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Likelihood of Null Effects of Large NHLBI Clinical Trials Has Increased over Time.

Kaplan RM, Irvin VL - PLoS ONE (2015)

Bottom Line: We explore whether the number of results in large National Heart Lung, and Blood Institute (NHLBI) funded trials has increased over time.We identified all large NHLBI supported RCTs between 1970 and 2012 evaluating drugs or dietary supplements for the treatment or prevention of cardiovascular disease.Industry co-sponsorship was unrelated to the probability of reporting a significant benefit.

View Article: PubMed Central - PubMed

Affiliation: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services, Rockville, Maryland, United States of America.

ABSTRACT

Background: We explore whether the number of 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 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 (χ2=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-sponsorship was unrelated to the probability of reporting a significant benefit. Pre-registration in clinical trials.gov was strongly associated with the trend toward 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 findings.

No MeSH data available.


Related in: MedlinePlus

Relative risk of showing benefit or harm of treatment by year of publication for large NHLBI trials on pharmaceutical and dietary supplement interventions.Positive trials are indicated by the plus signs while trials showing harm are indicated by a diagonal line within a circle. Prior to 2000 when trials were not registered in clinical trials.gov, there was substantial variability in outcome. Following the imposition of the requirement that trials preregister in clinical trials.gov the relative risk on primary outcomes showed considerably less variability around 1.0.
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pone.0132382.g001: Relative risk of showing benefit or harm of treatment by year of publication for large NHLBI trials on pharmaceutical and dietary supplement interventions.Positive trials are indicated by the plus signs while trials showing harm are indicated by a diagonal line within a circle. Prior to 2000 when trials were not registered in clinical trials.gov, there was substantial variability in outcome. Following the imposition of the requirement that trials preregister in clinical trials.gov the relative risk on primary outcomes showed considerably less variability around 1.0.

Mentions: Fig 1 plots the relative risks of the primary outcome by the publication year of the main outcome paper. Because it was an extreme outlier, the CAST study is excluded from the figure. Prior to publication in 2000, studies often showed benefits of treatments with the notable exception of CAST (not shown in figure). Following 2000, confidence intervals for relative risk ratios included 1.0 in all cases, with the exceptions of the PREVENT and the SANDS trials (benefit) and the Women’s Health Initiative (Harm). In addition, the variability in RRs was considerably reduced after the year 2000 (Fig 2).


Likelihood of Null Effects of Large NHLBI Clinical Trials Has Increased over Time.

Kaplan RM, Irvin VL - PLoS ONE (2015)

Relative risk of showing benefit or harm of treatment by year of publication for large NHLBI trials on pharmaceutical and dietary supplement interventions.Positive trials are indicated by the plus signs while trials showing harm are indicated by a diagonal line within a circle. Prior to 2000 when trials were not registered in clinical trials.gov, there was substantial variability in outcome. Following the imposition of the requirement that trials preregister in clinical trials.gov the relative risk on primary outcomes showed considerably less variability around 1.0.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4526697&req=5

pone.0132382.g001: Relative risk of showing benefit or harm of treatment by year of publication for large NHLBI trials on pharmaceutical and dietary supplement interventions.Positive trials are indicated by the plus signs while trials showing harm are indicated by a diagonal line within a circle. Prior to 2000 when trials were not registered in clinical trials.gov, there was substantial variability in outcome. Following the imposition of the requirement that trials preregister in clinical trials.gov the relative risk on primary outcomes showed considerably less variability around 1.0.
Mentions: Fig 1 plots the relative risks of the primary outcome by the publication year of the main outcome paper. Because it was an extreme outlier, the CAST study is excluded from the figure. Prior to publication in 2000, studies often showed benefits of treatments with the notable exception of CAST (not shown in figure). Following 2000, confidence intervals for relative risk ratios included 1.0 in all cases, with the exceptions of the PREVENT and the SANDS trials (benefit) and the Women’s Health Initiative (Harm). In addition, the variability in RRs was considerably reduced after the year 2000 (Fig 2).

Bottom Line: We explore whether the number of results in large National Heart Lung, and Blood Institute (NHLBI) funded trials has increased over time.We identified all large NHLBI supported RCTs between 1970 and 2012 evaluating drugs or dietary supplements for the treatment or prevention of cardiovascular disease.Industry co-sponsorship was unrelated to the probability of reporting a significant benefit.

View Article: PubMed Central - PubMed

Affiliation: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services, Rockville, Maryland, United States of America.

ABSTRACT

Background: We explore whether the number of 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 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 (χ2=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-sponsorship was unrelated to the probability of reporting a significant benefit. Pre-registration in clinical trials.gov was strongly associated with the trend toward 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 findings.

No MeSH data available.


Related in: MedlinePlus