The document summarizes discussions from an IPF/ILD Working Group meeting. It provides updates on several studies, including one characterizing the clinical features and healthcare utilization of IPF patients in the years before diagnosis. The study found increased healthcare resource use in the 2 years prior to an IPF diagnosis. Another study aims to evaluate diagnostic agreement across global sites. The working group discussed priorities for future research, including a Phase II study using digitized patient cases to assess diagnostic accuracy across different healthcare settings.

1. ERS 2017
Milan, 9th September 2017
IPF/ILD Working Group Meeting

2. Agenda
• Working group progress update
o ILD-MDT phase II
• Priorities for future research
o Research ideas
– Relevant, feasible, valid and a priority
o Setting priorities
• Additional items

3. Attendees
• Kevin Flaherty (chair)
• A Azuma
• P Rottoli
• V Cottin
• J Behr
• A Niimi
• F Luppi
• S Andarini
• C Youakim
• P Rivera Ortega

4. Progress update
• Published studies
o Martinez FJ, Chisholm A, Collard H R, et al 2017. The diagnosis of
idiopathic pulmonary fibrosis: current and future approaches. Lancet Resp
Med: 5 (1), 61-71

5. Active study update (1)
• REG-RES1510: Characterisation of the path to idiopathic
pulmonary fibrosis (IPF) and potential missed diagnostic
opportunities
o Presented at Working Group meeting at ERS 2016
o Final report complete December 2016

6. Study Aims
• With a view to identifying potential opportunities for earlier referral to
specialists and (ultimately) earlier diagnosis of IPF, the study aims
to:
1. Characterise the clinical features of patients at the time of their IPF
diagnosis
2. Evaluate patients’ patterns of HRU in the years preceding their IPF
diagnosis
3. Develop optimum code lists for IPF database research, i.e. variation in 1 & 2
for sensitive versus specific code lists

7. Methods
INCLUSION CRITERIA
• A diagnostic Read code for IPF
• Diagnosed with IPF between
1990 and 2015.
• A minimum of 2 years continuous
clinical records in the years
immediately preceding their
index diagnosis
• Aged 40 years or older at index
date

8. Clinical features of patients at the
time of their IPF diagnosis
• In this routine care IPF population from the UK:
o Demographics
– Mean age: 72-73 years
– Men accounted for 62-65% of the population
– Approximately 1/3 were never smokers; 2/3 current or ex-smokers
o Comorbidities
– 13-25% had obstructive lung disease (13-15% asthma; 19-25% COPD)
– Approximately 50% of patients:
 Had cardiovascular disease (46-53%)
 Consulted for cough (40-52%; ~10% in the 2 years preceding IPF diagnosis)
o Respiratory therapies
– 18-26% of patients received ≥1 prescription for SABA in the year preceding IPF diagnosis
– Prescribing of all other obstructive lung disease therapies (ICS, LABA, LAMA,
combinations) was low (<10%)

9. Patterns of HRU in the years
preceding their IPF diagnosis
• All markers of respiratory health resource use (HRU) increased
annually over the 10-years and quarterly within the last 2 years
leading up to patient’s IPF diagnosis:
o Primary care events
– LR consultations, LR antibiotics and oral steroids (acute and
maintenance)
o Secondary care attendances
– Hospital admissions, Out patient department attendances, Accident &
emergency attendances
o Other:
– Cough events, Chest X-rays, Incidence of pneumonia

10. Code lists: specific vs broad
• Compared with patients with a “specific” IPF diagnostic code, those with a
“broad” diagnostic label were similar in terms of their:
o Demographic presentation at the time of diagnosis
o Escalating trends in HRU in the years preceding IPF diagnosis
o Lung function: Similar mean(SD) FVC: 3.1(6.8) vs. 2.5(0.9) (p=0.405)
• Comorbidities broad IPF patients had:
o Similar burden of:
– Chronic respiratory conditions (incl. asthma; excl COPD); heart failure,
rhinitis, bronchiectasis, eczema, osteoporosis, cerebrovascular disease,
sleep apnoea, depression and anxiety
o Higher burden of :
– COPD, cardiovascular disease, ischaemic heart disease, Hypertension,
diabetes, myocardial infraction, GERD,CKD, lung cancer, cough
• Drug usage: broad IPF patients had higher use of short-acting
bronchodilator therapy in the year preceding IPF diagnosis (26 vs 18%)

11. Next steps
• Final report has been published
• No control group
o Write up without control group or secure funding to conduct
supplementary study with controls?
• Potential to publish comparison of specific vs. broad IPF
definitions

12. Active study update (2)
• REG-RES1505: Characterisation of interstitial lung disease (ILD)
diagnostic practice around the world and implications on
diagnostic agreement and access to licensed therapies
o Phase I:
– Presented at REG summit 2017 and ATS 2017
– Final report out for comments
– Poster presentation: 12.50pm-2pm on 12th September
o Phase II: Protocol under development

13. Centre type by economic status*
*Economic status: World Bank List of Economies, March 2017
Centre Type
High Income,
n (%)
Upper middle
income, n(%)
Lower middle
income, n(%)
Low income,
n(%)
ILD Academic Centre 148 (48.4) 49 (40.2) 6 (22.2) 2 (100)
Non-ILD Academic
Centre
83 (27.1) 42 (34.4) 8 (29.6) 0 (0.0)
Non Academic Centre 75 (24.5) 31 (25.4) 13 (48.1) 0 (0.0)
TOTAL 306 122 27 2
570 responses, of
which 457 were
unique and valid

14. Academic ILD centres
reported a higher caseloads
of both IPF-ILD and non-IPF
ILD than academic non-ILD or
non-academic centres
(Kruskal Wallis: p<0.001)
Caseload characteristic
ILD Academic
Centre (n=205)
Non-ILD
Academic
Centre (n=133)
Non Academic
Centre
(n=119)
All Centres
(n=457)
IPF ILD cases/
month
Median(IQR) 5.0(3.0-10.0) 4.0(2.0-5.0) 3.0(2.0-5.0) 4.0(2.0-7.0)
Range 0-50 0-35 0-50 0-50
Non-IPF ILD
cases / month
Median(IQR) 16.0(10.0-27.0) 10.0(5.0-20.0) 10.0(5.0-15.0) 11.0(6.0-20.0)
Range 1-130 1-101 0-200 0-200
Where, box=25th percentile, median and 75th percentile; whiskers= values
within 1.5 interquartile ranges of the 25th and 75th percentile.
Caseload of centre

15. Diagnostic meetings
Characteristics of formal meetings

16. Access to anti-fibrotic agents
• Anti-fibrotic agents were available to 81.4% (n=372) of centres, of which 31.7% (n=118)
required the permission of a multi-disciplinary team to access them.
• Access was more frequently reported in academic ILD centres (n=180, 87.8%) than
academic non-ILD (100, 75.2%) or non-academic centres (92, 77.3%).
• Neither of the two centres in low income countries had access to anti-fibrotics.

17. Conclusions
• While there were some differences in practice based on the
centre type, region of the world or the economic status of the
country the centre was located in, practice was broadly similar.

18. Objective
• Evaluate agreement of ILD MDT diagnosis across
a range of global sites and healthcare settings
• Evaluate accuracy of ILD MDT diagnosis across a
range of global sites and healthcare settings,
considering in particular agreement in IPF
diagnosis
• Identify features of current MDT diagnostic practice
associated with accurate diagnosis (including the
effect of bronchoscopic sampling for diagnosis)
• Produce a series of recommendations as to how
best to optimise the pathway to accurate ILD
diagnosis in real-world practice.
Proposed methodology
Design: Digitised reference ILD cases (including pathology data) will
be presented to participating centres.
Outcomes: Descriptive analysis of participating MDTs and MDT
diagnostic accuracy. Concordance across centres, and between
reported practice (phase I) and observed practice (phase II). Analysis
of independent MDT features associated with diagnostic accuracy.
Recommendations associated with optimising the diagnostic process
Next steps: Phase II
Tier 3:
Agrees with diagnostic
inference of available
follow-up data
Tier 2: Agrees with
diagnosis as assigned
by Study MDT
Tier 1: Agrees with
diagnosis as assigned
by reference case
provider
Reference
Case Review
Diagnosis assigned
by participating
centre
Yes
Yes
Yes
No
No
No
Accuracy appraisal of diagnosis

19. Next steps: Phase II questions
• How will cases be digitised, what platform, what
prompts/questions
• What cases
o Source of cases and case-mix
• Which centres
o 464 individuals from 394 (86.2%) centres in phase I stated the would be
happy to participate in phase II
• MDT definition
o How should we define an MDT?

20. Active study update (3)
• REG_P040: Characterise the natural history of IPF vs non-IPF
ILD in terms of FVC lung function decline
o Final report written
o Results presented at REG summit 2017
o A manuscript may be in development?

21. ≥18-month Study
Period
Index Date:
date of ILD diagnosis
Prospective Observational
Outcome Period ≥6 months
Cohort 1: IPF only (reference)
Cohort 2: IPF + non-IPF progressive
fibrotic lung diseases, only
Cohort 3: Non-IPF progressive fibrotic
lung diseases, only
Cohort 4: Non-IPF progressive fibrotic
lung diseases
Historical evaluation of healthcare
resource utilisation.
Period ≥12 months
Study Design
Inclusion criteria:
• Received their IPF diagnosis between
1991 and 2016
• Have a minimum of:
• 12 months of continuous clinical
records immediately preceding
index date
• 6 months’ continuous records
immediately following index date
• Aged 40 years or older at index date
Exclusion criteria:
None
• Electronic
medical records
from both the
Optimum
Patient Care
Research
Database
(OPCRD) and
the Clinical
Practice
Research
Datalink
(CPRD)

22. Health Care Utilisation (I)

23. Health Care Utilisation (II)

24. Mortality

25. Conclusions
• Individuals diagnosed with diseases compatible with ILD have
very similar demographic and clinical characterizes at the time of
or before diagnosis when compared to with those with IPF only
• A consistent increase in the use of healthcare resources 2-3 years
prior to diagnosis was observed in all 4 cohorts

26. Future research
• Phase II of the ILD-MDT project
• Is there another, smaller, project that could run at the same time?
o Relevant?
o Feasible?
o Valid?
o A priority?
• How do we set priorities in IPF/ILD research?
• How to we ensure these priorities are pursued?

27. Any other business?