# Presentation: 414577

##    Restructuring the National Cancer             Clinical Trials Enterprise

**   ****Restructuring the National Cancer ****            Clinical Trials Enterprise**

**James H. Doroshow, MD**
**February 6, 2007**

**Clinical Trials Working Group **
***NCAB Implementation Update***

## Common Themes of the Restructuring Plan

**Enterprise-Wide/Integrated Management **
**Prioritization/Scientific Quality**
**Coordination **
**Standardization**
**Operational Efficiency**

**Enterprise-Wide:  Integrated Management**** **

**Establish an ****external**** clinical trials oversight committee to advise NCI Director**
**Develop a coordinated organizational structure ****within NCI**** to manage the clinical trials enterprise**

**CTWG Recommendation:**

**Clinical Trials Advisory Committee (CTAC)**

**Federal advisory committee chartered in March 2006   ****http://deainfo.nci.nih.gov/advisory/ctac/ctac.htm**
**Membership:**
- Ten members current Boards (NCAB, BSA, BSC, DCLG)
- Fourteen new members from extramural clinical trials community
**First meeting: January 10, 2007**
**Functions:**
- Provide extramural oversight for CTWG  implementation initiatives institute-wide, including clinical trial informatics
- Strategic advice regarding entire NCI clinical trials portfolio
- Advise on use of correlative science and quality of life funds
- Develop recommendations for additional refinements to NCI-supported clinical trials system based on ongoing analyses: operational efficiency, financial analysis of phase III trial costs, and central IRB function
- Advise on  outcome of formal evaluations

**Clinical Trials Advisory Committee (CTAC)**

**Informatics working group**
**Provide interface with NCICB and oversight of CTWG clinical trials IT initiatives**
**Public/Private partnership working group**
**Initiatives to enhance NCI-sponsored clinical trials through prospective interactions with the private sector**
**Coordination working group**
**Bring together Cancer Center Directors, Cooperative Group Chairs, and SPORE PIs to harmonize program guidelines and facilitate clinical trials interactions**

**      ****Clinical Trials Operations Committee (CTOC)**
**            **

**Internal NCI committee established in December, 2005 to provide strategic oversight for NCI clinical trials programs and infrastructures**
**Chair, Dr. John Niederhuber**
**Membership from all NCI Divisions, Offices, and Centers involved in NCI-supported clinical trials including DCTD, DCP, OCTR, DCCPS, CCR, DCEG, NCICB, DEA and CCCT**

**CTOC  Activities Update**
** **

**Reviewed all RFAs and PAs involving clinical trials in past year**
**Provided input to NCICB on the CTWG informatics implementation plan**
**Evaluating feasibility of modifying clinical trials data reporting requirements for grant funded trials (e.g. R01, Program Project grants, etc.)**
**Approved minority accrual supplements**
**Portfolio reviews**
**Programmatic **
**Disease specific **

**Notes:**
In order to educate the members of CTOC about the clinical trials research taking place across the Institute, the Directors of NCI’s Extramural and Intramural Divisions/Centers/Offices have been presenting an overview of their clinical trials programs including associated resources to CTOC.    

Additionally, CTOC is interested in gaining a greater understanding of the clinical trials portfolio across the Institute by specific disease site.  There is currently not one source available that can look at the spectrum of clinical trials that are funded across the various Institute funding mechanisms and Divisions.  The goal is to analyze what is taking place across the clinical trials spectrum from screening and prevention to therapeutic intervention in a particular disease site so that gaps and areas of redundancy can be identified.  We are planning to start with ovarian cancer because it is a relatively small disease site and we should be able to determine the feasibility and value of the this in a relatively short period of time. 

## Integrated Management

**Integrated Management**

**NCI Director**

**Clinical Trials Advisory **
**Committee (CTAC)**

**Clinical Trials Operations **
**Committee (CTOC)**

**Coordinating Center**
**for Clinical Trials (CCCT)**

**Divisions, Centers, and Offices**

**Extramural Clinical Trials Community**

**Notes:**
In summary, an integrated management structure has been established in response to the CTWG report.  The Clinical Trials Advisory Committee provides a conduit for the extramural community to give advise to the NCI director regarding the Institute’s clinical trials enterprise.  The Clinical Trials Operations Committee provides a integrated picture of the clinical trials activities across the Institute and receives input from the Divisions, Centers, and Offices. 

The Coordinating Center for Clinical Trials is the management structure that provides coordination of these activities and supports CTAC and CTOC. 

## Common Themes of the Restructuring Plan

**Enterprise-Wide/Integrated Management**
**Prioritization/Scientific Quality: **Involve all stakeholders in design and prioritization of clinical trials that address the most important questions, using the tools of modern cancer biology
**Coordination **
**Standardization**
**Operational Efficiency**

## Progress:   Prioritization/Scientific Quality

**IDSC has been established with 5 task forces**
- Formally integrated into establishment of CTEP drug development planning
**Disease-specific Steering Committees**
- GI and GYN up and running
- H&N operational: Face-to-Face 12/06
- Symptom-Management/HRQOL launched: Face-to-Face 5/07
- SOPs developed
**SPORE members, community oncologists and advocates have been elected to all SC’s**
**Task Force defined prioritization criteria for correlative science studies**

## Prioritization/Scientific Quality:   2007 Goals

**Expand role of IDSC for early phase trial prioritization utilizing evolving Task Forces**
- Identify priority issues in phase II trial design
- Develop standards for biomarkers in early phase clinical trials
- Review the clinical development plans for angiogenesis and signal transduction inhibitors
**Complete implementation of H&N and Symptom Management SC’s; SOTS meeting in GI and GYN **
**Establish process to ensure that correlative science and quality of life studies conducted in association with clinical trials conform to standard protocols and standardized lab practices: Biomarker Standardization Workshop Spring ‘07**

## Common Themes of the Restructuring Plan

**Enterprise-Wide/Integrated Management**
**Prioritization/Scientific Quality**
**Coordination: **** **Coordinate clinical trials research through data sharing and providing incentives for collaboration
**Standardization**
**Operational Efficiency**

## Coordination Initiatives

**Establish a comprehensive database containing regularly-updated information on all NCI-funded clinical trials **
**Realign NCI funding, academic recognition, and other incentives to promote collaborative team science and clinical trial cooperation **

**Notes:**
The Coordination Initiatives include two new initiatives and three enhancement initiatives.  

Today we are going to focus on the discussing the new initiatives.  The first new initiative is the establishment of the comprehensive clinical trials database and will be covered later today by Dr. Buetow. 

The second new initiative calls for the realignment of NCI funding, academic recognition, and other incentives to promote collaborative team science and clinical trial cooperation.  

## Promote Collaborative Team Science

**Award Guideline Modification**
**Cooperative Group program guidelines are in the process of modification to reflect collaboration with SPOREs and Cancer Centers positively**
**Plan to modify SPORE and Cancer Center program guidelines to consider collaboration with Cooperative Groups positively**
**Funding Practice Modification**
**Evaluating feasibility of accruing patients to SPORE and Cancer Center clinical trials through NCI’s Cancer Trials Support Unit (CTSU)**
**New Forms of Recognition for Cancer Clinical Investigators**
_**Cancer Clinical Investigator Team Leadership Award**_**  to recognize mid-level clinical investigators for exceptional participation in NCI-funded collaborative clinical trials**

**Notes:**
This initiative involves three components:  Modification of Award Guidelines and Funding Practice as well as developing new forms of Recognition for Cancer Clinical Investigators. 

Progress during the past year includes the modification of Cooperative Group review guidelines to reflect collaboration with SPOREs and Cancer Centers positively.  These guidelines are currently under review at NIH (IS THIS CORRECT – need to check current status with Jeff)

During the coming year, we plan to modify SPORE and Cancer Center guidelines to promote collaboration with Cooperative Groups. 

This initiative also called for the examination of NCI funding practices to identify ways to promote collaborative science.  In order to implement this initiative, we have been working with CTEP to evaluate the feasibility of accruing patients to SPORE and Cancer Center clinical trials through NCI’s Cancer Trials Support Unit (CTSU).  

Finally, this initiative also included the development of new forms of recognition for Cancer Clinical Investigators.  Provided funding is available, we we plan to make a new award  - the Cancer Clinical Investigator Team Leadership Award to recognize mid-level clinical investigators for exceptional participation in NCI-funded collaborative clinical trials.  These are envisioned to be competitive supplemental awards to Cancer Center and Cooperative Group grants.

## Common Themes of the Restructuring Plan

**Enterprise-Wide/Integrated Management**
**Prioritization/Scientific Quality**
**Coordination **
**Standardization: **Standardize informatics infrastructure and clinical research tools
**Operational Efficiency**

## Standardization Initiatives

**Informatics infrastructure interoperable with caBIG****TM**** **
**Standard Case Report Forms incorporating Common Data Elements**
**Credentialing system for investigators and sites that is recognized and accepted by NCI, industry sponsors, clinical investigators and clinical trial sites**
**Establish commonly accepted clauses for clinical trial contracts**

**Notes:**
There are 3 NEW and 1 ENHANCEMENT Standardization initiatives.  The three new initiatives deal with standardization of informatics tools and will be reviewed by Dr. Buetow. 

The enhancement initiative calls for the establishment of commonly accepted clauses for clinical trial contracts. 

## Progress:  Standardization

**CaBig Clinical Trials Steering Committee created: Clinical trialists, statisticians, IT experts—First meeting March ‘07**
- Establish strategic priorities and oversight for all CTWG informatics initiatives
- Ensure coordination of CTWG informatics activities across NCI-supported clinical trials activities
**Inventory of NCI electronic CRFs is underway**
**Preliminary meeting with industry held to discuss standard clauses for clinical trials contracts**

## Common Themes of the Restructuring Plan

**Enterprise-Wide/Integrated Management**
**Prioritization/Scientific Quality**
**Coordination **
**Standardization**
**Operational Efficiency: **Use resources most efficiently through improved cost-effectiveness and accrual rates, and more rapid trial initiation

## Operational Efficiency Initiatives

**Restructure the funding model for phase III efficacy trials to incentivize more rapid rates of patient accrual**
**Identify the institutional barriers that prolong the time from concept approval to accrual of the first patient, and develop solutions for overcoming these barriers**
**Expand current outreach programs to increase the recruitment of minority populations to cancer clinical trials**
**Develop approaches for enhancing adoption of centralized Institutional Review Board processes**

**Notes:**
There were two NEW and three ENHANCEMENT operational efficiency initiatives identified in the report.  Today I will give you an update on thes status of four of these.  

## Financial Analysis

**     ****A financial analysis of phase III trial costs has been initiated:**
**Identify areas of inadequate funding, where increased financial compensation could significantly improve clinical trial conduct**
**Identify areas of overlap, duplication or redundancy which, if eliminated, could result in cost-savings**
**Identify best practices for budget allocations and financial management that could potentially be standardized across Cooperative Groups**
**Assess the cost savings that might result from closing sites that accrue very low numbers of patients**

**Notes:**
Before any restructuring of the funding model for phase III trials can be entertained, the implementation plan called for a financial analysis of phase III trial costs.  This study has been initiated and is expected to be completed in 2007.  

The goals of this analysis are: (verbatim) 

?too much info

## Process Flow Map for Phase III Study

**Dilts, D. M. et al. J Clin Oncol; 24:4553-4557 2006**

**Process Flow Map for Phase III Study**

** ****Process Flow Map for Phase III Studies**

**Notes:**
Progress towards the identification of institutional barriers to timely initiation of studies has been made through the funding of a study by 
Dr. David Dilts to conduct an analysis of the steps needed to take a clinical trials concept from the concept phase to protocol initiation at a cooperative group and a cancer center. 

In his analysis of CALBG, he studied the lifecycle of 13 phase III protocols and made this process map.  He found that there are more than 350 steps to get a protocol open with 43 major decision points.  

The median calendar time to activate a phase III study was more than 2 years!

The areas requiring the longest time were protocol development, forms development, and regulatory affairs. 

In 2007 Dr. Dilts will be conducting similar analyses at another cooperative group, CTEP, and other cancer centers to gain an overview of the entire NCI clinical trials enterprise which will form the basis for recommendations to improve the timeliness of clinical trials activation..  

##  Enhance Minority Accrual

**Trans-NCI Partnership formed to propose mechanisms and solicit concepts**
**Programs receiving FY06 supplemental funding included:**
_**Cancer Disparities Research Partnerships**_** to expand available trials beyond radiation oncology to surgical and medical oncology trials**
_**MBCCOP and Patient Navigator Research Program**_** to evaluate the impact of Patient Navigators on minority accrual in cancer  prevention and control trials capitalizing on the experience of both programs**
**Timeline calls for expansion in FY07**

**Notes:**
Another important area that we have made progress on is the enhancement of minority outreach programs. 

CCCT has met with NCI Clinical Trials Minority Recruitment Working Group which has representation from all areas of NCI that are involved in health disparities issues that have an impact on clinical trials.  

As a result of these meetings, we have established a trans-NCI partnership to propose mechanisms and solicit concepts from minority outreach programs to enchance minority accrual.

Funds for this are a CCCT budget item and included $500 thousand in 2006.  Programs that received supplemental funding for FY06 included:
  the Cancer Disparities Research Partnerships to expand available trials beyond radiation oncology to surgical and medical   oncology trials

And the 
MBCCOP and Patient Navigator Research Program to evaluate the impact of Patient Navigators on minority accrual in cancer  prevention and control trials capitalizing on the experience of both programs

The CTWG report timeline calls for an expansion of these funds to $2 annually in 2007 although we are uncertain if this will occur given the current budget situation. 

Minority Based-CCOP (Worta McCaskill-Stevens, Lori Minasian)
Patient Navigator Research Program (Roland Garcia)
Cancer Disparities Research Program (Frank Govern)
Minority Institution/Cancer Center Partnership (Nelson Aguila)

##  Enhance Adoption of Central IRB

**A analysis of the barriers to the acceptance of the NCI Central Institutional IRB (CIRB) has been initiated **
**An analysis of the potential cost savings that would result from the use of the CIRB has been funded**

**Notes:**
In order to address the recommendations that approaches for enhancing adoption of centralized Institutional Review Board processes be examined, we have initiated an analysis of the barriers to the acceptance of the NCI Central IRB process.  The results of this analysis are expected to be complete in 2007.  

Additionally, CTEP has funded an analysis of the potential cost savings that would result from the use of the CIRB which should provide additional information towards enhancing the adoption of a centralized IRB process.

## Evaluation and Outcome Measures

**Structured evaluation system**
**Designed by experienced evaluation specialists**
**Blend of quantitative and qualitative measures**
**External clinical trials expert panel has reviewed the  proposed measures**
**Baseline evaluation to be performed in FY07**
**Periodic evaluations to assess impact of restructuring**

**Notes:**
Finally, no major systems restructuring should be undertaken without an assessment of its impact.

A structured evaluation system has been into the plan.  

It has been designed by experience evaluation specialists.  

An external clinical trials expert panel has reviewed the evaluation plan and the proposed measures.  

We expect that the baseline evaluation will be performed in 2007 and will be followed by periodic evaluations to assess the impact of restructuring.

We look forward presenting the results of this evaluation to this Committee.