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Gunjan Y. Gandhi, MD, MSc; M. Hassan Murad, MD, MPH; Akira Fujiyoshi, MD, MPH; Rebecca J. Mullan, MS; David N. Flynn, BS; Mohamed B. Elamin, MBBS; Brian A. Swiglo, MD; William L. Isley, MD; Gordon H. Guyatt, MD, MSc; Victor M. Montori, MD, MSc

JAMA. 2008;299(21):2543-2549.

Context  Concerns about the safety and efficacy of diabetes interventions persist, in part because randomized clinical trials (RCTs) have not measured their effect on patient-important outcomes, ie, death and quality of life (morbidity, pain, function).

Objective  To systematically determine the extent to which ongoing and future RCTs in diabetes will ascertain patient-important outcomes.

Data Sources  On November 10, 2007, we searched primary RCT registries ClinicalTrials.gov (http://www.clinicaltrials.gov), International Standard Randomized Controlled Trial Number Register (http://isrctn.org), and Australian New Zealand Clinical Trials Registry (http://www.anzctr.org.au).

Study Selection  We identified phase 2 through 4 RCTs enrolling patients with diabetes. Of 2019 RCTs, 1054 proved eligible. We randomly sampled 50% of the eligible RCTs (527 of 1054) and selected 436 registered since registration became mandatory (2004).

Data Extraction  Pairs of reviewers working independently collected study characteristics and determined the outcomes measured and their type (physiological outcomes, surrogate outcomes thought to reflect an increased risk for patient-important outcomes, and patient-important outcomes).

Results  Of the 436 registered RCTs included in this analysis, 24 (6%) had not started enrollment, 109 (25%) were actively enrolling, and 303 (69%) had completed enrollment. Primary outcomes were patient-important outcomes in only 78 of 436 RCTs (18%; 95% confidence interval [CI], 14%-22%), physiological and laboratory outcomes in 69 of 436 (16%; 95% CI, 13%-20%), and surrogate outcomes in 268 of 436 (61%; 95% CI, 57%-66%). Patient-important outcomes were reported as primary or secondary outcomes in 201 of 436 (46%; 95% CI, 41%-51%). In multivariate analysis, large trials (odds ratio [OR], 1.10; 95% CI, 1.02-1.19 for every additional 100 patients) and trials of longer duration (OR, 1.03; 95% CI, 1.01-1.06 for every additional 30 days) were more likely while parallel design RCTs (OR, 0.15; 95% CI, 0.05-0.44) and type 2 diabetes trials (OR, 0.23; 95% CI, 0.09-0.61) were less likely to assess patient-important outcomes as a primary outcome.

Conclusion  In this sample of registered ongoing RCTs in diabetes, only 18% included patient-important outcomes as primary outcomes.

Author Affiliations: Division of Endocrinology, Diabetes, Metabolism and Nutrition (Drs Gandhi, Swiglo, Isley, and Montori), Knowledge and Encounter Research Unit (Drs Gandhi, Murad, Fujiyoshi, Swiglo, Elamin, Isley, and Montori, Ms Mullan, and Mr Flynn), and Division of Preventive, Occupational, and Aerospace Medicine (Dr Murad), College of Medicine, Mayo Clinic, Rochester, Minnesota, and Department of Clinical Epidemiology and Biostatistics, McMaster University, Hamilton, Ontario, Canada (Dr Guyatt).
Died September 27, 2007.

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