In his opening remarks at a workshop, “Implementing a National Cancer Clinical Trials System for the 21st Century,” Richard Schilsky, MD, said, “There is something for everyone to do here to optimize the system.” The goal of the workshop was to examine efforts to implement IOM’s 2010 recommendations on the NCI Cooperative Group Program, which suggested that the program be substantially changed. The meeting was hosted by ASCO and the Institute of Medicine (IOM) National Cancer Policy Forum, and held in Washington, DC. Dr. Schilsky is Professor of Medicine and Deputy Director, University of Chicago Comprehensive Cancer Center and Past President of ASCO.

NCI Claims Changes and Improvements

James H. Doroshow, MD, Director, NCI Division of Cancer Treatment and Diagnosis (CTEP), said that as a result of the IOM report, NCI has significantly speeded up the clinical trials process. The agency has made other changes as well (see sidebar below), “But we have to begin thinking seriously about the number of patients we can accrue,” he cautioned.”

Lori Minasian, MD, Acting Director, NCI Division of Cancer Prevention, said that in response to the IOM report, the NCI will reduce the number of Cooperative Groups from 10 to 5 (4 adult and 1 pediatric). As a consequence, only those 5 funded Cooperative Groups would be eligible to be Cooperative Group CCOP Research Bases. There will remain Cancer Center CCOP Research Bases. “In addition, because treatment does not always involve drugs, we are encouraging collaborative funding with NIH, the American Cancer Society, and other entities to study quality of life, survivorship, nutrition, and other interventions that have an effect on patients with cancer.”

Dr. Minasian also said that they are looking at ways that will enhance CCOP’s abilities to collect biospecimens in conjunction with the clinical trials that are run through the national system. “In addition, we are working to develop additional ways to improve diversity, although the Minority-Based CCOP program already contributes significantly to this effort. And perhaps most important, because many NCI investigators do not accrue patients, we need to improve outreach to our own physicians.”

Cooperative Group Chairs Report

Jan C. Buckner, MD, Professor of Oncology, Mayo Clinic College of Medicine and Chair of the North Central Cancer Treatment Group, said that the Cooperative Groups have been conducting “high-quality, multidisciplinary, practice-changing research for decades and will continue to do so.”

The groups have developed biobanking repositories to support translational research, which he said are among the largest and best annotated in the country. “They have driven a number of landmark trials in HER2-positive breast cancer, colon cancer, and non-Hodgkin lymphoma.

“We also have developed detailed technical specifications for a data capture system, developed plans for complying with new NIH timelines for clinical trial activation, created informatics tools for biospecimens, and developed innovative clinical trial designs and endpoint validation studies.”

But unaddressed issues remain: a system for setting research priorities; sufficient funding; scientific collaboration; coordinated review of translational science; and modern informatics.

Philip J. DiSaia, MD, Professor, Department of Obstetrics and Gynecology, University of California, Irvine, and Chair of the Gynecologic Oncology Group (GOG), wants to keep his group intact. “It is unclear how the recommended consolidations would improve outcomes.” He said that GOG is the only group that conducts trials in gynecologic cancers. It has established worldwide standards of staging and treatment and has conducted more phase I and II studies than any other group.

“GOG’s research has provided the basis for molecular approaches to gynecologic cancers, and our translational research teams have created the single largest tissue bank of gynecologic cancers in the world.”

Robert Gray, PhD, Professor of Biostatistics, Dana-Farber Cancer Institute, and a member of the Eastern Cooperative Oncology Group (ECOG), described his vision of a cooperative group system: one that facilitates participation in studies led by any of the groups, avoids duplication, and conducts studies to evaluate molecular and imaging markers.

“We also need common information statistical systems, as well as standardization of data collection and management. The current system is too competitive and multiple groups often develop separate systems to perform similar work,” he said.

Paying for Clinical Trials

Sharon Levine, MD, Associate Executive Director of Kaiser Permanente, described her organization’s reimbursement policies with regard to clinical trials: coverage for routine care and investigational drugs with therapeutic value. James D. Cross, MD, National Medical Director, Aetna, echoed Kaiser’s reimbursement policies and said the company encourages patients to enter trials.

“As a care delivery system of 15,000 physicians, we can accrue patients for clinical trials—and conduct them. We have direct access to a heterogeneous patient population, as well as multispecialty group practices that include oncologists. We also have a substantial investment in the clinical trials infrastructure,” said Dr. Levine.

Louis Jacques, MD, Director of the Center for Medicare & Medicaid Services (CMS) Coverage and Analysis Group talked about the methodology the agency uses to determine reimbursement and noted that the major focus is on clinical utility.

Interaction between Industry and FDA

Ira B. Steinberg, MD, Associate Vice President for Global Medical Affairs, sanofi-aventis, said that industry generally likes working with Cooperative Groups because they provide access to large numbers of patients, accrue quickly, and work with world-class institutions and physicians.

But there are problems. “It takes ages to initiate and open trials, data are too variable, and contracts are problematic because of the multiplicity of institutions and languages.”

He proposed a solution: Standard Terms of Agreement for Research Trial (START), which consists of a series of standard clauses designed to simplify and streamline the contracting process.

Richard Pazdur, MD, Director of the Oncology Program, FDA Center for Drug Evaluation and Research, said, “All companies conduct trials all over the world. The United States is not the sole player, and FDA is not the sole regulator.”

When FDA and the pharmaceutical industry cooperate, four principles are paramount, he said. First, responsibility for accurate data rests solely with the drug sponsor. Second, when a trial is conducted by a Cooperative Group, there must be clear communication about criteria, safety, and data distribution among all participants right from the beginning. This is best accomplished by joint meetings at all stages of the trial process.

Third and fourth, “Goals must be defined at the outset. Sponsors have to be upfront about their ultimate intentions, and it is they who determine the elements of group responsibilities.” ■

Financial Disclosure: Dr. Cross is National Medical Director, Aetna. Dr. Gray is a member of the Eastern Cooperaive Oncology Group. Dr. Levine is Associate Executive Director of Kaiser Permanente. Dr. Schilsky is a compensated member of the Scientific Advisory Board of Foundation Medicine, Inc. Dr. Steinberg is Associate Vice President for Global Medical Affairs, sanofi-aventis. Dr. Buckner, Dr. DiSaia, Dr. Doroshow, Dr. Jacques, Dr. Minasian, and Dr. Pazdur reported no potential conflicts of interest.