Racial Disparities in Cancer Survival Among Randomized Clinical Trials Patients of the Southwest Oncology Group

Purpose In March 1998, Common Toxicity Criteria (CTC) version 2.0 introduced the collection of attribution of adverse events (AEs) to study drug. We investigate whether attribution adds value to the interpretation of AE data. Patients and Methods Patients in the placebo arm of two phase III trials—North Central Cancer Treatment Group Trial 97-24-51 (carboxyamino-triazole v placebo in advanced non–small-cell lung cancer) and American College of Surgeons Oncology Group Trial Z9001 (imatinib mesylate v placebo after resection of primary gastrointestinal stromal tumors)—were studied. Attribution was categorized as unrelated (not related or unlikely) and related (possible, probable, or definite). Results In total, 398 patients (84 from Trial 97-24-51 and 314 from Trial Z9001) and 7,736 AEs were included; 47% and 50% of the placebo-arm AEs, respectively, were reported as related. When the same AE was reported in the same patient on multiple visits, the attribution category changed at least once 36% and 31% of the time. AE type and sex (Trial Z9001) and AE type and performance status (Trial 97-24-51) were associated with a higher likelihood of AEs being deemed related. Conclusion Nearly 50% of AEs were reported as attributed to study drug on the placebo arm of two randomized clinical trials. These data provide strong evidence that AE attribution is difficult to determine, unreliable, and of questionable value in interpreting AE data in randomized clinical trials.

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Fundamental dilemmas of the randomized clinical trial process: results of a survey of the 1,737 Eastern Cooperative Oncology Group investigators.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.9.1796 ◽

1994 ◽

Vol 12 (9) ◽

pp. 1796-1805 ◽

Cited By ~ 104

Author(s):

K M Taylor ◽

M L Feldstein ◽

R T Skeel ◽

K J Pandya ◽

P Ng ◽

...

Keyword(s):

Clinical Trials ◽

Randomized Clinical Trials ◽

Eastern Cooperative Oncology Group ◽

Oncology Group ◽

Future Design ◽

Actual Patient ◽

Critical Issues ◽

Accrual Rate ◽

The Impact ◽

Patient Accrual

PURPOSE We studied oncologists' attitudes and behavior with regard to their participation in randomized clinical trials. METHODS We surveyed the 1,737 physician members of the Eastern Cooperative Oncology Group (ECOG) using the Physician Orientation Profile (POP), a self-administered mailed questionnaire. A response rate of 86% was achieved (1,485 of 1,737); each physician's actual patient accrual was recorded. RESULTS All respondents indicated that they had a systematic pattern of patient preselection for entry onto trials beyond the formal inclusion/exclusion trial criteria. Eighty-nine percent stated that improving patient quality of life rather than prolonging survival was more personally satisfying. Sixty-two percent did not enter a single patient during the 12-month period following the survey, while 10% entered 80% of all patients during that time. Physicians overestimated their accrual rate by a factor of 6. Eighty-three percent defined randomization and adherence to trial protocol as a serious challenge to their ability to make individualized treatment decisions. CONCLUSION This study raises questions regarding the following: (1) the perceived generalizability of trial findings, (2) the role of end points other than survival for clinical trials, (3) the consequences of physician overestimation of patient accrual, and (4) the impact of randomized trials on the behavior of clinicians. Further investigation into these critical issues will provide meaningful recommendations to enhance the future design, implementation, and conduct of randomized clinical trials in cancer.

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