HEMOVIGILANCE SYSTEMS Pierre Robillard 1,2 MD 1 Québec Public Health Institute, Montréal, Canada 2 McGill University, Department of Epidemiology, Biostatistics.

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