seen in ECG
  data, or information derived from ECG data. The
  sponsor designs a protocol specifying the
  population to be studied, the data to be
  collected, the equipment to be used for gathering
  the ECG data, the analysis tools to use, and how
  any effects will be studied using the ECG data
  and analysis tools.

15
Annotated ECG Storyboard Narrative 2/5

• The sponsor or CRO hires investigators to collect
  the data, and the investigators in turn enroll
  subjects in the trial. The subject visits the
  collection site. During the subjects visit,
  equipment is connected to the subject. The
  equipment records the subjects ECG along with
  other physiologic parameters, if appropriate.
  Trial and subject identifying information is
  associated with the ECG data, such as subject id,
  gender, date of birth, investigator and site
  ids, protocol id, etc. After the individual
  ECGs are collected from the subject for that
  visit, it is transferred to a central ECG lab for
  analysis.

16
Annotated ECG Storyboard Narrative 3/5

• The ECG waveforms can be loaded into an analysis
  tool for making findings (measurements) and
  possibly deriving other data according to the
  trial protocol. The findings are oftentimes in
  the form of time and amplitude values for the
  parts of the cardiac process being studied. The
  analysis produces two types of information
  findings to be used for further statistical
  analysis on the entire population enrolled in the
  trial, and annotated ECG waveforms with trial
  specific fiducial markings, etc. indicating key
  features used for obtaining the findings.

17
Annotated ECG Storyboard Narrative 4/5

• The supporting annotated ECG waveforms become
  part of the sponsors submission to the
  regulatory agency. The communication of the
  annotated ECG waveforms from the sponsor to the
  regulatory agency is the primary focus of this
  standard.

18
Annotated ECG Storyboard Narrative 5/5

• During the regulatory agency's review of a
  submission, it may come across a conclusion drawn
  from a statistical analysis of ECG findings it
  wishes to investigate further. The reviewer may
  review the ECG analysis protocol and the analysis
  dataset. The reviewer may question an ECG
  finding in the dataset and review the annotated
  ECG waveforms. The reviewer may be satisfied
  with what he sees or may investigate further the
  ECG measurement protocol and its consistent
  application during the trial.

19
Reference Information Model (RIM)

• All message models are derived from the HL7 RIM.
• Provides a unified framework for, and a
  comprehensive source of, all information used by
  an HL7 specification.
• 2 main concepts Act and Entity.
• 3 concepts connect Act and Entity Participation,
  Role, and Act Relationship.

20
Base RIM Concepts
0..
Role
Entity
Act
1
(playing)
1
1
0..
0..1
(scoping)
Observation Substance Administration Procedure Ref
erral Patient Encounter Supply Working
List Financial Act Financial Contract Context
Structure
Patient Guarantor Employee Practitioner Assigned
Entity Certified EntitySchedulable
Resource Access
Organization Living Subject Person Non-Person
Living Subject Material Place
21
Act

• The concept Act (and its subclasses) represents
  all of the intentional actions documented by a
  healthcare professional in either a clinical or
  administrative context.

Act
22
Entity

• The concept Entity (and its subclasses) includes
  all living subjects (e.g. persons, animals),
  organizations (e.g. formal and informal),
  materials (e.g. durable and non-durable goods,
  food, tissue, containers,), and places that may
  be of interest in a healthcare messaging context.

Entity
23
Role

• A Role is a categorization of competency of the
  Entity that plays the Role as defined by the
  Entity that scopes the Role.
• An Entity, in a particular Role, can participate
  in an Act.

Role
24
Participation

• A Participation is an association between a Role
  and an Act. The Participation represents the
  involvement of the Entity playing the Role with
  regard to the associated Act.

Participation
25
Refined Message Information Model (R-MIM)

• Refined Message Information Models (R-MIMs)
  express the information content for one or more
  HMDs that originate from the root class
  identified by the Entry Point in the R-MIM.
• The R-MIM is the source of all other HL7 message
  artifacts, including the XML Schema.
• Created using Visio plug-ins developed by HL7
  membership.

26
R-MIM Modeling Language
27
Annotated ECG R-MIM
28
Protocol and Trial
29
Protocol and Trial XML

• ltsubjectAssignment classCode"CLNTRL"gt
• ltcomponentOfgt
• ltclinicalTrial classCode"CLNTRL"gt
• ltcode code"NMS-Q32-002" displayName"NoMoreSne
  ezes Trial 2"/gt
• ltactivityTimegt
• ltlow value"20020228"/gt
• lthigh value"20030220"/gt
• lt/activtyTimegt
• ltcomponentOfgt
• ltclinicalTrialProtocol classCode"CLNTRL"gt
• ltcode code"NMS-Q32" displayName"NoMoreSneez
  es Protocol"/gt
• lt/clinicalTrialProtocolgt
• lt/componentOfgt
• lt/clinicalTrialgt
• lt/componentOfgt
• lt/subjectAssignmentgt

30
Trial Participants
31
Trial Participants XML
ltclinicalTrial classCode"CLNTRL"gt ltauthorgt ltcl
inicalTrialSponsor classCodeCRSPNSRgt ltsponso
rOrganizationgt ltid root728989ec-b8bc-49cd-9a
5a-30be5ade1db5 extension1/gt ltnamegtABC
Drug Companylt/namegt lt/sponsorOrganizationgt lt/
clinicalTrialSponsorgt lt/authorgt ltlocationgt lttr
ialSite classCodeSDLOCgt ltid
root728989ec-b8bc-49cd-9a5a-30be5ade1db5
extension2/gt ltlocation classCodePLCgt
ltnamegtRiver City Trialslt/namegt ltaddrgt
ltcountrygtUnited States of Americalt/countrygt
lt/addrgt lt/locationgt lt/trialSitegt lt/location
gt ltresponsiblePartygt lttrialInvestigator
classCodeCRINVgt ltid root728989ec-b8bc-49cd
-9a5a-30be5ade1db5 extension3/gt ltinvestigat
orPerson classCodePSNgt ltid
root728989ec-b8bc-49cd-9a5a-30be5ade1db5
extension4/gt ltnamegtDr. John
Smithlt/namegt lt/investigatorPersongt lt/trialInv
estigatorgt lt/responsiblePartygt lt/clinicalTrialgt
32
Subject
33
Subject XML
lttimepointEvent classCodeCTTEVENTgt ltcode
codeVISIT5 displayName5th Visit/gt lteffectiv
eTimegt ltlow value200205091030/gt lthigh
value200205091310/gt lt/effectiveTimegt ltreasonC
ode codescheduled/gt ltcomponentOfgt ltsubjectAs
signment classCodeCLNTRLgt ltsubjectgt lttri
alSubject classCodeRESBJgt ltid
root728989ec-b8bc-49cd-9a5a-30be5ade1db5
extension8/gt ltsubjectDemographicPerson
classCodePSNgt ltnamegtRFGlt/namegt ltadm
inistrativeGenderCode codeM/gt ltbirthTime
value19340324/gt ltraceCode code2108-9
displayNameEuropean/gt lt/subjectDemographic
Persongt lt/trialSubjectgt lt/subjectgt ltdefi
nitiongt lttreatmentGroupAssignment
classCodeSBADMgt ltcode codePLCB1
displayNamePlacebo Group 1/gt lt/treatmentGro
upAssignmentgt lt/definitiongt ltsubjectAssignmen
tgt lt/componentOfgt lt/timepointEventgt
34
Timepoint
35
Timepoint XML
ltcomponentOfgt lttimepointEvent
classCodeCTTEVENTgt ltperformergt ltstudyEve
ntPerformer classCodeASSIGNEDgt ltid
root728989ec-b8bc-49cd-9a5a-30be5ade1db5
extension9/gt ltassignedPerson
classCodePSNgt ltnamegtGLMlt/namegt lt/ass
ignedPersongt lt/studyEventPerformergt lt/perfo
rmergt lt/timepointEventgt lt/componentOfgt ltdefini
tiongt ltrelativeTimepoint classCodeOBSgt ltco
de codePD30 displayName30 minutes
post-dose/gt ltcomponentOfgt ltpauseQuantity
value1800 units/gt ltprotocolTimepointEven
t classCodeCTTEVENTgt ltcode codeVISIT5
displayName5th Visit/gt ltcomponentgt lt
referenceEvent classCodeACTgt ltcode
codeDS2 displayName2nd Dosage/gt lt/refe
renceEventgt lt/componentgt lt/protocolTimepo
intEventgt lt/componentOfgt lt/relativeTimepointgt
lt/definitiongt
36
ECG Performer
37
ECG Performer XML
ltannotatedECG classCodeOBSgt ltid
root728989ec-b8bc-49cd-9a5a-30be5ade1db5
extension10/gt ltcode codeANN_ECG
displayNameAnnotated ECG/gt lttextgtAnnotated
ECG for FDA Submissionlt/textgt lteffectiveTimegt lt
low value"20020509113000.000" inclusive"true"/gt
lthigh value"20020509113010.000"
inclusive"false"/gt lt/effectiveTimegt ltconfidenti
alityCode codeBLINDED/gt ltreasonCode
codePER_PROTOCOL/gt ltperformergt ltecgPerformer
classCodeASSIGNEDgt ltid root728989ec-b8bc-
49cd-9a5a-30be5ade1db5 extension11/gt ltassig
nedPerson classCodePSNgt ltnamegtTJMlt/namegt
lt/assignedPersongt lt/ecgPerformergt lt/performergt
ltpertainsTogt ltsubjectFindingComment
classCodeOBSgt ltcode code
displayName/gt ltvalue value/gt lt/subjectF
indingCommentgt lt/pertainsTogt lt/annotatedECGgt
38
Annotated ECG
39
Annotated ECG XML
ltannotatedECG classCodeOBSgt ltlocationgt lttest
ingSite classCodeSDLOCgt ltid
root728989ec-b8bc-49cd-9a5a-30be5ade1db5
extension11/gt ltlocation classCodePLCgt
ltnamegtMt. Pleasant Heart Centerlt/namegt ltaddrgt
ltcountrygtUnited States of
Americalt/countrygt lt/addrgt lt/locationgt lt/t
estingSitegt lt/locationgt ltcontrolVariable1gt ltre
latedObservation classCodeOBSgt ltcode
codeAGE/gt ltvalue value47
unity/gt lt/relatedObservationgt lt/controlVaria
ble1gt ltcontrolVariable2gt lttransactionType
classCodeOBSgt ltcode codeNEW/gt lt/transac
tionTypegt lt/controlVariable2gt lt/annotatedECGgt
40
Waveforms
41
Waveform XML
ltseries classCodeOBSSERgt ltid
root728989ec-b8bc-49cd-9a5a-30be5ade1db5
extension12/gt ltcode codeECG_RHYTHM_WAVEFORMS
/gt lteffectiveTimegt ltlow value"20020509113000.
000" inclusive"true"/gt lthigh
value"20020509113010.000" inclusive"false"/gt lt/
effectiveTimegt ltcomponentgt ltsequenceSet
classCodeOBSCORgt ltcomponentgt ltsequence
classCode"OBS"gt ltcode codeGREGORIAN_TIME"
codeSystem"MDC"/gt ltvalue xsitype"GLIST_TS"
gt lthead value"20020509113000.000"/gt lt
increment value"0.002" unit"s"/gt lt/valuegt
lt/sequencegt lt/componentgt ltcomponentgt
ltsequence classCodeOBSgt ltcode
codeMDC_ECG_LEAD_II codeSystem"MDC"/gt ltva
lue xsitypeSLIST_PQgt ltorigin value0
unituV/gt ltscale value2.5
unituV/gt ltdigitsgt215 201 187 173 157 136
118 98 83 71 62lt/digitsgt lt/valuegt lt/seque
ncegt lt/componentgt lt/sequenceSetgt lt/component
gt lt/seriesgt
42
Waveform XML
ltseries classCodeOBSSERgt ltderivationgt ltSerie
s classCodeOBSSERgt ltid root728989ec-b8bc-4
9cd-9a5a-30be5ade1db5 extension13/gt ltcode
codeECG_REPRESENTATIVE_BEAT_WAVEFORMS/gt ltcon
trolVariablegt ltcontrolVariable
classCodeOBSgt ltcode codeMDC_ECG_LPFILTER
codeSystemMDC/gt ltvalue value150
unitHz/gt lt/controlVariablegt lt/controlVar
iablegt ltcomponentgt ltsequenceSet
classCodeOBSCORgt ltcomponentgt ltsequen
ce classCode"OBS"gt ltcode
codeEFFECTIVE_RELATIVE_TIME" codeSystem"MDC"/gt
ltvalue xsitype"GLIST_PQ"gt lthead
value"0.000"/gt ltincrement value"0.002"
unit"s"/gt lt/valuegt lt/sequencegt
lt/componentgt lt/sequenceSetgt lt/componentgt
lt/Seriesgt lt/derivationgt lt/seriesgt
43
Series Author
44
Series Author XML
ltseries classCodeOBSSERgt ltauthorgt ltmanufactu
redProduct classCode"MANU"gt ltmanufacturedDevic
e classCode"DEV"gt ltmanufacturerModelNamegtELI2
00lt/manufacturerModelNamegt ltsoftwareNamegt5.3lt/
softwareNamegt lt/manufacturedDevicegt ltmanufac
turerOrganization classCode"ORG"gt ltnamegtMorta
ra Instrument, Inc.lt/namegt lt/manufacturerOrgani
zationgt lt/manufacturedProductgt lt/authorgt lt/seri
esgt
45
Annotations
46
Annotation XML
ltseries classCodeOBSSERgt ltsubjectOfgt ltannota
tion classCodeOBSgt ltcode codeMDC_ECG_BEAT
codeSystemMDC/gt ltvalue valueMDC_ECG_BEAT_
NORMAL codeSystemMDC/gt ltactivityTime
value20020509113012.000/gt ltauthorgt ltassi
gnedEntity classCodeASSIGNEDgt ltid
extension13/gt ltassignedAnnotatorDevice
classCodeDEVgt ltmanufacturerModelNamegtELI2
00lt/manufacturerModelNamegt ltsoftwareNamegt5.3
lt/softwareNamegt lt/assignedAnnotatorDevicegt
ltrepresentedOrganization classCodeORGgt
ltnamegtNew England Core Lablt/namegt lt/represen
tedOrganizationgt lt/assignedEntitygt lt/author
gt ltcomponentgt ltAnnotation
classCodeOBSgt ltcode codeMDC_ECG_WAVC
codeSystemMDC/gt ltvalue codeMDC_ECG_WAVC_
PWAVE codeSystemMDC/gt ltAnnotationgt lt/co
mponentgt lt/annotationgt lt/subjectOfgt lt/seriesgt
47
ROI
48
ROI
ltannotation classCodeOBSgt ltcode
codeMDC_ECG_BEAT codeSystemMDC/gt ltvalue
valueMDC_ECG_BEAT_NORMAL codeSystemMDC/gt
ltcomponentgt ltAnnotation classCodeOBSgt
ltcode codeMDC_ECG_WAVC codeSystemMDC/gt
ltvalue codeMDC_ECG_WAVC_PWAVE
codeSystemMDC/gt ltsupportgt ltsupportin
gROI classCodeROIBND/gt ltcode
codeROIFS/gt ltcomponentgt ltboundar
y classCodeOBSgt ltcode
codeGREGORIAN_TIME codeSystemMDC/gt
ltvalue xsitypeIVL_TSgt ltlow
value20020509113004.980/gt lthigh
value20020509113005.076/gt lt/valuegt
lt/boundarygt lt/componentgt ltcompo
nentgt ltboundary classCodeOBSgt
ltcode codeMDC_ECG_LEAD_II codeSystemMDC/gt
lt/boundarygt lt/componentgt lt/supp
ortingROIgt lt/supportgt ltAnnotationgt lt/c
omponentgt lt/annotationgt
49
Annotated ECG R-MIM
50
Annotating QTc
Lead II
ltannotation classCodeOBSgt ltcode
codeMDC_ECG_ECG_CONTOUR_OBS codeSystemMDC/gt
ltvalue valueMDC_ECG_CONTOUR_QTC
codeSystemMDC/gt lt/annotationgt
root annotation for QTc
51
Annotating RR for QTc
RR
Lead II
ltannotation classCodeOBSgt ltcode
codeMDC_ECG_CONTOUR_OBS codeSystemMDC/gt ltva
lue valueMDC_ECG_CONTOUR_QTC
codeSystemMDC/gt ltcomponentgt ltAnnotation
classCodeOBSgt ltcode codeMDC_ECG_CONTOUR_OB
S codeSystemMDC/gt ltvalue
codeMDC_ECG_CONTOUR_RR codeSystemMDC/gt lts
upportgt ltsupportingROI classCodeROIBND/gt
ltcode codeROIFS/gt ltcomponentgt ltbo
undary classCodeOBSgt ltcode
codeGREGORIAN_TIME codeSystemMDC/gt ltv
alue xsitypeIVL_TSgt ltlow
value20020509113004.980/gt lthigh
value20020509113006.076/gt lt/valuegt
lt/boundarygt lt/componentgt ltcomponentgt
ltboundary classCodeOBSgt ltcode
codeMDC_ECG_LEAD_II codeSystemMDC/gt lt/
boundarygt lt/componentgt lt/supportingROIgt
lt/supportgt ltAnnotationgt lt/componentgt lt/annota
tiongt
52
Annotating QT for QTc
Lead II
ltannotation classCodeOBSgt ltcode
codeMDC_ECG_CONTOUR_OBS codeSystemMDC/gt ltva
lue valueMDC_ECG_CONTOUR_QTC
codeSystemMDC/gt ltcomponentgt ltAnnotation
classCodeOBSgt ltcode codeMDC_ECG_CONTOUR_OB
S codeSystemMDC/gt ltvalue
codeMDC_ECG_CONTOUR_QT codeSystemMDC/gt lts
upportgt ltsupportingROI classCodeROIBND/gt
ltcode codeROIFS/gt ltcomponentgt ltbo
undary classCodeOBSgt ltcode
codeGREGORIAN_TIME codeSystemMDC/gt ltv
alue xsitypeIVL_TSgt ltlow
value20020509113005.950/gt lthigh
value20020509113006.436/gt lt/valuegt
lt/boundarygt lt/componentgt ltcomponentgt
ltboundary classCodeOBSgt ltcode
codeMDC_ECG_LEAD_II codeSystemMDC/gt lt/
boundarygt lt/componentgt lt/supportingROIgt
lt/supportgt ltAnnotationgt lt/componentgt lt/annota
tiongt
53
Annotating a Beat
Lead II
ltannotation classCodeOBSgt ltcode
codeMDC_ECG_BEAT codeSystemMDC/gt ltvalue
valueMDC_ECG_BEAT_NORMAL codeSystemMDC/gt lt/a
nnotationgt
54
Annotating P Wave
Lead II
ltannotation classCodeOBSgt ltcode
codeMDC_ECG_BEAT codeSystemMDC/gt ltvalue
valueMDC_ECG_BEAT_NORMAL codeSystemMDC/gt ltc
omponentgt ltAnnotation classCodeOBSgt ltcode
codeMDC_ECG_WAVC codeSystemMDC/gt ltvalue
codeMDC_ECG_WAVC_PWAVE codeSystemMDC/gt lts
upportgt ltsupportingROI classCodeROIBND/gt
ltcode codeROIFS/gt ltcomponentgt ltbo
undary classCodeOBSgt ltcode
codeGREGORIAN_TIME codeSystemMDC/gt ltv
alue xsitypeIVL_TSgt ltlow
value20020509113005.683/gt lthigh
value20020509113005.736/gt lt/valuegt
lt/boundarygt lt/componentgt ltcomponentgt
ltboundary classCodeOBSgt ltcode
codeMDC_ECG_LEAD_II codeSystemMDC/gt lt/
boundarygt lt/componentgt lt/supportingROIgt
lt/supportgt ltAnnotationgt lt/componentgt lt/annota
tiongt
55
Annotating QRS Complex
Lead II
ltannotation classCodeOBSgt ltcode
codeMDC_ECG_BEAT codeSystemMDC/gt ltvalue
valueMDC_ECG_BEAT_NORMAL codeSystemMDC/gt ltc
omponentgt ltAnnotation classCodeOBSgt ltcode
codeMDC_ECG_WAVC codeSystemMDC/gt ltvalue
codeMDC_ECG_WAVC_QRSWAVE codeSystemMDC/gt
ltsupportgt ltsupportingROI classCodeROIBND/gt
ltcode codeROIFS/gt ltcomponentgt lt
boundary classCodeOBSgt ltcode
codeGREGORIAN_TIME codeSystemMDC/gt ltv
alue xsitypeIVL_TSgt ltlow
value20020509113005.950/gt lthigh
value20020509113006.327/gt lt/valuegt
lt/boundarygt lt/componentgt ltcomponentgt
ltboundary classCodeOBSgt ltcode
codeMDC_ECG_LEAD_II codeSystemMDC/gt lt/
boundarygt lt/componentgt lt/supportingROIgt
lt/supportgt ltAnnotationgt lt/componentgt lt/annota
tiongt
56
Annotating T Wave
Lead II
ltannotation classCodeOBSgt ltcode
codeMDC_ECG_BEAT codeSystemMDC/gt ltvalue
valueMDC_ECG_BEAT_NORMAL codeSystemMDC/gt ltc
omponentgt ltAnnotation classCodeOBSgt ltcode
codeMDC_ECG_WAVC codeSystemMDC/gt ltvalue
codeMDC_ECG_WAVC_TWAVE codeSystemMDC/gt lts
upportgt ltsupportingROI classCodeROIBND/gt
ltcode codeROIFS/gt ltcomponentgt ltbo
undary classCodeOBSgt ltcode
codeGREGORIAN_TIME codeSystemMDC/gt ltv
alue xsitypeIVL_TSgt ltlow
value/gt lthigh value20020509113006.436
/gt lt/valuegt lt/boundarygt lt/compo
nentgt ltcomponentgt ltboundary
classCodeOBSgt ltcode codeMDC_ECG_LEAD_I
I codeSystemMDC/gt lt/boundarygt lt/com
ponentgt lt/supportingROIgt lt/supportgt ltAnno
tationgt lt/componentgt lt/annotationgt
57
QT on Median Beat, All Leads
ltannotation classCodeOBSgt ltcode
codeMDC_ECG_CONTOUR_OBS codeSystemMDC/gt ltva
lue valueMDC_ECG_CONTOUR_QTC
codeSystemMDC/gt ltcomponentgt ltAnnotation
classCodeOBSgt ltcode codeMDC_ECG_CONTOUR_OB
S codeSystemMDC/gt ltvalue
codeMDC_ECG_CONTOUR_QT codeSystemMDC/gt lts
upportgt ltsupportingROI classCodeROIBND/gt
ltcode codeROIPS/gt ltcomponentgt ltbo
undary classCodeOBSgt ltcode
codeRELATIVE_TIME codeSystemMDC/gt ltva
lue xsitypeIVL_PQgt ltlow value345
unitms/gt lthigh value862
unitms/gt lt/valuegt lt/boundarygt
lt/componentgt lt/supportingROIgt lt/supportgt
ltAnnotationgt lt/componentgt lt/annotationgt
58
ISO/IEEE 11073 Annotations

• ISO/IEEE 11073-10101 Point-of-Care standard is
  compiling a comprehensive list of annotations
• List will be used in FDA submissions and in a
  wide range of devices
• Types of annotations
• Beat
• Wave Component
• Rhythm
• Noise
• Contour Observation

59
Beat Examples

• Normal
• Abnormal
• Supraventricular premature
• Atrial premature
• Junctional (nodal) premature
• Aberrated atrial premature
• Non-conducted p-wave
• Premature ventricular
• Fusion
• R on T
• Supraventricular escape
• Atrial escape
• Juctional (nodal) escape
• Ventricular escape
• Pre-excitation
• Wolf-Parkinson-White
• WPW type A
• WPW type B
• Lown-Ganong-Levine

• Bundle branch block
• Left bundle branch block
• Incomplete left bundle branch block
• Right bundle branch block
• Incomplete right bundle branch block
• Left anterior fascicular block
• Left posterior fascicular block
• Bifascicular block
• Trifascicular block
• Bilateral bundle-branch block
• Intraventricular conduction disturbance
• Paced beat
• Pacemaker fusion beat
• Unknown

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Wave Component Examples

• P
• P
• P
• P
• Q
• QS
• R
• R
• R
• Notch
• S
• S
• S
• T
• T
• U

• Delta
• I
• K
• PQRST
• QRST
• QRS
• Ventricular flutter wave
• PR segment
• ST segment
• Isoelectric point
• J point
• ST measurement point
• Artifact
• Various pacemaker events

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Rhythm Examples

• Sinus Rhythm
• Normal Sinus Rhythm
• Sinus Bradycardia
• Sinus Tachycardia
• Low heart rate variability
• Sinus Arrhythmia
• Respiratory Sinus Arrhythmia
• Non-respiratory Sinus Arrhythmia
• Wandering Sinus Pacemaker
• Atrial Ectopic Rhythm
• Atrial Bigeminy
• Atrial Tachycardia
• Paroxsysmal Atrial Tachycardia
• Multifocal Atrial Tachycardia
• Automatic Atrial Tachycardia
• Atrial Flutter
• Atrial Fibrillation
• Supraventricular Ectopic Rhythm
• Supraventricular Tachycardia

• AV Junctional Rhythm
• AV junctional escape rhythm
• Accelerated AV junctional rhythm
• Junctional Tachycardia
• AV reciprocating tachycardia
• Reentrant AV nodal Tachycardia
• First Degree AV Block
• Second Degreee AV Block
• Type I (Wenckebach)
• Type II (Mobitz)
• Third Degree AV Block
• AV Dissociation
• AV Dissociation with interference
• First Degree SA Block
• Second Degree SA Block
• Type I (Wenckebach)
• Type II
• Third Degree SA Block
• Atrial Fibrillation

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More Rhythm Examples

• Ventricular Rhythm
• Idioventricular Rhythm
• Ventricular Parasytole
• Accelerated Idioventricular Rhythm
• Slow Ventricular Tachycardia
• Ventricular Bigeminy
• Ventricular Trigeminy
• Ventricular Couplet
• Ventricular Run
• Ventricular Tachycardia
• Ventricular Flutter
• Ventricular Fibrillation
• Nonsustained Monomorphic Ventricular Tachycardia
• Polymorphic Ventricular Tachycardia
• Torsades de Pointes Ventricular Tachycardia
• T-wave Alternans
• Bradycardia (any type)

• Pre-excitation
• Wolf-Parkinson-White
• WPW Type A
• WPW Type B
• Lown-Ganong-Levine Syndrome
• Paced Rhythms
• Atrial Demand Mode
• Atrial Capture
• Atrial Failure to Capture
• Atrial Failure to Sense
• Ventricular Demand Mode
• Ventricular Capture
• Ventricular Failure to Sense
• Anti-Tachycardia Pacing
• Pause
• Asystole
• Irregular Rhythm
• ST Elevation
• ST Depression

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Noise Classifications

• Clean
• No abnormal noise
• Moderate
• Beats can be detected, but not classified
• Severe
• Beats can not be detected

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ECG Contour Examples

• QRS Morphology class number
• PVC focus number
• P duration
• PR duration
• QRS duration
• QT duration
• QTc duration
• P axis
• QRS axis
• T axis

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Control Variables

• ISO/IEEE 11073-10101 will also enumerate ECG
  control variables (device settings)
• Examples include
• Low pass filter
• High pass filter
• Power line filter
• May also enumerate annotation control variables,
  such as
• Rate limits for rhythm classifications
• Pause criteria for rhythm classifications
• Etc.

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View of Rhythm Waveforms
67
View of Representative Beat
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Sponsor Checklist

• Start collecting and managing ECGs digitally.
• Use digital tools for deriving the trials ECG
  findings and for producing annotated ECG
  waveforms in the FDA format.
• Collect annotated ECGs for submission and submit
  to the FDA according to the (to be updated)
  submission guidance.

69
Questions?
Barry BrownProduct Integration Manager Mortara
Instrument, Inc. Milwaukee, Wisconsin Voice 414
-354-1600 Fax [phone] Email
barry.brown_at_mortara.com Web www.mortara.com
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