Clinical R&D: Challenges & OpportunitiesAmarnath Sharma MPharm PhD
2nd Annual State of Clinical Development Cost Conference
This document provides an outline of a presentation and is incomplete without the accompanying oral commentary and discussion. Conclusions and/ or potential strategies contained herein are NOT necessarily endorsed by Pfizer management. Any implied strategy herein would be subject to management, regulatory and legal review and approval before implementation.
Amarnath Sharma, MPharm, PhDVice President, Clinical Research & Precision MedicineWorldwide Development OperationsJanuary 10, 2012
Outline
ChallengesLow R&D ProductivityLoss of product exclusivity
OpportunitiesBuild strategic partnership
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Build strategic partnershipGlobalization of clinical trials
Transformation of Dev Ops at PfizerKey elements of the new model
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Current R&D Model is Not Sustainable
Low R&D Productivity & Increasing Costs
$1,200
$1,500
R & D Costs to Bring a NME to Market
What will the future be?
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$0
$300
$600
$900
1970 1980 1990 2000 2010
Cos
t ($
Mill
ion)
s la
unch
ed
02-2
008
5
4
3
Successful Launches vs. R&D Spend
Individual R&D Productivity:A Snapshot
For External Presentation Purposes; Not for Distribution.Note: "Successful" NMEs are those that achieve >$600M/yr WW peak sales Source: EvaluatePharma, BCG analysis
0 10 20 30 40 50
Succ
essf
ul N
MEs
betw
een
200
2
1
0
R&D spend in $B 1998-2004
Each dot representsa biopharma company
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Loss of Exclusivity for Major Products & Patent Erosion
Potential Loss of Significant Revenue
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Multiple Reasons For Low R&D Productivity
Compound and / or target related issuesInadequate therapeutic indexThe drug target is not well understoodThe target is valid only in sub-group of patients
Clinical trial design issues
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Efficacy observed in the early clinical trials (phase II) have been relatively poor predictors of phase III success Appropriate patient population is not well defined
Clinical trial operations issuesCostQualitySpeed Qualified investigators and sites
Current Industry Trends
• More outsourcing to reduce fixed development costs
• Increased globalization of clinical trialsContinued advancement in execute studies with quality and cost-effectiveness in emerging markets and around the world
• Intensified regulatory focus on GCP compliance & quality
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“Quality by Design” in every step of the clinical trial process, from study concept, through protocol development, execution, and reporting
• Amplified clinical trial complexity & “Precision Medicine” approachIncreased complexity of clinical trial design, partnerships and reliance on third parties for trial conduct is likely to result in an increasing shift for sponsors to prove the integrity of their clinical trial dataNeed to prospectively identify patient cohorts of potential “responders” will require the use of biomarkers and alternate trial designs
Cost• The cost of clinical trials continues to increase by more than 20% per
year in developed markets• Conducting trials in developing countries can reduce costs by > 50%
Speed
What is Driving the Globalization of Clinical Trials?
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Speed• Patient recruitment in developing markets can more than 100% faster
compared to the U.S. and Western Europe
Availability of large, treatment naïve patient populations
Potential new biopharmaceutical markets for growth
Increased Globalization of Clinical TrialsA Shift to the East
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Sources: http://www.clinicaltrials.gov/ct2/search/map, date accessed: 16 January 2011.
Karlberg JPE. Responding to Emerging Queries on the Legitimacy and Validity of Globalization of Clinical Trials. Clinical Trial Magnifier. March 2009.
Tufts Center for the Study of Drug Development, Outlook 2008.
R&D centers are looking for opportunities in the emerging markets.
Overall level of comfort with the quality of deliverables/services provided by clinical service providers (including your own company) in each regions.
Providers: Quality by Region Results from 2011 Avoca CRO Oversight Survey
82%
77%
54%
43%
15%
21%
43%
52%
3%
2%
2%
5%
North America
Western/Central Europe
Australia/New Zealand
Eastern Europe
N
102
103
81
99
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34%
27%
15%
12%
11%
8%
48%
54%
51%
50%
36%
43%
19%
19%
34%
38%
53%
48%
0% 20% 40% 60% 80% 100%
Japan
Latin/South America
India
Asia, other than India/China/Japan
Africa
China
Very comfortable Somewhat comfortable Not very comfortable
80
89
94
78
73
83
Need for Qualified InvestigatorsA Supply and Demand Imbalance
More Investigators, Lots More Studies Non-US Investigators
8,373
11,22310,735
11,914
8 000
10,000
12,000New Studies New Investigators
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2,859 2,676
5,157
7,641
6,226 6,324
1,697 1,518
3,063
4,4613,526
3,038
4,0694,941
4,477 4,482
0
2,000
4,000
6,000
8,000
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
Source: CenterWatch Analysis, FDA, 2008. Published in “State of the Clinical Trials Industry” CenterWatch, 2008
Perceptions & Misperceptions Abound
Misperceptions regarding the globalization of clinical trials include:• Exploitation of vulnerable
clinical subjects• Purposefully seeking loose
regulatory frameworks in which
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regulatory frameworks in which to conduct trials
• Ignoring safety concerns• Exploiting loophole in FDA regs:
if studies in U.S. suggest a drug has no benefit, trials from abroad may be used in lieu to secure FDA approval
Increasing Oversight & Regulation
“FDA should expand its oversight of foreign
clinical trials.”
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FDA increased its number of inspections from 2007-2009, but still conducts relatively
fewer foreign inspections than domestic inspections - 11% of foreign establishments
inspected in 2009
Recent Trends in Regulatory Inspections
• Both FDA and PMDA have increased the number of inspectors and inspections
• Findings at the site level are increasing and resulting in more findings
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The CenterWatch Monthly, Vol 18, Issue 8, August 2010
resulting in more findings of GCP Violations and Warning Letters
Protocol Violations
Inadequate IC Process
Inadequate IRB Review
Requirement of IRB
Deviation
GCP Warning Letter Breakdown(FDA WLs Issued in 2009-10)
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http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/EnforcementActivitiesbyFDA/WarningLettersandNo iceofViolationLetterstoPharmaceuticalCompanies/default.htm
0 1 2 3 4 5 6 7 8 9 10
Inadequate Monitoring
Inadequate PI Oversight
Annual IRB Approval Missed
Inadequate Documentation
IRB Deviations PI Deviations Monitor Deviations(3)(18)(5)
How Does Industry Approachthese Issues?
• Ensure compliance with the applicable laws and regulationsNeed to consider all relevant laws in addition to specific medicines laws concerning the conduct of trials, e.g., Privacy laws
• Comply with internationally recognized guidelines and ethical principles
Examples: ICH, GCP, CIOMS and Declaration of Helsinki
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• Require a universal position to be adopted for all clinical research activities -- this is ideal
Example: Pfizer’s “Global Clinical Trials Standards” Policy• Support global programs designed to enhance infrastructure for
study conduct and oversightEthics committees, qualified investigators & investigator training
• Seek certification of Research Programse.g., AAHRPP
Site Training & Certification
AAHRPP certification Goal
• All Pfizer CRUs certified (a first for Industry)
• Core Research Sites in progress: Canada, USA, India
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India, Hong Kong
• Additional sites progressing towards certification in:
China Russia Brazil
• Global Health Fellows worked with AAHRPP to improve ethical research standards in China
Collaborative Training Workshops:E.g., Clinical R&D in Korea
• 5 Training Sessions on R&D with 550 University Graduate Students; Certificates IssuedCo-hosted with a local CRO (DreamCIS) and co-sponsored with KoNECT (Korea National Enterprise for Clinical Trial), Catholic University of Daegu, Korea University Anam Hospital Clinical Trial Center, Catholic Medical Center Clinical Research Coordinating Center, Inje University Pusan Paik Hospital Clinical Trial Center
• R&D Workshop for 200 physiciansSponsored with Hospitals in Daegu, Severance Hospital. Catholic Medical Center, Korea University Medical Center, Asan Medical Center, Seoul National University H it l B P ik H it l
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Hospital, Busan Paik Hospital.
• Research Operations Training for 40 Coordinators from CRS consortium (Asian Medical Center, Samsung Medical Center, Yeonsei University Severance Hospital, Seoul National University Hospital).
• Pfizer KOREA KoNECT: Expert Course for Clinical Research CoordinatorsSponsored by the Ministry of Health, Welfare, Family Affairs, KONECT, Daejeon City. Hosted with Chungnam National University Hospital CTC, Kyunghee University School of Nursing.
Focus on Quality, Compliance and Performance
% Non Performing Sites
13
23
0
5
10
15
20
25
Emerging Markets Developed Markets–213% –82%
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Emerging Markets Developed Markets
0%
20%
40%
60%
80%
100%
Emerging Markets
Developed Markets (ex US)
FDA Inspection results Sep-08 to Apr-10
Official Actions
Voluntary Actions
No actions
–100% –100%
Summary
• Significant trend towards more outsourcing to reduce fixed development costs
• Globalization of the clinical trials is creating “supply/demand” pressures on regulators, sponsors and clinical investigators in emerging marketsThe ind str m st in est reso rces to ens re q alit and
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• The industry must invest resources to ensure quality and compliance in the conduct of global clinical trials including a risk based approaches to quality management
• GCP training of investigators and clinical staff is essential• Ultimately, well conducted global clinical trials will improve the
R&D productivity and also increase patient access to medicines
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Transformation of the Dev Ops Model at Pfizer
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at Pfizer
Simple with Clear Accountability
17+ FSPs ICON & Parexel
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Key Elements of New Dev Ops Model
From Pfizer's previoussourcing model...
...to innovative, value-creatingstrategic partnerships
17+ Functional Service Providers for individual studies resulting in diffuse accountability & limited transparency
Full service model with alliance partners supporting entire assets with increased visibility and accountability
Quality = imposed Pfizer processes
Quality = AP responsibility for robust process with Pfizer accountable for oversight
Selection of best indi id al Collaboration for best o erall clinical de elopment q alit &
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Selection of best individual functional expertise
Collaboration for best overall clinical development quality & performance
Prescriptive specifications on clinical studies
Incentives towards innovative approaches from APs In the clinical development plan, on resourcing, site selection and timeline
Suppliers' competition on unit costs
Partners' competition on overall performance and joint value creation
With focus on speed & qualityImpact on NPV of assets
Transactional relationships Trusting environment / platforms in which innovative ideas can flourish
This is an industry-leading change
Extensive Due Diligence:Evaluation of Leading1 Global Clinical CROs
Quality was a primary driver of selection of the partners:Overall quality approaches/philosophy, quality quantification, learnings from past experienceTechnical capability to execute on plan, including IT support of tracking of qualityWillingness to be transparent and to work with us collaboratively on addressing challenges
Evidence-based process was followedDiscussions with senior management of each companyDeep technical discussions between Pfizer subject matter experts (SMEs) and partner SMEs
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on process and cultureOn-site audits by team of internal and external experts covering following areas:
1. Top 4 of 5 by revenue in the clinical development space
Regulatory Inspection ManagementCorrective action and remedial plansQC and QA activitySOP development and managementRecords managementStaff trainingSubcontracting and vendor oversightFacilities
Clinical trial related activitiesInvestigator recruitment and trainingStudy start up and close outProject managementMonitoringTrial Master FileSafety management and reconciliation Medical writing
Key document development (e.g. protocol, ICF)Information TechnologyValidation of computerized systemsClinical data management/clinical programmingData retention, security and recovery
Overarching Quality & Risk Mitigation Strategies
Quality & risk mitigation built into the agreement & operating plansBalanced Scorecard with metrics used as indicators of performance, includes specific quality metricsMetrics are used to assess performance and determine rewards/penalties Service Agreements contain requirements on specific quality/compliance Standards
Support for voluntary certification of Pfizer research programs
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Support for voluntary certification of Pfizer research programs Proposal to seek full certification by AAHRPP which is considered “Gold Standard” for independent accreditation of research programs
Regulatory agency considerationPosition of regulatory agencies (FDA, MHRA, EMA) was considered in advance of executing
Organizational model was “built for purpose” over the last 24 months
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Key Features of the New Model
• Partners input in operational plan and investigator selection to optimize quality, cost and execution timelines
• Partners commit to maintain/develop capabilities in all TAs where Pfizer needs support
• Post-PoC asset allocation to one AP with expectation that they will follow
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p ythrough the entire development / life cycle
• Expectation that all studies will be managed by one of the two APs
• Unconstraining the APs by having them use their systems and procedures to deliver value to Pfizer
With overall quality standards defining the “what” set by and actively monitored by Pfizer
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