Abstract
Background
We
explore whether the number of null results in large National Heart
Lung, and Blood Institute (NHLBI) funded trials has increased over time.
Methods
We
identified all large NHLBI supported RCTs between 1970 and 2012
evaluating drugs or dietary supplements for the treatment or prevention
of cardiovascular disease. Trials were included if direct costs
>$500,000/year, participants were adult humans, and the primary
outcome was cardiovascular risk, disease or death. The 55 trials meeting
these criteria were coded for whether they were published prior to or
after the year 2000, whether they registered in clinicaltrials.gov prior
to publication, used active or placebo comparator, and whether or not
the trial had industry co-sponsorship. We tabulated whether the study
reported a positive, negative, or null result on the primary outcome
variable and for total mortality.
Results
17
of 30 studies (57%) published prior to 2000 showed a significant
benefit of intervention on the primary outcome in comparison to only 2
among the 25 (8%) trials published after 2000 (χ
2=12.2,df= 1,
p=0.0005). There has been no change in the proportion of trials that
compared treatment to placebo versus active comparator. Industry
co-sponorship was unrelated to the probability of reporting a
significant benefit. Pre-registration in clinical trials.gov was
strongly associated with the trend toward null findings.
Conclusions
The
number NHLBI trials reporting positive results declined after the year
2000. Prospective declaration of outcomes in RCTs, and the adoption of
transparent reporting standards, as required by clinicaltrials.gov, may
have contributed to the trend toward null findings.
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