Wither the Cooperative Groups?

Abstract

The cooperative groups sponsored by the National Cancer Institute (NCI) were formed beginning in the mid-1950s and have provided a publicly funded standing infrastructure to conduct cancer clinical trials ever since (Appendix Fig A1, online only). The accomplishments of the US cooperative groups, often in collaboration with similar organizations in Europe and Canada, are notable for the development of curative therapies for most pediatric cancers; the introduction of effective combined modality treatments for many diseases, including head and neck cancer, cervical cancer, esophageal cancer, non–small-cell lung cancer, and anal cancer; the development of adjuvant chemotherapy as a standard of care for many solid tumors, particularly breast cancer and colorectal cancer; and the introduction of chemoprevention strategies for patients at high risk of developing breast and prostate cancer. The groups have also worked collaboratively with the pharmaceutical industry to introduce new cancer drugs into medical practice and to develop new indications for already approved drugs. Indeed, more than 20 new indications for cancer drugs have resulted directly from cooperative group studies. Clinical trials performed by the cooperative groups have also provided important insights into optimal scheduling and sequencing of chemotherapy drugs and the preferred route of drug administration that have established new standards of care, such as the introduction of dose-dense chemotherapy as part of adjuvant treatment of breast cancer and the demonstration of improved survival when intraperitoneal administration of chemotherapy is used for treatment of ovarian cancer. Importantly, cooperative groups have also rigorously evaluated purported advances in cancer care that were popularized by single individuals or centers and, in some cases, such as high-dose chemotherapy and autologous stem-cell transplant for breast cancer, have proven them ineffective. Finally, many important advances in supportive care for patients with cancer have come from cooperative group studies, such as the recent demonstration of the value of duloxetine to relieve symptoms of chemotherapyinduced painful peripheral neuropathy. In the current era of molecular medicine, the cooperative group biospecimen repositories, populated with specimens from clinical trial participants who received uniform treatments and have welldocumented outcomes, are invaluable resources for the development of new prognostic, predictive, and response biomarkers across a range of cancer types. These repositories will support a new generation of biomarker-driven clinical trials currently in development by the cooperative groups. And, with the heightened public interest in comparative effectiveness and cost, the cooperative groups, as publicly funded entities free from commercial bias, are ideally positioned to directly compare therapeutic approaches or drugs from competing commercial firms, combine drugs from different sponsors, develop treatments for rare diseases with small commercial markets, and rigorously examine the cost effectiveness of new treatments and their impact on patient quality of life. Beyond their scientific contributions, the cooperative groups have developed many of the standard methods to conduct multicenter clinical trials, extended clinical trials to community oncologists, and provided a fertile training ground for generations of clinical investigators and countless research staff. Despite their many contributions to cancer care and research, the cooperative groups have been subjected to scrutiny and criticism for nearly their entire existence. In the last 15 years alone, no fewer than five committees have been convened by NCI or at the request of NCI to evaluate the cooperative group program. Most recently the Institute of Medicine (IOM) of the National Academy of Sciences produced a report at the request of the NCI entitled, “A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program,” which identified the many challenges faced by the cooperative groups at the present time, including stagnant funding; inefficient and redundant processes; excessive and complex government oversight, with many layers of review performed by multiple agencies; long delays in the launch of clinical trials; and increasing competition from the pharmaceutical industry for patient accrual to studies. When the IOM report was issued, the time required to activate a phase III trial in the cooperative groups averaged nearly 2 years, and JOURNAL OF CLINICAL ONCOLOGY S P E C I A L A R T I C L E VOLUME 32 NUMBER 3 JANUARY 2