Anticipating Patient Engagement’s Impact on the Evolution of Clinical Research

CTO 2018 Conference

Ken Getz, MBA

Director of Sponsored Programs, Associate Professor

Tufts CSDD, Tufts University School of Medicine

Founder and Board Chair, CISCRP

March 2018

2

“The Future Ain’t What it Used to Be”

- Yogi Berra

Structural Changes

• Consolidation and integration of clinical research service providers

• CROs as innovation and efficiency facilitators

• Absorption of clinical research into clinical practice

Operating Changes

• New skills and competencies (e.g., data scientists and navigators)

• Enterprise adoption of select patient engagement strategies and practices– Flexible, patient-and-data informed protocol design and

study management

• Integration, management and sophisticated analysis of large, diverse data sets

A New Future – Notable Changes

2008 2009 2010 2011 2012 2013 2014 2015

Multi-year filers First time filers

Global FDA-Regulated Investigators

Source: Tufts CSDD

33,920

24,805

29,670

27,60428,521 28,872

30,069

32,816North

AmericaN. & W. Europe ROW

2008 63% 17% 20%

2011 58% 19% 23%

2015 55% 22% 23%

High Turnover and Inefficiency

Source: Tufts CSDD

Year1 Filing

per year2-3 Filingsper year

>4 Filingsper year

2008 48% 19% 2%

2009 51% 23% 3%

2010 50% 21% 3%

2011 49% 20% 3%

Investigator Turnover Rates

3.5

6.5

5.2

7.9

17.5

22

0 5 10 15 20 25 30 35 40

Repeat Sites

New Sites

Site ID Site Selection Study Start-up

26.2 weeks

36.4 weeks

Site Identification to InitiationCycle Times (Weeks)

Patient Enrollment Performance

Source: Tufts CSDD, 2016 and 2017

Plan to Actual Timelines

Fail to Enroll a Single

Patient11%

Under Enroll37%

Meet Enrollment

Targets39%

Well Exceed

Enrollment Targets

13%

Enrollment Activation

and Achievement RatesIncrease in Planned Study Duration to Reach Target

Enrollment

Overall 94%

Cardiovascular 99%

CNS 116%

Endocrine/Metabolic 113%

Oncology 71%

Respiratory 95%

111

139

266

245

263254

278269

2001 2003 2005 2007 2009 2011 2013 2015

Site Non-Compliance and Fraud

Source: FDA CDER Office of Compliance

Number of Complaints Received by FDA

Global Industry Health

• Approaching $1 Trillion (US) in annual sales volume at steady ~2.3% CAGR

• 20% of sales for rare and orphan disease treatments

• Strong M&A environment and improving market capitalization

• More positive climate for industry-government relations

$649$686

$719$751 $768

$825

2008 2010 2012 2014 2016 2018P

World Wide Prescription Drug Sales (in $US BB)

Source: EvaluatePharma

A Robust Innovation Engine

4,8855,482

6,4766,531

8,0108,617

9,34910,150

10,752 10,903

2000 2002 2004 2006 2008 2010 2012 2014 2016 2017

Total Active Drugs in Global R&D Pipeline

Pipeline Growth by Therapeutic Area

Source: FDA

2006 2016 10-Year CAGR

Anticancers 2,069 4,176 7.3%

Neurologics 1,519 4,051 10.3%

Anti-infectives 1,258 2,221 5.9%

Metabolic/Endocrine 1,011 1,999 7.1%

Musculoskeletal 787 1,499 6.7%

Cardiovascular 679 950 3.4%

Immunologics 404 869 8.0%

Respiratory 435 859 7.1%

Dermatologicals 403 831 7.5%

Structural and Pipeline Change

Percent of Active R&D

Pipeline

Percent of Total Approvals

2000 9% 11%

2005 11% 20%

2010 18% 29%

2015 40% 34%

Source: Pharmaprojects; Evaluate Pharma

Number of Companies with

Active Drugs in the R&D Pipeline

Non-Top 50 Pharma Company Share of

Active Pipeline

2000 1,043 49%

2005 1,621 53%

2010 2,207 56%

2015 3,286 61%

Growing Focus on Rare andSpecialty Diseases

Proliferation of Small Sponsors

Growing Reliance on Outsourcing

Source: Pharmaprojects; Evaluate Pharma

2000-2005

2006-2010

2011 - 2016

Total Industry-wide Layoffs

89,135 205,129 194,921

Annualized 17,827 41,025 38,984

Estimated Proportion from R&D

14% 24% 28%

Pharmaceutical Industry Downsizing

$18.7

$23.4

$25.8

$28.7

2010 2012 2014 2016

Global Spending on Contract Clinical Services

($US Billions)

Rising Protocol Complexity

Typical Phase III Pivotal Trial (means) 2001 -2005

2011-2015

Total Number of Endpoints 7 13

Total Number of Eligibility Criteria 31 50

Total Number of Procedures Performed 110 187

Total Number of Planned Volunteer Visits 12 15

Number of Investigative Sites 40 65

Number of Countries 5 10

Number of Patients Randomized* 729 597

Total Data Points Collected* 494,236 929,203

Proportion of Data ‘Non-Core’ 18% 32%

Average Number of Data Collection Applications Used 2 6

Source: Tufts, CSDD; Orphan Diseases have 5x fewer patients per NDA

Drug Development Durations

6.3 6.8 7.25.9 6.0 6.1 6.3 6.8 6.7 6.8

2.92.6 2

1.4 1.21.75 1.6

1.5 1.4 1.6

87-89 90-92 93-95 96-98 99-01 02-04 05-07 08-10 11-13 14-16P

Mean Clinical Time Mean Approval Time

Source: Tufts, CSDD

(Cycle Time in Years from IND Filing to NDA Approval)

$1,044

$2,558

2003 2013

($US millions in constant 2013 dollars)

Intensifying Market Pressures

Source: Tufts CSDD

2010 2015 5-YearChange

Average Forecasted Annual Peak Sales for an Approved Drug

$816 MM $416 MM -49%

Ave. Years Between First and Second Entrant in a Newly Approved Drug Class

4.7 years 2.3 years -51%

Capitalized Cost to Develop a Successful Drug Commercialization Realities

High and Rising Development Risk

Source: Tufts CSDD

Percentage of All Drugs Entering Clinical Testing that FAIL to Receive Approval

78.7%80.9%

83.6%88.1%

in the 1980s 1990s 2000s 2010s

26.1%

19.1%

15.1% 14.7%13.2% 12.8%

11.4% 11.1%

8.4%

6.6% 6.2%5.1%

Probability of Achieving Regulatory Approval by Disease

Optimizing Drug Development

16

• Multi-stakeholder mobilization and consensus• Relevance and ownership• Feasibility, simplicity and convenience• Transparency and disclosure

• Enlightened Design and Planning• Targeted Site and Patient Identification• Real time adaptation and adjustment• Ongoing line-of-sight• Predictive analytics

• Open Innovation• Utilization of existing and trusted infrastructure• Integration of clinical research and clinical care• Continuous patient response assessment and learning

Learning HealthSystems

PatientEngagement

Rich Data& Analytics

Shifting Positioning of Clinical Trials within Academia and Clinical Practices

Historically Today

Supplemental income, low prestige Mission critical source of revenue

Physician interest in frontiers of medicine Patient demand for treatment options

Rising fixed cost to manage peripheral/labor intensive/potentially distracting activities

Integrated into clinical practice; supported by automation, in-sourced and outsourced capabilities

Clinical trials largely in dedicated facilities, separated and partitioned

Clinical trials wherever study volunteers can mostconveniently participate

Recruitment increasingly augmented by advertising and promotion

Recruitment automated by data rich EHR/EMR

Largely multi-specialty based, limited focus on singletherapeutic area specialization

Increasing focus on highly targeted subpopulations, specialty, rare and orphan diseases

• ‘Sponsor of Choice’ with study volunteers and investigative sites

• Earnest Focus on convenience and drivers of participation satisfaction

• Heightened commitment to patient and investigator diversity

• Recognition of critical role for broad public and patient education and awareness

Sponsors’ Engagement Initiatives(Implemented/Piloted/Planned)

Source: Tufts CSDD, 2017 (N=38 sponsor and CRO companies)

77% 77%

70%

47%

40%37%

Advocacy GroupSupport

Patient AdvisoryBoards

ProfessionalAdvisory Panels

CT ResultsSummaries

Home NursingNetworks

WearableDevices

Percent of Companies

Dedicated Site Strategies

9%

11%

12%

16%

24%

26%

33%

37%

41%

59%

Informed Consent review with patients

Clinical trial drug availability

Retaining study volunteers

Regulatory compliance processes

Responding to CRF queries

IRB/EC review & approval

Sponsor/CRO responsiveness to inquiries

Screening study volunteers

Enrolling study volunteers

Budget, contract negotiation & approval

Source: CenterWatch/ACRP 2015 Global Site Operations Survey (n=371)

Percent of Sites

Primary Responses

Capabilities and Specialization Investment

• Business Development/Sales• Data managers• Operating and financial controls• Recruitment 2.0 • Patient data

Partnerships

• Network building and M&A• Partnerships with health systems

Top Causes of Delays

Health Systems

At the end of 2016:

• Average operating margins were 1.7% (down from 2.4% in 2015); 34% of the nations 626 health systems had negative operating margins

• 70% of all US hospitals and 50% of all US physicians were part of a Health System (HS)

• 82% of HSs are certified EHR/EMR users

• 69% of HSs offer ‘patient engaged’ functionalities

• 80% of HSs have capability to electronically query patient health data

Source: AHRQ, 2017

HCP as Engagement Enablers

38% 42%47%

48%46%

43%

18-44 45-64 65+

Very Valuable Somewhat Valuable

• 68% of patients rate their HCP as the top preferred source for information about clinical research

• 71% of patients say that they would speak with their physician or nurse prior to deciding to participate

• 83% of patients consider their physician’s recommendation a top factor influencing their decision to participate

• 91% of patients agree that having clinical study procedures conducted during regular doctor visits would be more convenient

• 93% of patients report feeling ‘Very’ and ‘Somewhat Comfortable’ having their medical health records routinely used to identify appropriate studies

Percent of patients feel it would be ‘Very’ and ‘Somewhat Valuable’ for clinical research options to be presented during regular office visits

Source: CISCRP 2017 Perceptions & Insights Study; N=12,427

HCP Readiness

MDs (N=755) Nurses (N=1,255)

Received special training on CT in school 40% 45%

Attended lecture(s) on CT at society meetings 39% 21%

Consider themselves familiar (SW/Very) with CTs 88% 69%

Comfortable (SW/Very) providing CT info to patients 88% 63%

Comfortable (SW/Very) discussing CT opportunities with patients 91% 72%

Have referred their patients to clinical trials 60% 17%

Median number of patients referred annually 5 2

Median number of patients seen annually 3,100 5,560

Source: Tufts CSDD. Examining the Role of Health Care Providers as Patient Engagement Facilitators in Clinical Trials. Clinical Therapeutics. Sept. 2017

CRO Strategies - A Key Indicator

6%15%

72%

94%85%

28%

Niche Mid-Sized Full Service Top 10

Non-Traditional Traditional

131

146

185

2015 2016 2017P

Nu

mb

er o

f Tr

ansa

ctio

ns

Annual Deals Completed

Source: Tufts CSDD Analysis

Deal Category

CRO Integration into Study Conduct Notable Recent Transactions/Alliances

Buyer Target Deal Type Transaction Date

QuintilesIMS HighPoint Solutions Acquisition Sep. 2017

ICON Mapi Group Acquisition July 2017

QuintilesIMS DrugDev Acquisition July 2017

QuintilesIMS Coté Orphan Acquisition May 2017

QuintilesIMS TKL Research Acquisition Nov. 2016

QuintilesIMSDaVita Dialysis Centers

Strategic Alliance Aug. 2016

Bioclinica Compass Research Acquisition July 2016

PPD Synexus Acquisition May 2016

Bioclinica Clinverse Acquisition Jan. 2016

ICON PMG Research Acquisition Dec. 2015

Bioclinica MediciGroup Acquisition July 2015

PPD CRA/Radiant Research Acquisition Apr. 2015

LabCorp Covance Acquisition Feb. 2015

Source: Tufts CSDD

Data and AnalyticsNotable Recent Transactions/Alliances

Buyer Target Deal Type Transaction Date

BioclinicaMDDX Research & Informatics

Acquisition Nov. 2017

Parexel Microsoft Strategic Alliance Oct. 2017

PRASymphony Health Solutions

Acquisition Aug. 2017

ICON TriNetX Strategic Alliance Oct. 2016

IMS Holdings Quintiles Acquisition Oct. 2016

PPD Evidera Acquisition Aug. 2016

Parexel Optum Strategic Alliance Jan. 2016

Parexel Health Advances Acquisition Jan. 2016

ICON IBM (Watson) Strategic Alliance Sep. 2015

Quintiles Quest Joint Venture May 2015

LabCorp Covance Acquisition Feb. 2015

Source: Tufts CSDD

CRO Date of Acquisition

Acquirer Other Assets

Parexel June 2017 Pamplona Capital • Formativ health, nThrive, Patientco

ThreeWire May 2017Arsenal Capital

(WCG)• WIRB, ePS, Clintrax Global,

Medavante/Prophase FDANews

Bracket March 2017 Genstar Capital • Catalent, ERT, PRA, ConnectiveRx

Premier Research Oct. 2016 Metalmark Capital• Aegis Sciences Corp., Healogics, Vanguard

Health Systems

Bioclinica Aug. 2016 Cinven • Medpace*, Synlab, AMCo

SynteractHCR May 2016Amulet Capital

Partners • Pharmanet*, Patheon, Advance PCS

PPD Dec. 2011Jaguar Holding • Synexus, Radiant Research, Acurian

Private Equity-Induced Integration

Source: Tufts CSDD

Structural Changes

• Consolidation and integration of clinical research service providers

• CROs as innovation and efficiency facilitators

• Absorption of clinical research into clinical practice

Operating Changes

• New skills and competencies (e.g., data scientists and navigators)

• Enterprise adoption of select patient engagement strategies and practices– Flexible, patient-and-data informed protocol design and

study management

• Integration, management and sophisticated analysis of large, diverse data sets

A New Future – Notable Changes

‘A Future that isn’t What it Used to Be’

• Customizable, flexible, intimate engagement with patients and their community of care

• Remote quality, risk and performance oversight and management

• Highly fluid and integrated infrastructure, systems and personnel supporting open, multi-party collaborations

• Continuous data mining, analysis and adaptation

• Premium on data scientist capabilities and flexible ‘roving’ infrastructure supported by digital and mobile technology

Ken Getz

Founder and Board Chair, CISCRP

Director, Sponsored Programs, Associate Professor

CSDD, Tufts University School of Medicine

617-636-3487, Kenneth.getz@tufts.edu