1. The REG COPD Control Working Group met on May 17th in Denver, Colorado to discuss plans to validate the concept of control in COPD through several research studies. 2. These included a non-interventional database study using the UK OPCRD, two Spanish pilot studies on changes in control versus severity and symptoms, and an international prospective study to validate the concept of control. 3. The group discussed objectives, timelines, and plans for implementation of these validation studies, as well as identifying new areas of research and disseminating results. The goal was to establish control as a valid concept that could help guide treatment decisions and motivate patients.

1. Sunday May 17th, 4.00-6.00pm (MST)
Altitude Room; Crowne Plaza, Denver, Colorado
REG COPD Control Working Group Meeting

2. 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

3. 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 pilot
o 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

4. Agenda
Time 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. 5

6. 6
Low
clinical impact
Clinical control
Stability
Impact
High
clinical impact
Cross-sectional evaluation
of impact
Stability
(Improvement or
absence of changes)
Inestability
(Clinical worsening)
V1 V2 V3 V4

7. 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. 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

9. 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

10. Agenda
Time 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

11. 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

12. 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

13. 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.

14. Study Design & timelines
Design
• Data source:
o Optimum Patient Care Research Database
• Cross-sectional study
• Study Period & duration?
• Population?
• Outcomes
o Impact
o Stratified by…?
Timelines and duration:
• Lead in to pilot study: Q2 to Q3 2015
• Report available by Q3 (September) 2015
14

15. Changes in control vs changes in severity
Observational, 6-month follow-up
Pilot study of control in Spain (1)

16. Objectives & timeline
• Objectives
o Compare variability in control with variability in
severity (FEV1 and BODE/BODEx).
• Timelines and duration:
o Recruitment: 2 months. FU= 6 months
o Sample size: 380 patients
o Pilot Study: Q1 to Q3 2015
o Pilot study report date:
– Available by Q3 (September) 2015.

17. Comparison of control and symptoms
Observational, 6-month follow-up
Pilot study of control in Spain (2)

18. Objectives & timeline
• Objectives
o Compare the changes in control with the prevalence
and changes in respiratory symptoms (E-RS).
• Timelines and duration:
o Recruitment: 2 months. FU= 6 months
o Sample size: 150 patients
o Pilot Study: Q1 to Q3 2015
o Pilot study report date:
– Available by Q3 (September) 2015.

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

20. 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 COPD
o 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.

21. 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.

22. Evaluations
Visit number 0 1 5
Time of Visit At Baseline At each visit Discontinuation
Inclusion/Exclusion criteria x
Information & Informed
consent
x
Clinical assessement x x x
Assesment of excarberations
since last visit
x x x
Assessement of clinical
status since last visit
CAT/CCQ
x
x
x
x
x
x
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.

23. 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.

24. Endpoints
• Primary endpoint: to evaluate control based on:
o Impact
o 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

25. Participating Centres…

26. Study Organisation & Delivery

27. 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.
•

28. Agenda
Time 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

29. 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

30. Proposals for dissemination
1.Meetings
2.Congresses
3.Publications
4.Other…?

31. Other Initiatives
…?

32. Backup / Reference
Core Research Definitions

33. 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.

34. 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.

35. 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.