Emma A. Meagher, MD
Transcript of Emma A. Meagher, MD
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A Case Study: Building a Research Program that Minimizes Legal Risk and Maximizes Compliance
Emma A. Meagher, MD
Vice Dean, Clinical Research
Senior Associate Vice Provost
University of Pennsylvania
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The Backdrop
Common themes prevailed in AHCs
• Clinical Research had questionable academic value
• Variable appreciation for the distinction between clinical practice and clinical research
• Variable appreciation for the rules of engagement
• Compliance expectations were perceived by those in Academia to be lower than those expected in Pharma
• Variable PI and staff expertise and limited resources
• Limited investment in infrastructure to support the enterprise
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What Changed?
Clinical Trials a way to differentiate competition in the health care market place
Early phase of drug development occurring in AHCs with greater frequency
Rapid growth in investigator initiated research• Manufacturing occurring in academia
• Increase in number and complexity of financial conflicts of interest
• Increase in management of multisite clinical trials
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Past V.s Present: A Model of Integration/Collaboration
Sci Transl Med 7 April 2010: Vol. 2, Issue 26, p. 26cm12
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Strategic Plan: Potential for Innovation
Foster Clinical Trials
Establish a Penn Venture fund to support early stage research
Provide ‘one stop shopping’ to faculty for discoveries and start-up companies
Academic Translational Research
Partner with the private sector
Research and development alliances
Translate discoveries into effective therapies, devices, products
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The Challenges/ Disincentives
Culture - limited incentive for faculty to engage
Administrative burden perceived to be inexorable
Cumbersome approval processes
Variably trained support staff with limited longevity
Limited ability of community to leverage existing resources
Funding for the support structure
Interface of IT support systems
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Recommendations of External Review
Centralizing clinical research support services
Adopting a service model for all functions that support principal investigators
Investing in IT infrastructure to facilitate access to information and provide support tools that enable clinical research
Establish a leadership position with accountable authority and responsibility to work across the institution to optimize clinical research standards at Penn Medicine
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Office of Clinical
Research
Clinical Trials Contracting
Unit
IT Infrastructure
Sponsor IND/IDE
Support Unit
Clinical Research
Operations
Monitoring/ Compliance
Program
Professional Development
Core
Financial Operations
Evolution of Central Resources
Institutes
Cancer CenterIRB
Center for Innovation
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Vice Dean & Chief Clinical Research
Officer
Director Cancer Center
Chief Financial Officer
Vice Dean Professional
Services
Director ITMAT
Chief Counsel
Vice Dean Integrative services
CPUP Academic Steering
Committee
Dean & EVP, PSOMVice Provost for research, University
Executive Vice Dean & Chief
Scientific Officer
Clinical Dept
Chairs
Engaged Leadership and Implemented Oversight
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1467
289
230
156
145
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116104 36
Clinical Trials
Human Data Sets
Tissue/biospecimen
Mechanistic or Physiologicstudy in human subjects
Sociobehavioral
Other
Survey research
Quality Improvementresearch
Epidemiological research
Penn’s Clinical Research Portfolio
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Continued growth in clinical trial volume and complexity
0
10,000,000
20,000,000
30,000,000
40,000,000
50,000,000
60,000,000
70,000,000
FY 2014 FY 2015 FY 2016
Unassigned
Universities and MedicalCenters
Other Non‐ProfitOrganizations
Federal Flow‐Thru
Federal
Commercial/ Industrial
100 100 100
170 170187
020406080100120140160180200
ApproximateIND/IDE/CTA
PennSponsors ‐July 2012
ApproximateIND/IDE/CTA
PennSponsors ‐July 2013
ApproximateIND/IDE/CTA
PennSponsors ‐July 2014
ApproximateIND/IDE/CTA
PennSponsors ‐July 2015
ApproximateIND/IDE/CTA
PennSponsors ‐July 2016
IND/IDE/CTAPenn
Sponsors ‐April 2017
Growthin#ofINDs # of protocols with > 1 site relying on
Penn IRB1 -5 sites 81
6-10 sites 5
11-20 sites 3
20-30 sites 3
# of active studies with Penn serving as IRB of record for other sites
91
Total # of additional sites relying on Penn 278
$ in funding
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Awareness of the Risk Proposition
• Study Subject Harm
• Reputational Risk
- Patient harm
- Ethical considerations
- Conflict of Interest
- Policy and regulatory compliance
• Financial Liability
- study subject, fundingagency
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Followed by
An FDA inspection………..
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Clinical trials are complex and highly regulated
Focus of RiskMitigation
FinancialFraud
Privacy & confidentiality
Data integrity
Patient Safety
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Standards are set by federal (FDA, OHRP, NIH, CMS) or state regulations and institutional policies
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Mitigating risk
Institutional commitment
Investigators
Research support staff
Education & Training
Facilitation & navigation
Technology
Oversight
Enabling Compliant Research – a shared responsibility
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Study Design
Create Study
Documents
IRB /other? Review
IRB Approval
Notification to Regulatory Authorities
Investigator meeting
Site Initiation
Establish research team
Patient Enrollment
Study Monitoring
End of Trial
Follow upVisit Activity
Statistical Review
Data Management
Final Report
Clinical Trial Lifecycle – Where does the risk exist?
StudyAuditing
Prospective review (QC)
Retrospective Review (QA)
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Another External Assessment…
Organization and oversight
Infrastructure (IT, space, personnel, and training)
Clinical Trial review and approval process
Conflict of interest policies
Define metrics for tracking compliance goals
Assess the need for ongoing external input
Recommend the frequency of reports to Trustees
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Key Observations
Drug manufacturing and management of investigational products
Academic Faculty serving as regulatory sponsors
Oversight of clinical trial conduct – Monitoring and Auditing
Education and retention of a trained workforce
Prospective reimbursement analysis and its compliance oversight
Clinical Trials.gov reporting requirements
Conflict of Interest
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Key elements of an effective compliance program include
• Establish standards and procedures to prevent and detect noncompliance.
• Exercise effective compliance oversight via engagement of multiple levels of management, including the board of directors, senior management and compliance personnel; organization’s governing authority must be knowledgeable about the content and operation of the compliance program.
• Exercise due diligence to avoid delegation of authority to individuals with a history of behavior inconsistent with an effective compliance program.
• Communicate and educate employees on relevant standards and procedures and other aspects of the compliance program.
• Monitor and audit compliance programs, evaluate periodically for effectiveness, and have and publicize a system for employees and agents to report or seek guidance regarding noncompliance without fear of retaliation.
• Promote and consistently enforce the compliance program via incentives and disciplinary measures.
• Respond appropriately to noncompliance and take steps to avoid future noncompliance, including making any revisions to the compliance program.
http://www.ussc.gov/guidelines/2015-guidelines-manual/archive/2014-chapter-8
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Penn Medicine Compliance Program
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Educating Research Professionals
Early Career
CRC B/C
Mid CareerCRC C
Project Managers
Reg Affairs specialist
Certificate Program Masters
Reg Affairs
CR 101
E learning Module
Access Training
Entry Level
CRC A
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Clinical Trials Risk Mitigation: Recommendations
Compliance• Bring Investigational Drug Service into compliance with
“Good Manufacturing Practices”• Expand research compliance program • Centralize and audit prospective reimbursement analysis• Monitor compliance with clinicaltrials.gov
Training• Mandate training for investigators, sponsors, monitors• Reduce coordinator turnover through career
advancement and training
Standardization and Oversight• Institute formal scientific reviews in Departments• Increase consistency and transparency in COI policies
and process • Standardize process and coordinate oversight across
Penn Med hospitals
Status
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Three years later…. Improving… not there yet
Strategic Plan
Focused on operational
improvements
Rapid growth in volume
and complexity
Focus on Compliance
Facilitating compliant research
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The End Game
Create a culture conducive to clinical research
Demonstrate regulation and facilitation can coexist
Enable entrepreneurial activity
Create a workforce of skilled clinical and translational investigators
Attract sponsors and commercial partners
Measure impact
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