The Institute of Medicine, The National Cancer Institute, and Clinical Trials

Abstract

In April 2010, the Institute of Medicine (IOM) of the National Academies released the report A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program (1Institute of MedicineA National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. The National Academies Press, Washington, DC2010Google Scholar). That report was in response to a request from the U.S. National Cancer Institute (NCI) that the IOM review the Cooperative Group Program and advise them on ways to improve that program. The IOM committee, chaired by John Mendelsohn, President of the University of Texas M.D. Anderson Cancer Center, with Harold L. Moses, Director Emeritus of the Vanderbilt-Ingram Comprehensive Cancer Center as Vice-Chair, produced a thoughtful report with which few could take exception. The committee noted that the clinical trials infrastructure has not evolved adequately to incorporate the rapid pace of biomedical discovery, that the processes are inefficient, and that funding is stagnant and inadequate. They looked for a better system that could respond efficiently to emerging scientific knowledge, involve a broad group of stakeholders, and leverage evolving technologies to produce high-quality research that would change the practice of medicine. The committee concluded that “…it is imperative to preserve and strengthen the unique capabilities of the Cooperative Group Program as a vital component in NCI’s translational continuum” (1Institute of MedicineA National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. The National Academies Press, Washington, DC2010Google Scholar).One of the observations included in the report was that government oversight has become extensive and complex. Yet, in response to this report, and in many ways seemingly contrary to the IOM effort, the NCI has proposed a reorganization of the cooperative groups (2Goldberg K.B. NCI proposes consolidation of nine cooperative groups to four, in two years.Cancer Lett. 2010; 36 (Available from:) (Accessed January 24, 2011)www.cancerletter.com/downloads/20101217/downloadGoogle Scholar, 3NCI Office of Media Relations. NCI announces plans to reinvigorate clinical trials (press release). Posted online December 23, 2010. Available from: http://www.cancer.gov/newscenter/pressreleases/CoopGroupsConsolidate.Google Scholar) that benefits a very few and quite possibly sets others up for struggles that the patients of North America do not deserve.The chairs of the nine Cooperative Groups studying adult cancers (American College of Radiology Imaging Network; American College of Surgeons Oncology Group; Cancer and Leukemia Group B; Eastern Cooperative Oncology Group; Gynecologic Oncology Group; National Surgical Adjuvant Breast and Bowel Project; North Central Cancer Treatment Group; Radiation Therapy Oncology Group; and Southwest Oncology Group) were summoned to a meeting in Rockville, Maryland on November 29, 2010, at which the NCI recommended integration of the nine groups into not more than four groups. Other recommendations included consolidation of data management and operations and reconfiguration of the NCI review of clinical trials. Certainly efforts to streamline the processes with the goal of reducing redundancy and improving efficiency are laudable; indeed, the IOM report suggested that a reduction in the number of Cooperative Groups would be a logical extension of their recommendation to consolidate disease site committees, statistical offices that generate and vet potential concepts and statistical designs for trials, and administration and data management operations (see pp 16–17 of the IOM report). The nature of the reorganization envisioned by the NCI, however, is problematic, as is the lack of any additional funds for the program (the IOM had recommended doubling the current funding)—or indeed, for the reorganization itself, which would be costly in terms of both time and resources. The experience with the reorganization of four children’s groups into the single Children’s Oncology Group a few years ago amply demonstrates the slowing of progress, the increased expenses, and the disenfranchisement of many investigators, all of whom are volunteers, during the reorganization process.The structure of the proposed reorganization is as follows. The Eastern Cooperative Oncology Group (ECOG) and the Southwest Oncology Group (SWOG) would remain unaltered, thus representing half of the proposed groups. A third group would combine the Cancer and Leukemia Group B (CALGB), the North Central Cancer Treatment Group (NCCTG), the American College of Surgeons Oncology Group (ACOSOG), and the American College of Radiology Imaging Network (ACRIN). A fourth group would comprise the Radiation Therapy Oncology Group (RTOG) and the National Surgical Adjuvant Breast and Bowel Project. Although the RTOG and National Surgical Adjuvant Breast and Bowel Project have had collegial working relationships and are currently pursuing an important intergroup study of partial breast irradiation, the National Surgical Adjuvant Breast and Bowel Project has had little experience with trials of central nervous system, head-and-neck, thoracic, or genitourinary tumors—areas that are major strengths of the RTOG. Moreover, the development, credentialing, and careful implementation of advanced technology, all hallmarks of the RTOG, are likely to be buried in the push for molecular techniques and targeting.The Gynecologic Oncology Group has yet to be assigned to any of these proposed combinations—which presumably reflects the Gynecologic Oncology Group supporters’ reaction to a previous attempt at consolidation, namely rising up in strength to challenge any diminution of the Gynecologic Oncology Group’s role.This is the fourth attempt at consolidation during my professional career. The obvious goal of the NCI leadership in the current proposal is control. It has been a desire of the NCI staff for many years to direct, even to dictate, the activities of the cooperative groups, rather than to rely on the expertise of leaders in the groups. This differs from the structure and processes of the cancer clinical trial groups in Europe such as the European Organisation for Research and Treatment of Cancer (EORTC), the German Hodgkin’s Lymphoma Study Group, the Groupe d’Etude des Lymphomes de l’Adulte (GELA), the Dutch Colorectal Cancer Group, and others. At least in the past, these groups have been much more productive in answering important questions on head-and-neck, prostate, rectal, and anal cancer and Hodgkin’s lymphoma. Although more trials are conducted in the United States than in any other country, the scientific and social effect of those trials lags behind that of trials conducted elsewhere.This is a time for commentary on the proposed reorganization. Perhaps wisdom will prevail in the long run. The best one could hope for is that the recommendations of the IOM with respect to increased funding will be heeded; unfortunately, the increasing pressure for cutbacks at the level of the NIH and NCI make it more likely that the cooperative group program will also be adversely affected. Nevertheless, the current clinical trials program, noted by the IOM to be a precious resource, should not be changed radically overnight. There is no more immediate method for achieving progress for cancer patients than well-conceived, well-conducted clinical trials. The patients of the United States and the world deserve proper use of the intellectual capabilities of large number of physicians and collaborators in the cancer cooperative groups, the vast majority of whom are volunteers. The proposed consolidation, coupled with increased NCI control, would impede progress rather than producing the increased efficiency envisioned by the IOM committee. In April 2010, the Institute of Medicine (IOM) of the National Academies released the report A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program (1Institute of MedicineA National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. The National Academies Press, Washington, DC2010Google Scholar). That report was in response to a request from the U.S. National Cancer Institute (NCI) that the IOM review the Cooperative Group Program and advise them on ways to improve that program. The IOM committee, chaired by John Mendelsohn, President of the University of Texas M.D. Anderson Cancer Center, with Harold L. Moses, Director Emeritus of the Vanderbilt-Ingram Comprehensive Cancer Center as Vice-Chair, produced a thoughtful report with which few could take exception. The committee noted that the clinical trials infrastructure has not evolved adequately to incorporate the rapid pace of biomedical discovery, that the processes are inefficient, and that funding is stagnant and inadequate. They looked for a better system that could respond efficiently to emerging scientific knowledge, involve a broad group of stakeholders, and leverage evolving technologies to produce high-quality research that would change the practice of medicine. The committee concluded that “…it is imperative to preserve and strengthen the unique capabilities of the Cooperative Group Program as a vital component in NCI’s translational continuum” (1Institute of MedicineA National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. The National Academies Press, Washington, DC2010Google Scholar). One of the observations included in the report was that government oversight has become extensive and complex. Yet, in response to this report, and in many ways seemingly contrary to the IOM effort, the NCI has proposed a reorganization of the cooperative groups (2Goldberg K.B. NCI proposes consolidation of nine cooperative groups to four, in two years.Cancer Lett. 2010; 36 (Available from:) (Accessed January 24, 2011)www.cancerletter.com/downloads/20101217/downloadGoogle Scholar, 3NCI Office of Media Relations. NCI announces plans to reinvigorate clinical trials (press release). Posted online December 23, 2010. Available from: http://www.cancer.gov/newscenter/pressreleases/CoopGroupsConsolidate.Google Scholar) that benefits a very few and quite possibly sets others up for struggles that the patients of North America do not deserve. The chairs of the nine Cooperative Groups studying adult cancers (American College of Radiology Imaging Network; American College of Surgeons Oncology Group; Cancer and Leukemia Group B; Eastern Cooperative Oncology Group; Gynecologic Oncology Group; National Surgical Adjuvant Breast and Bowel Project; North Central Cancer Treatment Group; Radiation Therapy Oncology Group; and Southwest Oncology Group) were summoned to a meeting in Rockville, Maryland on November 29, 2010, at which the NCI recommended integration of the nine groups into not more than four groups. Other recommendations included consolidation of data management and operations and reconfiguration of the NCI review of clinical trials. Certainly efforts to streamline the processes with the goal of reducing redundancy and improving efficiency are laudable; indeed, the IOM report suggested that a reduction in the number of Cooperative Groups would be a logical extension of their recommendation to consolidate disease site committees, statistical offices that generate and vet potential concepts and statistical designs for trials, and administration and data management operations (see pp 16–17 of the IOM report). The nature of the reorganization envisioned by the NCI, however, is problematic, as is the lack of any additional funds for the program (the IOM had recommended doubling the current funding)—or indeed, for the reorganization itself, which would be costly in terms of both time and resources. The experience with the reorganization of four children’s groups into the single Children’s Oncology Group a few years ago amply demonstrates the slowing of progress, the increased expenses, and the disenfranchisement of many investigators, all of whom are volunteers, during the reorganization process. The structure of the proposed reorganization is as follows. The Eastern Cooperative Oncology Group (ECOG) and the Southwest Oncology Group (SWOG) would remain unaltered, thus representing half of the proposed groups. A third group would combine the Cancer and Leukemia Group B (CALGB), the North Central Cancer Treatment Group (NCCTG), the American College of Surgeons Oncology Group (ACOSOG), and the American College of Radiology Imaging Network (ACRIN). A fourth group would comprise the Radiation Therapy Oncology Group (RTOG) and the National Surgical Adjuvant Breast and Bowel Project. Although the RTOG and National Surgical Adjuvant Breast and Bowel Project have had collegial working relationships and are currently pursuing an important intergroup study of partial breast irradiation, the National Surgical Adjuvant Breast and Bowel Project has had little experience with trials of central nervous system, head-and-neck, thoracic, or genitourinary tumors—areas that are major strengths of the RTOG. Moreover, the development, credentialing, and careful implementation of advanced technology, all hallmarks of the RTOG, are likely to be buried in the push for molecular techniques and targeting. The Gynecologic Oncology Group has yet to be assigned to any of these proposed combinations—which presumably reflects the Gynecologic Oncology Group supporters’ reaction to a previous attempt at consolidation, namely rising up in strength to challenge any diminution of the Gynecologic Oncology Group’s role. This is the fourth attempt at consolidation during my professional career. The obvious goal of the NCI leadership in the current proposal is control. It has been a desire of the NCI staff for many years to direct, even to dictate, the activities of the cooperative groups, rather than to rely on the expertise of leaders in the groups. This differs from the structure and processes of the cancer clinical trial groups in Europe such as the European Organisation for Research and Treatment of Cancer (EORTC), the German Hodgkin’s Lymphoma Study Group, the Groupe d’Etude des Lymphomes de l’Adulte (GELA), the Dutch Colorectal Cancer Group, and others. At least in the past, these groups have been much more productive in answering important questions on head-and-neck, prostate, rectal, and anal cancer and Hodgkin’s lymphoma. Although more trials are conducted in the United States than in any other country, the scientific and social effect of those trials lags behind that of trials conducted elsewhere. This is a time for commentary on the proposed reorganization. Perhaps wisdom will prevail in the long run. The best one could hope for is that the recommendations of the IOM with respect to increased funding will be heeded; unfortunately, the increasing pressure for cutbacks at the level of the NIH and NCI make it more likely that the cooperative group program will also be adversely affected. Nevertheless, the current clinical trials program, noted by the IOM to be a precious resource, should not be changed radically overnight. There is no more immediate method for achieving progress for cancer patients than well-conceived, well-conducted clinical trials. The patients of the United States and the world deserve proper use of the intellectual capabilities of large number of physicians and collaborators in the cancer cooperative groups, the vast majority of whom are volunteers. The proposed consolidation, coupled with increased NCI control, would impede progress rather than producing the increased efficiency envisioned by the IOM committee.