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

122

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









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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