Electronic Source (eSource) Data: Defined and Interpreted by Global Regulatory Authorities
Two recent regulatory publications from FDA and EMA address the topic of electronic source data in clinical investigations.
While the views are slightly different, these documents provide clarity concerning the expectations of regulatory authorities regarding electronic source data.
This Issue explores the topic of electronic source data and identifies some key concepts that are common (and seemingly agreed upon) within these publications.
8. %LECTRONIC 3OURCE $ATA #DkMDC @MC (MSDQOQDSDC AX KNA@K 1DFTK@SNQX TSGNQHSHDR
4HE )MPORTANCE OF 3OURCE
)F YOU HAVE EVER HAD THE GOOD FORTUNE TO TAKE WATER FROM THE PLACE 0(4 WAS FOUNDED ON A SIMILAR PURITY PRINCIPLE THE @PUREST DATA
WHERE IT LITERALLY @SPRINGS FORTH FROM THE GROUND
9. YOU KNOW WHAT A OBTAINABLE DURING A CLINICAL INVESTIGATION COMES FROM CAPTURING
REFRESHING EXPERIENCE THAT CAN BE 3EVERAL HIKING TRAILS IN THE 53 PATIENT REPORTED OUTCOMES DIRECTLY AT THE POINT OF EXPERIENCE m NOT
FEATURE A NATURAL SPRING TO kLL UP A CANTEEN 4RYING TO CAPTURE THE kLTERED THROUGH LATER RECALL
11. TASTE OF WATER FRESH FROM THE GROUND WHEN YOU RETURN HOME CAN OR INTERPRETED BY A CLINICIAN 3UCH E3OURCE METHODS CAN YIELD
BE A CHALLENGE 3OME OF THE BOTTLED WATER THAT WE CONSUME TODAY DATA OF HIGH QUALITY THAT REVEAL THE IMPACT OF DRUGS
13. TAKEN FROM MUNICIPAL DEVICES ON THE PATIENT S HEALTH AND QUALITY OF LIFE 'UIDANCES
WATER SUPPLIESIV $! REGULATIONS AROUND BOTTLED WATER EVEN FROM THE $! AND %-! ALONG WITH #$)3# DEkNITIONS SUPPORT USE
SPECIFY THAT
14. IN ORDER TO PROPERLY BE CALLED OF ELECTRONIC SOURCE METHODS SUCH
@SPRING WATER
15. THE BOTTLED WATER MUST BE AS E02/ ELECTRONIC PATIENT REPORTED
FROM A NATURALLY EMANATING SOURCE
18. PUMPED OR PROCESSED FROM OUT OF OTTLED 7ATER AND SPECIFY PRINCIPLES TO ENSURE THAT
THE GROUNDV
7HAT S THE gSOURCEu IS PROPERLY IDENTIkED AND
THAT THE E3OURCE RECORDS ARE TRUSTWORTHY
THE
3OURCE
21. 3OURCE $OCUMENT
%NGLISH LANGUAGE DEkNITIONS OF RNTQBD ARE CONSISTENT WITH THE CONCEPT AS USED
BY CLINICAL RESEARCHERS
/XFORD %NGLISH $ICTIONARY $EkNITION OF 3OURCE
! WORK
25. OR SERIES OF THESEVI
)N CLINICAL RESEARCH TRIALS
26. THE TERM QMSPAC IS USED TO IDENTIFY THE RECORDS AND THE DATA THAT PROVIDE THE INFORMATION TO BE ANALYZED IN A
TRIAL 4HIS IS NOT NECESSARILY THE kRST INSTANCE OF RECORDING A CERTAIN ELEMENT OF DATA SUCH AS A BIRTH DATE WHICH WOULD BE ON THE BIRTH
RECORD THIS MAY INSTEAD COME FROM THE PATIENT S MEDICAL CHART OR FROM AN INTERVIEW WITH THE PATIENT OR SOME OTHER QMSPAC
3URPRISINGLY
27. ONLY #$)3# DEkNES QMSPACä THE $! DOCUMENT AND THE %-! 2ElECTION 0APER DEkNE QMSPAC B?R? AND QMSPAC BMASKCLR
4HE #$)3# DEkNITION CAPTURES HOW THE WORD QMSPAC MAKES B?R? DIFFER FROM QMSPAC B?R?
#$)3# $EkNITION OF 3OURCE
4HE SPECIkC PERMANENT RECORD S UPON WHICH A USER WILL RELY FOR THE RECONSTRUCTION AND EVALUATION OF A
CLINICAL INVESTIGATIONVII
#$)3# ALSO NOTES THAT THE WORD SOURCE IS @3OMETIMES USED AS SHORTHAND FOR SOURCE DOCUMENTS ANDOR SOURCE DATAVIII
2EGULATORY %XPECTATIONS FOR 'OOD 1UALITY $ATA
$! #OMMISSIONER $R -ARGARET (AMBURG
29. THE $! DRAFT GUIDANCE SETS FORTH THE
AT $)! IN *UNE
30. SPOKE ABOUT THE $! FOCUS ON ADVANCING INTENT TO @PROMOTE THE CAPTURE OF SOURCE DATA IN ELECTRONIC
REGULATORY SCIENCE AND ENSURING THE SAFETY OF PATIENTS IN TRIALS
31. FORM 4HE 'UIDANCE WILL NOT REPLACE ANY PREVIOUS GUIDANCE OR
AS WELL AS THE SAFETY OF APPROVED DRUGS
37. THE HM KHMHB@K (MUDRSHF@SHNMRX 53 $! -AY @MC DMDQ@K
CAPTURE OF 02/ PATIENT REPORTED OUTCOME DATA IN PAPER FORM /QHMBHOKDR NE 2NESV@QD 5@KHC@SHNMXI 53 $! *ANUARY
IS FRAUGHT WITH A NUMBER OF CHALLENGES
42. THE %-! RElECTION PAPER SEEKS TO PROVIDE
DATA AND INCOMPLETE DATA )N THC@MBD ENQ (MCTRSQX $KDBSQNMHB A CONTEXTUAL FRAMEWORK FOR THE USE OF ELECTRONIC SOURCE AND
2NTQBD #NBTLDMS@SHNM HM KHMHB@K (MUDRSHF@SHNMR
43. THE $! FURTHER PAPER SOURCE IE TRANSCRIBED IN CLINICAL TRIALS 2ATHER THAN
BUILDS UPON AN EXISTING REGULATORY FRAMEWORK FOR THE CAPTURE
46. TRANSMISSION AND STORAGE OF ELECTRONIC DATA IN NOTES THAT MANY CLINICAL INVESTIGATIONS ARE USING ELECTRONIC
CLINICAL TRIALS 4HIS COMES SEVERAL MONTHS AFTER THE %-! S '#0 SOURCE
47. YET LITTLE REGULATORY FRAMEWORK EXISTS TO ENSURE THAT THE
'OOD #LINICAL 0RACTICE )NSPECTORS 7ORKING 'ROUP POSTED THEIR ELECTRONIC SOURCE DATA MEETS THE REQUIREMENTS FOR '#0 IN THE %5
kNAL VERSION OF A 1DlDBSHNM O@ODQ NM $WODBS@SHNMR ENQ $KDBSQNMHB %UROPEAN 5NION 4O PROVIDE A FRAMEWORK FOR ELECTRONIC SOURCE
2NTQBD #@S@ AND #@S@ 3Q@MRBQHADC SN $KDBSQNMHB #@S@ NKKDBSHNM DATA
48. THE '#0 )NSPECTORS 7ORKING 'ROUP CHOSE TO ADOPT
3NNKR HM KHMHB@K 3QH@KR
7HILE THE TWO DOCUMENTS COVER SIMILAR THE PRINCIPLES SET FORTH BY #$)3# IN XII
TOPICS
49. THE FOCUS AND OBJECTIVE OF EACH DOCUMENT IS DIFFERENT
51. FROM OUR !NALYSIS OF THE $! $RAFT 'UIDANCE AND %-! 3OURCE 0APER
0UT IT IN THE 0ROTOCOL
4HERE SHOULD BE INFORMATION IN THE PROTOCOL DESCRIBING WHO WILL BE THE CREATORS OF THE DATA
52. WHAT DATA WILL BE GATHERED AND WHEN
WILL IT BE GATHERED ! DATAlOW DIAGRAM CAN GREATLY ASSIST IN THE UNDERSTANDING OF ALL THE DIFFERENT TYPES OF DATA THAT ARE TO BE
GATHERED AND HOW THEY WILL EVENTUALLY MAKE IT INTO THE E#2 ELECTRONIC #ASE 2EPORT ORM
53. WHETHER PAPER OR ELECTRONIC SOURCE
!NY DEVICES OR SOFTWARE USED SHOULD BE LISTED IN THE PROTOCOL AS WELL
#APTURE IT %LECTRONICALLY
)T IS CONSIDERED BEST PRACTICE TO NOT USE PAPER SOURCE WHEN ELECTRONIC DATA CAPTURE IS USED IN A CLINICAL INVESTIGATIONXIII 7HEN
PAPER IS THE SOURCE
54. THERE SHOULD BE CLEAR QUALITY CONTROL STEPS AS IDENTIkED IN THE PROTOCOL TO ENSURE THAT ERRORS ARE MINIMIZED
!NY PAPER SOURCE SHOULD BE MAINTAINED IN THE kLES OF THE INVESTIGATOR ACCORDING TO APPLICABLE RETENTION REQUIREMENTS
55. WHICH ADDS
TO THE TIME AND COST BURDEN TO THE SITE 7HILE BOTH PAPERS SUGGEST THE DEVELOPMENT OF ADEQUATE CONTROLS
56. THE $! 'UIDANCE GOES
AS FAR AS TO STATE g$! RECOMMENDS THAT CLINICAL DATA BE ENTERED ELECTRONICALLY BY STUDY SITE PERSONNEL AT THE TIME OF THE SUBJECT
VISIT TO AVOID TRANSCRIPTION FROM UNNECESSARY PAPER RECORDSXIVu
%NTER THE $ATA IN 2EAL 4IME
#ONTEMPORANEOUS ENTRY OF DATA IS AN ESSENTIAL COMPONENT OF DATA QUALITY 4HE DELAY BETWEEN OBSERVING AND RECORDING SHOULD
BE MINIMIZED
57. ESPECIALLY IN THE CASE OF OUTCOME MEASURES WHICH CAN BE SUBJECT TO RECALL BIAS )T IS HELPFUL TO DOCUMENT THE
RECALL PERIOD AS PART OF THE PROTOCOL 3YSTEMS WHICH COLLECT ELECTRONIC DATA SHOULD RECORD THE TIME OF ENTRY AS WELL AS THE TIME OF
OBSERVATION OR EVENT !S SEEN IN WARNING LETTERSXV
58. EXACT ENTRY OF TIME POINTS INCLUDING DOSING IS IMPORTANT OBJECTIVE EVIDENCE
ENSURING THAT PATIENT CARE IS APPROPRIATE AND DONE PER PROTOCOL
3UPPORT -AINTENANCE OF $ATA UNDER THE !UTHORITY OF THE )NVESTIGATOR
OTH DOCUMENTS POINT OUT THAT THE INVESTIGATOR IS RESPONSIBLE FOR MAINTAINING CONTROL OF SOURCE DATA OR A CERTIkED COPY FROM
THE POINT OF COLLECTION THROUGHOUT THE LIFECYCLE OF THE DATA 7HAT DOES CONTROL MEAN IN THE CONTEXT OF SOURCE DATA 3OME DATA
RELATED TASKS MAY BE DELEGATED TO THIRD PARTIES OTHER THAN THE SPONSOR XVI
59. BUT THE INVESTIGATOR IS gULTIMATELY RESPONSIBLE FOR THE
QUALITYu OF ALL SOURCE DATA !NY CHANGES TO SOURCE DATA SHOULD BE DONE WITH THE KNOWLEDGE AND CONSENT OF THE INVESTIGATOR %VEN
IF THE DATA ARE STORED ON A COMPUTERIZED SYSTEM AT A THIRD PARTY
60. THE SPONSOR AND INVESTIGATOR SHOULD BE ABLE TO DEMONSTRATE TO
REGULATORY AUTHORITIES THAT THE INVESTIGATOR AND AUTHORIZED SITE STAFF HAD ACCESS AND ABILITY TO gMAINTAINu THE SOURCE DATA AT ALL
TIMES
61. AND THAT THE SPONSOR COULD NOT UNILATERALLY DO SO
64. CONTINUED
)NCLUDE !LL #HANGES IN AN !UDIT 4RAIL OF THE E3OURCE $OCUMENT
4HE CONTENT NECESSARY TO BE PART OF AN AUDIT TRAIL FOR ELECTRONIC RECORDS IS SET FORTH IN #2 4HE $! DRAFT @'UIDANCE FOR
)NDUSTRY %LECTRONIC 3OURCE $OCUMENTATION IN #LINICAL )NVESTIGATIONS GIVES SOME FURTHER SUGGESTIONS FOR THE META DATA AUDIT
TRAIL FOR E3OURCE RECORDS )N KEEPING WITH EXISTING RULES ON ELECTRONIC RECORDS
65. ALL MODIkCATIONS TO SOURCE DATA MUST HAVE AN
AUDIT TRAIL 4HE AUDIT TRAIL MUST BE INEXTRICABLY LINKED TO THE DATA AND MUST NOT OBSCURE THE ORIGINAL DATA )N GENERAL
67. EVEN IF IT IS NOT GOING TO BE INCLUDED IN ANALYSIS DATASETS 4HE
ORIGINAL OBSERVATIONS OF THE PATIENT OR CLINICAL STAFF SHOULD BE PRESERVED IN THE kLES OF THE INVESTIGATOR
$OCUMENT THE 3OURCES OF $ATA AND %NSURE !CCESS #ONTROLS ARE !DEQUATE
4HE SOURCE OF ANY DATA SHOULD BE CLEAR
68. WHETHER THE SOURCE RECORD IS CAPTURED FROM A PATIENT ON AN ELECTRONIC DEVICE
69. ENTERED
BY CLINICAL STAFF INTO AN %LECTRONIC $ATA #APTURE SYSTEM OR PART OF THE MEDICAL RECORD IN AN %(2 SYSTEM 4HIS WILL ALLOW FOR
REGULATORY INSPECTION OF THE PROCESSES PROTECTING SOURCE DOCUMENTS AND DATA !LL SOURCE DATA
70. SUCH AS VALUES FROM CENTRAL
LABORATORIES OR 02/ ENTRIES FROM PATIENTS
72. REGULATORY INSPECTORS OR
THOSE WHO CREATED THE DATA
0ERFORM 2ISK !SSESSMENTS WHEN USING %LECTRONIC (EALTH 2ECORDS AS E3OURCE
3YSTEMS THAT CONTAIN %(2 S MAY BE USED FOR MANY PURPOSES
75. INSTITUTIONAL %(2 SYSTEMS MAY EMPLOY CONTROLS AND
STANDARDS THAT DIFFER FROM THOSE EXPECTED FOR CLINICAL TRIALS 7HEN SUCH RECORDS ARE USED
76. IT SHOULD BE CLEAR FROM TRIAL
DOCUMENTS THAT THE SPONSOR HAS EVALUATED THE RISKS AND PREPARED
MITIGATIONS 4HE DATA PROTECTION REQUIREMENTS FOR SUCH SYSTEMS SHOULD
BE CONSIDERED AND BALANCED WITH THE VALUE OF THE INFORMATION RETRIEVED
77. 2ElECTION PAPER ON EXPECTATIONS FOR ELECTRONIC SOURCE DATA AND
I
#ONCLUSIONS DATA TRANSCRIBED TO ELECTRONIC DATA COLLECTION TOOLS IN CLINICAL TRIALS
78. WWWEMEAEUROPAEUDOCSEN?'DOCUMENT7#PDF
*ANUARY
4HESE DOCUMENTS FURTHER CLARIFY THE EXPECTATIONS OF REGULATORY HTTPWWWFDAGOVDOWNLOADS$RUGS
II
'UIDANCE#OMPLIANCE2EGULATORY)NFORMATION'UIDANCES5#-PDF
AUTHORITIES REGARDING ELECTRONIC SOURCE DATA
79. AND DESCRIBE A GROUP OF
HTTPWWWCDISCORGSTUFFCONTENTMGRkLESFECAFDFCAACBBDFA
III
HIGH
LEVEL PRINCIPLES
82. PROVIDE A GOOD DFDDMISCDOCSESDIPDF
BASIS FOR THE ACCEPTABILITY OF SOURCE DATA IV
@OTTLED 7ATER 0URE $RINK OR 0URE (YPE %RIK $ /LSON !PRIL
V
53 #2 e A VI
7HILE THEY EXPLORE THE TOPIC OF E3OURCE INDEPENDENTLY
85. 4HE /XFORD %NGLISH $ICTIONARY ND ED /%$
VI
SIMILAR CONCLUSIONS OTH DOCUMENTS SHOW AN INTENTION TO SUPPORT /NLINE /XFORD 5NIVERSITY 0RESS .OVEMBER HTTPWWWOEDCOM
VIEWDICTIONARYENTRY%NTRY .OTE 4HE ETYMOLOGY OF THE
EXPANDED USE OF ELECTRONIC SOURCE DATA IN CLINICAL TRIALS )F PROPERLY WORD @SOURCE IS TAKEN FROM OLD RENCH FOR THE ORIGIN OF A SPRING OR
STREAM OF WATER
DEPLOYED WITHIN THE GUIDANCE GIVEN FROM THESE DOCUMENTS
86. SYSTEMS
WITH ELECTRONIC SOURCE SHOULD PROVIDE GOOD QUALITY DATA TO SUPPORT THE VII
#$)3# 'LOSSARY 6
87. GOALS OF SPONSORS AND REGULATORY AUTHORITIES HTTPWWWCDISCORGSTUFFCONTENTMGRkLES
VIII
BEFEBFFAFCAADEEMISCCDISC??GLOSSARYPDF
%QUIVALENCE OF %LECTRONIC AND 0APER
AND
0ENCIL !DMINISTRATION OF
IX
0ATIENT
2EPORTED /UTCOME -EASURES ! -ETA
!NALYTIC 2EVIEW
92. X
%XPECTATIONS FOR %LECTRONIC 3OURCE $ATA AND $ATA WWWFDAGOV/(2-3$/#+%43FRD
GDL0$
*ANUARY
4RANSCRIBED TO %LECTRONIC $ATA #OLLECTION 4OOLS IN XI
'ENERAL 0RINCIPLES OF 3OFTWARE 6ALIDATION
93. HTTPWWWFDAGOV
#LINICAL 4RIALS IS A kNAL RELEASE FROM THE %-! MEDICALDEVICESDEVICEREGULATIONANDGUIDANCEGUIDANCEDOCUMENTS
UCMHTM *ANUARY
4HE $! DRAFT 'UIDANCE FOR )NDUSTRY %LECTRONIC #$)3# E
3OURCE 3TANDARD 2EQUIREMENTS #$)3# #LINICAL $ATA )NTERCHANGE
XII
3TANDARDS #ONSORTIUM 6ERSION .OVEMBER
3OURCE $OCUMENTATION IN #LINICAL )NVESTIGATIONS
'OOD #LINICAL $ATA -ANAGEMENT 0RACTICE
100. SUCH AS A TECHNICAL SERVICE
PROVIDER 4HERE SHOULD BE A FORMAL DOCUMENT AS PART OF THE TRIAL THAT SETS
OUT WHAT TASKS WILL BE EXECUTED BY THE THIRD PARTY
101. TYPICALLY DONE AS PART OF
A CONTRACTUAL AGREEMENT
53 (%!$15!24%23 %52/0%!. (%!$15!24%23
0(4 #ORPORATION 0(4 #ORPORATION 3·RL WWWPHTCORPCOM
2UTHERFORD !VENUE