REG COPD Control Working Group Meeting

Sunday May 17th, 4.00-6.00pm (MST)Altitude Room; Crowne Plaza, Denver, Colorado

REG COPD Control Working Group Meeting

COPD Control Members

Lead: Marc Miravitlles

Members• Dermot Ryan• Richard Costello• Nicolas Roche• Alberto Papi• Juan José Soler• Bernardino Alcazar• David Price

Participating collaborators• Luca Richeldi• Helgo Magnussen• Akio Niimi• Mona Bafadhel• Faisal Yunus

Meeting Objective

• Present the planned initiative to: test Control as a valid concept in COPD

• Plan the implementation of the planned COPD Control research activities:o Non-interventional, retrospective database study piloto Prospective studies:

o Spanish pilots (2) o International multicentre

• Identify REG collaborators interested in joining the research projects

• Identify new opportunities for research in the field of control in COPD

AgendaTime Item

Concept of Control in COPD

4.00-4.15pm The development and rationale of the concept of control

Group planning discussions 

4.15–5.45pm

Database Pilot: Non-interventional / observational database study using the Optimum Patient Care Research Database (OPCRD) as a lead-in to the prospective trials

Pilot studies of control in Spain: • Variation in control versus variation in severity of COPD. • Relationship between E-RS symptoms diary and control

Validation of control: • Multicenter, international and prospective study aimed to validate the concept

of control in COPD and its implications for clinical practice.• Identify centers and strategies to implement and conduct the study• Study organization / delivery and timeline / schedule

Additional items

5.45–6.00pm

Identify new areas of research and possible new protocols

Proposals for dissemination of the concept of control (meetings, congresses)

Other initiatives

5

6

Lowclinical impact

Clinical control

Stability

Impact

Highclinical impact

Cross-sectional evaluationof impact

Stability(Improvement or

absence of changes)

Inestability(Clinical worsening)

V1 V2 V3 V4

7

Clinical assessment

- Dispnea (mMRC)- Rescue medication

- Daily physical activity (time walking per day)

- Sputum color

Clinical control questionnaires

- CAT

- CCQ

0 - 1

≥ 60 min

Low impact

≤ 3 times / week

Absent or white

≤ 1

≥ 2

< 60 min

≥ 3 times / week

Dark

≤ 10 >10

> 1

High impact

Mild – moderate severity(BODE/BODEx ≤ 4 units)

8

Current clinical situation:

Clinical changes:(last 3 months)

- CAT

- CCQ

Low

Control

< 0.4

High

< 4 ≥ 4

≥ 0.4

No control

CONTROL

(any of the following) (any of the following)

or

- Exacerbationss No Yes

- Clinical changes (according to the patient)

Same or better Worse

Concepts

1.Control is not a prediction tool

2.Concept of control can potentially be used

to motivate and educate patients

3. It may help to step up or down treatment

and establish the frequency of clinical visits

AgendaTime Item

Concept of Control in COPD

4.00-4.15 The development and rationale of the concept of control

Group planning discussions 

4.15–5.45

Database Pilot: Non-interventional / observational database study using the Optimum Patient Care Research Database (OPCRD) as a lead-in to the prospective trials

Pilot studies of control in Spain: • Variation in control versus variation in severity of COPD. • Relationship between E-RS symptoms diary and control

Validation of control: • Multicenter, international and prospective study aimed to validate the concept of

control in COPD and its implications for clinical practice.• Identify centers and strategies to implement and conduct the study• Study organization / delivery and timeline / schedule

Additional items

5.45–6.00

Identify new areas of research and possible new protocols

Proposals for dissemination of the concept of control (meetings, congresses)

Other initiatives

Cross-sectional, non-interventional database study using the Optimum Patient Care Research Database (OPCRD) as a lead-in to the prospective trials

UK Database pilot

OPCRD UK Pilot: low impact • Clinical impact refers to the current repercussion the

disease has on the patient. • Observation suggests that the clinical impact may be

different for the same level of prognostic severity, thereby indicating that other factors (not identified) may contribute to the current clinical situation of the patient.

• An initial pilot study to be conducted in patients in the Optimum Patient Care Research Database (OPCRD) to examine what proportion of participants meet the definition of low impact.

Distribution of patients

Low impact High impact

Stable

Unstable

Definition: Impact

  Mild to moderate severity

(BODE/Ex ≤ 4 points)Severe/very severe COPD

(BODE/Ex > 5 points)

  Low impact High impact Low impact High impact

Clinical Evaluation

Dyspnea (mMRC) 0 – 1 ≥ 2 0 - 2 ≥ 3

Rescue medication≤ 3 times in the

last week> 3 times in the

last week≤ 2 times a day > 2 times a day

Daily physical activity*(time walked per day)

≥ 60 min < 60 min ≥ 30 min < 30 min

Sputum color Absent or White Dark Absent or white Dark

Questionnaires of clinical control:

- CAT ≤ 10 >10 ≤ 20 >20

- CCQ ≤ 1 >1 ≤ 2 >2

*Time walked per day: includes the total time the patient has walked whether at home or outside; CAT: COPD Assessment Test; CCQ: Clinical COPD Questionnaire.

Study Design & timelines

Design• Data source:

o Optimum Patient Care Research Database• Cross-sectional study • Study Period & duration?• Population?• Outcomes

o Impacto Stratified by…?

Timelines and duration:• Lead in to pilot study: Q2 to Q3 2015 • Report available by Q3 (September) 2015

14

Changes in control vs changes in severity

Observational, 6-month follow-up

Pilot study of control in Spain (1)

Objectives & timeline

• Objectiveso Compare variability in control with variability in

severity (FEV1 and BODE/BODEx).

• Timelines and duration:o Recruitment: 2 months. FU= 6 monthso Sample size: 380 patientso Pilot Study: Q1 to Q3 2015 o Pilot study report date:

– Available by Q3 (September) 2015.

Comparison of control and symptoms

Observational, 6-month follow-up

Pilot study of control in Spain (2)

Objectives & timeline

• Objectiveso Compare the changes in control with the

prevalence and changes in respiratory symptoms (E-RS).

• Timelines and duration:o Recruitment: 2 months. FU= 6 monthso Sample size: 150 patientso Pilot Study: Q1 to Q3 2015 o Pilot study report date:

– Available by Q3 (September) 2015.

Multicenter, international and prospective study to validate the concept of control in COPD and its implications for clinical practice

Validation of control:

Objectives

A multicenter, observational longitudinal study with the following objectives.• Primary objective:

o Identify the degree of control in an international cohort of unselected COPD patients.

o Compare the outcomes of controlled versus uncontrolled patients during two years follow-up.

• Secondary objectives:o Compare the clinical variables with CAT and CCQ as tool

to identify impact and stability in COPDo Identify differences in the degree of control according to

adequacy of treatment as suggested by current guidelines.

o Identify demographic and clinical characteristics associated with poor control of COPD.

Study design

Methodology: • Exploratory study to determine the measure of 'control' of

COPD through a combined measurement of 'impact' (cross-sectional) and 'stability' (longitudinal).

Participants:• ≥285 COPD patients from ≥5 participating centers

throughout Europe.

Ecology of care:• Throughout the trial, patients will be managed according to

the criteria of the investigators. • Patients will be visited every 6 months for a total of 5 visits

in which the level of control will be recorded. • The initial frequency of control will be analyzed and the

changes in control during the follow-up will be recorded.

EvaluationsVisit number 0 1 5Time of Visit At Baseline At each visit Discontinuation

Inclusion/Exclusion criteria x    

Information & Informed consent x    

Clinical assessement x x xAssesment of excarberations since last visit x x x

Assessement of clinical status since last visitCAT/CCQ

x x

xx

xx

Adverse events   x x

Patients will be visited every 6 months for a total of 5 visits in which the level of control will be recorded. The initial frequency of control will be analyzed and the changes in control during the follow-up will be recorded.

Control

• The degree of control of the patient will be:o Related to the underlying biological activity of the

disease (controlled patients should have less biological activity);

o Associated with different clinically relevant outcomes (greater control, better outcomes); and,

o Modified by the treatment in that the therapeutic objective involves seeking control for each level of basal severity.

o Considered complementary to:– Their clinical phenotype and – the level of prognostic severity of the disease.

• Control evaluations will be performed every time the patients visit their physician outside the periods of exacerbation and will obligatorily include assessment of impact and stability.

Endpoints

• Primary endpoint: to evaluate control based on: o Impacto Stability

• Secondary endpoints: o Comparison of CAT and CCQ as tools to identify

impact and stability in COPD o Differences in the degree of control according to

adequacy of treatment o Demographic and clinical characteristics associated

with poor control of COPD

Participating Centres…

Study Organisation & Delivery

Timeline for implementation

Recruitment / data collection:• Start: Q3 2015• End: Q3 2017

Reporting:• Non-Interventional Study Report date (interim/ final

report as applicable): o Cross-sectional Impact measurements available by

Q1 2016. o The final report including longitudinal study and

control measurements will be available Q3 2017.•  

AgendaTime Item

Concept of Control in COPD

4.00-4.15 The development and rationale of the concept of control

Group planning discussions 

4.15–5.45

Database Pilot: Non-interventional / observational database study using the Optimum Patient Care Research Database (OPCRD) as a lead-in to the prospective trials

Pilot study of control in Spain: • Variation in control versus variation in severity of COPD. • Rationale, objectives and working plan.

Validation of control: • Multicenter, international and prospective study aimed to validate the concept of

control in COPD and its implications for clinical practice.• Identify centers and strategies to implement and conduct the study

Study organization / delivery and timeline / schedule

Additional items

5.45–6.00

Identify new areas of research and possible new protocols

Proposals for dissemination of the concept of control (meetings, congresses)

Other initiatives

New Ideas

1.Include the EQ-5D in the local pilot studies

2.Explore the use of RCT databases to evaluate control and test for outcomes related to control

Proposals for dissemination

1.Meetings

2.Congresses

3.Publications

4.Other…?

Other Initiatives

…?

Backup / Reference

Core Research Definitions

Definition: control   Control No Control

Current clinical situation:    

- Impact(adjusted according to severity)

Low High

  And all of the following Or any of the following

Clinical changes in the last 3 months:

Deterioration in the CAT <2 ≥2

Deterioration in the CCQ <0.4 ≥0.4

- Exacerbations in the last 3 months No Yes

Patients fulfilling the control criteria may be classified as controlled; all others should be classified as not controlled or badly controlled.

Definition: Impact

  Mild to moderate severity

(BODE/Ex ≤ 4 points)Severe/very severe COPD

(BODE/Ex > 5 points)

  Low impact High impact Low impact High impact

Clinical Evaluation

Dyspnea (mMRC) 0 – 1 ≥ 2 0 - 2 ≥ 3

Rescue medication≤ 3 times in the

last week> 3 times in the

last week≤ 2 times a day > 2 times a day

Daily physical activity*(time walked per day)

≥ 60 min < 60 min ≥ 30 min < 30 min

Sputum color Absent or White Dark Absent or white Dark

Questionnaires of clinical control:

- CAT ≤ 10 >10 ≤ 20 >20

- CCQ ≤ 1 >1 ≤ 2 >2

*Time walked per day: includes the total time the patient has walked whether at home or outside; CAT: COPD Assessment Test; CCQ: Clinical COPD Questionnaire.

Definition: stability

• To establish the stability of a patient with COPD the following two criteria must be fulfilled: 1. Absence of exacerbation, including the inherent phase

of recovery from the exacerbation. 2. Absence of significant clinical worsening during a

period of time, that is, that stability includes the absence of significant clinical changes and/or the presence of improvement (positive changes).

• The questionnaires of clinical control such as CAT or CCQ may also be potentially useful to evaluate clinical changes over time. In the case of the CAT it has been described that a change of greater than 2 points may indicate clinically significant deterioration, with the same occurring with a change greater than 0.4 points for the CCQ.