Abstract
Objective
To assess the frequency and features of secondary publications of randomized controlled
trials (RCTs).
Study Design and Setting
For 191 RCTs published in high-impact journals in 2009, we searched for secondary
publications coauthored by at least one same author of the primary trial publication.
We evaluated the probability of having secondary publications, characteristics of
the primary trial publication that predict having secondary publications, types of
secondary analyses conducted, and statistical significance of those analyses.
Results
Of 191 primary trials, 88 (46%) had a total of 475 secondary publications by 2/2014.
Eight trials had >10 (up to 51) secondary publications each. In multivariable modeling,
the risk of having subsequent secondary publications increased 1.32-fold (95% CI 1.05–1.68)
per 10-fold increase in sample size, and 1.71-fold (95% CI 1.19–2.45) in the presence
of a design article. In a sample of 197 secondary publications examined in depth,
193 tested different hypotheses than the primary publication. Of the 193, 43 tested
differences between subgroups, 85 assessed predictive factors associated with an outcome
of interest, 118 evaluated different outcomes than the original article, 71 had differences
in eligibility criteria, and 21 assessed different durations of follow-up; 176 (91%)
presented at least one analysis with statistically significant results.
Conclusions
Approximately half of randomized trials in high-impact journals have secondary publications
published with a few trials followed by numerous secondary publications. Almost all
of these publications report some statistically significant results.
Keywords
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Article info
Publication history
Published online: July 04, 2016
Accepted:
May 6,
2016
Footnotes
Funding: There were no sponsors for this study. S.E. was supported by postdoctoral awards from MITACS Elevate and SickKids Restracomp, Z.N.S. by a doctoral award from the Canadian Diabetes Association and the Ontario Graduate Scholarship, and S.B. by a doctoral award from the Social Sciences and Humanities Research Council. The Meta-Research Innovation Center at Stanford (METRICS) is funded by a grant from the Laura and John Arnold Foundation. Sponsors providing individual financial support to authors did not have a role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the article; and decision to submit the article for publication.
Conflict of interest: None.
Identification
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© 2016 Elsevier Inc. All rights reserved.
