REG ACOS Working Group Meeting 25/09/15

DATE: FRIDAY SEPTEMBER 25TH
VENUE: Wyndham Apollo Hotel, Amsterdam
ROOM: Boardroom
TIME: 9:00-10.30AM
CHAIR: Jerry A. Krishnan, Professor of Medicine and Public
Health & Associate Vice President for Population Health
Sciences, University of Illinois Hospital & Health Sciences
System, Chicago, Illinois, USA
ACOS WORKING GROUP
MEETING

Agenda (revised)
• Welcome / introductions (Jerry)
• Proof of concept study design (Jerry)
• Available datasets (Alison)
• OPCRD Pilot Data as use case (Alison /
Victoria)
• Next steps / alignment between WG
Members and Supporting Collaborators
(David)

FINALISATION & SIGN-OFF OF THE REG ACOS
WORKING GROUP STUDY PROTOCOL
Stage 1: Proof of Concept (POC) study

Background / rationale
• 2014, GINA and GOLD published their first joint statement on
Asthma-COPD Overlap Syndrome (ACOS)1
• Various criteria for diagnosis of ACOS have been proposed2-4
• The lack of a gold standard definition is a barrier to ACOS research,
i.e. to understanding the biology of the condition and to exploring
optimum management approaches.5
1. GINA-GOLD Diagnosis of disease of chronic airflow limitation: Asthma, COPD and asthma-COPD overlap syndrome (ACOS), 2014
2. Miravitlles M, et al. Arch Bronconeumol 2014
3. Koblizek V, et al. Pap Med Fac Univ Palacky Olomouc Czech Repub 2013
4. Kankaanranta H, et al. Basic Clin Pharmacol Toxicol. 2015
5. Postma DS, Rabe KF. NEJM 2015

Ambiguity is a barrier to progress
Postma D, Rabe K. NEJM 2015

January 2012 to December 2012
ATS Multiple Chronic Conditions Workshop, 2014
Medicare administrative
claims, United States, 2012

(mostly due todisability claim) % %
Asthmaprevalence 7.4 Asthmaprevalence 4.3
Top 10co-morbidities Top 10co-morbidities
Hypertension 64.5 Hypertension 80.6
Depression 50.9 Hyperlipidemia 64.0
Hyperlipidemia 47.0 Arthritis (RA/OA) 50.2
Arthritis (RA/OA) 42.8 IschemicHeartDisease 47.3
Diabetes 40.7 COPD 42.1
COPD 34.9 Anemia 41.5
Anemia 34.9 Diabetes 38.6
IschemicHeartDisease 30.2 HeartFailure 32.7
HeartFailure 21.3 ChronicKidney Disease 27.4
ChronicKidney Disease 20.0 Depression 25.5
Notes:
Prepared by CMS/OIPDA on October6, 2014.
Beneficiaries65yearsandolder(N =1,197,869)Beneficiarieslessthan65years(N =462,346)
DataSource: CMS administrative claims data, January 2012- December2012, fromthe Chronic
Condition Warehouse (CCW), ccwdata.org.

Beneficiaries65yearsandolder(N=3,161,723)
% %
COPDprevalence 11.0 COPDprevalence 11.3
Top 10co-morbidities Top 10co-morbidities
Hypertension 70.7 Hypertension 81.4
Hyperlipidemia 52.3 Hyperlipidemia 61.3
Depression 47.3 IschemicHeartDisease 57.6
IschemicHeartDisease 42.8 Anemia 45.4
Diabetes 42.5 Arthritis(RA/OA) 44.1
Arthritis(RA/OA) 42.3 HeartFailure 42.7
Anemia 36.3 Diabetes 38.6
HeartFailure 30.3 ChronicKidney Disease 34.3
ChronicKidney Disease 24.7 Depression 26.6
Asthma 23.4 Alzheimier'sDisease 20.2
Notes:
Preparedby CMS/OIPDA onOctober6, 2014.
Beneficiarieslessthan65years(N=688,542)
DataSource: CMSadministrative claims data, January 2012- December2012, fromthe Chronic
ConditionWarehouse (CCW), ccwdata.org.

POC study
• To estimate prevalence of ACOS (age, smoking,
obstruction, reversibility) in different population series
(asthma, COPD, ACOS, neither asthma/COPD)
• To compare results when same ACOS case definition
used in different datasets
• Benefits of completing the POC study
o Answer important scientific questions
o Assess feasibility of using different datasets
o Build relationships for future projects (e.g., more detailed
characterization, response to therapy)

POC design: population definitions
Definition Criterion
Population Series 1:
COPD diagnosis
ACOS diagnosis
Asthma diagnosis
No diagnosis of asthma
or COPD (“control”)
A B C A B C A B C A B C
Age >40 years Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Smoking*
Smoking
history ever
Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Obstruction
Post BD
FEV1/FVC
<70%
Ignore Yes Yes Ignore Yes Yes Ignore Yes Yes Ignore Yes Yes
Reversibility
post-BD
increase in
FEV1 by ≥12%
and ≥200mL
Ignore Ignore
Yes Ignore Ignore Yes Ignore Ignore Yes Ignore Ignore Yes
Diagnosis
Physician
diagnosis,
billing
“diagnosis”
COPD dx
ACOS or asthma &
COPD dx
Asthma dx
Neither asthma nor
COPD nor ACOS dx
*Hx of past or current smoking, or smoking cessation advice

Analysis (I)
Study period – current protocol
• Most recent 12-month characterization period
o Clinical practice (and use of billing codes) evolves over time

Analysis (II)
• Prevalence of “ACOS” (age, smoking, obstruction,
reversibility) within different parent populations with
asthma or COPD dx
o Series 1 (COPD dx): C/A X 100%, C/B X 100%
o Series 2 (ACOS dx): C/A X 100%, C/B X 100%
o Series 3 (Asthma dx): C/A X 100%, C/B X 100%
• Prevalence of “ACOS” in population without asthma or
COPD dx
o Series 4 (Control): C/A X 100%, C/B X 100%
• Assess agreement using different case definitions of
ACOS
o Series 1C vs. 2C vs. 3C vs. 4C (kappa statistic)

WHICH DATABASES WILL BE INCLUDED IN STAGE I
OF THE FINAL PROTOCOL…?
Available datasets

Available datasets
• Databases for Phase 1 will be limited to population-based or
administrative/billing-based sampling methods to increase the
external validity of the study.
• Databases resulting from completed research studies/trials will not
be eligible for Phase I, but may be eligible for subsequent phases.
• Information has not been provided for: COBRA (France);
COLIBRI (France); INITIATIVES (France); SPIROMICS
(USA); CONCERT(USA); COSYCONET (Germany).
o As these databases do not contain “random or representative
population samples” they are not be eligible for inclusion in Stage 1

Population Series 1
A B C
Age >40 years Yes Yes Yes
Smoking
Smoking history
ever*
Yes Yes Yes
Obstruction
Post BD
FEV1/FVC <70%
Ignore Yes Yes
Reversibility
post-BD increase
in FEV1 by ≥12%
and ≥200mL
Ignore Ignore Yes
Diagnosis
Physician
diagnosis, billing
“diagnosis”
COPD dx
NUMBER OF DATABASES
CHARACTERISED
8 8 8
NUMBER OF DATA BASES IN
WHICH THE POPULATION IS
OPERATIONALIZABLE
8 6 (4 + 2 subsets*) 6 (4 + 2 subsets*)
NAME OF DATABASES IN WHICH
THE DEFINTION IS
OPERATIONALIZABLE
1. Dutch ASTHMA / COPD Service
2. Adelphi Respiratory Disease
Specific Programme
3. OPCRD
4. HealthCore
5. SIDIAP
6. MAJORICA
7. Market Scan (except smoking*)
8. Optum (except smoking)
Specific Programme*
3. OPCRD
4. SIDIAP
5. MAJORICA
6. Healthcore*
Specific Programme*
3. OPCRD
4. SIDIAP
5. MAJORICA
6. Healthcore*
“COPD series”

“ACOS series”
Population Series 2
A B C
Smoking
Smoking history
ever*
Yes Yes Yes
Obstruction
Post BD
FEV1/FVC <70%
Ignore Yes Yes
Reversibility
post-BD increase
in FEV1 by ≥12%
and ≥200mL
Ignore Ignore Yes
Diagnosis
Physician
diagnosis, billing
“diagnosis”
ACOS dx or asthma and COPD dx
NUMBER OF DATABASES
CHARACTERISED
8 8 8
OPERATIONALIZABLE
8 6 (4 + 2 subsets*) 6 (4 + 2 subsets*)
THE DEFINTION IS
OPERATIONALIZABLE
Specific Programme
3. OPCRD
4. HealthCore
5. SIDIAP
6. MAJORICA
Specific Programme*
3. OPCRD
4. SIDIAP
5. MAJORICA
6. Healthcore*
Specific Programme*
3. OPCRD
4. SIDIAP
5. MAJORICA
6. Healthcore*

“Asthma series”
Population Series 3
A B C
Smoking
Smoking history
ever*
Yes Yes Yes
Obstruction
Post BD
FEV1/FVC <70%
Ignore Yes Yes
Reversibility
post-BD increase
in FEV1 by ≥12%
and ≥200mL
Ignore Ignore Yes
Diagnosis
Physician
diagnosis, billing
“diagnosis”
Asthma dx
NUMBER OF DATABASES
CHARACTERISED
8 8 8
OPERATIONALIZABLE
8
6
(4 in all patients; 2 subsets*)
6
(4 in all patients; 2 subsets*)
THE DEFINTION IS
OPERATIONALIZABLE
Specific Programme
3. OPCRD
4. HealthCore
5. SIDIAP
6. MAJORICA
Specific Programme*
3. OPCRD
4. SIDIAP
5. MAJORICA
6. Healthcore*
Specific Programme*
3. OPCRD
4. SIDIAP
5. MAJORICA
6. Healthcore *

“Control series”
Population Series 4
A B C
Smoking
Smoking history
ever*
Yes Yes Yes
Obstruction
Post BD
FEV1/FVC <70%
Ignore Yes Yes
Reversibility
post-BD increase
in FEV1 by ≥12%
and ≥200mL
Ignore Ignore Yes
Diagnosis
Physician
diagnosis, billing
“diagnosis”
Neither asthma nor COPD nor ACOS
NUMBER OF DATABASES
CHARACTERISED
8 8 8
OPERATIONALIZABLE
7
5
(3 in all patients; 2 in subsets*)
5
(3 in all patients; 2 in subsets*)
THE DEFINTION IS
OPERATIONALIZABLE
2. OPCRD
3. HealthCore
4. SIDIAP
5. Market Scan (except smoking)
7. MAJORICA
2. OPCRD
3. SIDIAP
4. Healthcore*
5. MAJORICA
2. OPCRD
3. SIDIAP
4. Healthcore *
5. MAJORICA

Available datasets: summary
DATABASE Time for completion of Stage 1 Cost for completion of Stage 1
1. Dutch ASTHMA / COPD Service 8 weeks
EUR 10,000
(~2 months post-doc salary)
Specific Programme
≤ 4 weeks £0
3. Optimum Patient Care Research
Database (OPCRD)
4-6 weeks £10,000
4. SIDIAP 6 weeks EUR 1,500
5. MAJORICA TBC TBC
6. PCORnet Common Data Model
Data available Sept 2016;
analysis estimate ?
TBC
7. HealthCore 3 weeks
$4,167
(if manual programming required)
8. MarketScan "1 day" ?
9. Optum Humedica "1 day" ?
Which databases should be included in the Protocol?

Available datasets: summary
DATABASE Time for completion of Stage 1 Cost for completion of Stage 1
1. Dutch ASTHMA / COPD Service 8 weeks
EUR 10,000
(~2 months post-doc salary)
Specific Programme
≤ 4 weeks £0
3. Optimum Patient Care Research
Database (OPCRD)
4-6 weeks £10,000
4. SIDIAP 6 weeks EUR 1,500
5. MAJORICA TBC TBC
6. PCORnet Common Data Model
Data available Sept 2016;
analysis estimate ?
TBC
7. HealthCore 3 weeks
$4,167
(if manual programming required)
8. MarketScan "1 day" ?
9. Optum Humedica "1 day" ?
Which databases should be included in the Protocol?
?
✓
X Valuable for repeat analysis and validation when available

Methodological approach
• Review all patients with ≥2 healthcare contacts in the evaluation
year
• Based on coded reason for consultation (where available),
categorise as:
o COPD Population: ≥2 consultations coded for COPD
o Asthma Population: ≥2 consultations coded for asthma
o ACOS Population: ≥1 consultation coded for COPD plus ≥1
consultation coded for asthma
– Asthma/ACOS: ≥2 consultations for asthma and ≥1 consultation for
COPD
– COPD/ACOS: ≥2 consultations for COPD and ≥1 consultation for
asthma
NB. There is no ACOS code in the UK

Degree of overlap & starting numbers
≥2 Asthma
Consultations
≥2 COPD
Consultations
≥1 Asthma
consultation and
≥1 COPD consultation
Patients Group(s)
No No No 986,072 None
No No Yes 2,254 ACOS
No Yes No 10,938 COPD
No Yes Yes 1,683 COPD/ACOS
Yes No No 27,462 Asthma
Yes No Yes 701 Asthma/ACOS
Yes Yes Yes 750 Asthma/COPD/ACOS
Want to agree the right diagnostic starting point.
Thereafter, obstruction, reversibility, smoking and age criteria must be
applied (i.e. total population count numbers will reduce further).

Degree of overlap & starting numbers

OPCRD Pilot Data
Taking a Diagnostic Coding approach

Methodological approach
• Diagnosis:
o “Asthma diagnosis, Yes”: patients with an asthma diagnosis ever
o “COPD diagnosis, Yes”: patients with an COPD diagnosis ever
o “ACOS diagnosis, Yes”: patients who received a diagnosis of asthma and COPD
within 12 months of each other, ever
o “Control diagnosis, Yes”: patients with no asthma or COPD diagnostic code, ever
• Age, obstruction, reversibility, smoking status evaluated during or closest to
the 12-month characterization period 1 April 2012–31 March 2013
• Sensitivity analysis:
o Patients with ≥2 lower respiratory consultations during the evaluation year
o Why? To show how this reduces (perhaps without clinical “appropriateness”) the
number of eligible patients in a UK clinical data where consultations are often not
coded and where asthma patients often only go to the doctor once a year for their
asthma review (at most). It possibly also biases the population to be a more severe
population in the UK.

Population counts
Criteria Series 1: COPD Series 2: ACOS Series 3: Asthma Series 4: None
Diagnosis Yes 27,721 8,082 259,712 734,345
Age >= 40
>=40 27,575 8,005 126,053 449,334
<40 146 77 133,659 285,011
missing 0 0 0 0
Smoking History ever
Current or ex-smoker 23,926 6,450 55,680 204,998
non-smoker 2,852 1,471 67,480 228,711
missing 797 84 2,893 15,625
Definition A 23,926 6,450 55,680 204,998
Obstruction
<0.7 Fev1 percent pred or
FeV1/FCV
13,485 4,089 6,397 7,834
>= 0.7 Fev1 percent pred
and FeV1/FCV
4,194 1,251 9,157 18,642
Missing 6,247 1,110 40,126 178,522
Definition B 13,485 4,089 6,397 7,834
Reversability
≥12% and ≥200 mL
increase in FEV1 post-
bronchodilator or ≥15%
increase in FEV1
222 89 175 258
<12% or 200ml increase 701 170 238 595
Missing 12,562 3,830 5,984 6,981
Definition C 222 89 175 258

Population counts with ≥2 consults
Criteria Series 1: COPD Series 2: ACOS Series 3: Asthma Series 4: None
Diagnosis Yes 27,721 8,082 259,712 734,345
2+ resp consults in year Yes 15,563 5,487 56,858 56,545
Age >= 40
>=40 15,505 5,453 35,816 37,307
<40 58 34 21,042 19,238
missing 0 0 0 0
Current or ex-smoker 13,978 4,464 17,310 19,484
non-smoker 1,476 974 18,289 17,472
missing 51 15 217 351
Definition A 13,978 4,464 17,310 19,484
Obstruction
<0.7 Fev1 percent pred
or FeV1/FCV
8,514 2,962 3,398 1,825
>= 0.7 Fev1 percent pred
and FeV1/FCV
2,480 868 4,077 4,593
Missing 2,984 634 9,835 13,066
Definition B 8,514 2,962 3,398 1,825
Reversability
≥12% and ≥200 mL
increase in FEV1 post-
bronchodilator or ≥15%
increase in FEV1
137 62 77 46
<12% or 200ml increase 414 107 133 136
Missing 7,963 2,793 3,188 1,643
Definition C 137 62 77 46

Effect of ≥2 LR consults
COPD Series ACOS Series Asthma Series Control Series
Criteria
No
consult
criteria
≥2 LR
consults
No consult
criteria
≥2 LR
consults
No consult
criteria
≥2 LR
consults
No consult
criteria
≥2 LR
consults
Diagnosis Yes 27,721 27,721 8,082 8,082 259,712 259,712 734,345 734,345
Respiratory Consultations NA 15,563 NA 5,487 56,858 NA 56,545
Age >= 40
>=40 27,575 15,505 8,005 5,453 126,053 35,816 449,334 37,307
<40 146 58 77 34 133,659 21,042 285,011 19,238
missing 0 0 0 0 0 0 0 0
Current or ex-smoker 23,926 13,978 6,450 4,464 55,680 17,310 204,998 19,484
non-smoker 2,852 1,476 1,471 974 67,480 18,289 228,711 17,472
missing 797 51 84 15 2,893 217 15,625 351
Definition A 23,926 13,978 6,450 4,464 55,680 17,310 204,998 19,484
Obstruction
<0.7 Fev1 percent
pred or FeV1/FCV
13,485 8,514 4,089 2,962 6,397 3,398 7,834 1,825
>= 0.7 Fev1 percent
pred and FeV1/FCV
4,194 2,480 1,251 868 9,157 4,077 18,642 4,593
Missing 6,247 2,984 1,110 634 40,126 9,835 178,522 13,066
Definition B 13,485 8,514 4,089 2,962 6,397 3,398 7,834 1,825
Reversability
≥12% and ≥200 mL
increase in FEV1
post-bronchodilator or
≥15% increase in
FEV1
222 137 89 62 175 77 258 46
<12% or 200ml
increase
701 414 170 107 238 133 595 136
Missing 12,562 7,963 3,830 2,793 5,984 3,188 6,981 1,643
Definition C 222 137 89 62 175 77 258 46

Demographics
27,721 100.0% 8,082 100.0% 259,712 100.0% 734,345 100.0%
27,721 100.0% 8,082 100.0% 259,712 100.0% NA NA
Male 15,338 55.3% 3,994 49.4% 124,526 47.9% 343,530 46.8%
Female 12,383 44.7% 4,088 50.6% 135,186 52.1% 390,815 53.2%
>= 40 27,575 99.5% 8,005 99.0% 126,053 48.5% 449,334 61.2%
mean 72 70 40 45
Non-smoker 2,878 10.4% 1,496 18.5% 147,008 56.6% 343,440 46.8%
Current smoker 9,445 34.1% 2,136 26.4% 45,175 17.4% 123,677 16.8%
Ex-smoker 14,587 52.6% 4,365 54.0% 49,668 19.1% 152,397 20.8%
Missing 811 2.9% 85 1.1% 17,861 6.9% 114,831 15.6%
Underweight 1,300 4.7% 278 3.4% 18,167 7.0% 33,088 4.5%
Healthy weight 8,931 32.2% 2,454 30.4% 78,463 30.2% 194,628 26.5%
Overweight 8,832 31.9% 2,705 33.5% 65,598 25.3% 194,708 26.5%
Obese 7,462 26.9% 2,536 31.4% 60,042 23.1% 153,109 20.8%
Missing 1,196 4.3% 109 1.3% 37,442 14.4% 158,812 21.6%
BMI
Series 4: None
Age
Physician recorded read code
Smoking History
Gender
Total Population
Metric Series 1: COPD Series 2: ACOS Series 3: Asthma
Male Female Male Female Male Female
Male FemaleMale Female

Clinical characteristics (I)
Series 4: NoneMetric Series 1: COPD Series 2: ACOS Series 3: Asthma
Mild 4,217 15.2% 1,285 15.9% 23,975 9.2% 43,524 5.9%
Moderate 13,313 48.0% 3,984 49.3% 14,207 5.5% 16,026 2.2%
Severe 5,704 20.6% 1,820 22.5% 2,885 1.1% 2,315 0.3%
Very Severe 1,499 5.4% 478 5.9% 808 0.3% 548 0.1%
Missing 2,988 10.8% 515 6.4% 217,837 83.9% 671,932 91.5%
FEV1 <0.7 predicted 16,153 58.3% 5,040 62.4% 10,865 4.2% 10,156 1.4%
Yes 399 1.4% 186 2.3% 895 0.3% 1,327 0.2%
No 90 0.3% 23 0.3% 191 0.1% 540 0.1%
Not Measured 27,232 98.2% 7,873 97.4% 258,626 99.6% 732,478 99.7%
Other Chronic Resp. Diseases390 1.4% 96 1.2% 738 0.3% 2,054 0.3%
Cardiovascular 11,873 42.8% 3,135 38.8% 26,757 10.3% 94,961 12.9%
IHD 6,845 24.7% 1,813 22.4% 11,339 4.4% 43,321 5.9%
Heart Failure 1,882 6.8% 487 6.0% 2,025 0.8% 6,251 0.9%
Hypertension 3,963 14.3% 1,433 17.7% 14,111 5.4% 59,284 8.1%
Diabetes 7,425 26.8% 2,455 30.4% 27,906 10.7% 95,918 13.1%
Bronchiectasis 1,067 3.8% 451 5.6% 1,903 0.7% 2,470 0.3%
Rhinitis 2,559 9.2% 1,461 18.1% 58,423 22.5% 79,754 10.9%
Rhinitis (active) 1,118 4.0% 766 9.5% 22,693 8.7% 32,491 4.4%
Eczema 4,804 17.3% 1,952 24.2% 70,089 27.0% 129,156 17.6%
Osteoporosis 3,146 11.3% 1,351 16.7% 7,868 3.0% 23,936 3.3%
GERD 3,026 10.9% 1,170 14.5% 17,673 6.8% 49,262 6.7%
GERD (active) 2,183 7.9% 880 10.9% 10,470 4.0% 28,474 3.9%
Cerebrovascular 2,759 10.0% 670 8.3% 4,990 1.9% 20,092 2.7%
Chronic Kidney Disease 4,302 15.5% 1,273 15.8% 8,162 3.1% 33,195 4.5%
Myocardial Infarction 2,541 9.2% 582 7.2% 3,484 1.3% 15,258 2.1%
Anxiety and Depression 1,150 4.1% 452 5.6% 10,008 3.9% 25,383 3.5%
Comorbidities
Obstruction
Reversibility
(≥12% and ≥200
mL increase in

Clinical characteristics (II)
Series 4: NoneMetric Series 1: COPD Series 2: ACOS Series 3: Asthma
NONE 6,037 21.8% 736 9.1% 123,032 47.4% 684,064 93.2%
SABA 3,068 11.1% 354 4.4% 26,996 10.4% 31,598 4.3%
SAAC 247 0.9% 20 0.2% 89 0.0% 421 0.1%
SAAC + SABA 529 1.9% 61 0.8% 153 0.1% 316 0.0%
LABA +/- SAAC +/- SABA 726 2.6% 56 0.7% 446 0.2% 199 0.0%
LAMA +/- SAAC +/- SABA 2,967 10.7% 336 4.2% 401 0.2% 438 0.1%
LABA + LAMA +/- SAAC +/-
SABA
403 1.5% 41 0.5% 36 0.0% 18 0.0%
ICS +/- SAAC +/- SABA 1,363 4.9% 548 6.8% 55,076 21.2% 11,936 1.6%
ICS + LABA +/- SAAC +/-
SABA
5,140 18.5% 2,598 32.1% 41,801 16.1% 3,650 0.5%
ICS + LAMA +/- SAAC +/-
SABA
506 1.8% 187 2.3% 229 0.1% 75 0.0%
ICS + LABA + LAMA +/-
SAAC +/- SABA
6,457 23.3% 2,504 31.0% 2,315 0.9% 349 0.0%
LTRA +/- SAAC +/- SABA 23 0.1% 11 0.1% 789 0.3% 728 0.1%
LABA + LTRA +/- SAAC +/-
SABA
2 0.0% 5 0.1% 34 0.0% 4 0.0%
LAMA + LTRA +/- SAAC
+/- SABA
14 0.1% 23 0.3% 30 0.0% 5 0.0%
ICS + LTRA +/- SAAC +/-
SABA
3 0.0% 12 0.1% 1,874 0.7% 303 0.0%
ICS + LAMA + LTRA +/-
SAAC +/- SABA
6 0.0% 10 0.1% 17 0.0% 1 0.0%
ICS + LABA + LAMA +
LTRA +/- SAAC +/- SABA
140 0.5% 308 3.8% 498 0.2% 13 0.0%
ICS + LABA + LTRA +/-
SAAC +/- SABA
79 0.3% 270 3.3% 5,880 2.3% 185 0.0%
LABA + LAMA + LTRA +/-
SAAC +/- SABA
1 0.0% 0 0.0% 1 0.0% 0 0.0%
OTHER 10 0.0% 2 0.0% 15 0.0% 42 0.0%
Treatment

Question for the protocol…
• For a clinical database (where diagnosis does not need to be
inferred from coded consultations but can be identified by
physician diagnosis) start from:
o Coded consultations or
o Diagnosis (ever)
By Consults
By prior diagnosis
codes
Series 1: COPD 13,371 27,721
Series 2: ACOS 4,687 8,082
Series 3: Asthma 28,913 259,712
Series 4: None 986,072 734,345

Alignment between REG WG ideas
& Collaborating Supporter identified needs
Future research goals / needs discussion

Study Design: population definitions
COPD diagnosis
ACOS diagnosis
Asthma diagnosis
No diagnosis of asthma
or COPD (“control”)
A B C A B C A B C A B C
Age >40 years Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Smoking*
Smoking
history ever
Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes
Obstruction
Post BD
FEV1/FVC
<70%
Ignore Yes Yes Ignore Yes Yes Ignore Yes Yes Ignore Yes Yes
Reversibility**
post-BD
increase in
FEV1 by ≥12%
and ≥200mL
Ignore Ignore
Yes Ignore Ignore Yes Ignore Ignore Yes Ignore Ignore Yes
Diagnosis
Physician
diagnosis,
billing
“diagnosis”
Yes Yes Yes Yes Yes Yes Yes Yes Yes No No No
*History of past or current smoking, or smoking cessation advice
**There is no single definition of acute bronchodilator response. Some of the more commonly used definitions include:
1. ≥12% and ≥200 mL increase in FEV1 post-bronchodilator (GINA and GOLD 2014 ACOS definition; Pelligrino R ,ERS/ATS Task Force, ERJ 2005; ATS Am Rev
Respir Dis 1991; Tashkin D, Chest 2003);
2. ≥15% increase in FEV1 (ACCP, Chest 1974; COMBIVENT study group, Chest 1997);
3. ≥10% absolute increase in FEV1 predicted (Anthonisen NR Am Rev Respir Dis 1986; Eliasson O Am Rev Respir Dis 1985; Brand PL Thorax 1992)
Whether or not an individual is classified as having FEV1 reversibility depends on various factors, including the starting FEV1, gender, smoking status, type and dose of
bronchodilators, and timing of assessment post-bronchodilator. Using a change in volume or an absolute change in % predicted helps guard against favoring low
starting FEV1s in identifying patients with “reversibility.” As there is no clear consensus, we will employ the criteria proposed by the ERS/ATS Task Force and
GINA/GOLD ACOS definition documents (i.e. ≥12% and ≥200mL increase post-bronchodilator). Secondary analyses can examine other definitions.
In each diagnostic series (1–4): C is a subset of B, which is a subset of A

Database information: summary (I)
DATABASE
Details Provided Type of Sample Country
Source of data – Clinical Data (EMR) or
Administrative/Billing Data
To establish the "representativeness" of the population within
the database
(e.g. selected for trial inclusion; unselective convenience
sampling; representative of the population as a whole)
National origin of the
patients within the dataset
To indicate whether the data includes direct
information about a helathcare encounter (i.e.
recorded in their electronic medical records) or
indirect information as coded for insurance or
administrative claims purposes
Indication of the ability of each dataset to identify the 12
populations (COPD A–C; Asthma A–C; ACOS A–C and
Control A–C) proposed for revaluation
Dutch ASTHMA /
COPD Service
People with respiratory symptoms treated by their
GP. With or without inhalation medication. Both
diagnostic and follow up.
The Netherlands
Electronic medical record, but not all
visits are recorded for other encounters
other than the visits to the A/C service
12 of 12
Adelphi Respiratory
Disease Specific
Programme
Convenience sample of consecutive outpatients
visiting their physician (both primary and specialist
care settings)
France, Germany,
Italy, Spain, UK, USA,
Japan, China, Canada
Electronic Medical Records
9 of 12
• Unable to identify the 3x Control Populations as
survey only includes patients with a asthma or
COPD diagnosis
Optimum Patient
Care Research
Database (OPCRD)
Patients registered at UK primary care practices that
receive the Optimum Patient Care Clinical Service.
Enriched sample of patients with ≥1 prescription or
diagnosis of obstructive lung disease (as initially only
OLD pts received the OPC review)
UK Electronic Medical Records
12 of 12
• Only a subgroup of patients will have reversibility
data (required to evaluate the 4 x C Populations)
SIDIAP
Records for patients treated by the Catalan Health
Institute (CHI) – the chief provider of medical services
in Catalonia. 5,8 million patients (>80% population);
274 Primary Care Centres in Catalonia; 3,400 GPs
Spain (Catalonia
Region)
Electronic Medical Records 12 of 12
MAJOrca Real-world
Investigation in
COPD and Asthma
database
(MAJORICA)
Combined data from the primary care system (e-
SIAP), the hospital claims system (FIC), and the
pharmacy database (RELE) in the Balearics, Spain.
Covers all health-care utilisation of the permanent
inhabitants of the Balearics (≥1.1 million people)
Majorca Electronic medical records 12 of 12 (TBC)
PCORnet Common
Data Model
Population-based (anyone with ≥1 healthcare
encounter for any reason at contributing healthcare
facilities)
USA Electronic Health Records 12 of 12
HealthCore
Automated computerized claims data and enrollment
for approximately 51 million lives with at least medical
enrollment, and nearly 33 million lives with medical
and pharmacy enrollment information from 14 Blue
Cross and/or Blue Shield (BCBS) licensed plans
USA
Adminsitrative/Billing Data
+
linked medical records (from EMR review
study)
12 of 12
• All A populations will be identifiable
• All B and C populations (requiring reversibility and
obstruction data) will only be identifieable in those
with linked claims + chart review data
MarketScan
Commercial, Medicare Supplemental, and Medicaid
contain >200 million patients since 1995.
USA Adminsitrative/Billing Data
4 of 12
• Only group A can be evaluated and only based on
codes for smoking cessation (i.e. no smoking code,
but inference of smoking history based on code for
smoking cessation advice)
Optum Humedica
Proprietary database containing health plan
administrative and claims records. The data derive
from commercial health plans and Medicare
Advantage programs.
USA Adminsitrative/Billing Data
4 of 12
• Only group A can be evaluated and only based on
codes for smoking cessation (i.e. no smoking code,
but inference of smoking history based on code for
smoking cessation advice)
Information has not been provided for: COBRA (France); COLIBRI (France); INITIATIVES (France); SPIROMICS (USA); CONCERT(USA); COSYCONET (Germany). These databases do not meet
the eligibility criteria of “random or representative samples” so will not be eligible for inclusion in the first phase of this population characterization and agreement study

Database information: summary (II)
DATABASE
Evaluation year
Number of unique patients with ≥1
HCP contact
(for asthma, COPD, both of ACOS)
in the evaluation year
Number of unique patients with
≥2 HCP contacts
(for asthma, COPD, both of
ACOS) in the evaluation year
≥1 HCP contact
not coded for asthma, ACOS or
COPD in the evaluation year
≥2 HCP contact
(for any reason) in evaluation
year
Latest 12-month period for which
data are available
This criterion is designed to capture the total
number of asthma, COPD and ACOS
patients in the database within the proposed
12-month evaluation period
Patients with ACOS based co-coding of
asthma and COPD within a 12-month
window & presumptive diagnosis of
asthma or COPD in patients 2
consistent asthma or COPD codes in
the 12-month period
Total number of potential control
patients in the database within the
proposed 12-month evaluation period
Number of potential control patients
within the database – those with ≥2
encounters, neither of which have a
diagnosis of Asthma, COPD or ACOS
in the 12-month period
Dutch ASTHMA /
COPD Service
Jan 2013–31 Dec 2014
Asthma: 1694
COPD: 946
ACOS: 324
Unnecessary as code for ACOS
exists within the Netherlands
Control: 3918 TBC
Adelphi
Respiratory
Disease Specific
Programme
Dec 2014–Nov 2015
Asthma: 5,501
COPD: 5,071
ACOS: 449 (physician-confirmed)
0; database contains pt data from
1 encounter only
Control: not available (n=0) Control: not available (n=0)
Optimum Patient
Care Research
Database (OPCRD)
March 31 2011 – April 1
2012
Asthma, COPD or Both: 119,540
Asthma: subset of above
COPD: subset of above
ACOS: subset of above
Asthma, COPD or Both: 40726
Control: 40726 TBC
SIDIAP Jan 07 2013–Dec 31 2013
TBC TBC
MAJORICA
1 January 2014–31
December 2014
(data collection period 2011-
2014)
based on ICD ever
Asthma: 45,800
COPD: 27,871
ACOS: 5,093
Asthma: <45,800
COPD: <27,871
ACOS: <5100
Subset of 68,578 Subset of 68,578
PCORnet Common
Data Model
1 January 2014 – 31
December 2014
All patients: 100,000,000 million
records (total)
Asthma: ~6 million asthma patients
(based on prevalence estimate);
COPD: ~6 million asthma patients
(based on prevalence estimate);
ACOS: TBC
Asthma: TBC
COPD: TBC
ACOS: TBC
TBC TBC
HealthCore May 1 2014 – April 30 2015
(ICD-9 codes 491.xx–496.xx)
(ICD-9 codes 491.xx–496.xx)
TBC TBC
MarketScan Jan 01 2013–Dec 31 2013
Asthma, COPD or Both: 1,998,509
Asthma, COPD or Both:
1,436,631
Control: ? Control: ?
Optum Humedica Jan 01 2013–Dec 31 2013
Asthma, COPD or Both: 1,248,091
Control: ? Control: ?

ACOS Definitions Prospectus Paper
Prospectus Paper…?

Prospectus paper…?
• Rationale:
o Optimising the value of the definition creation & database
characterization process carried out to date
o Save other groups doing similar ground work
o Set up the planned analysis
• Content:
o The process the group has used to create the ACOS
definitions
o Key characteristics necessary for contributing databases
o Plans for evaluation (and future study opportunities)
• ATS Abstract – OPCRD analysis? (deadline 4 November)

REG ACOS Working Group Meeting 25/09/15

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REG ACOS Working Group Meeting 25/09/15