# Presentation: 162583

## Clinical Trials Working Group 

***Clinical Trials Working Group ***
***Draft Recommendations to the ***
***National Cancer Advisory Board***
**James H. Doroshow M.D., Chair**
**Howard A. Fine M.D., Co-Chair**
**February 17, 2005**
**Bethesda, Maryland**

## Clinical Trials Working GroupRationale

- Advances in molecular medicine offer enormous potential to improve cancer clinical practice
- To successfully address these compelling opportunities will require a coordinated approach to enhancing interdisciplinary, scientifically-driven clinical trials

**Notes:**
The Charge of the CTWG, given by Dr. von Eschenbach, is to advise the NCAB and its Subcommittee on Clinical Investigations on the development, conduct, infrastructure, and support necessary for the optimal coordination and future progress of NCI extramural and intramural clinical research trials including diagnosis, treatment, and prevention studies.

## Clinical Trials Working GroupRationale

- Urgent need to integrate the successful but functionally diverse elements of the current clinical trials system to:
- Enhance the timeliness of clinical trial accrual
- Increase efficiency by improving the scientific and bioinformatic infrastructure for clinical studies
- Expand the involvement of all stakeholders in clinical trial development, prioritization, and completion

**Notes:**
The Charge of the CTWG, given by Dr. von Eschenbach, is to advise the NCAB and its Subcommittee on Clinical Investigations on the development, conduct, infrastructure, and support necessary for the optimal coordination and future progress of NCI extramural and intramural clinical research trials including diagnosis, treatment, and prevention studies.

## Clinical Trials Working GroupCharge

- Advise the NCAB and its Subcommittee on
- Clinical Investigations:
- Development
- Conduct
- Infrastructure
- Support
- Coordination
- For Cancer Clinical Trials Across NCI

**Notes:**
The Charge of the CTWG, given by Dr. von Eschenbach, is to advise the NCAB and its Subcommittee on Clinical Investigations on the development, conduct, infrastructure, and support necessary for the optimal coordination and future progress of NCI extramural and intramural clinical research trials including diagnosis, treatment, and prevention studies.

## Clinical Trials Working GroupSubcommittees

- Patient Accrual
- Regulatory
- Core Research Services
- Standardization and Infrastructure
- Coordination
- Prioritization

## Clinical Trials Working GroupProgress Since September 2004 Report to NCAB

- Subcommittees developed a series of proposed recommendations, revised through several rounds of review and comment
- Obtained input from the extramural community about their major concerns regarding cancer clinical trials
- Draft recommendations to improve the conduct of cancer clinical trials refined and accepted by the CTWG
- Leverage the unique components and capabilities of the NCI’s current clinical trials enterprise
- Enhance the interactivity of the existing system
- Focus on improving the scientific basis for cancer clinical trials research
- Analyzed issues and challenges and developed initial strategies for implementation pending approval by the NCAB and NCI director

**Notes:**
The Charge of the CTWG, given by Dr. von Eschenbach, is to advise the NCAB and its Subcommittee on Clinical Investigations on the development, conduct, infrastructure, and support necessary for the optimal coordination and future progress of NCI extramural and intramural clinical research trials including diagnosis, treatment, and prevention studies.

## Clinical Trials Working GroupGoal for Today

- 	Seek guidance from the NCAB prior to developing a final series of recommendations and plans for implementation

**Notes:**
The Charge of the CTWG, given by Dr. von Eschenbach, is to advise the NCAB and its Subcommittee on Clinical Investigations on the development, conduct, infrastructure, and support necessary for the optimal coordination and future progress of NCI extramural and intramural clinical research trials including diagnosis, treatment, and prevention studies.

## Clinical Trials Working Group Input from Internet Forum

- Web-based forum; open from November 29, 2004 to January 15, 2005
- Questions from each of the six CTWG subcommittees
- Total of 2228 responses to questions
- Responses were used in real time by the subcommittees to augment and clarify the draft recommendations
- A summary of the responses will be available today at _http://integratedtrials.nci.nih.gov/_

## Clinical Trials Working GroupDraft Recommendations

- Patient Accrual: Richard Schilsky
- Regulatory: Steven Averbuch
- Core Research Services: Fred Appelbaum
- Standardization & Infrastructure: David Parkinson
- Coordination: David Alberts
- Prioritization: James Abbruzzese

**Notes:**
The Charge of the CTWG, given by Dr. von Eschenbach, is to advise the NCAB and its Subcommittee on Clinical Investigations on the development, conduct, infrastructure, and support necessary for the optimal coordination and future progress of NCI extramural and intramural clinical research trials including diagnosis, treatment, and prevention studies.

## Patient Accrual SubcommitteeChair

| Amy Langer
National Alliance of Breast Cancer Organizations | Mack Roach, M.D.
University of California, San Francisco
 |
| --- | --- |
| 
Lori Minasian, M.D.
National Cancer Institute
 | 
Jamie Zwiebel, M.D.
National Cancer Institute |
|  |  |

| Richard Schilsky, M.D. 
University of Chicago |
| --- |

_**Members**_

- Patient Accrual Subcommittee_**Chair**_

## Patient Accrual SubcommitteeGoals of Recommendations

- Increase the rate of patient accrual to cancer clinical trials
- Increase accrual of under-represented segments of the population to clinical trials

## Patient Accrual Subcommittee Draft Recommendations

- Provide standardized materials and other resources to help sites plan, staff, implement and manage clinical trials
- Funding for required site personnel
- Funding for community outreach to recruit a diverse patient population
- Web-based trial initiation tools
- Educational materials for patients

## Patient Accrual Subcommittee Draft Recommendations

- Increase public visibility of NCI programs with the goal of expanding the rate of patient accrual to NCI-sponsored clinical trials
- Develop promotional and marketing programs for high-priority studies
- Partner with community groups, consumer media and physicians to communicate patient benefits of trial participation
- Create tailored programs and community partnerships to engage minorities and special populations

## Patient Accrual Subcommittee Draft Recommendations

- Provide incentives that encourage patients and community oncologists to participate in clinical trials
- Develop an NCI certification program for clinical oncologists
- Educate patients about the unique qualifications of an “NCI-certified investigator”** **
- Seek reimbursement for clinical care within qualified clinical trials including counseling, education, etc.
- Communicate trial results to patients and emphasize their contribution to the care of future patients

## Patient Accrual Subcommittee Draft Recommendations

- Improve access to clinical trials for community oncologists and patients
- Develop CCOP mentoring programs for interested community oncologists, especially those serving minority populations
- Expand use of community-based regional IRBs to decrease lead time and conserve resources
- Improve the awareness, functionality and utilization of the CTSU
- Create multiple, user-friendly channels, including comprehensive websites, where patients and physicians can find information on cancer clinical trials

## Regulatory SubcommitteeChairs

| Steven Averbuch, M.D. 
Merck Research Laboratories
 | Richard Pazdur, M.D.
 U.S. Food and Drug Administration |
| --- | --- |

_**Members**_

- Regulatory Subcommittee_**Chairs**_

| Jean deKernion, M.D.
University of California, Los Angeles | Sean Tunis, M.D.
Centers for Medicare and Medicaid Services
 |
| --- | --- |
| Jeffrey Abrams, M.D.
National Cancer Institute | Michaele Christian, M.D.
National Cancer Institute
 |
|  |  |

## Enhance cooperation between federal agencies, industry, and other key stakeholders to reduce regulatory burdens and accelerate drug and device development

Develop approaches for increasing the involvement of industry, CMS and other payers in the NCI cancer clinical trials enterprise

- Develop approaches for increasing the involvement of industry, CMS and other payers in the NCI cancer clinical trials enterprise

- Regulatory Subcommittee _Goals of Recommendations_

## Regulatory SubcommitteeDraft Recommendations

- Develop guidelines/procedures for joint participation of FDA and NCI in meetings, including those with industry, concerning new agents and diagnostics in order to coordinate and accelerate drug and device development

## Regulatory SubcommitteeDraft Recommendations

- Reduce the auditing, monitoring, and regulatory burden on clinical trial sites by coordinating requirements of NCI, FDA, and OHRP in order to identify specific changes that can eliminate redundancy and reduce costs

## Regulatory SubcommitteeDraft Recommendations

- Increase use of the NCI-FDA expedited concept/protocol approval process, including use of the FDA Special Protocol Assessment (SPA), for NCI sponsored trials that are intended to impact product labeling

## Regulatory SubcommitteeDraft Recommendations

- In collaboration with CMS and other payers and stakeholders, establish a robust and transparent process for identifying clinical studies that would warrant reimbursement of appropriate clinical trial and investigational costs. These studies would address critical questions about cancer practice faced by patients, clinicians, and other decision makers

## Regulatory SubcommitteeDraft Recommendations

- In collaboration with FDA, ASCO, AACR, and other interested organizations, support training programs designed to increase the number of cancer investigators who are qualified to guide new agents and devices through the development and regulatory process

## Core Research Services SubcommitteeChair

| Frederick Appelbaum, M.D. 
Fred Hutchinson Cancer Research Center
 |
| --- |

_**Members**_

- Core Research Services Subcommittee_**Chair**_

| Colin Begg, Ph.D.
Memorial Sloan-Kettering Cancer Center | Eberhard Mack, M.D.
University of Wisconsin-Madison |
| --- | --- |
| Edith Perez, M.D.
Mayo Medical School
 | James Doroshow, M.D.
National Cancer Institute |
| Sheila Taube, Ph.D.
National Cancer Institute |  |

## Core Research Services SubcommitteeGoals of Recommendation

- Enhance access to the scientific infrastructure necessary to facilitate the conduct of high priority correlative science studies to translate new discoveries into clinical practice
- Integrate, in an efficient and timely manner, strong scientific review of correlative studies with development and review of clinical protocols

## Core Research Services SubcommitteeDraft Recommendation

- Establish annual budgets for studies ancillary to clinical trials, including correlative science, health economics, and quality of life investigations, that can be accessed on a protocol by protocol basis

## Standardization and Infrastructure SubcommitteeChairs

| Mitchell Schnall, M.D., Ph.D.
Hospital of the University of Pennsylvania
 | Kenneth Buetow, Ph.D.
National Cancer Institute
 |
| --- | --- |
| Michaele Christian, M.D.
National Cancer Institute
 | Dan Sullivan, M.D.
National Cancer Institute
 |
| Sheila Taube, Ph.D.
National Cancer Institute |  |

| Peter Adamson, M.D.
 Children’s Hospital of Philadelphia | David Parkinson, M.D. 
Amgen |
| --- | --- |

_**Members**_

- Standardization and Infrastructure Subcommittee_**Chairs**_

## Improve efficiency, reduce duplication of effort, and achieve cost savings
Facilitate innovation and promote integration across trials
Facilitate data interpretation and data comparison across trials
Allow for closer integration of biological measurements and clinical trial findings

- Improve efficiency, reduce duplication of effort, and achieve cost savings
- Facilitate innovation and promote integration across trials
- Facilitate data interpretation and data comparison across trials
- Allow for closer integration of biological measurements and clinical trial findings

## Standardization and Infrastructure SubcommitteeDraft Recommendations

- With concurrence from FDA, establish standards for the essential data to be collected in clinical trials and the format in which it is collected
- Define core data elements
- Define standardized Case Report Forms (CRFs)
- Develop the caBIG standard infrastructure necessary to support clinical trials and interface caBIG with other databases utilizing standard elements
- As caBIG is implemented, consolidate redundant systems, where possible

## Standardization and Infrastructure SubcommitteeDraft Recommendations

- Establish a process for official credentialing of research personnel and sites and create a national, central database of credentialed investigators and sites

## Standardization and Infrastructure SubcommitteeDraft Recommendations

- In collaboration with clinical research sites and industry sponsors, establish a set of standard clauses for clinical research contracts that address complex issues such as intellectual property and publication rights

## Standardization and Infrastructure SubcommitteeDraft Recommendations

- Establish a process for development of biomarker standards; set an expectation that correlative science studies will be performed according to standard protocols in credentialed reference labs

## Coordination SubcommitteeChairs

| Martin Abeloff, M.D.
Johns Hopkins University | John Niederhuber, M.D.
University of Wisconsin-Madison |
| --- | --- |
| Karen Antman, M.D.
National Cancer Institute | Leslie Ford, M.D.
National Cancer Institute |
| Ernie Hawk, M.D., M.P.H.
National Cancer Institute | Julia Rowland, Ph.D.
National Cancer Institute |
| Dan Sullivan, M.D.
National Cancer Institute

 |  |

| David Alberts, M.D.
University of Arizona | David Johnson, M.D. 
Vanderbilt University Medical School |
| --- | --- |

_**Members**_

- Coordination Subcommittee_**Chairs**_

## Coordination SubcommitteeGoals of Recommendations

- Promote and reward team science and collaborative clinical trial participation
- Facilitate information exchange and collaboration among clinical investigators
- Enhance the design and planning of new clinical trials by providing investigators with access to comprehensive, up-to-date information about ongoing and completed studies
- Enable patients and community oncologists to make better decisions about cancer care by providing access to comprehensive, up-to-date clinical trial information

## Establish a comprehensive database containing regularly updated descriptive information (protocol, eligibility criteria, sites, accrual, etc.) on all federally funded cancer trials (CTEP, Cancer Centers, SPOREs, P01, R01, etc.), which would be linked to all publicly available information on each trial. Data on adverse events, toxicity, and efficacy would be available to the extramural community as soon as approved for public release 
Create a web-based interface to provide investigators with easy access to information for research planning, prioritization and resource allocation 
Create additional web-based interfaces to enable other interested parties such as patients to access information 

- Create a web-based interface to provide investigators with easy access to information for research planning, prioritization and resource allocation
- Create additional web-based interfaces to enable other interested parties such as patients to access information

- Coordination Subcommittee_Draft Recommendations_

## Coordination SubcommitteeDraft Recommendations

- Realign NCI funding, academic recognition, and other incentives to promote collaborative team science and the clinical trial cooperation needed to effectively address the most compelling opportunities in cancer research today

## Prioritization SubcommitteeChairs

| Louise Grochow, M.D.
AstraZeneca
 | Richard Kaplan, M.D.
University of Leeds
 |
| --- | --- |
| Michael Katz
International Myeloma Foundation
 | Gershon Locker, M.D.
Northwestern University
 |
| Michaele Christian, M.D.
National Cancer Institute
 | James Doroshow, M.D.
National Cancer Institute |
| Howard Fine, M.D.
National Cancer Institute | Jamie Zwiebel, M.D.
National Cancer Institute
 |

| James Abbruzzese, M.D. 
University of Texas M.D. Anderson  | Mark Ratain, M.D. 
University of Chicago |
| --- | --- |

_**Members**_

- Prioritization Subcommittee_**Chairs**_

## Provide broad-based scientific and clinical advice to ensure the development and design of the most clinically important and scientifically informative clinical trials

Increase efficient use of resources through an open collaborative process for setting national cancer clinical trial priorities and reducing duplication and overlap

Increase involvement of patients and community oncologists in clinical trial prioritization

- Provide broad-based scientific and clinical advice to ensure the development and design of the most clinically important and scientifically informative clinical trials
- Increase efficient use of resources through an open collaborative process for setting national cancer clinical trial priorities and reducing duplication and overlap
- Increase involvement of patients and community oncologists in clinical trial prioritization

## Prioritization SubcommitteeDraft Recommendations

- Establish an external Investigational Drug Working Group (IDWG) to collaborate with NCI staff on strategy, design, and prioritization of drug-specific development plans in early clinical trials for which NCI holds an IND

## Prioritization SubcommitteeDraft Recommendations

- Develop a formal Working Group mechanism for development and prioritization of disease-oriented Phase III trials that leverages the Disease Intergroup structure, involves the broad oncology community, and facilitates open communication about all relevant studies

## Prioritization SubcommitteeDraft Recommendations

- Enhance involvement of community oncologists and patient advocates in the cancer clinical trials prioritization process through representation on Working Groups and creation of advisory committees and focus groups

## Working Group-Wide Draft Recommendations

- Establish a permanent clinical trials subcommittee with broad representation from extramural clinical investigators, community oncologists, regulatory agencies, industry, and patient advocacy groups to advise the NCI director on the conduct, oversight, and implementation of clinical trials across the Institute

## Working Group-Wide Draft Recommendations

- Develop the necessary organizational structure within the NCI to coordinate the entire clinical trials enterprise supported by the Institute

## Clinical Trials Working Group Common Themes from Recommendations

- Proactive involvement of all stakeholders in design, conduct, and prioritization of clinical trials
- Standardization of clinical research tools, from case report forms to contracts and credentialing
- Coordinating clinical trials research through data sharing and providing incentives for collaboration
- Efficient use of resources by avoiding duplication of effort and supporting the best designed trials that address the most important questions

**Notes:**
The Charge of the CTWG, given by Dr. von Eschenbach, is to advise the NCAB and its Subcommittee on Clinical Investigations on the development, conduct, infrastructure, and support necessary for the optimal coordination and future progress of NCI extramural and intramural clinical research trials including diagnosis, treatment, and prevention studies.

## Clinical Trials Working GroupLong-Term Goal

**	**Combine the best of all of the components of the NCI-supported clinical trials system to develop a cooperative enterprise built on a stronger scientific infrastructure, and on a broadly-developed and engaged coalition of critical stakeholders who are essential for the viability of a collaborative national clinical trials research endeavor**  **

**Notes:**
The Charge of the CTWG, given by Dr. von Eschenbach, is to advise the NCAB and its Subcommittee on Clinical Investigations on the development, conduct, infrastructure, and support necessary for the optimal coordination and future progress of NCI extramural and intramural clinical research trials including diagnosis, treatment, and prevention studies.