GARFIELD-AF Investigators Meeting Johannesburg, 27 th October 2017 - - PowerPoint PPT Presentation

GARFIELD-AF Investigators’ Meeting

Johannesburg, 27th October 2017

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Agenda

08:30 Registration and coffee 09:00 Welcome Overview of findings from the global data set Professor the Lord Kakkar 09:30 Global status update Gloria Kayani 10:15 Clinical perspectives of atrial fibrillation from South Africa. GARFIELD-AF: How does South Africa compare with rest of the world? Professor Barry Jacobson 10:45  GARFIELD-AF Risk Score: Can GARFIELD help improve risk stratification for patients with AF?  GARFIELD-AF: Health economics analysis Professor the Lord Kakkar

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Thrombosis Research Institute:

Welcome

Professor the Lord Kakkar and Prof Barry Jacobson

4

Thrombosis Research Institute (TRI)

• TRI is an independent global academic organisation
• We have a 45 year track record and are dedicated to working in thrombosis and our pioneering research

programmes across the world, continue to provide breakthrough solutions

• We undertake research though a network of 2500 centres in 40 countries

Garfield-AF:

• Past and Present

GARFIELD-AF journey – review of how far we have come

• First patient

in

2009

• Methods

paper published

2012

• Cohort 1

baseline paper published

2013

• 2-year
• utcomes

paper published

2016

• 1-year follow-

up locked for all prospective patients

• Treatment

patterns paper published

2017

Mission statement

• To enhance understanding of the burden of thromboembolic stroke and identify
• pportunities for the incorporation of innovations designed to improve safety, outcomes and

utilisation of healthcare resources

• The unique design and methodology of GARFIELD-AF will provide representative, real-world

insights, and will clarify AF treatments and outcomes for patients, clinicians and healthcare providers as they evolve over time

• GARFIELD-AF is governed by the highest academic and ethical standards in the generation,

dissemination, and communication of its research findings

Why did we need a global AF registry?

• Uncertainty persisted about how AF is managed in the real world and how these treatment

patterns affect patient and population outcomes

• This was a problem in relation to treatment guidelines, in specific patient populations,

across various care settings

• There was a large burden of preventable stroke in patients with AF and historical

underutilization and poor VKA control for stroke prevention in AF

• NOACs had been introduced for stroke prevention in AF

8

GARFIELD program – where we are today

• This year we reached a momentous milestone, completing patient enrolment across the

GARFIELD programme

• Between GARFIELD-AF and GARFIELD-VTE we have:
• Recruited 68,140 patients in 39 countries
• Captured over 100,000 prospective patient years and will soon have more than 150,000
• Our data concordance remains at a remarkable level above 95%

Prospective registries in AF

• 1. Kakkar AK et al. Am Heart J. 2012;163:13-19 e1; 2. Huisman MV et al. Am Heart J. 2014 Mar;167(3):329-34; 3. Piccini JP et al. Am Heart J. 2011;162:606-612.e1; 4. Steinberg BA.

Am Heart J. 2014;168:160-7. 5. Kirchhof P et al. Europace. 2014;16:6-14. Registry Population size Patient enrolment – key design features Follow-up duration GARFIELD-AF1 57,262

• Prospective patients (approx.52,000) enrolled <6 weeks after AF diagnosis in 5 sequential

cohorts

• Retrospective patients (approx. 5,000) enrolled 6–24 months after diagnosis
• ≥1 additional investigator-determined risk factor for stroke

≥2 years, up to 8 years GLORIA-AF2 Target: 56,000 To date: >38,000

• Prospective patients enrolled <3 months after AF diagnosis in 3 phases
• CHA2DS2-VASc score ≥1

0–3 years Phase 1 (pre-NOAC): none Phase 2 (Dabigatran): 2 years Phase 3 (VKA/NOAC): 3 years ORBIT-AF I3 10,132

• Incident or prevalent AF
• Patients excluded if anticipated life expectancy <6 months

≥2 years ORBIT-AF II4 13,415

• Prospective patients enrolled <6 months after AF diagnosis; or enrolled <3 months after

initiation or transition to a NOAC

• Patients excluded if anticipated life expectancy <6 months

≤2 years PREFER in AF5 7243

• Prospective patients enrolled <12 months after AF diagnosis

1 year

GARFIELD-AF’s unique study design

GARFIELD-AF – looking ahead

• There is now only 1 year of the programme remaining as we complete the follow-up period
• f our final cohorts
• Already we have produced and published many excellent analyses, including the GARFIELD-

AF risk score

• The first manuscript from the collaboration with ORBIT-AF is about to be published
• GARFIELD-AF is also generating insights on the management and outcomes of patients with

comorbid conditions

Garfield-AF:

• Early Insights

Evolution in baseline treatment for patients enrolled in sequential cohorts of GARFIELD-AF

4.2 13.8 26.3 37.3 43.1

20 40 60 80 100

Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5

Proportion of patients on treatment, %

VKA±AP FXaI/DTI±AP AP None

Cohorts 1–5, N=52,081; AP, antiplatelet; DTI, direct thrombin inhibitor; FXaI, factor Xa inhibitor; VKA, vitamin K antagonist 57.4% 71.2%

2010–2011 2011–2013 2013–2014 2014–2015 2015–2016

Event rates for data collected prospectively starting from the date

• f the first study visit up to 1 year

1.34 0.72 3.04 1.07 0.82 4.05

0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 5.0

Stroke/SE Major bleeding All-cause mortality

Rate (95% CI) per 100 person-years

Retrospectively enrolled cohort Prospectively enrolled cohort

Stroke/SE Major bleeding All-cause mortality Enrolment Retrospective Prospective Retrospective Prospective Retrospective Prospective Person-years 3432.7 5144.1 3466.7 5146.3 3491.1 5166.1 Events 46 55 25 42 106 209

Cohort 1: retrospectively enrolled (n=5069), prospectively enrolled (n=5501)

One-year event rates following a new diagnosis of AF

Outcome Events Event rate (per 100 person-years) 95% CI All-cause mortality 2103 4.38 4.20 to 4.57 Cardiovascular 789 1.64 1.53 to 1.76 Non-cardiovascular 771 1.61 1.50 to 1.72 Undetermined cause 543 1.13 1.04 to 1.23 Stroke/systemic embolism 650 1.36 1.26 to 1.47 Major bleeding 407 0.85 0.77 to 0.94 Acute coronary syndromes 378 0.79 0.71 to 0.87 Congestive heart failure 1052 2.22 2.09 to 2.35

Cohorts 1–5, N=52,081

Event rates by country (0.0 = global mean) after adjustment of all factors in the model

Fixed effects included in the models: gender, age group, diabetes, hypertension, congestive heart failure, vascular disease, previous stroke*, previous bleed**, ethnicity, smoke, type of atrial fibrillation, moderate-to-severe chronic kidney disease. *Not included in the model for major

• bleeding. **Not included in the model for stroke/systemic embolism (SE).

ARG, Argentina; AUS, Australia; AUT, Austria; BEL, Belgium; BRA, Brazil; CAN, Canada; CHE, Switzerland; CHL, Chile; CHN, China; CZE, Czech Republic; DEU, Germany; DNK, Denmark; EGY, Egypt; ESP, Spain; FIN, Finland; FRA, France; GBR, United Kingdom; HUN, Hungary; IND, India; ITA, Italy; JPN, Japan; KOR, South Korea; MEX, Mexico; NLD, Netherlands; NOR, Norway; POL, Poland; RUS, Russia; SGP, Singapore; SWE, Sweden; THA, Thailand; TUR, Turkey; UAE, United Arab Emirates; UKR, Ukraine; USA, United States of America; ZAF, South Africa. EB, empirical Bayes estimate. Fox KAA, presentation at Satellite Symposium, ESC Congress 2016

Causes of death during first-year follow-up

Events % Cardiovascular deaths (n=789)1 Congestive heart failure 262 33.2 Sudden or unwitnessed death 127 16.1 Myocardial infarction 89 11.3 Ischaemic stroke 86 10.9 Other 223 28.3 Non-cardiovascular deaths (n=771)2 Malignancy 233 30.2 Infection/sepsis 155 20.1 Respiratory failure 142 18.4 Accidental/trauma 17 2.2 Other 221 28.7

Cohorts 1–5, N=52,081; 1missing: 2 deaths; 2missing: 3 deaths

Types of stroke during first-year follow-up

Cohorts 1–5, N=52,081

Events % Stroke (not including systemic embolism) 585 100 Primary ischaemic stroke 406 69.4 Primary intracerebral haemorrhage 71 12.1 Undetermined 108 18.5

Increasing age

Integrated care is needed for comorbid conditions with common risk factors and pathologies

Diabetes Kidney disease Vascular disease CAD ACS Heart failure

AF

Stroke/TIA

Electrical remodel- ling

Myocyte damage Atrial dilation

Impaired cardiac function

Prothrom- botic state

Vascular pathology

Altered haemo- dynamics

ACS, acute coronary syndromes; AF, atrial fibrillation; CAD, coronary artery disease; TIA, transient ischaemic attack

GARFIELD-AF is providing important insights into registry design

Retrospectively enrolled cohort Prospectively enrolled cohort

Differences in type of AF between retrospectively and prospectively enrolled patients

13.3 30.9 19.4 36.3 44.8 24.5 16.5 14.1 5 10 15 20 25 30 35 40 45 50 Unclassified Paroxysmal Persistent Permanent Proportion of patients (%) Type of AF

Retrospectively enrolled Prospectively enrolled

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Thrombosis Research Institute:

Global Operations Update

Gloria Kayani

Roles and responsibilities

Sponsor: Thrombosis Research Institute Clinical Research Organisations:

Quintiles, ADDS, Apothecaries Global project management Clinical Operation Dendrite Clinical System Electronic Data Capture (EDC)

Co-ordinating Centres:

Thrombosis Research Group in USA (TRG) University of Birmingham in UK Funded by unrestricted grant from Bayer

57,626 patients in 35 countries

Austria Belgium Czech Republic Denmark Finland France Germany Hungary Italy The Netherlands Norway Poland Russia Spain Sweden Switzerland South Africa Ukraine United Kingdom Australia China Egypt India Japan Singapore South Korea Thailand Turkey United Arab Emirates Argentina Brazil Canada Chile Mexico United States of America

5009 4370 3913 3759 2845 2830 2823 2602 2160 2091 1880 1863 1714 1564 1502 1450 1388 1372 1283 1215 1046 1046 1046 994 758 728 666 641 586 533 453 389 348 306 89 1000 2000 3000 4000 5000 6000

Patients enrolled in eDC

Cohort 1 – 5050 (Retrospective), 5505 (Prospective) Cohort 2 – 11,681 Cohort 3 – 11,485 Cohort 4 – 11,310 Cohort 5 – 12,201

Total Country Level Recruitment (57,262)

Follow-Up Extension Update (Global)

185 15 13 506 125 43 193 34 572 99 9 199 654 286 143 297 505 28 26 181 68 274 486 28 36 237 208 22 220 192 50 571 312 109 471 489 266 644 507 465 414 1618 602 170 114 325 905 1762 566 534 1167 2519 1729 540 675 151 1433 995 155 323 1616 681 1 700 190 1712 905 218

Consented/In follow up Extention Potential Patients/pending Consent

Patients in Extension – 6926 Pending patients – 25562

Garfield-AF follow-up extension implementation

2010 2011 2012 2013 2014 2015 2016 2017 2018 Cohort 1 Dec-09 Oct-13 Aug-18 Cohort 2 Oct-11 Jun-15 Aug-18 Recruitment Cohort 3 Jun-13 Aug-16 Aug-18 Minimum follow-up Cohort 4 Aug-14 Aug-17 Aug-18 Extended follow-up Cohort 5 Aug-15 Aug-18

Follow-up extension was implemented as a part of part of protocol amendment 4 (implementation – June 2013 – Jan 2015)

277 1625 2540 2484

Start of Protocol amendment 4 implementation End of Protocol amendment 4 implementation

Data Lock Status

Milestone Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5 Baseline

99.98% 99.90% 99.71% 99.81% 99.54%

Month 12

99.85% 99.79% 99.71% 99.60% 98.17%

Month 24

99.77% 99.79% 99.22% 96.24%

Month 36

94.40% 90.87% 62.70%

Month 48

96.67% 68.04%

Month 60

94.58%

Garfield-AF: Quality control and quality assurance

GARFIELD-AF registry – QA and QC measures

• Ongoing electronic database monitoring of all data entered into the registry database
• Remote site monitoring by iCRAs (International Clinical Research Associates)
• Onsite monitoring which includes SDV at selected sites once a year
• Ongoing monitoring of quality by the audit committee

Modified Monitoring Phases to meet the target number of patients for SDV

Phase Time of the year Number of patients monitored

Phase 1 2010 15 Phase 2 2013 - 2014 1012 Phase 3 2014 - 2015 1172 Phase 4 2016 2247 Phase 5 2017 7000 Total 11446

Results: Comparison

Phase 2 Phase 3 Phase 4 Number of Sites 110 (24 countries) 112 (24 Countries) 146 (31 Countries) Number of Patients 1012 1172 2247 Concordance 94.0% 95.6% 96.18% Missing Events

• Death
• Bleed
• Stroke

12 23 14 12 10 3 4 30 3 GCP Findings 2 1 2

Garfield-AF Audit Paper

Publication Plan

GARFIELD-AF has published 16 papers

1. Kakkar AK, Mueller I, Bassand J-P, Fitzmaurice DA, Goldhaber SZ, Goto S, Haas S, Hacke W, Lip GYH, Mantovani LG, Verheugt FWA, Jamal W, Misselwitz F, Rushton-Smith S, Turpie AGG, for the GARFIELD Registry Investigators. International longitudinal registry of patients with atrial fibrillation at risk of stroke: GARFIELD (Global Anticoagulant Registry in the FIELD). Am Heart J 2012;163(1):13-19.e1. Methods paper. http://www.ahjonline.com/article/S0002- 8703%2811%2900696-X/fulltext 2. Apenteng PN, Murray ET, Holder R, Hobbs FDR, Fitzmaurice DA; UK GARFIELD Investigators and GARFIELD Steering Committee. An international longitudinal registry of patients with atrial fibrillation at risk of stroke (GARFIELD): the UK protocol. BMC Cardiovascular Disorders 2013;13:31. UK protocol paper. http://www.biomedcentral.com/1471-2261/13/31 3. Kakkar AK, Mueller I, Bassand J-P, Fitzmaurice DA, Goldhaber SZ, Goto S, Haas S, Hacke W, Lip GYH, Mantovani LG, Turpie AGG, van Eickels M, Misselwitz F, Rushton-Smith S, Kayani G, Wilkinson P, Verheugt FWA, for the GARFIELD Registry Investigators. Risk profiles and antithrombotic treatment of patients newly diagnosed with atrial fibrillation at risk of stroke: perspectives from the international, observational, prospective GARFIELD Registry. PLOS ONE 2013;8(5):e63479. http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0063479 4. Sun Y, Hu D; Chinese Investigators of GARFIELD. [Chinese subgroup analysis of the global anticoagulant registry in the FIELD (GARFIELD) registry in the patients with non-valvular atrial fibrillation]. Zhonghua Xin Xue Guan Bing Za Zhi 2014;42(10):846-50. [Article in Chinese] http://www.cjcv.org.cn/xinxueguan20144210/33942.htm?locale=zh_CN 5. Lip GY, Rushton-Smith SK, Goldhaber SZ, Fitzmaurice DA, Mantovani LG, Goto S, Haas S, Bassand JP, Camm AJ, Ambrosio G, Janský P, Mahmeed WA, Oh S, van Eickels M, Raatikainen P, Steffel J, Oto A, Kayani G, Accetta G, Kakkar AK; for the GARFIELD-AF Investigators. Does sex affect anticoagulant use for stroke prevention in nonvalvular atrial fibrillation? The prospective global anticoagulant registry in the FIELD-Atrial Fibrillation. Circ Cardiovasc Qual Outcomes 2015;8(2 suppl 1):S12-20. http://circoutcomes.ahajournals.org/content/8/2_suppl_1/S12.long 6. Haas S; im Namen des GARFIELD-AF Steering Committee. [GARFIELD-AF - First data on healthcare of patients with atrial fibrillation in Germany]. Dtsch Med Wochenschr 2015;140(suppl 1):S13-4. [Article in German] https://www.thieme-connect.com/DOI/DOI?10.1055/s-0041-101750 7. Stępińska J, Kremis E, Konopka A, Wożakowska-Kapłon B, Ruszkowski P, Kukla P, Kayani G. Stroke prevention in AF patients in Poland and other European countries: insights from the GARFIELD-AF registry. Kardiol Pol 2016;74(4):362-71. https://ojs.kardiologiapolska.pl/kp/article/view/9383 8. Fitzmaurice DA, Accetta G, Haas S, Kayani G, Lucas Luciardi H, Misselwitz F, Pieper K, Ten Cate H, Turpie AG, Kakkar AK; GARFIELD-AF Investigators. Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists. Br J Haematol 2016;174(4):610-23. http://onlinelibrary.wiley.com/doi/10.1111/bjh.14084/abstract

GARFIELD-AF has published 16 papers

9. Ten Cate V, Ten Cate H, Verheugt FW. The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) : Exploring the changes in anticoagulant practice in patients with non-valvular atrial fibrillation in the Netherlands. Neth Heart J. 2016;24(10):574-80. http://link.springer.com/article/10.1007%2Fs12471-016- 0874-y 10. Bassand JP, Accetta G, Camm AJ, Cools F, Fitzmaurice DA, Fox KA, Goldhaber SZ, Goto S, Haas S, Hacke W, Kayani G, Mantovani LG, Misselwitz F, Ten Cate H, Turpie AG, Verheugt FW, Kakkar AK; GARFIELD-AF Investigators. Two-year outcomes of patients with newly diagnosed atrial fibrillation: results from GARFIELD-

• AF. Eur Heart J. 2016;37(38):2882-2889. http://eurheartj.oxfordjournals.org/content/early/2016/06/28/eurheartj.ehw233

11. Haas S, Ten Cate H, Accetta G, Angchaisuksiri P, Bassand JP, Camm AJ, Corbalan R, Darius H, Fitzmaurice DA, Goldhaber SZ, Goto S, Jacobson B, Kayani G, Mantovani LG, Misselwitz F, Pieper K, Schellong SM, Stepinska J, Turpie AG, van Eickels M, Kakkar AK; GARFIELD-AF Investigators. Quality of vitamin K antagonist control and 1-year outcomes in patients with atrial fibrillation: A global perspective from the GARFIELD-AF registry. PLoS One. 2016;11(10):e0164076. http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0164076 12. Oh S, Goto S, Accetta G, Angchaisuksiri P, Camm AJ, Cools F, Haas S, Kayani G, Koretsune Y, Lim TW, Misselwitz F, van Eickels M, Kakkar AK; GARFIELD-AF

• Investigators. Vitamin K antagonist control in patients with atrial fibrillation in Asia compared with other regions of the world: Real-world data from the GARFIELD-AF
• registry. Int J Cardiol 2016;223:543-7. http://www.internationaljournalofcardiology.com/article/S0167-5273(16)31942-8/abstract

13. Camm AJ, Accetta G, Ambrosio G, Atar D, Bassand JP, Berge E, Cools F, Fitzmaurice DA, Goldhaber SZ, Goto S, Haas S, Kayani G, Koretsune Y, Mantovani LG, Misselwitz F, Oh S, Turpie AG, Verheugt FW, Kakkar AK; GARFIELD-AF Investigators. Evolving antithrombotic treatment patterns for patients with newly diagnosed atrial fibrillation. Heart. 2017;103(4):307-314. http://heart.bmj.com/content/early/2016/09/19/heartjnl-2016-309832.long 14. Camm AJ, Accetta G, Al Mahmeed W, Ambrosio G, Goldhaber SZ, Haas S, Jansky P, Kayani G, Misselwitz F, Oh S, Oto A, Raatikainen P, Steffel J, van Eickels M, Kakkar AK; GARFIELD-AF Investigators. Impact of gender on event rates at 1 year in patients with newly diagnosed non-valvular atrial fibrillation: contemporary perspective from the GARFIELD-AF registry. BMJ Open. 2017;7(3):e014579. http://bmjopen.bmj.com/content/7/3/e014579 15. Fox KAA, Gersh BJ, Traore S, Camm AJ, Kayani G, Krogh A, Shweta S, Kakkar AK, for the GARFIELD-AF Investigators. Evolving quality standards for large-scale registries: the GARFIELD-AF experience. Eur Heart J Qual Care Clin Outcomes. 2017;3(2):114-122. https://academic.oup.com/ehjqcco/article- abstract/3/2/114/2687709 16. Fox KAA, Accetta G, Pieper KS, Bassand JP, Camm AJ, Fitzmaurice DA, Kayani G, Kakkar AK; GARFIELD-AF Investigators. Why are outcomes different for registry patients enrolled prospectively and retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF). Eur Heart J Qual Care Clin Outcomes. 2017 Aug 16. doi: 10.1093/ehjqcco/qcx030. https://academic.oup.com/ehjqcco/article-lookup/doi/10.1093/ehjqcco/qcx030

Q3 2017 Q4 2017 J A S O N D

Q2 2017

GARFIELD-AF – ORBIT joint paper (Steinberg) GARFIELD-AF risk model (Fox, Pieper, Lucas) Audit paper (Fox) Patients receiving AP (Verheugt) Russia (Panchenko) UK (Apenteng) Predictors of outcomes (Bassand) France (Le Heuzey)

Q3 / Q4 2017

CKD (Goto) ACS (Verheugt) Elderly patients (Goldhaber) Japan (Koretsune) India (Sawhney) Latam (Sánchez)

GARFIELD-AF ─ 2017 publication plan

Eur Heart J - QCCO

(further) Analyses Co-author review Published Submission (anticipated)

BMJ Open AHJ Accepted Kardiologia EHJ – Minor comments for stats team \\ RE-submission (Plos One) BMJ Heart – Responded to reviewers 27 Sep Am J Med New analyses JACC or EHJ Arch CardioVascular Dis Circulation Journal (Official J of Jap Circul Soc) Circulation Indian Heart Journal New analyses Clin Cardiol

Q4 2017 Q1 2018 O N D J F M

Q4 2017 / Q1 2018 papers

Geographic variation events (Fox)* Early mortality (Bassand/ Goldhaber)* NOACs vs VKAs baseline predictors (Camm)* Guideline-defined trx (Camm)*

NCI-led papers

Heart failure (Corbalan/Ambrosio)* Type of AF (Atar)*

• Asymptom. AF (Gibbs/Freedman)*

Discontinuations of OACs (Cools)

Q1/ Q2 2018

BMI (Goldhaber) Hypertension (Camm)* Dementia Frail patients /at risk of falls

GARFIELD-AF ─ 2017- 2018 [Q1] publication plan

(further) Analyses Co-author review Published Submission (anticipated)

Few data Few data

*Data to be updated

2013 2014 2015 2016 2017 2018

Submitted /Published

UK (Apenteng)

X X

China (Sun)

X

Germany (Haas)

X

Poland (Stępińska)

X

Netherlands (Ten Cate)

X

Asia vs ROW (Oh)

X

Mexico / Chile /Brazil?? Russia (Panchenko)

X

In progress/planned

Latam (Corbalan)

X

France (Le Heuzey)

X

Japan (Koretsune)

X

India (Sawhney)

X

Scandinavia (DK, Fin, Nor,

Swe)

X

Italy

X

Spain

X

Canada

X

GARFIELD-AF ─ National / Regional Papers

In preparation Planned Revista Médica de Chile

No published national data

2013 2014 2015 2016 2017 2018

Argentina Australia Austria Belgium Czech Republic

Denmark

Egypt Hungry Italy Norway Singapore South Africa South Korea Switzerland Thailand Turkey Ukraine UAE USA

GARFIELD-AF ─ National / Regional Papers to be developed

National papers – current plan for 2018

Country Working group Target journal (s) Spain Viñolas X, Baron Esquivias G, Fernandez Escobar E, Almeida Fernandez C, Jimenez Gonzalez M, Alvarez Garcia P, Europace or Revista Española de Cardiología Canada Connolly S, Ayala-Paredes F, Nadeau R, Lavoie A, Dresser G, Dhillon R. Cardiol Res or Canadian J Cardiol Scandinavia Atar D, Hole T, Berge E (Norway), Nielsen JD, Schou M, Hintze U (Denmark) Rosenkvist M (Sweden), Crisby M, Thulin J Raatikainen P, Airaksinen J (Finland), Scandinavian Cardiovascular Journal or Acta Scandinavia or Stroke Tidsskr Nor Laegeforen (Norway) Ugeskrift for laeger (Denmark) Lakartidningen (Sweden) Finnish Med J (Finland) Italy Agnelli G, Santoro R, Testa S, Martini G, Poli D, Cosmi F. Giornale Italiano di Cardiologia or Haematologica

Q4 2017 2018 O N D Q1 Q2 Q3 Lorenzo Mantovani Europe – cost of care and work years

lost in 9 European countries

Asia – Global Healthcare resource use

in Asian countries

Latam – Global Healthcare resource

use in latam countries

Global burden of AF – based on 2yr

• utcomes in 5 cohorts

Asia - cost of care and work years lost

in China and Japan

GARFIELD-AF - ORBIT Stats: Prediction models (Lucas) Stats: Comparative effectiveness modelling (Pieper/Thomas) Baseline paper Outcomes papers TALENT programme At-risk under anticoagulated/ Low-risk over anticoagulated Collaboration with Prof Goto

GARFIELD-AF ─ Collaborations

(further) Analyses Co-author review Published Submission (anticipated)

To be discussed today Status to be confirmed To be discussed today To be discussed today

How to submit a publication proposal?

Who can submit a proposal

Members of the Steering Committee and National Coordinating Investigators (NCIs) National investigators enrolling patients in the registry will always do proposals in collaboration with a Steering Committee member or National Coordinator A non-investigator working in collaboration with a Steering Committee member and an investigator (e.g., expert in health economics)

Process for submitting a Proposal

UNRESTRICTED GLOBAL USE

http://www.garfield registry.org/

APPROVED

Global analyses National analyses

GARFIELD SC, NCIs and national investigators

Lead by designated first author(s)

ASF specification Data analysis Draft paper Co-author review Journal submission

PUBLICATION/ PRESENTATION

Proposal to Publication Committee for review Steering Committee review priorities for future analyses NCIs /Investigators invited as authors

Stage One: Plan research question Stage Two: Electronic submission Stage Three: Proposal review Stage Four: Analysis & Authorship GARFIELD website

Complete electronic submission form

Email acknowledgement, receipt of proposal Electronic submissions stored

garfieldproposals@ tri-london.ac.uk

Stage One – Develop research questions

Global analyses National analyses

GARFIELD SC, NCIs and National investigators

• A proposal from a national investigator may initiate

a new collaborative effort with a Steering Committee member or National Coordinator - prior awareness of GARFIELD expert coverage and potential collaborative matches would be advantageous

• Before submitting a proposal, check the list of

existing proposals on the GARFIELD website to confirm that that your new proposal is not a duplication of an existing proposal

• Consider:
• Brief rationale
• Research Questions
• Analysis and comparison groups
• Cohort(s) and study population

Stage Two – Electronic submission

• Go to the GARFIELD website to complete and ‘Submit a Proposal’
• The form comprises of the following lines
• Keywords
• Working Title
• Study Population
• Co-authors/working group
• Primary outcome
• Secondary outcome
• Brief rationale
• Research Questions
• Analysis and comparison groups
• Cohort(s) and study population
• An automatic reply will generate an acknowledgement of submission
• All proposals and their status are stored on the website

Stage Three: Proposal review and priorization

Timeline for acceptance of a proposal is usually up to two months:

• 1. The TRI team will notify authors if a proposal duplicates an existing

proposal

• 2. The Publication Committee (PC) assesses bi-monthly the

appropriateness of new proposals

• 3. Accepted proposals will be considered as part of list of potential

topics for future analyses (for congress presentations and manuscripts)

• 4. The Steering Committee reviews twice a year the priorities for

analyses over the next 12 months

• 5. NCIs and Investigators who have submitted proposals or expressed

an interest in a clinical topic will be invited to be (co)authors

Considerations

Qualification for authorship

• The Publication Committee (PC) is central in chairing the scientific direction of each

publication and verifying the project authorship

• Lead authorship of key GARFIELD publications (based on global data) will be the Steering

Committee or nominated NCIs

• Investigators are limited to first authorship on no more than two papers in progress

High-priority papers

• The Steering Committee will review the list of all ongoing manuscripts at least twice each year,

with special attention to high-priority classification. Criteria for classifying a paper as high priority include:

1. Scientific importance of potential findings 2. Potential impact of publication on the future of the GARFIELD-VTE Registry 3. Potential for high visibility in wide circulation scientific journals 4. Urgency in making findings available to scientific community and/or public

Stage Four: Analyses and Authorship

Lead by designated first author(s)

ASF specification Data analysis Draft paper Co-author review Journal submission

PUBLICATION/ PRESENTATION

• Each publication proposal is fully described in an analysis

specification form (ASF) that gives adequate statistical and technical details for an independent statistician to replicate the analysis.

• The details of the ASF are confirmed during a teleconference with the

lead authors and statistician

• Once the statistical report of results have been received, the lead

author has 3-6 months in which to write the manuscript and circulate it to the PC for review.

• Milestones (deadlines) are generated by TRI, in discussion with all

parties, for: > Data analyses > Draft paper > Co-author review and comment > Journal submission

TRI Publications Support Group

• Publications Committee will be assisted by a publications support group at the TRI, who will assist in daily

administrative tasks and, when needed

• Include roles such as the Lead Garfield-VTE Statistician and Garfield-VTE Medical Writer
• Interact with registry investigators and National Coordinators to identify, consolidate, and facilitate

publication and presentation opportunities on a national and global level

• Responsible for publication plan management

From proposal to published manuscript – working with statisticians

Steps in the analytic process

• Topic is submitted, approved, and is at the top of prioritized list
• Request form is assigned to a statistician and programmer
• Statistical team has a conference call with the P.I. to clarify hypotheses, definitions, population of

interest...

• Statistician writes a analysis plan which includes details of the above plus all proposed tables, figures

and analyses

• Analysis plan is shared with the P.I. for sign-off
• All analyses are performed, a statistical report is generated, and the P.I. should now have enough data to

write a first draft From here it is an iterative process between the P.I., editor, statistician, co-authors and steering committee to take the paper to publication

Successful collaborations with statisticians include:

Quick response time

• When a statistician is waiting for answers to questions or new requests, they will

have to move on to another project if your project goes dormant

• After too much delay, the data will be outdated and time will need to be allocated

to update to the latest data harvest

Communications:

• Communication Activities at major

congresses

• Garfield in Focus
• Garfield - AF website

Introduction to Garfield-AF website

1. 2.

Introduction to the new GARFIELD-AF website

Where? Why? What? When?

With enrolment complete and significantly more registry data and insights expected, a dedicated website will enable us to swiftly and effectively communicate updates to the community first, and keep other interested stakeholders informed The phase 1 soft launch ‘go-live’ date was in August 2016, just before ESC, and since then we have been working on phase 2 content, features and updates The website offers a range of engaging and valuable content for all audiences, including background information, findings for each tree branch, news and events, publications and presentations, a media page and community-specific content

www.garfieldregistry.org

Introduction to the new GARFIELD-AF website

Home

Navigation to content via main tabs, carousel with key highlights and featured content cards

Introduction to the new GARFIELD-AF website

About

Background information on NVAF, GARFIELD-AF and the registry leadership teams

Introduction to the new GARFIELD-AF website

Key Findings

Access to the latest GARFIELD- AF data via the drop-down menu

• r the tree branches

Introduction to the new GARFIELD-AF website

Publications & Presentations

Bibliography and information on published data by type, with links to external publication sources

Introduction to the new GARFIELD-AF website

News & Events

News reports and videos from attended events, calendar with key upcoming events

Introduction to the new GARFIELD-AF website

Media

Media releases, backgrounders, infographics and videos for use by healthcare and medical journalists

Epic activities:

Communications achievements at ESC 2017

Materials

• Curtain raiser (in 4 languages)
• Data press releases (in 4 languages)
• Backgrounder
• Infographic

Coverage

Syndications and

• riginal articles

UK/Global: 46 France: 8 Germany: 7 Italy: 13

Press release views

UK/Global: 1.2K France: 408 Germany: 153 Italy: 228

Potential audience

UK/Global: 70.1M France: 236.4K Germany: 381.8K Italy: 208K

Data press release results

Epic activities:

Communications achievements at ESC 2017

Filming

• TRI camera used onsite
• 7 interviews conducted with Steering

Committee members & NCIs

• 5 data showcases filmed
• Satellite symposium filmed by ESC

Social Media

• Carousels updated to promote ESC
• 2 press releases, 1 backgrounder and 1

infographic added to Media section

• 2 pre-ESC and 1 post-ESC articles added

to News & Events section

• Periscope video content added to Media

section

• Filmed interviews and showcases to be

uploaded once edited

Website Updates

• 60 tweets issued before, during and after

the congress

• Twitter engagement levels: 51 retweets,

61 likes

• 12 new followers
• Periscope live broadcast of the TRI

Satellite Symposium with promoted tweets

• 160 views of the Periscope

www.garfieldregistry.org @GARFIELD_reg

Thrombosis Research Institute:

GARFIELD In Focus Newsletter

Sign-up and survey

Survey available with the TRI project management team!

68

Thrombosis Research Institute:

GARFIELD-AF Operational Priorities

Shweta

Operational Priorities

• Follow-up and Follow-up Extension
• Data Collection and Query Resolution
• Site Close-Out

Operational Update

• Site Payments
• Garfield-AF website
• Garfield-AF monitoring Phase 5

Session Overview

Achievements! What's Next?

Current

• perational

priorities What have we achieved?

• Study start and

implementation in 19 countries

• Completion of

recruitment - Retrospective patients and Cohort 1

• Bringing all the 35

countries on board and initiating over 11,00 sites

• Recruitment period

down to 12 months

• Average recruitment

250 patients per week

• Over 95% data lock

for each critical milestone

• Over 95%

concordance between the source data and CRF value

• Recruitment

completion with

• ver 57,000

patients

• Follow-up and

Follow-up Extension

• Data Collection

and Query Resolution

• Site Close-out
• On-site

Monitoring

2009-2011 2011 2013 2014-2015 2016

Patient Follow-Up

EVERY 4 MONTHS 6 WEEKS

DATE OF DIAGNOSIS DATE OF ASSESSMENT 12-MONTH FOLLOW-UP 24-MONTH FOLLOW-UP 36 MONTH FOLLOW-UP 48-MONTH FOLLOW-UP 60-MONTH FOLLOW-UP

EVERY 4 MONTHS EVERY 12 MONTHS EVERY 12 MONTHS EVERY 12 MONTHS

All Cohorts

Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5

(Ongoing)

Cohort 1 Cohort 2 Cohort 3 Cohort 4

(Ongoing)

Cohort 1 Cohort 2 Cohort 3

(Ongoing)

Cohort 1 Cohort 2

(Ongoing)

49878 39251 7867 4512 2135

Follow-up extension Cohort 1

114 51 17 17 13 12 9 9 9 8 6 5 3 3 1 615 254 36 360 174 47 67 34 31 345 493 60 128 157 156 88 34 349 82 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100%

In Extension Pending Consent

19 countries Patients in Extension – 277 Pending consent/potential patients – 3510

Follow-up extension Cohort 2

171 171 163 143 86 82 79 78 70 64 64 61 56 52 47 46 43 37 25 24 18 9 9 9 8 5 4 1 273 563 528 377 388 352 206 455 299 191 289 390 508 276 319 94 116 65 192 41 167 194 401 505 55 167 154 86 127 138 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% In Extension Pending Consent

30 countries Patients in Extension – 1625 Pending consent/potential patients – 7916

Follow-up extension Cohort 3

270 226 223 194 182 172 133 110 104 93 92 77 74 70 70 67 55 48 45 42 39 29 24 24 24 20 10 10 5 4 4 663 557 158 375 345 274 281 177 346 179 305 209 189 203 245 196 201 36 147 448 74 53 122 414 20 111 381 102 58 86 33 107 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% In Extension Pending Consent

32 countries Patients in Extension – 2540 Pending consent/potential patients – 7095

Follow-up extension Cohort 4

270 192 187 178 170 149 146 122 108 97 97 85 84 69 63 61 57 55 54 54 50 26 22 21 15 11 10 9 8 6 4 3 1 81 239 171 580 243 1311 300 314 183 272 279 287 209 141 182 133 162 84 141 87 83 1 49 42 116 115 114 58 23 121 350 454 9 106 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% In Extension Pending

35 countries Patients in extension – 2484 Pending – 7040

Follow- Up Extension Status – South Africa

1 1 12 12 10 14 3 2 30 7 23 14 29 70 26 6 9 12 1 8 18 30 2 19 0% 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% In Extension Pending

20 sites Patients in extension – 36 Pending – 323

Follow-up extension discussion

Pre – Amendment Patients

• Re-consenting
• Remote re-consenting
• Re-consent at next patient visit
• Don’t re-consent - where possible

Post Amendment Patients

• Cohort 3 (Partly) and Cohort 4

Re-consent –X All Patients

• Lost contact with the patients
• Misunderstanding regarding the burden of data entry
• Misunderstanding regarding patient fee during the phase

Contact patients during there regular follow-up Information on events of special interest required only on annual basis Every milestone is paid for

Follow-up extension data collection

Data not included in follow-up extension 82 data points have been removed from the extension follow-up data (compared to minimum 2-year follow- up data):

• All other data points for selected events
• INR results
• Cardioversion
• Medical history update
• Hospitalization

Data entry: Follow-up extension period

Date of consent is same as date of re-consent for patients that have been enrolled under protocol amendment 4 – All of Cohort 4 patients, list of Cohort 3 patients that need no re-consenting will be provided 1. Patient completes the initial 24 months follow-up. 2. Click “Add” button 3. Insert Re-consent date

Data entry: Follow-up extension period

Adding patients that died after month 24 and have not been re-consented for follow-up extension:

• 1. Click on Add Follow-up
• 2. Enter the date of initial consent as date of re-consent
• 3. Add the date of death on Death page and mark other question as Unknown
• 4. Lock the record

Ongoing data management

Ongoing data cleaning and query resolution continues to ensure high standard of data for the registry

• Resolution of queries post onsite monitoring
• Collection of missing events data
• Resolution of queries raised by data management team based at TRI

Data Cleaning – Jan 2017 – March 2017

• Information on drug names and doses has been collected from over 12,000 patient records

globally.

Site Close-out

Closed sites To be closed sites

Number of sites closed in South Africa – 3 Number of sites to be Closed - 2

• ZAF3703 - Into Research
• ZAF3705 - Kelfkens, Y

Sites with no patients Sites that were interested to be closed Patient data entered and locked Site payments up to date EC and other regulatory body notified where necessary Site provide with site level data Site close-out remote visit performed followed by site close-

• ut visit letter

Garfield-AF Phase 5 On-Site Monitoring Sites in South Africa to be monitored – 4

• ZAF3711 – Clinical Projects Research SA (PTY) LTD
• ZAF3713 – Murray, AN
• ZAF3721 – Dr JM Engelbrecht Practice
• ZAF3727 - Ueckermann, V

Sites to make Investigator Site File available for review Corrective and Preventative actions are implemented Monitoring findings are notified Post monitoring visit letter is sent out

On-site visit at your site

Site notification sent

• ut 2 weeks prior to

the visit List of patients sent to the site Site to prepare medical records for the patients along with the access to electronic medical records where necessary Monitoring visit to be completed in 1-2 days depending on the number of patients to be monitoring

Post visit at your site

Site Payment Process

Site fee calculated based on the patient data entered and locked Payment calculation sent for approval Invoice generated for the approved payment calculation

Signed invoice to be sent back to the payments team, banking details and currency is required on the invoice, the sponsor name and study protocol etc must be mentioned

The invoice is then routed to the finance team to have the payment processed and paid to site. Payments are made 2 times a year – February and August.

GARFIELD-AF website Hands-on session

http://www.garfieldregistry.org/

Visit the website

GARFIELD-AF website and community portal

Before you log in you have access to:  All the information that’s available to everyone on the 5 tabs: About, Key Findings, Publications, News & Events, Media When logged in, community members have access to:  Additional information within the 5 tabs and information on tab 6: Working on the Registry

Community Portal Content (1/2)

Standard annual data cut is posted reporting on Global, Regional and Country level data Monthly newsletter plus Operational priorities is provided

• Increase utilisation of

this space in final year Upcoming IMs and presentations from the previous IMs Updates about the Garfield-AF audit strategy and Phase 1-4 audit results

Community Portal Content (2/2)

Garfield-AF registry protocol FAQs related to working

• n the registry

Protocol and database training Slide template available, can be downloaded and used for any presentations – Ask charlotte

How we plan to provide updates

Remote Monitoring Call

Agenda -

• Operational priorities

discussed

• National data presentation
• Site level issues discussion

National Teleconference Garfield-AF Website

91

Topics for discussion

• Follow-up extension
• Site Payments
• Website
• Publication proposal
• Site closure
• Feedback for TRI