DEVELOPING CLINICAL TRIALS INFRASTRUCTURE

SESSION IV of IOM Workshop: Envisioning a Transformed Clinical Trials Enterprise in the United States: Establishing an Agenda for 2020

PAUL EISENBERG PETRA KAUFMANN JANET WOODCOCK

Senior Vice President Director, Office of Clinical Research Director, Center for Drug Global Regulatory Affairs & Safety Natl. Inst. Neurol. Dis.&Stroke Evaluation and Research

Amgen Inc. NINDS/NIH US Food & Drug Administration

November 7-8, 2011

Washington, DC

Outline Petra Kaufmann MD

I. Introduction

Infrastructure to improve trial implementation

Paul Eisenberg MD

II. Participant recruitment

II. Regulatory process

Jane Woodcock PhD

III. Opportunities

Potential elements of a trials infrastructure

• Investigator Recruitment

• Contractual agreements

• Participant recruitment plan

• Coordination of investigators (US and globally)

• Quality control systems

• Data collection, management, and analysis

• Data standards

• Communication of results

• Registration of trials and results with ct.gov

Good Clinical Practice (GCP)

• Informed consent (ICF)

• Ethical review (Institutional Review Board, IRB)

• Protocol development

• Human research participant protection

• Privacy

• Investigator training and qualification

• Adverse event (AE) reporting

Issues to be addressed:

• What would constitute an optimal clinical trials infrastructure in the U.S.?

• How would such an infrastructure address the problems stated above?

• Should infrastructure solutions be universal, tailored to specific research settings, or integrated through common standards?

• What would be required to develop a clinical trials infrastructure? What is achievable in the near- versus long-term?

I. TRIAL IMPLEMENTATION Areas that infrastructure could address:

• Investigator Training

– Standardized core content

– CME

– Standardized online training and certification

• Central certification

– Online system for sponsors and institutions to centrally verify qualifications

Investigator Recruitment

• IT solutions for matching investigators to sponsors

• Central information on – Expertise

– Capacity

– Resources

– Patient access

– Track record?

• Patient access data could be drawn in de-identified manner for clinical databases

Potential Approaches: Performance sites

• Non-traditional contributors:

– Clinicians with limited research experience

– Private practice settings

– Non-academic hospitals

• Benefits:

– Trials are conducted in relevant settings

– Results may be more broadly applicable

– Obtain data that are needed to implement the US Healthcare Reform Act

Investigator networks

• Selecting primary care or specialty care providers

– based on affiliation with academic center or geographic proximity

– Through a web-based approach

What would be required?

• Disease specific networks that include community practitioners and use standardized data collection

– “hub and spoke”

– “virtual coordinator”

• Networks that focus on a group of diseases or particular population

• Flexible networks with broad scope

• Support from multiple stakeholders, tax?

Web-based approach to trial development

• Clinical concept and question posted online

• Investigators and sponsors could propose trials

• Patients and other stakeholders could pose question to be answered through trials

• Engaging patients in developing key research questions could help facilitate downstream recruitment

• Online system would serve many stakeholders – partnership?

Infrastructure to engage potential trial participants

– Make research discussion part of the clinical encounter

– EMR notification to physicians

– Document similar to advanced directive

– Part of hospital admission or clinic check in

– Clinical trial card (like organ donor card)

Novel approach to trial coordination

• Expanding support to non-traditional centers

• Flexible infrastructure to provide coordination and administrative help

• Web-supported beyond data management

• Built-in central data-driven monitoring

• Integrated with training and certification elements for investigators

Potential approaches: Technology

• Web-based trial

• “Trial in a box”

• Mobile technology

• Social media (e.g. for recruitment)

II. Regulatory Issues

• Impact of regulatory processes and policies:

– Efficiency, cost and strategy for clinical trials

• IND vs other processes for approval of early phase studies

• Clinical trial notification vs applications

• Clinical trial material and manufacturing issues

• Companion diagnostics (“personalized medicine”)

• Investigative product co-development

• Devices

– Adverse event notification processes

– GCP inspection expectations

Clinical Trial Implementation Issues

• Institutional issues:

– Lack of consistent trial contract expectations

– Variable criteria for defining appropriate clinical trial policies and processes

– Variability in Informed Consent expectations

– Ethical Review Board (ERB) timing and processes

– Management of privacy requirements

– Variability in institutional infrastructure to support clinical trials

– Challenges in working across therapeutic areas

IRB and Protocol Opportunities

• Central IRB’s

– Enhances protection of human subjects

– Cede initial review to central IRB

– Short period for local comments

• Online protocol tools • Authoring

• Amendments

• Communication

• Continued development of e-tools for AE reporting, integration of EMR, etc.

Regulatory Opportunities

• Regulatory agency cooperation and harmonization opportunities: – Development of harmonized clinical trial application

modules (e.g. common technical document)

– Cooperation in assessment of technical components (e.g. clinical trial material, diagnostic tests, devices)

– Flexible processes for phase and/or type of trial

– Standardized nomenclature with respect to key regulatory definitions

– International identification scheme for clinical trials

– Development of a global clinical trial database

Safety-Related Regulatory Opportunities

• Global harmonization of regulatory requirements for AE reporting to agencies, investigators, and IRBs

• Adoption of DSUR (Develoment Safety Update Report)

• Uniform approach to assessment and reporting of safety issues

• Reduce AE reporting to investigators and IRBs by focusing on significant new information

• Online management of ICF

Disruptive Regulatory Approaches

• Global clinical trial database would allow regulators to leverage other regulatory decisions

• Further development of regulator cooperation in evaluating clinical trials would be facilitated by more explicit involvement of stakeholders

• Development of mechanisms to transparently share pre-approval data with stakeholders

Communication of Clinical Trials • Clinicaltrials.gov

– Benefits from requirement for accurate and current information

– Nonetheless data may be incomplete or insufficient

– Not designed for patients or public

• Is there value in fit for purpose alternatives for available trials and results (i.e. consumer friendly, searchable, linked to consumer and professional sites)

e-based Medical Research Model

• Principle of social network and crowd sourcing

• Develop an e-based “market” for medical research (trusted “owner”)

– Stakeholders – e.g. investigators, scientists, patients, investors, clinical trial coordinators, pharmacists, others?

– Utilize a certification process for participation

– Include participation “opt-in” mechanism

– Socialize trials (interventional and observational), concepts, protocols, clinical trial networks, etc.

III. Opportunities

Issues to be addressed:

• What would constitute an optimal clinical trials infrastructure in the U.S.?

• How would such an infrastructure address the problems stated above? Should infrastructure

• solutions be universal, tailored to specific research settings, or integrated through common

• standards?

• What would be required to develop a clinical trials infrastructure? What is achievable in the – near- versus long-term?