By Christopher Guadagnino, Ph.D.

Published December 1997

DISCUSSION FORUM

• Differences in quality?

• React to this article in the Discussion Forum.

Robert L. Comis, M.D., is chair of the Eastern Cooperative Oncology Group (ECOG) and president of the board of directors of the Coalition of National Cancer Cooperative Groups, Inc. He also directs both the Allegheny Cancer Clinical Trials Research Center, Philadelphia and the Allegheny Cancer Center, Pittsburgh.

PND: What are the primary sources of funding for clinical cancer research?

RC: The two primary resources for funding cancer and clinical trials are the National Cancer Institute at the NIH, and industry. The clinical trials programs in the cooperative groups are funded primarily by the NCI and to a less extent, at least at this point, through industry. ECOG [Eastern Cooperative Oncology Group] is one of the largest cancer clinical trials organizations in the world, treating somewhere between 4000 an 6000 patients every year. There are about 365 university- or community-based hospitals and practices and roughly 4500 participating doctors, nurses, clinical research associates, pharmacists, etc. There are eleven such major groups in the United States.

PND: How are those funding sources becoming threatened?

RC: If you look now at NIH funding, we are funded at about 50 percent of our approved level. The Cancer Institute has been working very hard to increase that level of funding, but unfortunately the level has dropped so low that it’s going to be tough to get back to full funding.

PND: What caused that?

RC: I think the adjustments that occurred in the federal budget over the last ten, fifteen years. The National Cancer Institute was once almost the exclusive drug development force in the United States. Now industry has increasingly become a force. We have to be able to work more closely with industry in clinical cancer trials. How patients get access to clinical trials and how doctors deliver the most innovative treatment, both in the community and academia, are threatened because their margin of operation is threatened. With regard to the NCI-funded work, it is pretty much gratis in the sense that it’s only half funded. Nationally, the operation is roughly $90 to $100 million short of what we should be receiving.

PND: How are researchers looking to private sources of funding?

RC: What we have done on the cooperative group level is to reorganize ourselves. We have established the Coalition of National Cancer Cooperative Groups, which is a coalition of six of the major cancer groups. This is a new organization that was just incorporated. I’m the president of the Coalition and was recently elected the chairman, the spokesman for all the cooperative groups in the United States. The Coalition consists of the Eastern Cooperative Oncology Group (ECOG), The Cancer and Leukemia Group B (CALGB), the North Central Cancer Treatment Group (NCCTG), the National Surgical Adjuvant Breast and Bowel Project (NSABP), the Radiation Therapy Oncology Group (RTOG) and the Pediatric Oncology Group (POG). We’re coming together to develop flexibility to be able to interact with not only the NCI, but also with industrial partners and other interested constituencies—in particular, the patient advocate groups, health outcomes research groups, foundations interested in cancer, etc. If industry is developing an important pipeline of new types of treatments in order to give patients the opportunity to participate, you have to be able to interact efficiently with industry. The Coalition will provide a scientific, legal and administrative framework to interact with industry which will be user friendly to all the constituencies. The key difference is that we are a functioning not-for-profit legal entity now, which makes things a lot simpler for industry to deal with. Before we established this coalition, the groups were essentially unincorporated associations. We’re also trying to convince the payers that the clinical trials process that we have operational is the optimal and most cost-effective way to manage patients.

PND: How will the Coalition compete with private clinical research organizations (CROs)?

RC: Clinical research organizations are generally for-profit businesses that were paid directly by the pharmaceutical firms to go out and recruit individuals to participate in clinical trials and develop varying degrees of support for that participation. CROs, in my estimation, have clearly made an impact on the clinical trials scene on a nationwide level. There’s no CRO that has the expertise in cancer that exists in the cancer clinical cooperative group structure. We have centralized data management, we audit all of our records. It’s not been viewed this way, but we have the best cancer clinical trials support program in the country and I can’t imagine that a CRO could ever reach that quality level. There’s tremendous competition to enter patients on to clinical trials from a whole variety of sponsorships. There’s no question that challenge is out there.

PND: With declining federal funding of clinical research and reportedly handsome reimbursement incentives offered through CROs to recruit clinical researchers, isn’t it difficult to lure physicians away from participating in industry-sponsored, CRO-executed clinical trials?

RC: It’s a difficult choice. Doctors both from academia and the community are pressured to the extent that they are going to use all kinds of resources to try to make up those differentials. Historically we have been able to compete because of the quality of the work that we do. That is still an edge. But because of the economic environment, that edge is being challenged. Pharmaceutical studies often are designed to ask questions which are specific and minutely focused on regulatory issues. They may or may not be the most attractive to the patient or to the physician. Most of the major advances in cancer have been proven in our system. Our studies are pretty much the engine for the development of clinical practice in the United States and the world. But it’s not very attractive if you’re only getting paid half of what you need. Thank God we have thousands of doctors throughout the country who are still committed to the quality issue.

PND: How serious a threat are CROs to research integrity, in your view?

RC: I don’t feel that there is an a priori question about integrity of a pharmaceutical firm involved with a CRO. But there are differences in how trials are managed, what the support systems are and how patient risk issues are handled. The cooperative groups funded through the NCI are peer reviewed every five years at a minimum. Our scientific portfolio, how we manage patients, how we manage all the regulatory and patient safety issues, and how we audit our records are scrutinized routinely. The driving force really is not monetary, it’s a quality force. In the for-profit, CRO-type arena, the demands are driven by issues in the marketplace which aren’t reviewed in the same kind of way.

PND: Do you think that research integrity is compromised when a competitive model replaces one of peer-reviewed, independent research?

RC: I think there’s a great danger there for sure. But I think that both types of models that are high quality and of impeccable integrity are an advantage and I’m not sure that the goals should be to have an exclusive model one way or the other. In a highly specialized area like cancer, I don’t think there is an advantage to using a CRO, but our system has to be able to interact with the pipeline coming through industry as efficiently as possible. The CROs have an expeditious way to deal with industry and, until we recently reorganized along this coalition line, we didn’t. We’re hoping that the adjustments we make will show that we can work to the advantage of both the industry and the NCI in the best way possible.

PND: Is it a problem that the highly regulated nature of the NIH-funded model might be a disincentive for physicians to continue to participate in clinical trial groups through the cooperative groups?

RC: Yes. But oncologists in the United States and the rest of the world still want the best for their patients. Patients have to become more aware what’s best for them. Those issues of quality and integrity still give us an edge. That’s a natural inclination, to go the less-regulated route. I think that the optimal path is somewhere in between, so that the regulations don’t impede the opportunity for a patient to go on clinical trials or for interested oncologists to deliver that treatment, and yet it’s not unattractive so that the good drugs that are coming through industry can be evaluated properly.

PND: A commission was convened by the NIH to review the practice of funding clinical cancer research groups. What significance will it have for clinical researchers?

RC: There is a committee run by Dr. James Armitage from Nebraska, working with the Cancer Institute, to look at the entire clinical trials program of the National Cancer Institute. The committee report very pointedly recommended that the cooperative groups be brought back up to full funding. If we come back up to full funding, we could pay our doctors what they need, we could pay for the research infrastructure that we require and we could enhance our ability to get patients on the best clinical trials that are available.

PND: What’s the next step for your coalition?

RC: Putting together the structures and administrative and financial plans. We would hope to have our structures developed and our membership defined and our initial thrust in place within the next six months. The first order of business is going to be to continue an initiative that we started in ECOG which tries to engage the payers in the clinical trials process. We can’t ignore the fact that we need to get the managed care and other types of plans into the mind frame that this is a very organized, efficient, highest quality care kind of approach to cancer management. They can help expedite entry of patients on to clinical trials and assure that the clinical costs are covered. On September 19th, we announced that certain HMOs in Minnesota and Wisconsin had agreed to this proposal, and we’re working hard in Indiana, Illinois, Pennsylvania and a variety of other areas.