HEMOVIGILANCE SYSTEMS
Pierre Robillard1,2 MD
1 Québec Public Health Institute, Montréal, Canada2 McGill University, Department of Epidemiology, Biostatistics and Occupational Health, Montréal, Canada
SCOPE• Products
– Blood components (mainly)– Plasma derivatives (in some countries)
• In many countries under pharmacovigilance (drug post-market surveillance)
• Donations– Donor safety
• Incidence of undesirable effects of donations in donors
– Blood safety• Prevalence of ID markers in first-time donors• Incidence of ID markers in repeat donors• Surveillance of donor exclusion factors
SCOPE….2
• Transfusion process– Errors at blood center
• Blood center tracking systems
• MERS-TM system
– Errors at the hospital• Near-misses
• MERS-TM system, UK SHOT, Canadian TESS
– Blood utilization– Traceability
SCOPE…3
• Recipients– Identification of transfusion-transmitted infections
• Traceback and lookback activities
• Post-transfusion screening (low yield)
• Matching recipient database with reportable disease databases
– Incidence of adverse transfusion events• Serious only UK SHOT
• All French Hemovigilance System
– Identification of long term effects of transfusion• Matching databases
– Recipient with death registry
– Recipient with tumour registry
– Recipient with hospital discharge database
Modern Hemovigilance
Recipient Process Donor
AE ER NM ID AE
Recipients Processes / Products Donors
continuous improvement of transfusion safety
collection / analysis of data
Adapted from JC Faber, Luxembourg Red Cross
• Local– Hospital
• Regional– Health District– State– Province
• National– Blood organizations– Public Health– Regulatory Agency– Professional bodies
• Supra national– Voluntary organizations
• EHN
– Existing organizations• ISBT WP Haemovigilance
SETTINGS
Requirements
• Hospital– Personnel dedicated to blood safety
• Transfusion safety officer• Blood bank director• Chief technologist• Role
– Investigation and reporting of transfusion reactions and errors– Training– Oversee implementation of preventive measures
– Transfusion committee• Multidisciplinary• Review transfusion reactions• Propose and evaluate preventive actions
Requirements….2
• Regional or national level– STANDARDIZATION
• Data elements collected
• DEFINITION of data elements
• Reporting forms?
– Centralized body for analysis• Regular feedback to those who report
– Mandatory or voluntary system?
Requirements….3
• International– STANDARDIZATION
• Patience
• Commitment
• Leadership
– Centralized analysis
10
TYPES OF GOVERNANCE FOR HAEMOVIGILANCE SYSTEMS
• Blood regulator– France, Switzerland, Germany
• Blood manufacturer– Singapore, Japan, South Africa, Denmark
• Professional organizations– Netherlands (TRIP), UK (SHOT)
• Public Health– Canada (TTISS)
• Public-private partnership– USA Biovigilance Network
11
BLOOD REGULATOR
FRANCE
12
EFS
AFSSaPS
Medical & nursing team
Regionalcoordinator
TSHC Haemovigilanceofficers (HO)
Medical & nursing team
13
The local level
Healthcare facility HO + EFS HO
trainingtransfusion safety committee
various procedures
traceability
transfusion reactions
information
14
training
traceability
transfusion reactions
transfusion procedures
organization of transfusion
The local transfusion safety and hemovigilance committee
information
Management, HO, prescribers, nurses, regional coordinator
15
The regional level
annual report
traceability
transfusion reactions
organization of blood transfusion
organization of haemovigilance
information
Local level
National level
16
The national level Hemovigilance unit – Afssaps Hemovigilance unit – EFS Hemovigilance unit - LFB National Health Surveillance Institute - InVS Regional coordinators’ national conference National committee for the computerization of
traceability National commission for hemovigilance French Society of Vigilance and Transfusion
Therapeutics
17
Agence Française de Sécurité Sanitaire des
Produits de Santé(AFSSaPS)
The regulatory agency
quality control
Regional and local blood
establishments
ÉtablissementFrançais du Sang
(EFS)
Centre de Transfusion
Sanguine des Armées (CTSA)
Ministry of Health
European Commission
Annual report
adverse reactions
Donor - Patient
Healthcare establishments
Regional coordinator
Annual report
InVS
epidemiology of donors
18
Advantages The centralization :
Definition and implementation of national policies Development and use of standardized tools Uniform standardized practice in adverse event
reporting and traceability Hemovigilance part of global healthcare risk
management Easier detection of rare events
The manpower : Essential for good results
The multidisciplinary approach
19
Disadvantages
The centralization : A top heavy organization, very dependent on political
whim and public opinion A vigilance system mostly concerned with blood
components – what about transfusion practice ?
The manpower : The cost : is the system cost-effective ? What is the real place of clinical medical staff in the
system ?
Reporting to the regulator might prevent some institutions to report errors
20
BLOOD MANUFACTURER
SINGAPORE
21
Adverse reaction
Physician
Inform hospital blood bank/ Transfusion medical officer
Report to Haemovigilance Program Coordinator
Deputy Director /Director of Blood Center
Transfusion reaction workup
Evaluate and Manage
Source: Mickey Koh, Centre for Transfusion Medicine, Health Sciences Authority, Singapore
22
Reporting Numbers
Source: Mickey Koh, Centre for Transfusion Medicine, Health Sciences Authority, Singapore
23
Advantages: Supplier
1. Tighter feedback loop: Intimate knowledge of the transfusion process
2. “better qualified” to develop the system and to intepret and analyse the data
3. Regulators often come from a different perspective and mindset
4. Impetus for change stronger and quicker5. Less fear of reprisals from hospitals due to
accumulation of long term records of possible defects in care
Source: Mickey Koh, Centre for Transfusion Medicine, Health Sciences Authority, Singapore
24
Diasdvantages: Supplier
1. One of the major participants in the transfusion process. What if analysis of data casts a spotlight on blood centre/provider’s deficiencies?
2. Pressure to highlight the achievements of the blood centre; disregarding the shortfalls.
3. Public perception on accuracy of data4. Higher stakes: if something does emerge and
doubts emerge from public on preservation of self interest from the supplier
5. Protection of data a more complex issue.
Source: Mickey Koh, Centre for Transfusion Medicine, Health Sciences Authority, Singapore
25
PROFESSIONAL ORGANISATIONS
NETHERLANDS
26
Development of hemovigilance
BoardMedical Societies
(Hospital associations, Sanquin)
national TRIP office
Hospitals
blood Tx comm.
Hospital
laboratory
clinicians
Sanquin
HV
programme
Sanquin
blood bank
Tx specialist
QA manager
side effects products
recall products & look-back
TRIP foundation created in 2001
Source: M. Schipperus, TRIP, Netherlands
27
TRIP (Transfusion Reactions In Patients)
Hitherto ‘voluntary’ participation, – regarded as the norm by Inspectorate– professional standard in consensus guideline
Reporting system what types, definitions, recommended further
investigationhow to report: paper / online
Verification (expert review)
Denominator data, statistical analysis
Publication (transparency)Source: M. Schipperus, TRIP, Netherlands
28
Participation by hospitals
Source: TRIP, English Newsletter 2008/1
29
Reports per year
862
1267
1548
1984 2030
0
500
1000
1500
2000
2500
2002 2003 2004 2005 2006
Source: M. Schipperus, TRIP, Netherlands
30
Advantages of the TRIP system
• scientifically validated data using agreed definitions
• user-friendly system• stimulus for research• strengthening of (international) scientific ties,
learning from each other• not just product focus, but chain-wide
approach• findings available to professionals in the
transfusion and transplantation chains• development of professional standards
Source: M. Schipperus, TRIP, Netherlands
31
Weaknesses of TRIP system
• Dependent on willingness of professionals to report
• Late reporting (cold hemovigilance)
• Difficult to fund staff in the hospitals
• Simultaneous initiatives on the same subject possible (no official central steering)
• “Polder model”: many people decide. Democratic, effective but slow !
Source: M. Schipperus, TRIP, Netherlands
32
PUBLIC HEALTH
CANADA
33
Background In collaboration with Canadian
Provinces/Territories, Health Canada Regulatory and Canadian Blood Manufacturers, the Public Health Agency of Canada (PHAC) implemented a voluntary Transfusion Transmitted Injuries Surveillance System (TTISS) to monitor adverse transfusion events (ATEs)
34
Infrastructure for National TTISS ReportingInfrastructure for National TTISS Reporting
National Transfusion Transmitted Injuries Surveillance System (TTISS)
Public Health Agency of Canada
Public HealthCommunityClinicians
HOSPITALS
ReportableDiseases
Provincial/Territorial Blood Offices
Adverse Events•Acute
•Delayed
Health Canada Regulatory
Mandatory Reporting•Death = 24 hrs
•Severe = 15 days
ReportableDiseases
Blood Manufacturers
Plasma Manufacturers
Volunteer Reporting
35
National TTISS Working Group
• MembershipAll provinces/territories representedBlood manufacturersHealth Canada regulators
• Terms of Reference Identify and address issues related to a national
surveillance program to determine the risk of transmission of infections and injuries by blood transfusions
Recommend future directions, quality, efficacy and effectiveness of the TTISS as a national surveillance program
36
National Data Review Group • Membership
Members are selected for their individual medical/scientific expertise in the fields of: public health infectious diseasesepidemiology transfusion medicine
Ex-officio representatives are from PHAC, Health Canada, Canadian Blood Services and Héma-Québec
• Terms of Reference Reviewing and evaluating surveillance based epidemiological data
concerning the risk of transmission of infections and injuries through blood, blood components and plasma derivatives
Develop research questions and hypotheses for investigation purposes
Identify signals or unusual events that should be further investigated
37
Methods• Data on Adverse Events is collected at
the hospitals/sites •Most sites voluntarily report the data to
a provincial/territorial office •Few sites report directly to the Public
Health Agency of Canada
• Non-nominal data are transferred as per the provincial/federal TTISS agreement to the Public Health Agency of Canada
Disadvantages of Public Health Governance
• No prior knowledge of transfusion medicine in public health
• Lack of trust and credibility by the transfusion community at the outset
• No established network between public health and transfusion community
• Not perceived as a major public health issue within public health
How to handle disadvantages
1. LISTEN TO THOSE WHO HAVE EXPERTISE IN TRANSFUSION MEDICINE
2. START WITH A PILOT PROJECT TO ESTABLISH TRUST AND CREDIBILITY
3. PROVIDE REGULAR FEEDBACK TO DATA PROVIDERS
4. HIRE PEOPLE WITH EXPERTISE TO HELP BUILD THE SYSTEM
Advantages of Public Health Governance
• Extensive knowledge in surveillance methodology
• Extensive experience in managing surveillance databases
• Extensive knowledge in analysing and interpreting surveillance data
• Some guarantee of sustainability once endorsed by public health
41
PUBLIC-PRIVATE PARTNERSHIP
USA
42
AABB BSI US:CDCABC CAP US:CMSARC US:DHHS US:FDA
AABB ARC CAP PPTA US:CDCAATB ASH Publ Hlth Ag of Can Prov of Quebec US:CMSABC ASBMT ISBT Transfusion Alliance US:FDAAdvamed ASH JCAHO UNOS US:HRSAAHA BSI NMDP US:AHRQ US:NHLBI
US:DHHS – Asst. Sec., OPHS
Georges Andreu, MD (Fr) Mickey Koh, MD (SG)Simon Benson, MD (NZ) Mike Murphy, MD (UK)Emer Lawlor, MD (Irl) Paul Strengers, MD (ISBT)
James AuBuchon, MD, chair Nancy McCombie Neil Blumberg, MD Barbara Rabin-FastmanJeannie Callum, MD Pierre Robillard, MDRodeina Davis Kent Sepkowitz, MD Anne Eder, MD, PhD Beth Shaz, MDMark Fung, MD Tait Stevens, MD Linda Hahn Leon Su, MD Barbee Whitaker, PhD, staff
The US Biovigilance NetworkThe US Biovigilance NetworkBiovigilance Network Task Force
Biovigilance Network Steering Committee
Biovigilance Network Working GroupPHASE I: Transfusion Service Operations Biovigilance Network
International Correspondents
“Moral support” Encouragement for participationRoutes to ongoing fundingSupport for implementing changes
DirectionReviewMore encouragement for participation
Make it happen!Critiques from experience
43
Biovigilance Through a Public-Private PartnershipBiovigilance Through a Public-Private Partnership
Governmental AgenciesGovernmental Agencies
Charged with overseeing public healthCharged with overseeing public healthConcerned about “critical infrastructure”Concerned about “critical infrastructure”Offer epidemiologic expertiseOffer epidemiologic expertise
Private EntititiesPrivate Entitities
Generate the dataGenerate the dataOffer the field-specific expertiseOffer the field-specific expertiseNeed legal protectionNeed legal protectionNeed fundingNeed funding
Can offer legal protectionCan offer legal protectionCan provide fundingCan provide funding
44
The Public-Private PartnershipThe Public-Private Partnership
CDC is providing:CDC is providing:- Support for initial programming effort- Support for initial programming effort- Access to NHSN programmers and structure- Access to NHSN programmers and structure- Program managers- Program managers- Support for AABB staff- Support for AABB staff- Confidentiality and legal protections- Confidentiality and legal protections
Blood Banking (through Task Force) is providing:Blood Banking (through Task Force) is providing:- Technical expertise for system design- Technical expertise for system design- “Marketing”- “Marketing”- Fundraising for ongoing operation- Fundraising for ongoing operation- Data analysis through expert groups- Data analysis through expert groups
45
USBVN TimelineUSBVN Timeline
Phase I: Transfusion Service HemovigilancePhase I: Transfusion Service HemovigilanceTerminology and definitions: CompletedTerminology and definitions: CompletedDesign specifications: CompletedDesign specifications: CompletedProgramming initiation: Programming initiation: Winter 2008Winter 2008Pilot trials: Spring, 2008Pilot trials: Spring, 2008Opening of system: Fall, 2008Opening of system: Fall, 2008
Phase II: Collection Center HemovigilancePhase II: Collection Center HemovigilanceTerminology and definitions: UnderwayTerminology and definitions: UnderwayDesign specifications: Early 2008Design specifications: Early 2008Programming initiation: ContractedProgramming initiation: Contracted
Phase III: Tissue Transplantation BiovigilancePhase III: Tissue Transplantation BiovigilanceTTSN: Development underway (CDC/UNOS/AATB)TTSN: Development underway (CDC/UNOS/AATB)
(almost)(almost)
46
.France Singapore Netherlands Canada Québec/
CanadaHemovigilance Hemovigilance TRIP TTISS QHS
1994 2002 2002 2002 2000
Confidential Confidential Confidential Anonymous Confidential
Mandatory Voluntary Voluntary Voluntary Voluntary
Non-punitive Non-punitive Non-punitive Non-punitive Non-punitive
All reactions All reactions All reactions Only serious reactions
All reactions
Types of haemovigilance systems
2383 2358
972
568
1787
1349
2,10
5,54
4,65
3,53
7,13 7,07
0
250
500
750
1000
1250
1500
1750
2000
2250
2500
2000 2001 2002 2003 2004 2005
0,00
2,00
4,00
6,00
8,00
10,00
N Rate
0
500
1000
1500
2000
2500
2002 2003 2004 2005 2006
0
0,5
1
1,5
2
2,5
3
3,5
after closing date
in report
reports /1000
Blood components(1000s)
Reporting in haemovigilance
systems
FRANCE QHS
TRIP
48
.Country/
region
*Reports/
1000 units
What is reportable
Type of system
UK 0.20 Serious reactions + IBCT
Voluntary
Canada 0.31 Serious reactions not IBCT
Voluntary
Ireland 1.22 Serious reactions + IBCT
Voluntary
France 2.83 All reactions Mandatory
Netherlands 2.90 All reactions Voluntary
Québec 7.07 All reactions Voluntary
Reporting in haemovigilance systems
49
Data utilization• Setting priorities for transfusion safety• Evaluation of implementation of preventive measures• France:
– Traceability– ABO mistransfusions– Bacterial contaminations
• UK– ABO mistransfusions– TRALI
• Québec– Bacterial contaminations– ABO mistransfusions
50
Traceability FRANCE
51
ABO mistransfusions FRANCE
52
Bacterial contaminations FRANCE
53
ABO incompatible red cell transfusionsABO incompatible red cell transfusions1996 - 20051996 - 2005
63
110136
200190
346 348
439
485
1019262217
34263613
0
100
200
300
400
500
600
1996/97 1997/98 1998/99 1999/00 2000/01 2001/02 2003 2004 2005
IBCT casesanalysed
ABOIncompatiblered cells
54
Cases of TRALI with relevant donor antibody analysed Cases of TRALI with relevant donor antibody analysed by implicated component and by year 2003-2005by implicated component and by year 2003-2005
0
1
2
3
4
5
6
7
8
FFP FFP+Other Platelets Cryoprecipitate RBC OA
2003 2004 2005
3,0
6
8,5
2
4,9
2,4
7,27,9
11,5
2,1
10,5
4,9
6,3
3,1
14,4
9,58,4
3,4
0,0
2,5
5,0
7,5
10,0
12,5
15,0
ABO Inc AHTR DHTR
2000 2001 2002 2003 2004 2005
N
ABO mistransfusions QUÉBECABO mistransfusions QUÉBEC
56
Frequencies and Ratios/100,000 BC - Platelet pools
0 0
7
4
7
0
1
24,7
44,143,8
8,30
1
2
3
4
5
6
7
8
2000 2001 2002 2003 2004 2005 2006
0
5
10
15
20
25
30
35
40
45
50
N Rate
N Rate
Diversion pouch
*
Bacterial detection
57
Pre-post for diversion pouch WBDPC
Year N Rate
2000-2002 18 1:2,655
2003-2004 1 1:27,737
Pre-post for diversion pouch + bacterial detection WBDPC
X2 =8.09, p = 0.0044
Year N Rate
2000-2002 18 1:2,655
2003-2006 1 1:40,662
X2 = 12.68, p = 0.0003
58
The Canadian Transfusion Error Surveillance System
(TESS)
2005-2006
59
Background
• TESS is an abbreviated error tracking system designed for non-academic use
implement a tool for systematic capture of errors, including near-misses
Coding scheme comparable to what will be used in USA biovigilance network
60
Methods• Actual event vs. Near-miss
• Severity
Severity Description
High Potential for serious injury or death
Medium Potential for minor harm
Low No realistic potential for harm
Type Description
1 Actual – harm
2 Actual – no harm
3 Near-miss – unplanned recovery
4 Near-miss - planned recovery
61
ResultsClassification of hospital size by RBC Utilization
Size RBC Utilization per year No.
Small <2,000 RBC transfusions/year 3
Medium 2,000 – 10,000 RBC transfusions/year 5
Large >10,000 RBC transfusions/year 3
62
Results• 20,979 errors reported from 11 hospitals
over 2 years
6.8% with the potential for patient harm (high severity)
0.2% with actual patient harm 74% detected within 48 hours of the error 85% occurred between 08:00-20:00 Weekday 31/day vs. weekend 25/day
63
Actions taken
3451Other
1650Events with products loss
3969Patient sample recollected
814Additional testing
7051Floor/clinic notified
5242Record corrected
300Product retrieved
NAction
64
Products destroyed
$232,241379Plasma derivatives
N $CDN
$668,294
$456,053
7,097
14,877
15,476
18,624
51,253
348,726
479FFP
146PLT
2355TOTAL
1976Total Components
47CRYO-SUP
27APH-PLT
194CRYO
1083RBC
65
Person Involved in Error
Job Description N %
Nurse 9972 47.6
Technologist 7572 36.2
MD 2149 10.3
Clerk 294 1.4
Lab Assistant 283 1.4
Supplier 197 0.9
Supervisor 32 0.2
QA/TSO 7 0.03
Other 436 2.1
TOTAL* 20,942 100%*37 (0.2%) not specified
66
Type of errors reported
Clinical N %
PR Product/Test
Request
1487 7.1
SC Sample Collection 5444 25.9
SH Sample Handling 1832 8.7
RP Request for Pick-up 322 1.5
UT Unit Transfusion 4292 20.5
MS Miscellaneous 186 0.9
Subtotal 13563 64.7
Laboratory N %
PC Product Check-in 1156 5.5
DC Donor Codes 204 1.0
SR Sample Receipt 1114 5.3
ST Sample Testing 2588 12.3
US Unit Storage 636 3.0
AV Available for Issue 149 0.7
SE Unit Selection 79 0.4
UM Unit Manipulation 355 1.7
UI Unit Issue 1135 5.4
Subtotal 7416 35.3
67
High SeverityTop 5 List
Event Type & Description N %
SC 01 Sample labeled with incorrect name 356 26.9
SH 02 Sample label and requisition do not match 216 16.3
SC 02 Sample with no label 181 13.7
SC 07 Other mislabeling 99 7.5
RP 01 Request for pick-up on wrong patient 83 6.3
Subtotal 935 70.6
68
0 500 1000 1500 2000 2500 3000
2005
2006
PC - Product Check-in
PR - Product/ Test RequestSC - Sample Collection
SH - Sample Handling
SR - Sample ReceiptST - Sample Testing
SE - Unit Selection
US - Unit Storage
UM - Unit ManipulationUI - Unit Issue
UT - Unit Transfusion
RP - Request for Pick-UpDC - Donor Codes
Rates for Event Codes per 100,000 n=436,223 products received; n=986,608 tests performed
SAMPLE COLLECTION1 IN 37
UNIT TRANSFUSION1 IN 92
SAMPLE COLLECTION1 IN 51
UNIT TRANSFUSION1 IN 92
69
0 100 200 300 400 500 600
SC 01 - Sample labelled with wrongt patient name
SC 02 - Not labelled
SC 03 - Wrong patient collected
SC 04 - Collected in wrong tube type
SC 05 - Sample with insufficient quantity
SC 06 - Sample hemolyzed
SC 07 - Label incomplete/ illegible
SC 08 - Sample collected in error
SC 09 - Requisition without samples
SC 10 - Armband incorrect/ not available
SC 99 - Other
Rates for Sample Collection Errors
1:776
1:1615
1:12,623
1:2170
1:170
1:277
1:171
1:2620
1:1129
SC 01
SC 02
SC 03
SC 04
SC 06
SC 07
SC 08
SC 10
SC 99
SC 05
SC 09
1:2620
1:27,770
70
Error rates by locationSample Collection
Location Rate Denominator
Emergency 1 in 16 14,397
Operating room 1 in 18 749
Intensive care 1 in 29 6,996
Medical/surgical ward 1 in 30 18,740
Out patient procedures 1 in 82 9,054
Obstetrics 1 in 245 10,782
Outpatients 1 in 285 18,250
Denominator – 77,576 of 138,850 (55% of total)
71
72
70% of transfusion activity in Canada
73
74
75
76
77
78
79
80
CONCLUSION• Hemovigilance is now an integral part
of a quality system in transfusion
• Hemovigilance covers donors, processes and recipients
• Hemovigilance helps identify priorities for transfusion safety and monitors effects of preventive measures
• Hemovigilance works