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THE COLLABORATIVE ADVANTAGE OF BIOPHARMA COMPANIES AND GLOBAL SERVICE PROVIDERS October 26, LA JOLLA, CA Ubavka DeNoble CONFIDENTIAL © 2016 PAREXEL INTERNATIONAL CORP. AGENDA • Drug development trends • The growing significance of Genomics and biomarkers • The importance of the real-time data access and predictive analytics • How trial design complexity impacts the service provider • Future critical alignment elements between biopharma and the service provider © 2016 PAREXEL INTERNATIONAL CORP. / 2 CONFIDENTIAL TOKYO, JAPAN DRUG DEVELOPMENT TRENDS © 2016 PAREXEL INTERNATIONAL CORP. / 3 CONFIDENTIAL FDA APPROVAL FOR ORPHAN DRUG SETS RECORD AGAIN IN 2015 • Improving NAS approval trend; highest since 1997 • Many first-in-class medicines • Orphan therapy approvals also increasing Sources: FDA.gov and Jefferies Report, February 2016 © 2016 PAREXEL INTERNATIONAL CORP. / 4 CONFIDENTIAL ONCOLOGY AND SPECIALTY DRUGS GAIN MOMENTUM Sources: Citeline, Express Scripts,2013, Drug Trend Report; IMS Health Report, 2014; JPM Healthcare Technology Report, 2013; Wells Fargo Report, 2013, PwC Specialty drug report, Fierce Biotech, DCAT, Cowen – Therapeutic Categories Outlook (Feb 2015), Strategy& analysis • Biopharma companies’ pipelines are shifting to oncology and other areas of specialty medicine – High unmet medical need Source: “Medicine Use and Spending in the U.S.: A Review of 2015 and Outlook to 2020,” IMS Institute for Healthcare Informatics, April 2016 • Significant growth in approvals for targeted oncology products in recent years • Targeted therapies expected to make up 91% of novel active substances (NAS) in oncology in 2016–2020 – Better margins – Leaner operating model • By 2020, >225 new medicines will be introduced, one-third for cancer • 2/3 of drug sales will be for specialty drugs vs. 1/3 currently © 2016 PAREXEL INTERNATIONAL CORP. / 5 CONFIDENTIAL TAIPEI, TAIWAN THE GROWING SIGNIFICANCE OF GENOMIC & BIOMARKERS © 2016 PAREXEL INTERNATIONAL CORP. / 6 CONFIDENTIAL BIOMARKERS ARE INCREASINGLY BEING UTILIZED IN STRATIFYING CLINICAL TRIALS The proportion of stratified trials is increasing Percent oncology trials selecting or stratifying using biomarkers • 73% of all ongoing/planned trials using biomarkers are oncology related; 94% of all patient reselection /stratification trials are cancer related Top sponsors of ongoing/planned oncology trials using biosimilars to select or stratify patients • Approvals rose for programs utilizing biomarkers for patient selection to 25.9%, 3x higher than development programs not utilizing biomarkers (8.4%), per a BioMedTracker analysis Sources: Citeline’s Trialtrove - data accessed January - April 2015 © 2016 PAREXEL INTERNATIONAL CORP. / 7 CONFIDENTIAL GENOMICS ARE BECOMING MORE CRITICAL IN DRUG DEVELOPMENT Target Preclinical Target Validation Drug Metabolism, Transport Drug Repositioning © 2016 PAREXEL INTERNATIONAL CORP. / 8 Clinical Launch PostMarket Differentiated Medicines Differentiated Medicines Patient Enrichment Patient Enrichment Patient Stratification Patient Stratification Efficacy Efficacy Safety Safety CONFIDENTIAL REGULATORS SEEK GENOMIC INFORMATION TO INFORM DECISION-MAKING Definitions SAD: single ascending dose MAD: multiple ascending dose PK: pharmacokinetic PD: pharmacodynamic DDI: drug-drug interaction PGx: pharmacogenomic CYP: cytochrome P450 TQT: Thorough QT study © 2016 PAREXEL INTERNATIONAL CORP. / 9 CONFIDENTIAL IDENTIFYING DRUG REPURPOSING OPPORTUNITIES Background: Drug repurposing can accelerate medicine development. While in pharma, we worked with our clinical colleagues to identify additional indications for an existing medicine. Atopic Dermatitis Acne What we did: Our experts conducted a comprehensive, clinical transcriptomics analysis across multiple dermatologic conditions. Value we added: Our experts identified additional dermatology indications for this medicine, discovered mechanistic connections between skin diseases and generated new hypotheses to accelerate medicine development. PAREXEL Genomic Medicine can advise clients on lifecycle management strategies Drug Discovery Today (2014) 19 (9): 1364-71 © 2016 PAREXEL INTERNATIONAL CORP. / 10 CONFIDENTIAL Psoriasis BERLIN, GERMANY THE IMPORTANCE OF THE REAL-TIME DATA ACCESS AND PREDICTIVE ANALYTICS © 2016 PAREXEL INTERNATIONAL CORP. / 11 CONFIDENTIAL CAPITALIZING ON REAL-TIME DATA DESCRIPTIVE – REPORTING INVESTIGATIVE – DIAGNOSTIC PREDICTIVE – SIMULATION What happened? Why did it happen? What could happen? © 2016 PAREXEL INTERNATIONAL CORP. / 12 CONFIDENTIAL THE SOLUTION Speed and Simplify Your Journey to Market NOVEL TECHNOLOGY © 2016 PAREXEL INTERNATIONAL CORP. / 13 EXPERT SERVICES CONFIDENTIAL INDUSTRY STANDARDS IMPACT CLINICAL DEVELOPMENT PLATFORM END TO END CLINICAL PROCESS CONVERGENCE Country Allocation Site Start-Up Randomization Trial Supply Management Clinical Trial Management System Electronic Data Capture Imaging Patient Reported Outcomes Protocol Deviations Data-Driven Monitoring LEVERAGE OF SMAC TECHNOLOGIES Social Mobile Analytics Cloud About How We Interact About Big Data and Analytics Patients Sites Clinical Services Teams Access to Digitized Information Combined Insight Right Decisions © 2016 PAREXEL INTERNATIONAL CORP. / 14 CONFIDENTIAL Regulatory Platform BENEFITS TO THE BUSINESS DRIVE DOWN COSTS ACCELERATE DEVELOPMENT TIMES Reduce monitoring costs while enhancing quality Make better decisions faster IMPROVE COMPLIANCE Turning data into knowledge Moving from transactional to transformational © 2016 PAREXEL INTERNATIONAL CORP. / 15 CONFIDENTIAL PEOPLE, PROCESS & TECHNOLOGY Focus on your core competency BOSTON, MASSACHUSETTS HOW TRIAL DESIGN COMPLEXITY IMPACTS THE SERVICE PROVIDER © 2016 PAREXEL INTERNATIONAL CORP. / 16 CONFIDENTIAL INCREASING TRIAL COMPLEXITY • Major shift in business mix toward more complex studies (e.g., oncology) • Patients for targeted indications more difficult to find • Specialized centers with internal IRBs* delay startup $194 *Institutional Review Boards Source: Medidata PICAS database score for therapeutic areas: high>70, medium= 20-70, low<20 © 2016 PAREXEL INTERNATIONAL CORP. / 17 CONFIDENTIAL CLINICAL DEVELOPMENT OPTIMIZATION = PAREXEL Optimization Innovations DYNAMIC PLANNING DESIGN START-UP EXECUTE SUBMIT Commercialization and Outcomes Plan Regulatory and Ethical Approval Recruitment and Retention Data Management / Statistics Aggregation Regulatory Strategy Investigator Grants and Contracts Adaptive Monitoring Regulatory Services Study Training Data Surveillance Clinical Study Report Site Regulatory Documentation Trial Management and Analytics Publications Critical Path Management Imaging and Spirometry Study Transparency / Disclosure Clinical Trial Logistics Payments Cross Data Analysis Quantitative Clinical Development Protocol Optimization Country and Site Selection Risk Assessment End-to End Data Standards and Trial Master Storage First Protocol Approval First Subject First Visit (FSFV) Last Subject Last Visit (LSLV) DYNAMIC PLANNING © 2016 PAREXEL INTERNATIONAL CORP. / 18 CONFIDENTIAL Clinical Study Report Approved PROTOCOL OPTIMIZATION - HOW DOES THIS WORK? OUR GOAL 5 4 Help clients develop multiple study designs in order to find the optimal one. 3 2 1 A Standard Building Blocks in Every Study Considerations for Each Building Block Leverage 30 Years of PAREXEL Experience & Data Interrogate Relevant Building Blocks Scenarios that assist Clients with tradeoff decisions B C D E © 2016 PAREXEL INTERNATIONAL CORP. / 19 CONFIDENTIAL THE PHILOSOPHY BEHIND BETTER INFORMED DECISION MAKING INVESTIGATOR & PATIENT VOICE THE BIG DATA ENGINE The Power to Identify the “right countries, sites & patients” Bringing in the Investigator & Patient Voice PREDICTIVE ANALYTICS Turning Data Into Knowledge CLIENT DISCUSSIONS & ACTIONABLE DECISIONS Effective Strategy Planning by Understanding Risk DATA-DRIVEN INSIGHTS TO YIELD CONSENSUS ON ACCEPTABLE RISK 20 © 2016 PAREXEL INTERNATIONAL CORP. / 20 CONFIDENTIAL TAIPEI, TAIWAN FUTURE CRITICAL ALIGNMENT ELEMENTS BETWEEN BIOPHARMA AND THE SERVICE PROVIDER © 2016 PAREXEL INTERNATIONAL CORP. / 21 CONFIDENTIAL BIOPHARMA FACE ENORMOUS PRESSURES • Demonstrating proof-of-concept • Creating Target Product Profiles with endpoints that support regulatory approval • Identifying the right partner for protocol design, site selection and data collection/integrity PERCENT OF R&D ORIGINATED OUTSIDE THE TOP 25 PHARMACEUTICAL COMPANIES • Managing ever-changing regulatory and reimbursement landscapes 80% © 2016 PAREXEL INTERNATIONAL CORP. / 22 CONFIDENTIAL KEY ELEMENTS FOR SUCCESS Whether you seek to license your compound, reach proof-ofconcept, or enter the clinic and commercialize, the PAREXEL BioPharm Unit’s flexible model will help you extract maximum value from your compound or portfolio by: • Enhancing internal capabilities • Helping reach faster go/no-go decisions • Increasing compound value by demonstrating PoC and understanding regulatory and reimbursement landscape • Accelerating study start-up and site selection • Ensuring logistical planning and execution is integrated into the entire trial process © 2016 PAREXEL INTERNATIONAL CORP. / 23 CONFIDENTIAL BENEFITS OF PARTNERING To reach your goals faster, the PAREXEL BioPharm unit: • Assigns a senior PAREXEL executive to lead a dedicated team • Develops a strategy to minimize complexity, accelerate timelines, and reduce fixed costs • Designs commercialization solutions to accelerate development, substantiate value and vet evidence • Provides access to sites and patients across Europe, Asia and the Americas • Differentiates your company and compound in the eyes of potential investors and partners • Helps you derive the most value from your compound © 2016 PAREXEL INTERNATIONAL CORP. / 24 CONFIDENTIAL THANK YOU © 2016 PAREXEL INTERNATIONAL CORP. / 25 CONFIDENTIAL ONGOING VIRTUALIZATION OF BIOPHARMA INDUSTRY • Small-to-midsize companies, including virtual companies, rely heavily on outsourced services: • Large, established companies increasingly willing to extend the range & breadth of outsourced services: • Executing clinical trials • Expanding regulatory and commercial capabilities • Regulatory • Managing cost and time to market • Clinical IT © 2016 PAREXEL INTERNATIONAL CORP. / 26 CONFIDENTIAL • Commercial Virtualization of Biopharma ACCELERATED REGULATORY PATHWAYS • 64% used at least one accelerated pathway • More than a third used multiple accelerated pathways Drug Pipelines and Specialty Products © 2016 PAREXEL INTERNATIONAL CORP. / 27 CONFIDENTIAL HEALTHCARE SPENDING OUTPACES GDP AND WAGES INDEXED GROWTH IN HEALTHCARE SPENDING, GDP AND WAGES IN FOUR COUNTRIES 350 300 250 200 150 100 19921997200220072012 350 300 250 200 150 100 19921997200220072012 350 300 250 200 150 100 19921997200220072012 350 300 250 200 150 100 19921997200220072012 Healthcare Spending G DP • Healthcare spend growing at an unsustainable pace • Limited objective data on value • Biopharmaceutical companies face external pressures to reduce drug costs • Biopharmaceutical products help bend cost curve down Wage s Note: Index on basis of local currency Sources: BCG Analysis; OECD Health Data 2009; EIU, GBE (Gesundheitsberichterstattung des Bundes), CMS, INSEE, Office for National Statistics UK; All data indexed to 100 Importance of Payers © 2016 PAREXEL INTERNATIONAL CORP. / 28 CONFIDENTIAL REAL-WORLD EVIDENCE PLATFORM • Advances in computing power to integrate real-world data Patient Population from Secondary Data Assets Patient Population from Clinical Trials Phases I-III Approv al © 2016 PAREXEL INTERNATIONAL CORP. / 29 Post-Approval Research CONFIDENTIAL • Allows study of heterogeneous patient populations beyond those studied in clinical trials • Age groups • Disease progression • Patient lifestyle variance • Compliance PERSONALIZED MEDICINES ARE BECOMING MORE AVAILABLE 138 FDA approved drugs with biomarker information on their label 20% of FDA approvals in 2014 were for targeted therapies Adapted from Pharmaceutical Research and Manufacturers' Association (PhRMA): Value of Personalized Medicine (2015) © 2016 PAREXEL INTERNATIONAL CORP. / 30 CONFIDENTIAL 55% OF PERSONALIZED MEDICINES ARE WITHIN ONCOLOGY/HEMATOLOGY AND PSYCHIATRY © 2016 PAREXEL INTERNATIONAL CORP. / 31 CONFIDENTIAL MARKET DRIVERS INFLUENCING NEED FOR GENOMIC MEDICINE SERVICES Decision Maker Decision Drivers Clients Looking for information to drive drug development decision making Regulators Seek pharmacogenomic information to understand who will benefit or be harmed by the drug Payers Want companies to demonstrate value over current medicines Patients Want medicines that work for them and don’t cause side effects © 2016 PAREXEL INTERNATIONAL CORP. / 32 CONFIDENTIAL INTEGRATED MULTI-OMICS APPROACHES FOR NOVEL TARGET DISCOVERY Transcriptomics: IL23 vs IL12 Proteomics: IL23 vs. IL12 200 150 Comp.2 [12.25%] 100 50 0 -50 -100 -150 -200 -300 -200 -100 0 100 200 300 Comp.1 [25.66%] Integrated Multi-omics Network Causal Reasoning & Inference Novel Target Candidates J Immunol (2014) 192: 2527-8 EBI Immunogenomics Conference 2015 Background: While working in pharma, we partnered with pre-clinical scientists to develop and implement a multi-omics strategy to discover novel, specific drug targets in the IL23 pathway. What we did: Our experts supported multi-omics strategy design and applied cuttingedge methodologies (e.g., causal reasoning, advanced network analysis) to analyze, integrate, and interpret the multi-omics experimental findings. Value we added: In close collaboration with our bench scientist colleagues, we discovered novel drug targets that are validated in follow-up experiments. PAREXEL Genomic Medicine can help clients select and validate drug targets. CONFIDENTIAL © 2016 PAREXEL INTERNATIONAL CORP. / 33 ADME GENETICS EXPLAINS EXPOSURE DIFFERENCES Drug X plasma concentrations over time by CYP2B6 genotype • In a Phase I drug-drug interaction study, a subset of healthy volunteers had elevated levels of Drug X when administered with the client’s medicine. • Drug X is primarily metabolized by CYP2B6. Our experts assessed genetic variation in the CYP2B6 gene to determine if genetic variants leading to reduced CYP2B6 enzyme activity might account for increased exposure of Drug X. • The poor metabolizer CYP2B6 *6/*6 genotype was associated with elevated exposure of Drug X. The client’s medicine did not impact Drug X exposure; however, Drug X increased metabolism of the client’s medicine (data not shown) so dose adjustments of the client’s medicine are recommended. © 2016 PAREXEL INTERNATIONAL CORP. / 34 CONFIDENTIAL QUANTITATIVE CLINICAL DEVELOPMENT • Model based development is critical to take the right steps to get into IND – pave the way for successful Phase I (the right data without surprises) A fit-for-purpose modeling tool, always Create definable value in early development Cost avoidance, focus only on what is truly needed Enhancement of pharmacology data with focus on exposure response, occupancy Clear definition of “target” or “candidate” Establishing high-confidence stopping rules, eliminating clouded judgment Successful modeling helps sponsors create optimal Proof-of-Principle and Proof-of-Concept studies, delivering more valuable data earlier in development cycle Exposure to Target © 2016 PAREXEL INTERNATIONAL CORP. / 35 Binding to Target CONFIDENTIAL Expression of Pharmacology SMALL AND MIDSIZED CLIENTS YEAREND CASH AT SMALL/MIDSIZED BIOPHARMA ($ IN BILLIONS) $78 $62 • Industry as a whole has approximately $350 billion of cash • New business from segment remains strong $48 $33 • Despite recent slowdown in funding, smaller biopharma companies have about $78 billion of cash $38 • Willing and ready to deploy capital 2011 2012 2013 2014 2015 Grow the Core Source: Chestnut Partners © 2016 PAREXEL INTERNATIONAL CORP. / 36 CONFIDENTIAL DATA CAPTURE & MANAGEMENT Typical challenges • Timely availability of a data capture framework prior to first patient in • Cost effectively capture data • Leveraging ‘real time’ clinical data PAREXEL® solution Customer results: Largest study 16,000+ SUBJECTS ENROLLED IN 1,900+ SITES © 2016 PAREXEL INTERNATIONAL CORP. / 37 Robust technology platform and infrastructure supporting large trials Allow rapid study-build process with design specification generation DataLabs closely integrated with Data-Driven Monitoring to improve study oversight CONFIDENTIAL SOURCE DATA VERIFICATION & SOURCE DATA REVIEW Typical challenges • Capturing, reviewing and analyzing patient data in timely manner • Managing multiple source of information • Reporting and exporting of data • Inspection ready SDV and SDR PAREXEL® solution Customer results: 20% SDV & SDR THRESHOLD for some studies Focus SDV within EDC to critical elements Efficiently document SDR in CTMS via customizable checklists Dashboard view of site and patients Improved patient data surveillance enhances data quality safety © 2016 PAREXEL INTERNATIONAL CORP. / 38 CONFIDENTIAL PAYMENT MANAGEMENT Typical challenges • Effective control and management of contracts and trial budgets • Greater visibility into committed costs vs. projected budgets • Projecting under/over spend areas throughout the process Customer results: Impact CTMS 880,000+ SUBJECTS ENROLLED IN PAREXEL® solution Dynamically forecast and adjust spend in real time 25,000+ Easy generation of proposed payments for hundreds of sites at once STUDIES Straightforward interfacing with Accounts Payable systems © 2016 PAREXEL INTERNATIONAL CORP. / 39 CONFIDENTIAL INVESTIGATOR PERFORMANCE Typical challenges • Lengthy study start-up times • Difficulty selecting and managing investigators • Maintenance of investigator database impairs planning and study timelines Customer results: Impact CTMS 380,000+ 70+ SITES IN COUNTRIES © 2016 PAREXEL INTERNATIONAL CORP. / 40 PAREXEL® solution Reduce the cost and risk of clinical trial study start-up Have confidence that you are using the right investigators in your study Expedite site selection and patient recruitment CONFIDENTIAL DATA DRIVEN MONITORING Typical challenges • Addressing cost pressure without compromising data quality • Regulatory pressure • Maximizing the value of limited resources • Timely ability to monitor quality and safety issues Customer results: 10-25% reduction in STUDY MONITORING COSTS © 2016 PAREXEL INTERNATIONAL CORP. / 41 PAREXEL® solution Reduce costs by assessing workload to drive site visits Enhances study data integrity and scientific credibility Predictability of outcomes that withstand regulatory scrutiny CONFIDENTIAL TRIAL TRACKING & MANAGEMENT Typical challenges • Site recruitment takes too long • Large number of global sites and patients • Lack of centralized information management for Clinical Operations PAREXEL® solution Timely access to enrollment and milestones Track submissions, approvals and the study start-up process Focus on the sites that need attention with on-screen filtering and drill-through to action items © 2016 PAREXEL INTERNATIONAL CORP. / 42 CONFIDENTIAL EXAMINING RULE BASED VS MODEL BASED DESIGN ACCRUAL NUMBER FOR ILLUSTRATIVE PURPOSES ONLY Data on treatment effect + LBM Biomarker + 15 LBM5 LBM+ | 5 LBM- 7 (16) 3 + 10 LBM+ + 20(?) LBM T Accrual = 35 T Accrual = 55 3 OBD All Tox Enrichment data Reduced timeline Exploring efficacy Reduce P2b $$ ~$55K/Pat* $3.1M 3 Model Based 3 T Accrual = 55 3 3 40 3(15) 3 Rule Based No MTD DLT? Exploring safety ~$43K/Pat* $2.4M No data on treatment effect 3 3 1 2 3 4 5 6 Timeline in Months © 2016 PAREXEL INTERNATIONAL CORP. / 43 CONFIDENTIAL 7 8 9 * Operation fees only WELL POSITIONED FOR PHASE IIB • • • • Reduce timeline to acquire efficacy data Reducing risk of 2b design with defined patient enrichment Increase Investigator interest in 2b (improved enrolment) Reduce $ Investment for Phase 2b and time to Phase 3 Data on treatment effect + LBM Biomarker + 15 LBM5 LBM+ | 5 LBM- 7 (16) 3 + 10 LBM+ + 20(?) LBM T Accrual = 35 T Accrual = 55 OBD All Tox Enrichment data Exploring Efficacy ~$55K/Pat $3.1M 3 Prospective hypothesis testing Confirm LBM Response rate 3 3 3 1 2 3 © 2016 PAREXEL INTERNATIONAL CORP. / 44 4 5 6 CONFIDENTIAL 7 8 9 REGULATORS SEEK GENOMIC INFORMATION TO INFORM DECISION-MAKING Graphic courtesy of: Issam Zineh Office of Translational Sciences CDER U.S. Food and Drug Administration FDA, EMA and PMDA have all recognized the importance of genomic sampling in clinical trials: – published guidance to industry on pharmacogenomics – ICH guideline E18 on genomic sampling and management of genomic data has been released for public consultation © 2016 PAREXEL INTERNATIONAL CORP. / 45 CONFIDENTIAL DRUG DEVELOPMENT CHALLENGES • Clinical studies are becoming more complex • Cycle times too long • Cost pressure • Lack of real-time and standardized data and analytics © 2016 PAREXEL INTERNATIONAL CORP. / 46 CONFIDENTIAL PHASE III FAILURES Success Rates by Phase, 2010 vs. 2011 vs. 2012 vs. 2013 (lead and secondary indications) Approximately 40% fail! Source: Korieth, Karyn.. “Facing protocol amendments head-on.” The CenterWatch Monthly 23.4 (April 2016): 1-13. Print © 2016 PAREXEL INTERNATIONAL CORP. / 47 CONFIDENTIAL PHASE III FAILURES - Recent PAREXEL analysis, we collected and evaluated data on 38 Phase III failures from mid-2012 through 2015 from a variety of publicly available sources - Failed to meet primary or secondary efficacy endpoints - Phase III trials that failed due solely to safety issues are not included - These 38 failed trials collectively enrolled nearly 150,000 patients © 2016 PAREXEL INTERNATIONAL CORP. / 48 CONFIDENTIAL ADAPTIVE DESIGNS TRADITIONAL DESIGN (CARGO) ADAPTIVE DESIGN (PASSENGER) How could these designs reduce amendment & failure risk? Prospectively planned opportunity to revisit initial assumptions based on interim data – e.g., Drop a dose arm that is ineffective or adapt sample size based on observed treatment effect differences © 2016 PAREXEL INTERNATIONAL CORP. / 49 CONFIDENTIAL HOW DO WE FIND THE RIGHT INVESTIGATIVE SITES? A COMPREHENSIVE PICTURE OF THE INVESTIGATOR AND SITE LANDSCAPE DATA QUALITY DIAGNOSTICS EXPERIENCE PATIENT POPULATION SITE PERFORMANCE DATA IN THE BROADEST SENSE ENROLLMENT INVESTIGATOR VOICE RESPONSIVENESS © 2016 PAREXEL INTERNATIONAL CORP. / 50 CONFIDENTIAL A SEA OF DATA CTMS Geo Profiling Imaging Validation of instruments IRB Clinical Trial Data Surveys Lab Data © 2016 PAREXEL INTERNATIONAL CORP. / 51 IVRS CONFIDENTIAL Audits IDENTIFYING SIGNALS FROM THE NOISE INTERNAL & EXTERNAL DATASETS • Master the datasets − Investigator − Study − Site © 2016 PAREXEL INTERNATIONAL CORP. / 52 NORMALIZE THE DATA • Compare to the median performance on the same study in the same country TURNING DATA INTO KNOWLEDGE • Gain real insights CONFIDENTIAL INCREASED STUDY PREDICTABILITY • Get the right sites, countries and patients for your study ACCESSIBLE DATA REGIONAL AND COUNTRY HEAT MAPS WITH SITE LEVEL DRILL-DOWN Filter for Best Sites in Japan © 2016 PAREXEL INTERNATIONAL CORP. / 53 CONFIDENTIAL DO THE PATIENTS EXIST? Electronic Health Records (EHR) Insights Early identification of potential issues with protocol inclusion and exclusion criteria will enable a risk based approach to feasibility and clinical trial management Most Challenging Eligibility Criteria Number of Record Queries Independent Criteria Impact 18,536 (100%) Criteria 1 16,152 (87%) Criteria 2 17,996 (97%) Criteria 3 © 2016 PAREXEL INTERNATIONAL CORP. / 54 Identifying the impact certain criteria will have on the patient pool allows management of risk sharing 5,795 (32%) CONFIDENTIAL 18,536 16,152 15,612 2,871 Potential patient population for study CLINICAL TRIAL INTELLIGENCE Industry benchmark data Competitive site landscape MAGNITUDE OF EXISTING TRIAL DATA Previous study outcomes © 2016 PAREXEL INTERNATIONAL CORP. / 55 CONFIDENTIAL Study and drug pipelines Study duration and timelines DIGITAL LISTENING: PROVIDES UNCENSORED INSIGHT DIGITAL LISTENING is Data Collected in Real-time via Social Media to Support Better Decision-Making • Analyze conversations • Understand and advise clients TWITTER BLOGS Key Benefits Develop strategies to mitigate potential challenges NEWS FORUMS • Engage patients and/or influencers • Understand Sentiment – assess what is said, whether good, bad or neutral What We Learn from Digital Listening: Examples Understanding Patient Perceptions Tracking Top Physicians and Patient Influencers Patients speak openly about illnesses, conditions and drugs on social media Social media influencers range from top doctors to recent cancer survivors to authors and more Accurate insight into patient/medical staff experiences Target bloggers/tweeters to push information Cost effective Global reach © 2016 PAREXEL INTERNATIONAL CORP. / 56 CONFIDENTIAL COUNTRY DECISION MAKING SUPPORTED BY PREDICTIVE ANALYTICS A data-driven approach to country selection takes into account key parameters to gain a better awareness of the risks associated with country selection SELECT THE RIGHT COUNTRIES DATA-DRIVEN ALLOCATION Identify the most desirable countries from the beginning Use the data to drive allocation of countries Validate protocol feasibility with local clinical operations Enforce indication and protocol specific assessment STRATEGY TRANSPARENCY Allow efficient and effective conversations on country allocation RESULTS RESULTS RESULTS Increase quality of country selection Increase predictability of country performance Increase sponsor confidence in country selection capabilities © 2016 PAREXEL INTERNATIONAL CORP. / 57 CONFIDENTIAL RISK ASSESSMENT Feasibility allows us to maximize what we know, firm up what we suspect, and minimize what we don’t know Undiscovered Knowledge Feasibility Undiscovered Knowledge Feasibility What We Do Know What We Don’t Know What We Don’t Know What We Suspect What We Suspect Feasibility will never be perfect. There will always be risk in the delivery of clinical trials. Reducing risk to an acceptable level is the goal. © 2016 PAREXEL INTERNATIONAL CORP. / 58 CONFIDENTIAL ADAPTIVE TRIAL DESIGN CAN POTENTIALLY REDUCE COST OF FAILURE • About 50% of Phase III trials fail • Average cost of $20 M makes it an expensive problem • Root cause attributed to traditionally rigid, inflexible design • Adaptive trial design (ATD) allows to revisit initial assumptions and change course © 2016 PAREXEL INTERNATIONAL CORP. / 59 CONFIDENTIAL REAL-TIME DATA AND PREDICTIVE ANALYTICS TRANSFORMING STUDY EXECUTION Value Adaptive Trials Strategic Planning Proactive Interventions Modelling Normality Data Driven Interventions Data Aggregation Maturity Resource required Silo’ed Systems Data Driven Interventions Alerts Raw Data Modelling Normality Anomaly Detection Proactive Decisions Actionable Information # People/Study Monitored © 2016 PAREXEL INTERNATIONAL CORP. / 60 CONFIDENTIAL DATA-DRIVEN FEASIBILITY REQUIREMENTS TURNING DATA INTO KNOWLEDGE UNDERPINNING BIG DATA ENGINE INVESTIGATOR AND PATIENT VOICE PREDICTIVE ANALYTICS Power to identify the “right countries, right sites, right patients” Supporting Solutions Analysis and Scenario Modeling + Visualization A Single Intelligence Platform CRO Site Forecast CTMS EDC Medical Imaging RTSM / IRT External Data Sources DATABASE 2 DATABASE 3 Site Optimization DATABASE 4 © 2016 PAREXEL INTERNATIONAL CORP. / 61 Investigator Surveys Pre-Screening Platform CONFIDENTIAL What We Do Know What we Risk Patient Feasibility Survey DATABASE 1 Decisions based on consensus of acceptable risk Country Allocation Digital Listening EHR INSIGHTS UNDERSTANDING RISK Study Optimization Risk Management THE IMPACTS CHURN? COSTS? DELAYS? A big factor contributing to delay is the 'churn rate’ among investigators. In some estimates, over 50% of investigators have only completed one study. The average cost to develop and gain marketing approval for a new prescription medicine, a process often lasting longer than a decade, is now $2.56 billion dollars.* On average, 2-3 protocol amendments can delay a trial by 2 months, with each amendment adding $500,000 in additional costs.* * Tuft CSDD Outlook 2015 * Tufts May 12, 2014, International Journal of Environmental Research And Public Health. HOW TO MITIGATE THESE CHALLENGES WITH BETTER DATA- DRIVEN DECISIONS © 2016 PAREXEL INTERNATIONAL CORP. / 62 CONFIDENTIAL INDUSTRY CHALLENGES Site landscape is highly fragmented with variable performance 40% of participating Investigators never conduct another FDA regulated study About 30% of sites don’t enroll a single patient Source: CenterWatch Reports © 2016 PAREXEL INTERNATIONAL CORP. / 63 CONFIDENTIAL Studies don’t meet their enrollment timelines 80% of the time POSITIVE TREND IN FDA APPROVALS CONTINUES NME Approvals Total Orphan First-in-class Breakthroughs 50 45 41 39 40 30 30 24 27 26 21 18 20 10 0 2007 • 2008 2009 2010 2011 2012 2013 2014 2015 Growth in the number of approvals is observed for orphan drugs FIPCOs defined as companies with annual R&D spend of $500 million or over. SEBPCO defined as companies with annual R&D of less than $500 million. Sources: www.fda.gov. Pink Sheets 2010 -2015. PAREXEL Biopharmaceutical R&D Statistical Sourcebook 2016/2017. Michael Lanthier, Kathleen L. Miller, Clark Nardinelli and Janet Woodcock; “An Improved Approach To Measuring Drug Innovation Finds Steady Rates Of First-In-Class Pharmaceuticals, 1987-2011,” Health Affairs, 32, no.8 (2013):1433-1439 © 2016 PAREXEL INTERNATIONAL CORP. / 64 64 CONFIDENTIAL