Anticipating Patient Engagement’s Impact · Structural Changes • Consolidation and integration...
Transcript of Anticipating Patient Engagement’s Impact · Structural Changes • Consolidation and integration...
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, [email protected]