Beaten at the Alamo by the Europeans

Author: Harold J. Burstein MD, PhD
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Trend-spotters looking back at 2010 have noted it as a year of lament over clinical trials in the United States, particularly in oncology. A widely cited Institute of Medicine report1 called for reinvigorating cooperative groups. Documenting need for reform, a study of the activation of phase III clinical trials in the NCI system revealed over 750 separate steps, 36 approval stages, and median 2.5 years to activation.2 Clearly, that process will not encourage investigators, clinical cancer centers, or pharmaceutical or other sponsors to engage more actively in clinical research. Moving into 2011, plans are afoot for a dramatic overhaul and consolidation of the cooperative groups. In addition, gains in accrual to European-based clinical trials have been well publicized. Reports suggest superior accrual in Europe to clinical trials in lymphoma and stem cell therapies. On a population basis, European oncologists have been accruing better to clinical trials than have American oncologists. Reports at the 2010 San Antonio Breast Cancer Symposium brought home the power of that improved accrual. The major results were dominated by out-of-U.S. clinical trials. A series of large, provocative, biologically-based neoadjuvant studies (neoALTTO, neoSPHERE, GeparQuinto) were presented on behalf of European investigators. The negative AZURE study originated in the United Kingdom, and the negative MA27 study, which included the U.S. Intergroup, originated in NCI-Canada. Texas hosted a triumph for out-of-U.S. oncology. Part of the problem is an overly burdened study approval process in the United States. A recent study compared lung cancer clinical trial activation and accrual at...

Trend-spotters looking back at 2010 have noted it as a year of lament over clinical trials in the United States, particularly in oncology. A widely cited Institute of Medicine report1 called for reinvigorating cooperative groups. Documenting need for reform, a study of the activation of phase III clinical trials in the NCI system revealed over 750 separate steps, 36 approval stages, and median 2.5 years to activation.2 Clearly, that process will not encourage investigators, clinical cancer centers, or pharmaceutical or other sponsors to engage more actively in clinical research. Moving into 2011, plans are afoot for a dramatic overhaul and consolidation of the cooperative groups.

In addition, gains in accrual to European-based clinical trials have been well publicized. Reports suggest superior accrual in Europe to clinical trials in lymphoma and stem cell therapies. On a population basis, European oncologists have been accruing better to clinical trials than have American oncologists.

Reports at the 2010 San Antonio Breast Cancer Symposium brought home the power of that improved accrual. The major results were dominated by out-of-U.S. clinical trials. A series of large, provocative, biologically-based neoadjuvant studies (neoALTTO, neoSPHERE, GeparQuinto) were presented on behalf of European investigators. The negative AZURE study originated in the United Kingdom, and the negative MA27 study, which included the U.S. Intergroup, originated in NCI-Canada. Texas hosted a triumph for out-of-U.S. oncology.

Part of the problem is an overly burdened study approval process in the United States. A recent study compared lung cancer clinical trial activation and accrual at 2 centers—one in the United State and one in Italy.3 The American center had longer times to submission and activation, longer times to first accrual, longer times to contract approvals, and lower accrual per study.

Regulatory processes, however, can only account for some of the differences in accrual among cancer centers and countries. In many European and Canadian areas, cancer care is delivered in regionalized centers, while private practice models, with their mixed incentives for clinical trial participation, are less of a factor. Many European specialists can reach an “internal consensus” that facilitates trial accrual when broad agreement on treatment patterns can be achieved. In addition, European studies often represent closer allegiances between investigators and pharmaceutical sponsors than is seen in many large U.S. trials. In the study by Wang-Gillam et al.,3 the trials in Italy were quicker off the mark but were also far more likely to be industry sponsored and less likely to be initiated by an institutional or cooperative group.

Much reform is needed to facilitate greater trial access and participation in the United States. Various initiatives are needed, including changes in local and federal policy to speed up study activation and changes in the culture of care to encourage more doctors and patients to participate. Maybe some of these changes will start in 2011. Until they do, look for more presentations from our international colleagues.

The ideas and viewpoints expressed in this editorial are those of the author and do not necessarily represent any policy, position, or program of the NCCN.

References

  • 1.

    U.S. Board on Health Care Services. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. April 2010. Available at http://www.iom.edu.

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  • 2.

    Dilts DM, Cheng SK, Crites JS. Phase III clinical trial development: a process of chutes and ladders. Clin Cancer Res 2010;16:53815389.

  • 3.

    Wang-Gillam A, Williams K, Novello S. Time to actiate lung cancer clinical trials and patient enrollment: a representative comparison study between two academic centers across the Atlantic. J Clin Oncol 2010;28:38033807.

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Harold J. Burstein, MD, PhD, editor-in-chief of JNCCN, is an Associate Professor of Medicine at Harvard Medical School and a medical oncologist at Dana-Farber Cancer Institute and Brigham & Women's Hospital. He is a clinician and clinical investigator specializing in breast cancer.

Dr. Burstein attended Harvard College and earned his MD at Harvard Medical School, where he also earned a PhD in immunology. He trained in internal medicine at Massachusetts General Hospital and was a fellow in medical oncology at Dana-Farber before joining the staff.

Dr. Burstein's clinical research interests include novel treatments for early- and advanced-stage breast cancer and studies of quality of life and health behavior among women with breast cancer. He has written widely on breast cancer in both traditional medical journals and on the web, including New England Journal of Medicine and Journal of Clinical Oncology. International committees focusing on cancer treatments that he has or continues to participate in include the NCCN Clinical Practice Guidelines Breast Cancer Panel, St. Gallen Breast Cancer Panel, CALGB Breast Cancer Committee, ASCO Health Services Research and Clinical Research Committees, the National Quality Forum Breast Cancer Technical Panel, and other ASCO expert panels.

  • 1.

    U.S. Board on Health Care Services. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. April 2010. Available at http://www.iom.edu.

    • Export Citation
  • 2.

    Dilts DM, Cheng SK, Crites JS. Phase III clinical trial development: a process of chutes and ladders. Clin Cancer Res 2010;16:53815389.

  • 3.

    Wang-Gillam A, Williams K, Novello S. Time to actiate lung cancer clinical trials and patient enrollment: a representative comparison study between two academic centers across the Atlantic. J Clin Oncol 2010;28:38033807.

    • Search Google Scholar
    • Export Citation
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