Pfizer

1. Case Study
Transformation of the global clinical trials
footprint in a big Pharma company
Key Learnings as to How International BioPharma views
Ireland
Damian O’Connell MD PhD BSc
VP Clinical Research
Pfizer
Company
logo here
1

2. 2 2
Overview
 Rationale for change
 Baseline status and end game vision
 Country selection process
 The new foot print
 Why Ireland is Non-Core
 Developing a Functioning Clinical Research System

3. 3 3
Rationale for change
 Drug development costs are increasing dramatically
although output is flat or declining
 It takes more trials and more patients per trial to get a
new drug application approved;
 New approaches e.g. pharmacogenomics, and reduced
attrition is resulting in increased expenditure on
development operations activities
 Study start up and subject recruitment are major challenges
 Speed, Quality and Cost reduction are strategic imperatives

4. 4 4
Rationale for change:
Length of Protocols is Increasing
Length of Protocol incl. Appendix vs. Median
FAP-LSFV Cycle Time
Median Length of Protocol incl. Appendix Over
Time
• Median length of Pfizer protocols grew
18 pages
• This trend is not phase or TA
dependent
• Protocols longer than 100 pages have
FAP-LSFV cycle time medians 97% >
than with < 60 pages
• This is not driven by phase of study or
TA
MedianFAP-LSFVCycleTime
• (n=1, 9,
10)
Length of Final Protocol incl. Appendix in Pages
• (n=8,
11, 15)
• (n=6, 5,
10)
MedianLengthofFinalProtocolincl.Appendix
• (n=18)
LSFV Year
• (n=26) • (n=32)
* Source: Data manually extracted from 76 protocols that span all Phases and CVMED, GU, Neurology, Oncology, and Pain Therapeutic Areas
• (Phase
I, II, III)

5. 5 5
Rationale for Change:
Number of Eligibility Criteria is Increasing
Number of Eligibility Criteria vs. Median FAP-
LSFV Cycle Time
Median Number of Eligibility Criteria Over Time
• Median # of eligibility criteria (sum of
inc/exc) grew most b/w 2005 and 2006
• Trend is not phase or TA dependent
• # of eligibility criteria has some impact
on FAP-LSFV cycle times; most often
with >30 criteriaMedianFAP-LSFVCycleTime
• (n=3, 7,
4)
Number of Eligibility Criteria
• (n=3,
15, 6)
• (n=12,
10, 14)• (n=18)
LSFV Year
• (n=26) • (n=32)
MedianNumberofEligibilityCriteria
* Source: Data manually extracted from 76 protocols that span all Phases and CVMED, GU, Neurology, Oncology, and Pain Therapeutic Areas
• (Phase
I, II, III)

6. 6 6
Rationale for Change:
Number of Protocol Procedures is Increasing
Number of Procedures/Protocol vs. Median FAP-
LSFV Cycle Time
Number of Procedures/Protocol Over Time
• Number of procedures are increasing by year
• Trend consistent with industry data (Tufts
CSDD, Getz)
• Trend consistent across all phases and in the
Oncology and Pain TAs.
• Increase in the number of procedures
correlates with increase in cycle times;
especially if > 60 procedures
MedianFAP-LSFVCycleTime
• (n=3, 5,
3)
Number of Procedures/Protocol Criteria
• (n=1, 8,
10)
• (n=2, 3,
12)
* Source: Data manually extracted from 76 protocols that span all Phases and CVMED, GU, Neurology, Oncology, and Pain Therapeutic Areas
• (Phase
I, II, III)
MedianNumberProceduresperProtocol
LSFV Year
• (n=18) • (n=25) • (n=29)
20%
19%
11%
2%
24%
5%
9%
2%
1%
18%
2%
10%
3%
3%
52
41
35

7. 7 7
Rationale for Change:
Number of CRF Enterable Fields is Increasing
# of Enterable Fields Over Time
• Median # of enterable fields increased
by 103%
• Pfizer protocols require investigators
to collect more data per protocol
• Upward trend seen across all phases
and TAs
• Increase in the number of
enterable fields appears to
increase cycle times
# of Enterable Fields vs. Median FAP-LSFV Cycle
Time
• (n=15)
LSFV Year
• (n=20) • (n=31)
MedianNumberofEnterableFields
MedianFAP-LSFVCycleTime
• (n=2, 6,
10)
Number of Enterable Fields
• (n=2, 3,
6)
• (n=4, 4,
4)
• (n=1, 8,
5)
• (n=4, 4,
4)
* Source: Data manually extracted from 76 protocols that span all Phases and CVMED, GU, Neurology, Oncology, and Pain Therapeutic Areas
• (Phase
I, II, III)

8. 8 8
Baseline Country Clinical Trials
Footprint
Indicates country where an R&D based office is located
Indicates country where R&D studies are being conducted, but no office
62 Country Clinical Operations groups
20+ additional countries where clinical studies are performed

9. 9 9
Europe
Asia
Can/Africa/Middle
East
Study Distribution - September 2008
Canada
Protocols 88 22%
Patients 3871 4%
US
Protocols 308 78%
Patients 34599 32%
EU Non EM
Protocols 165 42%
Patients 26590 24%
LA/AFME
Protocols 83 21%
Patients 13386 12%
Global
Protocols 395
Patients 109256
Asia (excl. AU, KOR)
Protocols 43 11%
Patients 6776 6%
Korea
Protocols 50 13%
Patients 2573 2%
Australia
Protocols 53 13%
Patients 2155 2%
EU EM
Protocols 71 18%
Patients 19306 18%

10. 1010
Baseline Status
Pfizer patient recruitment cycle times (FAP to LSFV) exceed industry benchmarks and inhibit Pfizer’s
ability to quickly bring drugs to market
• Not in Scope: Phase 1 volunteer, Ph 3b/4 regional and country sponsored studies
• Baseline Data Set included: 273 protocols, 75 countries, 8313 total sites, 5666 unique sites, 89,587
patients across 11 therapeutic areas
465
441
Pfizer Actual - All patient
studies, all TAs, phases I, II, III
and globally sponsored IV, with
LSFV on or after 01-Jan-2005
Pfizer Targets – “Best in class”
cycle time
CMR Industry Benchmark -
Centre for Medicines Research
Global Clinical Programmed
Rpt v1.0 (May 2007)
FAP to FSFV
FSFV to LSFV
Cycle Time Performance 2005 – 2008*
Project and Data Analysis Scope * Calendar Days

11. 1111
Country Selection
• Recommendations from root cause analysis:
– ≥50% reduction in number of countries with Pfizer has infrastructure/staff
• Assumed a significant reduction in global clinical trial volume
• Assumed reduction in relative allocation of EU patient volume
• Anticipated shift of clinical trial placement to lower cost and/or high speed regions
(NB quality maintained)
• Classified country operations into core and non core countries
Definitions
Non
Core
• No interruption to ongoing, committed studies that will be
performed by Pfizer staff
• Attrition of staff until all commitments accomplished
• New studies (by exception) to be conducted by CROs in these
countries
Core
• No interruption to ongoing, committed studies
• Place studies actively and increase staff accordingly

12. 1212
12
Country Selection
Quality and
risk filter
1
Core
Non Core
All
countries
 Countries with
high political
instability and/or
environ-mental
risk are excluded
 Population is
defined as ages
15 – 65
 Countries with
population ≤ 3M
are excluded
 Performance-based metrics
include startup speed, cycle time
(regulatory to LSFV), subjects /
site, recruitment reliability, MBR*,
and subjects/ FTE**
 Metrics were grouped into three
categories: high, medium, and
low
Population
filter
2
Evaluate
countries based
on performance
metrics
3 Prioritize based on
quantitative and qualitative
analysis
4
*Monitor Burden rate
** FTEs include both permanent and contracted staff at all levels

13. 1313
Country Selection
Quality and
risk filter
All
countries
1
• Political stability – Economist Intelligence Unit
• Availability of qualified, experienced Investigators
• Adequacy of Pfizer in-country clinical research/monitoring
infrastructure
• Audit performance history

14. 1414
Country Selection
Population
filter
Remaining
countries
2
• Population is defined as ages
15 – 65 years
• Countries with population ≤ 3M
are excluded

15. 1515
Country Selection
• Country performance is assessed against evaluation criteria broken
down into three categories: good, acceptable, and poor performance for
each metric
Assessment
of
performance
metrics
3
Startup
Speed
Cycle
Time
Subjects
per site
Recruitment
Reliability
MBR
($000)
Pts/FTE
Good
Acceptable
Poor
≤90
90-135
>135
≤270
270-360
≥360
≥12
8-12
≤ 8
≥115
75-115
≤75
≤ 150
150-250
≥250
≥55
40-55
≤40
Start up speed – median #days from receipt of protocol package to latter of regulatory approval or ethics approval
Cycle time – median #days from regulatory approval to LSFV
Recruitment reliability - # actual subjects randomised as percentage of # planned per study
Monitor Burden Rate (MBR) – Fully loaded annual cost of a monitor/CRA

16. 1616
Ranges for Performance Metrics
Clinical Trial Metrics & Ranges
Metric Range Average
Startup Speed 57 – 656 days 154 days
Final approved
protocol to last
subject first visit
109 – 1508 days 373 days
Subjects /site 4 – 83 subjects 15 subjects
Recruitment
reliability
9 - 494 % 133 %
Monitoring
Burden Rate*
$26K – $363K $141K
Subjects/ FTE 6 – 284 subjects 60 subjects
Performance
metrics
*Monitoring Burden Rate is the fully loaded cost of supporting a monitor in a country.

17. 1717
Recruitment Reliability
(Actual Patients * Planned Recruitment Period)
(Planned Patients * Actual Recruitment Period)
Actual Patients = Number of randomized patients in the study in the country (RighTrack II)
Planned Recruitment Period = Study planned last subject first visit (EPM) – country planned
first subject first visit (eCPM via initial CMA)
Planned Patients = Number of planned patients in the study in the country (eCPM via initial
CMA)
Actual Recruitment Period = Study actual last subject first visit (EPM) – country actual first subject first
visit (RighTrack II or ClinrepNet)

18. 1818
Ranges for Performance Metrics
Clinical Trial Metrics & Ranges
Metric Range Average
Startup Speed 57 – 656 days 154 days (206)
Subjects /site 4 – 83 subjects 15 subjects (5)
Recruitment
reliability
9 - 494 % 133 % (69%)
Performance
metrics
*Monitoring Burden Rate is the fully loaded cost of supporting a monitor in a country.

19. 1919
Country Selection
Low volume cohort
<1,600 patients
High volume cohort
≥1,600 patients
Core
Non core
Core
Non core
Prioritize based on
quantitative and
qualitative analysis
4

20. 2020
Europe – 14 Core countries
Asia – 9 Core countries
Can/LA/Africa/Middle East – 10 Core countries
New Country Clinical Trials Footprint
US

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Why is Ireland Non-Core
• Fragmented – research infrastructures not
connected and hard to find. The key opinion leaders
and researchers are there and are performing at
individual level with individual companies. This
activity is not collated, communicated and
connected to showcase Irelands capacity as a
country level.
• Ireland is “person dependent” – you need to know
individuals in order to get connected to the right
chain of knowledge – it is not a “system”
• Performance - not predictable – research approval
processes – especially ethics, protracted negotiation
process for trial cost negotiation as each facility has
different costs for the same service, access to
patient populations in quite diffused with lack of
connectivity between the various points of care e.g.
hospital, GP interface

22. 2222
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Why is Ireland Non-Core
• Cost of patients – for the number of patients
Irelands can contribute – the cost is too high to
justify the effort. Coupled with the fact that Ireland
has a limited patient population and also a limited
market for the sale of products – the cumulative
effect of the investment risk is not a positive one
• For a number of companies there have been more
findings (and of a more serious nature) in regulatory
inspections in Irish sites compared to sites in the UK
which colours views when it comes to allocating
clinical research between sites in the UK & Ireland
• Industry has been evaluating cost cutting and
productivity enhancement for several years – this
means decisions are made on countries to involve in
trials is not as it used to be “who the medical
director knew”. It is now in the hands of procurement
departments, operational departments whose
bonuses are based on performance of countries
chosen. Ireland has not evolved from the person
based influencing strategy.

23. 2323
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Why is Ireland Non-Core
• In recent times – the issue of hiring freezes of
nurses has impacted. This has already been
heard in the corridors of BioPharma and once
this message starts to move – the perception is
very hard to shake. The fact that the Irish
economic status and actions are communicated
at global level will not add to confidence in this
area
• Communication strategy for what Ireland has
to offer is fragmented and does not have a
strategic lead. Ireland is NOT the right country
for EVERYTHING and an uncoordinated
communication plan just adds to the perception
of confusing, complicated and not joined up

24. 2424
Conclusions
• Robust root cause analysis as part of a Lean six sigma
continuous improvement process identified a reduction in the
country clinical trials foot print as an imperative to increase
study execution speed and reduce costs while maintaining
quality.
• Analysis of performance data with consideration of cost and
risk factors led to proposed core county foot print of 34
countries representing an approximately 50% reduction.
• Ireland did not make core country footprint
• Ireland has many of the clinical trial jigsaw pieces in place –
but they are not joined to form a picture of a good research
country.

25. 2525
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Developing a Functioning Clinical Research
System
• The development of a functioning clinical research
system is fundamental to the evolution of LifeSciences
in Ireland.
• Healthcare practitioners play a vital role in identifying
unmet medical needs and giving direction and support
to LifeSciences research.
• The Strategy for Science, Technology & Innovation,
2006 – 2013 (SSTI), highlighted the relatively low levels
of translational and/or clinical research underway in
Ireland and stated that “the introduction of an R&D
culture within mainstream health service has been
relatively slow (and) there is a need to strengthen
considerably the health services research and policy
research capacity nationally”
• The reality today is that the resource pressures faced
by the hospital system means that research has tended
to take ‘second place.’

26. 2626
Summary
• If Ireland is to become a core site for clinical trials
everyone must be committed to making Ireland a
beacon for clinical research and we are currently far
from that
• There is no national vision on how we want to
partner as a country with biopharma re research
• A shared vision would help us focus on what each
part of the chain needs to deliver whilst maintaining
their independence
• All parts of the chain must be working correctly from
hospitals, universities, ethics committees to IMB etc.

27. 2727
Summary
Clinical Trial Research is not a commodity, but a
sophisticated element of technology in a very competitive
environment. Countries wishing to attract high-level clinical
research must offer:
– sophisticated healthcare environment
– professional investigational environment - doctors need explicit
incentives to conduct research (ie "good investigators are good
doctors”)
– institutions should have explicit objectives to engage in CR; they often
charge overheads, so this is a revenue stream, but may be poorly
organized
– countries need to offer access to modern diagnostics and treatments,
so that data generated will have relevance in a rapidly developing
healthcare environment ("future compatibility")
– comprehensive, integrated information systems are very valuable –
they enable effective review/follow up of patients on new treatments
with critical evaluation of new treatments.

28. 2828
Acknowledgements
• Pfizer:
– Dennis Joseph
– Rory O’Connor
– Anthony Chan
– John Farrell
• Amgen:
– Charles Brigden
• MMI:
– Marie Mellody

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