Is there evidence of implicit exclusion criteria for elderly subjects in randomized trials? Evidence from the GUSTO-1 study☆

Received 8 October 2002; accepted 7 April 2003.

Abstract

Background

Some experts have raised concerns about the ability to generalize randomized trials, emphasizing that patients who participate in these studies are often not representative of those seen in clinical practice, particularly in the case of elderly patients. To determine the effect of implicit exclusion criteria on a trial study sample, we compared data from the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) trial with data from a retrospective registry from selected hospitals, the National Registry of Myocardial Infarction (NRMI), and a nationally representative study of myocardial infarction care, the Cooperative Cardiovascular Project (CCP).

Methods

We compared GUSTO subjects aged 65 years and older who were enrolled in the United States with similarily aged patients in the 2 observational studies who met the trial's eligibility criteria. We examined baseline characteristics, clinical presentation, treatments, procedures, clinical events, and in-hospital mortality rates.

Results

We found modest, although significant, differences between patients in NRMI, CCP, and GUSTO in demographic and clinical characteristics, treatment, and outcome. For example, GUSTO patients were significantly younger (73.1 ± 5.7 vs 74.7 ± 6.8 for NRMI and 75.8 ± 7.2 for CCP), less likely to have Killip class III/IV at presentation (3.1% vs 6.2% for NRMI and 32.7% for CCP), and more likely to receive aspirin (95.5% vs 86.3% for NRMI and 86.5% for CCP) and β-blockers (71.9% vs 43.5% for NRMI and 52.7% for CCP). Overall, NRMI and CCP patients had a lower risk of 30-day mortality after adjustment for demographic, clinical, and hospital characteristics than patients in GUSTO (odds ratio, 0.79; 95% CI, 0.73–0.86 for NRMI; odds ratio, 0.65; 95% CI, 0.59–0.71 for CCP).

Conclusions

Older patients enrolled in a randomized trial without an age restriction had many similarities compared with patients seen in clinical practice. The higher mortality rate of the GUSTO patients does not support the hypothesis that the trial enrolled a healthier cohort than is seen in practice.

a Section of Cardiovascular Medicine, Department of Medicine, Yale University School of Medicine, New Haven, Conn, USA

b Yale-New Haven Hospital Center for Outcomes Research and Evaluation, New Haven, Conn, USA

c Yale-New Haven Health Center for Outcomes Research and Evaluation, New Haven, Conn, USA

d Qualidigm, Middletown, Conn, USA

e Section of Health Policy and Administration, Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, Conn, USA

f Department of Medicine, Yale University School of Medicine, New Haven, Conn, USA

g Duke Clinical Research Institute, Durham, NC, USA

h Departments of Epidemiology and Biostatistics and Medicine (Cardiology), University of California, San Francisco, Calif, USA

i Department of Medical Affairs, Genentech Inc, South San Francisco, Calif, USA

j Ovation Research Group, Chicago, Ill, USA

k Frazier and Company, Seattle, Wash, USA

Reprint requests: Harlan M. Krumholz, MD, Yale University School of Medicine, PO Box 208088, New Haven, CT 06520-8088, USA.

☆ Dr Gross was supported by a Cancer Prevention, Control and Population Sciences Career Development Award (1K078CA-90402) and the Claude D. Pepper Older Americans Independence Center at Yale (P30AG21342).

The analyses on which this publication is based were performed under contract number 500-99-CT01, titled “Utilization and Quality Control Peer Review Organization for the State of Connecticut,” sponsored by the Centers for Medicare and Medicaid Services, Department of Health and Human Services. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does the mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. The author assumes full responsibility for the accuracy and completeness of the ideas presented. This article is a direct result of the Health Care Quality Improvement Program initiated by the Centers for Medicare and Medicaid Services, which has encouraged identification of quality improvement projects derived from analysis of patterns of care, and therefore required no special funding on the part of this contractor. Ideas and contributions to the author concerning experience in engaging with issues presented are welcomed.

Guest editor for this manuscript was A. Michael Lincoff, MD, Cleveland Clinic Foundation, Cleveland, Ohio.

PII: S0002-8703(03)00408-3

doi:10.1016/S0002-8703(03)00408-3

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