HOW CAN WE INTEGRATE GRADE AND A FORMAL CONSENSUS
METHOD INTO AN INTERNATIONAL GUIDELINE PROJECT?
THE EXAMPLE OF AN INTERNATIONAL CONSENSUS CONFERENCE ON PATIENT BLOOD
MANAGEMENT (ICC-PBM)
HANS VAN REMOORTEL
COORDINATING RESEARCHER
CENTRE FOR EVIDENCE-BASED PRACTICE (CEBAP)
BELGIAN RED CROSS
WWW.CEBAP.ORG

Conflicts of interests
 Employee of Belgian Red Cross-Flanders, providing safe blood products
to hospitals in Flanders and Brussels which did not influence his
contribution to ICC-PBM 2018 Frankfurt
 No conflicts of interest to declare

Outline
1.Patient Blood Management: 3 topics of interest and 17
PICO questions
2. Using a formal consensus methodology: the Consensus
Development Conference
3. Using an evidence-based methodology: the GRADE approach

Patient blood management (PBM) is a patient-
focused, evidence-based and systematic
approach to optimize the management of
patient and transfusion of blood products for
quality and effective patient care.

Goodnough 2012

Scientific Committee: formulating 3 topics
of interest and 17 PICO questions
Scientific Committee
Pierre Albaladejo (Grenoble University Hospital, France/ISTH)
Shubha Allard (NHS Blood & Transplant/ISBT)
Cécile Aubron (Academic Hospital of Brest, France/SFTS)
Kari Aranko (European Blood Alliance/EBA)
Dana Devine (Canadian Blood Services/CBS)
Craig French (Western Health, Melbourne Australia)
Kathrine P. Frey (Fairview Health Services and Patient Readiness
Institute, Minneapolis MN/AABB)
Christian Gabriel (Ludwig Boltzmann Institute for clinical and
experimental traumatology, Austria/DGTI)
Richard Gammon (One Blood, Orlando/AABB)
Andreas Greinacher (Institut für Immunologie und
Transfusionsmedizin Greifswald/ICTMG)
Marian van Kraaij (Sanquin, the Netherlands/EBA)
Jerrold Levy (Duke University School of Medicine, North Carolina/ISTH)
Giancarlo Liumbruno (Italian National Institute of Health/EBA)
Patrick Meybohm (University Clinics of the Johann Wolfgang Goethe University Frankfurt/Main)
Markus Müller (Institute for Transfusion Medicine and Immunohaematology Frankfurt/EBA)
Mike Murphy (NHS Blood & Transplant and AABB/EBA)
Hans Van Remoortel (Centre for Evidence-Based Practice, Belgian Red Cross)
Ben Saxon (Australian Red Cross Blood Service/ARCBS)
Erhard Seifried (German Red Cross Blood Transfusion Services/EBA) (chair)
Nadine Shehata (Mount Sinai Hospital Toronto/ICTMG)
Pierre Tiberghien (French National Blood Service/EBA)
Claudio Velati (Società Italiana di Medicina Trasfusionale e Immunoematologia)
Erica Wood (Epidemiology and Preventive Medicine at Monash University/ISBT)
Face-to-face meeting SciCom February 2017

Topic 1: Preoperative anaemia
 Definition and diagnosis (PICO 1 and PICO 2)
 Treatment (PICO 3)
Topic 2: RBC transfusion triggers
 Intensive care and acute interventions (PICO 4-9 & PICO 14)
 Haematology and oncology (PICO 10 & PICO 11)
 Neurology (PICO 12 & PICO 13)
Topic 3: PBM implementation
 Effectiveness implementation of ‘comprehensive’ PBM programs (PICO 15)
 Effectiveness behavioural interventions (PICO 16)
 Effectiveness decision support systems (PICO 17)
Face-to-face meeting SciCom February 2017
Scientific Committee: formulating 3 topics
of interest and 17 PICO questions
Scientific Committee

Outline
1. Patient Blood Management: 3 topics of interest and 17 PICO
questions
2.Using a formal consensus methodology: the Consensus
Development Conference
3. Using an evidence-based methodology: the GRADE approach

2-day International Consensus Conference on Patient Blood
Management
(24 & 25 April, Frankfurt, Germany)
- 200 medical experts
- From 5 continents
- Representing more than 10
disciplines (e.g. transfusion
medicine, surgery,
anesthesiology and
haematology)
- Co-sponsors: AABB, ISBT,
DGTI, SFTS, SIMTI, EBA
- Participation: ARCBS, TBS,
ICTMG, ISTH, NBA, ÖGBT,
SFAR
- Presence: WHO, EU
Commission, DGAI, National
Health Authority Australia

Scientific Committee
Decision-
making
panelists
Speakers
(Co-)chairs
Audience
Rapporteurs
Consensus Development Conference (CDC)

Consensus Development Conference (CDC)
*Nair R et al., Semin Arthritis Rheum, 2011; Sher G and Devine D, Transfusion, 2007
Major steps in the Consensus Development Conference format?
1) Evidence presented by the SCIENTIFIC COMMITTEE to the conference,
CHAIRED in a public (open) session followed by discussion (AUDIENCE)
2) Private (executive) session by DECISION-MAKING panel to further deliberate
on the evidence and discussion to reach consensus -> result: draft
consensus statement.
3) Presentation of draft consensus statement in a plenary session +
review/comment/indicative voting by conference attendees.
4) Final executive session with final consensus statement by DECISION-
MAKING PANEL.

Outline
1. Patient Blood Management: 3 topics of interest and 17 PICO
questions
2. Using a formal consensus methodology: the Consensus
Development Conference
3.Using an evidence-based methodology: the GRADE
approach

GRADE approach
From evidence to recommendations – transparent and sensible
P
I
C
O
Outcome
Outcome
Outcome
Outcome
Critical
Critical
Important
Not
High
Moderate
Low
Very low
GradedownGradeup
1. Risk of bias
2. Inconsistency
3. Indirectness
4. Imprecision
5. Publication
bias
1. Large effect
2. Dose
response
3. Confounders
Summary of findings
& estimate of effect
for each outcome
Systematic review
Randomization
Experimental: High
Observational: Low
Scientific Committee

GRADE
overall quality of the evidence
across outcomes based on
lowest quality
of critical outcomes
Guideline development
GRADE recommendations
Evidence to recommendation
• For or against (direction) ↑↓
• Strong or conditional/weak
(strength)
By considering balance of consequences
(evidence to recommendation)
 Quality of evidence
 Balance benefits/harms
 Values and preferences
 Resource use (cost(-effectiveness)
 Equity – Acceptability - Feasibility
• “We recommend using…”
• “We recommend against using…”
• “We suggest using…”
• “We suggest against using…”
EtD framework
GRADEpro Guideline Formulate recommendations
Transparency, clear, actionable
Research?
Decision-making
panelists
Audience
Rapporteurs
(Co-)chairs
Panelists
GRADE approach
From evidence to recommendations – transparent and sensible

CRITERIA JUDGEMENT
RESEARCH
EVIDENCE
ADDITIONAL CONSIDERATIONS
1. DESIRABLE EFFECTS How substantial are the desirable anticipated effects?
2. UNDESIRABLE EFFECTS How substantial are the undesirable anticipated effects?
3. CERTAINTY OF EVIDENCE What is the overall quality of the evidence of effects?
4. VALUES
Is there important uncertainty about or variability in how
much people value the critical outcomes?
5. BALANCE OF EFFECTS
Does the balance between desirable and undesirable
effects favor the intervention or the comparison?
6. RESOURCES REQUIRED How large are the resource requirements (costs)?
7. COST EFFECTIVENESS
Does the cost-effectiveness of the intervention favor the
intervention or the comparison?
8. EQUITY What would be the impact on health equity?
9. ACCEPTABILITY Is the intervention acceptable to key stakeholders?
10. FEASIBILITY Is the intervention feasible to implement?
Evidence-to-Decision framework
Rapporteurs
Rapporteurs
Rapporteurs
Rapporteurs
Rapporteurs
Rapporteurs
Rapporteurs
Rapporteurs
Rapporteurs
Rapporteurs
Audience
Audience
Audience
Audience
Audience
Audience
Audience
Audience
Audience
Audience

Outline
1. Patient Blood Management: 3 topics of interest and 17 PICO
questions
2.Using a formal consensus methodology: the Consensus
Development Conference
3.Using an evidence-based methodology: the GRADE
approach
+

1 year of preparation
• Feb 2017: SciCom meeting,
Frankfurt (Germany)
• June 2017: Sponsors meeting,
ISBT Copenhagen (Denmark)
• March 2017 – April 2018:
12 SciCom teleconferences
• Jan/Feb 2018: two face-to-face
meetings with SciSec and chairs,
Frankfurt (Germany)
• March 2017 – January 2018:
systematic reviews 17 PICO
questions (+/- 18.000 references
screened, 145 studies included)
• Dec 2017 – April 2018:
• 2 SciCom webinars
• 4 panellists webinars
• 3 chairs webinars
• 1 webinar rapporteurs
• 1 tutorial rapporteurs
• 2 speakers webinars

Start day 1 (24 April 2018)

3 Parallel sessions
Session 1: Preoperative anaemia
 Definition and diagnosis
(PICO 1 and PICO 2)
 Treatment
(PICO 3)
Session 2: RBC transfusion triggers
 Intensive care and acute interventions
(PICO 4-9 & PICO 14)
 Haematology and oncology
(PICO 10 & PICO 11)
 Neurology
(PICO 12 & PICO 13)
Session 3: PBM implementation
 Effectiveness implementation of
‘comprehensive’ PBM programs
(PICO 15)
 Effectiveness behavioural interventions
(PICO 16)
 Effectiveness decision support systems
(PICO 17)
Day 1 (24 April 2018)
Part 1: Plenary
• Evidence presented by
• Based on Evidence-to-Decision (EtD) framework
• Discussion with
moderated by
• Notes recorded by
AudienceRapporteurs
(Co-)chairs Panelists
Speakers

Day 1: 3 parallel/open sessions

Day 1: 3 parallel/open sessions

3 Parallel sessions
Session 1: Preoperative anaemia
 Definition and diagnosis
(PICO 1 and PICO 2)
 Treatment
(PICO 3)
Session 2: RBC transfusion triggers
 Intensive care and acute interventions
(PICO 4-9 & PICO 14)
 Haematology and oncology
(PICO 10 & PICO 11)
 Neurology
(PICO 12 & PICO 13)
Session 3: PBM implementation
 Effectiveness implementation of
‘comprehensive’ PBM programs
(PICO 15)
 Effectiveness behavioural interventions
(PICO 16)
 Effectiveness decision support systems
(PICO 17)
Day 1 (24 April 2018)
+
+
+
Part 1: Plenary
Part 2: Closed (private/executive session)
• Evidence presented by
• Based on Evidence-to-Decision (EtD) framework
• Discussion with
moderated by
• Notes recorded by
• Based on EtD framework
• Draft recommendations
by
• Moderated by
• Notes recorded by
AudienceRapporteurs
(Co-)chairs Panelists
Speakers

Day 1: closed session with decision-making panels

Draft conclusions at the end of day 1
TYPE OF
RECOMMENDATION
Strong recommendation
against the intervention
Conditional recommendation
against the intervention
Conditional recommendation
for either the intervention or
the comparison
Conditional recommendation
for the intervention
Strong recommendation for
the intervention
RECOMMENDATION Option 1: Formulation of a strong or conditional recommendation
Terminology strong recommendation: “we recommend…” – “clinicians should…” – “clinicians shoud not….” – “Do….” – “Don’t…..”
Terminology weak/conditional recommendation: “we suggest…” – “clinicians might….” – “we conditionally recommend…”
Option 2: No recommendation
Option 3: Research recommendation
JUSTIFICATION
…
SUBGROUP
CONSIDERATIONS …
IMPLEMENTATION
CONSIDERATIONS …
MONITORING AND
EVALUATION …
RESEARCH PRIORITIES
…
Closed session with chairs/decision-making panels/rapporteurs

 Plenary session with the general audience (all 3 topics)
 Presentation draft recommendations/justifications by
AudienceRapporteurs
(Co-)chairs Panelists
Day 2 (25 April 2018)

 Plenary session with the general audience (all 3 topics)
 Presentation draft recommendations/justifications by
 Discussion with/indicative voting by , moderated by the
 Notes recorded by
AudienceRapporteurs
(Co-)chairs Panelists
Day 2 (25 April 2018)

 Plenary session with the general audience (all 3 topics)
 Presentation draft recommendations/justifications by
 Discussion with/indicative voting by , moderated by the
 Notes recorded by
 Closed sessions with the decision-making panelists and (co-)
chairs
 Formulation of final recommendations by , moderated by the
AudienceRapporteurs
(Co-)chairs Panelists
Day 2 (25 April 2018)

Day 2: closed session with decision-making panels

Conclusions: 10 evidence-based recommendations
 Topic 1: Preoperative anaemia
 4 recommendations (1 strong, 3 conditional)
 Topic 2: RBC transfusion triggers
 4 recommendations (2 strong, 2 conditional)
 Topic 3: PBM implementation
 2 recommendations (2 conditional)
 Research recommendations for all topics

Lessons learned to improve a future
guideline project
 Preparation: time versus resources
 2 face-to-face meetings between methodologists and experts
 Beginning: PICO + selection criteria (lumping vs splitting!)
 Intermediate: to discuss results systematic review
 Improve sense of ownership and knowledge of evidence-based methodology by
different groups (panel members, chairs)
 More rigorous process to select panel members (COI!) and formal/blind voting system
on draft/final recommendations
 Organization Consensus conference immediately before/after blood transfusion
conference (e.g. ISBT) could increase participation (by general audience).

Acknowledgments
Prof. Dr. Erhard Seifried (German Red Cross Blood Transfusion
Services/EBA) (chair)
Dr. Kari Aranko (European Blood Alliance/EBA)
Willemijn Kramer (European Blood Alliance/EBA)
Dr. Markus Müller (Institute for Transfusion Medicine and
Immunohaematology Frankfurt/EBA)
Prof. Dr. Patrick Meybohm (University Clinics of the Johann
Wolfgang Goethe University Frankfurt/Main)
Chairs of the Plenary Sessions:
Prof. Dr. Reinhard Burger, Robert-Koch-Institute, Berlin, Germany
Prof. Dr. Klaus Cichutek, Paul-Ehrlich-Institute, Langen, Germany
Prof. Dr. Jimmy Volmink, Faculty of Medicine and Health Sciences at
Stellenbosch University, South Africa
Decision-making panel ‘Preoperative anaemia’
Prof. Dr. Yves Ozier, University Hospital of Brest, France (Chair)
Prof Dr. Emmy De Buck, Centre for Evidence Based Practice, Belgian Red
Cross-Flanders, Belgium (Co-Chair)
Decision-making panel ‘RBC transfusion triggers’
Prof. Dr. Reinhard Burger, Robert-Koch-Institute, Berlin, Germany (Chair)
Prof. Dr. Jimmy Volmink, Faculty of Medicine and Health Sciences at
Stellenbosch University, South Africa (Co-Chair)
Decision-making panel ‘PBM implementation’
Prof. Dr. Jonathan Waters, Magee-Womens Hospital of the University of
Pittsburgh Medical Center (Chair)
Prof. Dr. Dean Fergusson, Ottawa Hospital Research Institute, University of
Ottawa, Canada (Co-Chair)
Stefan Holtzem (Photographer)

Acknowledgments
Centre for Evidence-Based Practice (CEBaP)
Belgian Red Cross
www.cebap.org
@CEBaP_evidence