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The Metrics of Clinical Trials

Jurafvinski Cancer Centre at Hamilton Health Sciences and McMaster University, Hamilton, Ontario, Canada

Lee Fairclough

University Health Network/Princess Margaret Hospital, Toronto, Ontario, Canada

Janet Manzo

Ontario Cancer Reseach Network, Toronto, Ontario, Canada

Lynda Phippard

Lakeridge Durham Regional Cancer Centre, Oshawa, Ontario, Canada

Bobbi Smuck

London Regional Cancer Program, London, Ontario, Canada

Joanne Lacourciere

Thunder Bay Regional Health Sciences Centre, Regional Cancer Care, Thunder Bay, Ontario, Canada

To the Editor:

Goffman and Glatstein¹ raised many interesting issues in their re-evaluation of a trial previously reported by Whelan et al² evaluating hypofractionated breast irradiation. It was of particular interest that they raised concern with the fact that only 31% of patients deemed initially eligible were entered onto the trial.

Clinical trial recruitment is a complex multistep process. Potentially eligible or initially eligible patients are usually considered to be those patients who meet the inclusion criteria of a trial. A limited number of broad inclusion criteria, to include, for example, only the site and stage of disease, would best facilitate this determination. Obviously, not all cancer patients who meet the inclusion criteria for a specific trial are eligible to participate. In addition to refining the population of interest, there are also potential safety and regulatory reasons to exclude a proportion of these patients; these patients are collectively described by exclusion criteria. Eligible patients are only those initially eligible patients who do not meet any of a trial’s exclusion criteria. Ultimately, only a minority of patients actually consent to participate and are enrolled onto an active clinical trial.

To declare with certainty that all initially eligible patients were identified for a specific study would require detailed patient reviews. There are a few examples in the literature of such reporting from a larger programmatic perspective. Two of these come from the Community Clinical Oncology Program Physician’s Patient Log where data were compiled from physician-generated reviews of eligibility criteria for each patient. The first Log³ was published in 1987, and reported on the 44,156 newly diagnosed cancer patients seen throughout the member institutions between August 1984 and November 1985. Of those 44,156 patients, 17,773 patients (40.2%) were initially eligible because they fulfilled the broad inclusion criteria of active National Cancer Institute approved protocols; 9,953 patients (56.0%) of those 17,773 patients were clinically eligible; and 3,377 patients (34.0%) of those 9,953 patients then entered clinical trials. In total, 19.0% (3,377 of 17,773) of all initially eligible patients entered clinical trials. In a subsequent report published in 1999,⁴ 17.7% of all initially eligible patients entered trials.

From a single institution report, the oncologists at the University of California Davis Cancer Center (Sacramento, CA) were asked to prospectively complete questionnaires regarding a cohort of 276 patients.⁵ These were new patients seen over three periods, totaling 13 months throughout 1997, 1998, and 2000. One hundred seventy-four (63.0%) of these 276 patients were initially eligible for one of the more than 100 active clinical trials, and 76 were actually eligible. But only 39 patients, or 22% of all initially eligible patients, were entered onto clinical trials.

In comparison to these two series, it seems that the hypofractionation trial did exceptionally well by recruiting 31% of patients deemed initially eligible onto the trial. Most importantly from our perspective, the authors should be congratulated for actually providing such detail in their publication. Despite suggestions to include this information more consistently,⁶ most co-operative groups do not collect and are therefore unable to report data regarding initially eligible patients. As a result, the metrics of clinical trials’ activity are poorly reported and subsequently not well understood. As members of the Clinical Trials Network (CTN) of the Ontario Cancer Research Network (OCRN) we are very interested in detailing such metrics for all clinical trials conducted within the province of Ontario. This task would be much less daunting if more protocols and subsequent publications described patient eligibility with broad inclusion and detailed exclusion criteria. More importantly, this information would allow investigators to better appreciate and potentially improve the recruitment process of their trials, whereas readers would better understand the generalizability of the results.

Authors’ Disclosures of Potential Conflicts of Interest

The authors indicated no potential conflicts of interest.

REFERENCES

1. Goffman TE, Glatstein E: Hypofractionation redux? J Clin Oncol 22:589-591, 2004[Free Full Text]

2. Whelan T, MacKenzie R, Julian J, et al: Randomized trial of breast irradiation schedules after lumpectomy for women with lymph node-negative breast cancer. J Natl Cancer Inst 94:1143-1150, 2002[Abstract/Free Full Text]

3. Hunter CP, Frelick RW, Feldman AR, et al: Selection factors in clinical trials: Results from the Community Clinical Oncology physician’s patient log. Cancer Treat Rep 71:559-565, 1987[Medline]

4. Klabunde CN, Springer BC, Butler B, et al: Factors influencing enrolment in clinical trials for cancer treatment. South Med J 92:1189-1193, 1999[CrossRef][Medline]

5. Lara PN, Higdon 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]

6. Gross CP, Mallory R, Heiat A, Krumholz M: Reporting the recruitment process in clinical trials: Who are these patients and how did they get there? Ann Intern Med 137:10-16, 2002[Abstract/Free Full Text]

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