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Potential Influence of Health Systems in Accrual to Clinical Trials in Lymphoma

Department of Medicine, Division of Hematology/Oncology, University of Florida, Gainesville, FL

To the Editor:

It has been estimated that in the United States, as few as 2% to 4% of eligible adult patients participate in cancer clinical trials and that only 30% to 40% of oncologists actively accrue patients onto these trials.^1,2 Potential explanations include physician priorities, lack of academic credit for enrolling patients on large trials versus investigator-initiated trials, lack of public awareness, public misconception, stringent entry criteria, and funding/reimbursement issues.

Furthermore, it has been suggested that health systems significantly shape the patterns of clinical trial enrollment via their economic structure. Single-payer publicly funded systems administered through health ministries have a financial incentive to combine the costs of patient care with research. These systems may be better suited to address broad treatment questions that have significant impact on physician decision-making and that are typically answered by large randomized controlled trials. In the United States multipayer system, however, all research costs must be born by practitioners whether in the private setting or by each individual institution in the academic setting. Since support for industry-sponsored trials is usually far more generous than that from Federal sources, the US multipayer system creates an economic incentive to address questions of interest to industry. Pharmaceutical company–sponsored trials are often phase I and II evaluations of novel agents that siphon participation from larger randomized controlled studies such as those performed through the traditional cooperative groups.

If one compares accrual rates between the United States (population 291 million) and Germany (population 81million) with respect to Hodgkin's disease, clear differences are obvious. Easter Cooperative Oncology Group (ECOG) 2496, comparing Stanford V (mechlorethamine by vein once every 4 weeks; doxorubicin by vein every odd week; vinblastine by vein every odd week; vincristine by vein every even week; bleomycin by vein every even week; etoposide by vein 2 days in a row weeks 3, 7, 11; prednisone by mouth every other day) with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) opened in April 1999 with a goal of 850 patients and is projected to complete accrual in December 2005. In contrast, the German HD9 trial accrued 1,200 patients over 5 years,³ and the most recent trial, HD12, which like the ECOG trial opened in 1999, completed accrual of 1,396 patients by 2002, and initial data from this trial were presented at the American Society of Hematology meeting in December 2004.⁴

To determine whether clinical trial enrollment rates for lymphoma from comparable population bases with different health systems were consistent with a substantial effect of the system, we analyzed the published literature from 2000 to 2004 to compare enrollment of adult patients in such trials in the United States and a group of European countries with single-payer health systems and a combined population comparable to that of the United States. A PubMed search was undertaken for lymphoma with limits of "randomized controlled trials" for the period of January 2000 to December 2004. Trials of chronic lymphocytic leukemia, multiple myeloma, and of pediatric patients were excluded. Abstracts for each citation were reviewed, and only those described as randomized controlled trials were included in the analysis. The quality, clinical relevance, and numbers of patients on each trial varied greatly. A detailed statistical analysis was not performed.

As noted in Table 1, in the United States, with an estimated 2003 population of 291 million, there were 17 published trials with a total of 3,317 patients. In contrast, studies from Germany, France, Italy, the Netherlands, and the United Kingdom, with an estimated combined population of 273 million, totaled 58 trials and 19,433 patients. Data from all European trials, as well as number of trials according to numbers of patients and to type of lymphoma, are also included in Table 1.

Authors' Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Lara Jr PN, Hidgdon R, Lim N, et al: Prospective evaluation of cancer clinical trial accrual patterns: Identifying potential barriers to enrollment. J Clin Oncol 19:1728-1733, 2001[Abstract/Free Full Text]

2. McNeil C: Clinical trial accrual efforts: Some progress amid ongoing debate. J Natl Cancer Inst 96:1417-1418, 2004[Free Full Text]

3. Diehl V, Franklin J, Pfreundschuh M, et al: Standard and increased-dose BEACOPP chemotherapy compared with COPP-ABVD for advanced Hodgkin's disease. N Engl J Med 348:2386-2395, 2003[Abstract/Free Full Text]

4. Diehl V, Franklin B, Greil H, et al: Beacopp chemotherapy for advanced HD: Results of further analysis of the HD9 and HD12 trials fo the German Hodgkin's Study Group, the Competence Network Malignant Lymphoma. Blood 104:91a, 2004 (abstr 307)

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This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Hagler, K. T. Articles by Lynch, J. W. Search for Related Content PubMed PubMed Citation Articles by Hagler, K. T. Articles by Lynch, J. W., Jr Social Bookmarking                            What's this?