2015 ERS EVENTS

DATE: SATURDAY SEPTEMBER 26TH

VENUE: Wyndham Apollo Hotel, AmsterdamROOM: BoardroomTIME: 13.00–14.30PM

CHAIR/WORKING GROUP LEAD:

Eric van Ganse: PharmacoEpidemiology Lyon (PEL)Respiratory Medicine, Croix Rousse University Hospital, Lyon, FranceUMR CNRS 5558, Claude-Bernard University, Lyon, France

ADHERENCE WORKINGGROUP MEETING

Agenda

Alexandra Dima, Faculty of Social and Behavioural Sciences, University of Amsterdam, Amsterdam, The Netherlands

Bidirectional Adherence Study Update

The study

• Title: Exploring the bidirectional relationship between database markers of asthma treatment adherence and asthma-related outcomes

• Research team:

REG collaborators RiRL [data extraction]

Gene Colice (Lead Investigator)David PriceAlexandra DimaHilary PinnockIain SmallCynthia RandMichelle EakinJanet HolbrookMiguel Román RodríguezEric van GanseRandy BrownAlison Chisholm

Julie von Ziegenweidt

Utrecht University [Phase I]

Ellen KosterPatrick Souverein

NIVEL [Phase II]

Marcia Vervloet

Study design• Dataset: Optimum Patient Care Research Database

(OPCRD)

Inclusion / Exclusion criteria

• Inclusion Criteria:• 3 years of continuous records (1 prior & 2 after IPD)• Physician-diagnosed asthma ≥ 1 year prior to IPD• Aged ≥6 years at IPD (i.e. ≥5 years at time of diagnosis)• First ICS prescription at IPD via MDI or DPI• On active asthma therapy (≥ 2 prescriptions for ICS and/or

SABA at different points during each outcome year)

• Exclusion Criteria:• Any prescriptions for LABA, combination ICS/LABA

therapy, and/or LTRA during the baseline year• Received maintenance oral steroids during

baseline year

Measures

• ICS adherence

• Asthma outcomes:• Moderate-to-severe exacerbations• Risk domain asthma control• Overall asthma control• Treatment stability• Prescription-derived mean daily SABA dosage• Prescription-derived controller to total asthma meds ratio

• Covariates:• At IPD: age, gender, BMI, smoking status, device type, ICS

dosage, ICS drug, asthma duration, comorbidities, etc.• Prior to baseline: any ICS prescription

Analyses

• Phase I: Feasibility evaluation

Analyses

• Phase II: Longitudinal evaluationo Cross-lagged panel modelso Hierarchical longitudinal models

ICS adherence

• The new consensus-based taxonomy

Vrijens et al. 2012DOI: 10.1111/j.1365-2125.2012.04167.x

ICS adherence

CMA I & II  CMA I method CMA II methodCharacteristic No. of

patients

No. of episode

s

Adherence% (mean, SD)

Adherence

≥ 80%

No. of patient

s

No. of episodes

Adherence% (mean, SD)

Adherence

≥ 80%Full 2-year follow-up period 90 day gap * 13 922 24 924 88.9 (12.9) 78.8%  Sensitivity analysis for permissible gap:   30 day gap 13 922 38 339 97.3 ( 4.5) 99.0%  182 day gap 13 922 18 603 79.7 (19.4) 55.3%  Follow-up period by time interval, using 90 day gap: 0-12 months 13 922 18 337 89.0 (14.8) 76.1%12-24 months 12 419 14 309 89.1 (15.6) 75.6% 12 419 14 218 87.2 (16.7) 71.4%  0-6 months 13 922 14 623 90.2 (15.5) 77.9%6-12 months 10 828 10 942 92.1 (15.0) 82.7% 10 828 10 938 87.3 (18.4) 72.0%12-18 months 10 635 10 752 92.4 (14.5) 83.5% 10 635 10 744 87.2 (18.2) 71.5%18-24 months 11 267 11 759 90.3 (15.7) 78.4% 10 444 10 552 87.5 (18.4) 72.7%  0-8 months 13 922 15 732 89.6 (15.5) 76.7%8-16 months 11 479 12 041 89.9 (15.8) 77.5% 11 479 12 000 87.0 (17.5) 70.8%16-24 months 11 267 11 759 90.3 (15.7) 78.4% 11 267 11 723 87.4 (17.9) 72.2%

CMA I & II  CMA I method CMA II methodCharacteristic No. of

patients

No. of episode

s

Adherence% (mean, SD)

Adherence

≥ 80%

No. of patient

s

No. of episodes

Adherence% (mean, SD)

Adherence

≥ 80%Full 2-year follow-up period 90 day gap * 13 922 24 924 88.9 (12.9) 78.8%  Sensitivity analysis for permissible gap:   30 day gap 13 922 38 339 97.3 ( 4.5) 99.0%  182 day gap 13 922 18 603 79.7 (19.4) 55.3%  Follow-up period by time interval, using 90 day gap: 0-12 months 13 922 18 337 89.0 (14.8) 76.1%12-24 months 12 419 14 309 89.1 (15.6) 75.6% 12 419 14 218 87.2 (16.7) 71.4%  0-6 months 13 922 14 623 90.2 (15.5) 77.9%6-12 months 10 828 10 942 92.1 (15.0) 82.7% 10 828 10 938 87.3 (18.4) 72.0%12-18 months 10 635 10 752 92.4 (14.5) 83.5% 10 635 10 744 87.2 (18.2) 71.5%18-24 months 11 267 11 759 90.3 (15.7) 78.4% 10 444 10 552 87.5 (18.4) 72.7%  0-8 months 13 922 15 732 89.6 (15.5) 76.7%8-16 months 11 479 12 041 89.9 (15.8) 77.5% 11 479 12 000 87.0 (17.5) 70.8%16-24 months 11 267 11 759 90.3 (15.7) 78.4% 11 267 11 723 87.4 (17.9) 72.2%

Compare to 2y

r CMA4: 60%

Variation in adherence – 2yrs, 90-day gap

Variation in adherence – 6-mo intervals

Asthma control

• Moderate-to-severe exacerbationso Asthma-related hospitalizations / ED attendance

– Asthma A&E or hospits– COPD/respiratory-related/generic hospits +

Lower_respiratory_consultation (excl: lung function test)

Lower Respiratory read codes (incl. asthma, COPD, LRTI) Asthma/COPD review codes (excl: monitoring letter codes) Lung function, asthma monitoring

o OCS prescriptions

! If within 1 week – 1 event

Asthma control• Risk domain asthma control

o No moderate-to-severe exacerbationso No AB + evidence of respiratory review (± 7days)

– Lower_respiratory_consultation– Any additional respiratory examinations, referrals,

chest x-rays or eventso Asthma-related outpatient attendance

• Overall asthma controlo + SABA dose ≤200mcg salbutamol / ≤500mcg terbutaline

• Treatment stabilityo + no add-on therapy / 50% dose increase

Asthma control

• Individual elements Number of patients per 1 yr (N=13922)

Baseline yr FU yr 1 FU yr 2 All FU

Asthma hospit 46 (0.4%) 101 (0.7%) 85 (0.6%) 164 (1.2%)

COPD hospit 5 (<0.1%) 12 (<0.1%) 10 (<0.1%) 22(0.16%)

Resp hospit 39 (0.3%) 106 (0.8%) 91 (0.7%) 175(1.26%)

≥ 1 OCS Rx event 1207 (8.7%) 2392 (17.2%) 1969 (14.1%) 3473(25%)

≥ 1 rAB Rx event 1272 (9.1%) 1913 (13.7%) 1699 (12.2%) 2982(21.4%)

Any of the above 5229(37.6%)

Max per person per year – 10 OCS & 7 rAB eventsMax per person per 2yrs – 19 OCS & 11 rAB events

Next steps for AC markers

• Read codes & computation procedure for each marker – to clarify details?

• Are hospitalizations less recorded in OPCRD?

• To merge different types of events OR consider outcomes individually (e.g. OCs)?

Next steps

• Phase I – finish report & paper (end October)o + ICPE & ERS posters; ESPACOMP oral presentation

• Phase II – 6 months planned after end of Phase I

Alexandra Dima, Faculty of Social and Behavioural Sciences, University of Amsterdam, Amsterdam, The Netherlands

ASTRO-LAB Model of Asthma Adherence Determinants

https://prezi.com/md6w9_noynia/asthma-model-of-care-11-june-2015/

Alison Chisholm, REG

Barcelona Adherence Expert Panel Meeting May 2015: update

Meeting Rational: develop a roadmap for Respiratory Adherence Research*

Rationale:• To promote consistency and

comparability of results across studies and improve the efficiency and value of adherence research findings, there is a need to consider the:o Current priorities in adherence

researcho Methods used to measure

adherenceo Taxonomy employed in

conceptualizing adherence behaviours and determinants.

*International Expert Panel Meeting organised by the Respiratory Effectiveness Group with the support of Teva Pharmaceutical Industries Ltd

The Challenge: • There is no single determinant of non-adherence to

respiratory therapies • There is no ‘one-size-fits-all’ intervention to improve

adherence in the eyes of healthcare professionals and payors.

• Interventions need to be tailored to the individual needs of each patient.

Barcelona Meeting Panel MembersChair: David Price: REG Chairman, Academic Centre of Primary Care, University of Aberdeen, UK

Panel Members:• Aji Barot: Patient Connect Service Limited,

Surrey, UK• Richard Costello: Royal College of

Surgeons, Ireland and Beaumont Hospital, Dublin, Ireland

• Alex Dima: Amsterdam School of Communication Research ASCoR, University of Amsterdam, Amsterdam, The Netherlands

• Michelle Eakin: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland

• Juliet Foster: Clinical Management Group, Woolcock Institute of Medical Research, University of Sydney, Sydney, Australia

• Jonathan Grigg: Asthma UK Centre for Applied Research, Centre for Paediatrics, Blizard Institute, Queen Mary, University of

London, London, UK• Job van Boven: Department of Pharmacy,

Unit of Pharmaco-Epidemiology & PharmacoEconomics University of Groningen, Groningen, The Netherlands

• Thys van der Molen: Primary Care Respiratory Medicine, University of Groningen, Groningen, The Netherlands

• Dermot Ryan: Clinical Strategic Advisor at Optimum Patient Care; EAACI Primary Care Lead and Research Fellow at University of Edinburgh, UK

• Bernard Vrijens: Department of Biostatistics and Medical Informatics, University of Liège,Liège, Belgium

Agenda: presentationsSession I: “Adherence – What Is It?”Taxonomy – how do we currently describe adherence in chronic diseases Bernard Vrijens

Understanding adherence within the process of asthma care: the Astrolab model Alexandra Dima

Implications of delivery (mode of delivery) on adherence Thys van der Molen

Adherence challenges in children and the effect on outcomes Jonathan Grigg

Adherence challenges in older populations and the effect on outcomes Richard Costello

Inherent adherence challenges within health system Michelle Eakin

Implications of adherence on health economic outcomes Job van Boven

Session II: “Adherence – How Do We Measure It?”Measurement of adherence within respiratory RCTs and observational studies Bernard Vrijens

Patient-reported adherence: how to optimize data quality Alexandra Dima

Technology-based approaches to adherence monitoring Michelle Eakin &Richard Costello

Session III: “Adherence – How Can We Improve It?” Role of the clinician in optimizing adherence Dermot Ryan

Role of the pharmacist in optimizing adherence Aji Barot

Interventions with proven effect and potential for scaling up to real-life clinical settings Juliet Foster

System & Payer-driven solutions Michelle Eakin

Meeting OutputAdherence-themed Special Issue of JACI: In Practice • Editorial • 5 papers

1. Terminology / Taxonomy2. Determinants of Adherence – the

ASTRO-LAB ModelFocus on patient determinants3. Delivery route & implementation4. Age & cognitionFocus on HCP- and Payer determinants5. The role of the health system, cost-

effectiveness & scalability & health care professionals

Publication dates: • Online early Q1 2016

• Special Issue September 2016

Special Issue Overview (I)Paper Working Title Co-authors Status & approx.

submission date

Editorial Introduction to main themes of the special issue David Price & ?

• Alison Chisholm to draft• Additional authors TBC• Draft to be informed by content of Papers 1-5

Paper 1 What we mean when we talk about adherence in respiratory medicine

Bernard Vrijens; David Price; Alex Dima; Michell Eakin; Juliet Foster; Job van Boven; Marjin de Bruin; Eric van Ganse

• Alison Chisholm to draft; • Vrijens et al• Full author order TBA.• Submission mid November

Paper 2Moving towards a complete map of medication adherence determinants within asthma – the ASTRO-LAB Model

Alex Dima; Marjin de Bruin; Eric van Ganse + ASTRO-LAB colleagues

• Alexandra Dima to draft• Draft underway. • ASTRO-LAB to agree author order• Submission mid November

Paper 3Patient-level adherence determinants – Wanting, but unable – the role of inhaler technique and mode of delivery

David Price; Thys van der Molen;Victoria Carter & iHARP Collaborators

• Alison Chisholm to draft• Victoria Carter liaising with iHARP collaborators • Full iHARP author list TBC.• Submission mid November

Paper 4Patient-level adherence determinants – 7 stages of man – the role of age and cognition on medication adherence

Richard Costello; Michell Eakin; Jonathan Grigg; Juliet Foster; Dermot Ryan

• Richard Costello to draft• Costello et al?• Full author order TBA.• Submission mid November

Paper 5Freedom within a framework – the role of the healthcare system on medication adherence

Job van Boven; Juliet Foster; Michell Eakin; Aji Barot; Dermot Ryan

• Job van Boven to draft• van Boven et al?• Full author order TBA.• Submission mid November

Special Issue Overview (I)Paper Working Title Co-authors Status & approx.

submission date

Editorial Introduction to main themes of the special issue David Price & ?

• Alison Chisholm to draft• Additional authors TBC• Draft to be informed by content of Papers 1-5

Paper 1 What we mean when we talk about adherence in respiratory medicine

Bernard Vrijens; David Price; Alex Dima; Michell Eakin; Juliet Foster; Job van Boven; Marjin de Bruin; Eric van Ganse

• Alison Chisholm to draft; • Vrijens et al• Full author order TBA.• Submission mid November

Paper 2Moving towards a complete map of medication adherence determinants within asthma – the ASTRO-LAB Model

Alex Dima; Marjin de Bruin; Eric van Ganse + ASTRO-LAB colleagues

• Alexandra Dima to draft• Draft underway. • ASTRO-LAB to agree author order• Submission mid November

Paper 3Patient-level adherence determinants – Wanting, but unable – the role of inhaler technique and mode of delivery

David Price; Thys van der Molen;Victoria Carter & iHARP Collaborators

• Alison Chisholm to draft• Victoria Carter liaising with iHARP collaborators • Full iHARP author list TBC.• Submission mid November

Paper 4Patient-level adherence determinants – 7 stages of man – the role of age and cognition on medication adherence

Richard Costello; Michell Eakin; Jonathan Grigg; Juliet Foster; Dermot Ryan

• Richard Costello to draft• Costello et al?• Full author order TBA.• Submission mid November

Paper 5Freedom within a framework – the role of the healthcare system on medication adherence

Job van Boven; Juliet Foster; Michell Eakin; Aji Barot; Dermot Ryan

• Job van Boven to draft• van Boven et al?• Full author order TBA.• Submission mid November

Selected by the Journal Editors as CME papers within the Issue. Requirements:• Authors write a short (5 question) multiple-choice exam to accompany

their article• Complete a AAAAI Information Document for each CME activity

Manon Belhassen & Eric Van Ganse, PharmacoEpidemiology Lyon (PEL)Respiratory Medicine, Croix Rousse University Hospital, Lyon, FranceUMR CNRS 5558, Claude-Bernard University, Lyon, France

“Lyon Adherence Projects”

ADHERENCE IN ASTHMA : OVER 20 YEARS, FROM FIELD STUDIES TO COMPUTERIZED DATA

Eur J Clin Pharmacol, 1997

Eur J Clin Pharmacol, 1997

TODAY, THANKS TO NATIONAL CLAIMS DATA:

CMA, PERSISTENCE & TYPOLOGIES

A. Measurement of adherence proxies to anti-asthma inhaled steroids in French Claims Data

o Primary objective : The main objective was to provide, in patients treated by given ICs packagings, reference values for the proportion of days covered during a 12-month period for the corresponding ICs packagings

o Secondary objective: The secondary objective was to provide in newly-treated patients reference values for 12-month persistence to ICs molecules

o Study design: – An initial historical cohort of ICS-treated asthma patients– Specific cohorts were then specifically identified from this initial cohort

for each studied dimensions of adherence (CMA, persistence)

o Data source: EGB (French claims data)

A. Measurement of adherence proxies to anti-asthma inhaled steroids in French Claims Data

o Inclusion criteria: “new treatment episodes”o ≥ 3 canisters of the same molecule of ICs consecutively

dispensed between 2007 and 2013 according to the following rules:– Dispensed at 2 or 3 different dates – The time-interval between the first and the third dispensed

canisters will not exceed 120 days (for this computation a canister was assumed to last 60 days)

– Age 6-40 years at the date of the first dispensed ICs canister (older patients were excluded)

A. Measurement of adherence proxies to anti-asthma inhaled steroids in French Claims Data

o CMA

Children

Teenagers

Children &

Teenagers

Women Men Adults Total

N 1,606 538 2,144 1,667 1,285 2,952 5,096

Mean CMA in % (σ)

58.3 (28.5)

56.1 (28.7) 57.7 (28.6)51.4

(28.4)52.7 (28.5)

52.0 (28.4)

54.4 (28.6)

24% of patients had a CMA ≥ 80%

Mean CMA=54.4%

A. Measurement of adherence proxies to anti-asthma inhaled steroids in French Claims Data

o 12 months non-persistence

Drug classes Children Teenagers

Children &

TeenagersWomen Men Adults TOTAL

               

Any ICs molecule 314/404 (77.7%)

95/115 (82.6%)

409/519 (78.8%)

379/462 (82.0%)

237/302 (78.5%)

616/764 (80.6%)

1,025/1283(79.9%)

B. TYPOLOGIES OF TREATMENT BEFORE HOSPITALIZATION

• Subjects: o >=3 dispensations of asthma-related medications

during any 12-month window from 2006 to 2013 o Aged between 6 years and 45 years

o Within this cohort, we selected patients who experienced asthma-related hospitalization defined as a hospital discharge with asthma (J45 and J46 ICD-10 codes)

B. TYPOLOGIES OF TREATMENT BEFORE HOSPITALIZATION

• Typologies:o Based on recorded drug dispensations, subjects were

categorized on exposure to ICS alone, LABA alone or FDC of LABA+ICS, in the 12 months before asthma-related hospitalization

o Cluster and discriminant analyses. Ward’s minimum-variance hierarchical clustering method was performed using an agglomerative (bottomup) approach and Ward’s linkage

o At each generation of clusters, samples were merged into larger clusters to minimize the within-cluster sum of squares or to maximize the between-cluster sum of squares.

B. TYPOLOGIES OF TREATMENT BEFORE HOSPITALIZATION

B. TYPOLOGIES OF TREATMENT BEFORE HOSPITALIZATION

• 20,633 asthma patients : 301(0,45%) with hospitalization for asthma

• 3 typologies:o Cluster 1 : 176 patients (58,5%):

– Few treatments!o Cluster 2 : 108 patients (35,9%) :

– Regular FDC therapyo Cluster 3: 17 patients (5,7%) :

– Free Combinations IC + LABA (unbalanced)

CONCLUSIONS

• Hospitalization is “the” outcome of interest, if power allows it

• Interest to “view” (Dutch method, ie graphs) patterns of use of therapy

• Clustering?• Determinants?... Answer = PROs + linkage with

computerized datasets• Interventions? … close/quick/effective

interaction with asthma patients is needed…

Future Projects & Activities

What next for the Group…?

Adherence-related questions in respiratory research• Dose management – real-time data transfer (IT),

and effective self-care (patient empowerment)• Health care professionals – their role in adherence

in respiratory care (and alternatives?)• Continuity of regular ICS use – changing beliefs of

patients and practitioners (paradigm shift)• Technology in adherence – how can we optimize

data use for research and clinical purposes

Other ideas…