Abstract
Objective
To determine whether the early trials in chronic medical conditions demonstrate an
effect size that is larger than that in subsequent trials.
Methods
We identified randomized controlled trials (RCTs) evaluating a drug or device in patients
with chronic medical conditions through meta-analyses (MAs) published between January
1, 2007, and June 23, 2015, in the 10 general medical journals with highest impact
factor. We estimated the prevalence of having the largest effect size or heterogeneity
in the first 2 published trials. We evaluated the association of the exaggerated early
effect with several a priori hypothesized explanatory variables.
Results
We included 70 MAs that had included a total of 930 trials (average of 13 [range,
5-48] RCTs per MA) with average follow-up of 24 (range, 1-168) months. The prevalence
of the exaggerated early effect (ie, proportion of MAs with largest effect or heterogeneity
in the first 2 trials) was 37%. These early trials had an effect size that was on
average 2.67 times larger than the overall pooled effect size (ratio of relative effects,
2.67; 95% CI, 2.12-3.37). The presence of exaggerated effect was not significantly
associated with trial size; number of events; length of follow-up; intervention duration;
number of study sites; inpatient versus outpatient setting; funding source; stopping
a trial early; adequacy of random sequence generation, allocation concealment, or
blinding; loss to follow-up or the test for publication bias.
Conclusion
Trials evaluating treatments of chronic medical conditions published early in the
chain of evidence commonly demonstrate an exaggerated treatment effect compared with
subsequent trials. At the present time, this phenomenon remains unpredictable. Considering
the increasing morbidity and mortality of chronic medical conditions, decision makers
should act on early evidence with caution.
Abbreviations and Acronyms:
MA (meta-analysis), RCT (randomized controlled trial)To read this article in full you will need to make a payment
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Article Info
Publication History
Published online: February 21, 2018
Footnotes
For editorial comment, see page 273
Potential Competing Interests: The authors report no competing interests.
Identification
Copyright
© 2017 Mayo Foundation for Medical Education and Research
