This is a critical appraisal of a randomized, controlled, double-blind trial on the effects of colchicine to patients with chronic coronary disease. A clinical scenario was presented to determine the applicability of the trial to an actual patient from the general population. The evaluation method followed the population (P), intervention (I), comparison (C), outcome (O) design. Overall, the appraisal revealed that all valdiity criteria were met in this study.  The trial provide evidence suggesting that inflammation plays a causal role in the pathogenesis of cardiovascular disease and related complications and that interventions to mitigate inflammation, like the colchicine, may reduce the risk of cardiovascular events.

A number of publishers and funders, including PLOS, have recently adopted policies requiring researchers to share the data underlying their results and publications. Such policies help increase the reproducibility of the published literature, as well as make a larger body of data available for reuse and re-analysis. In this study, we evaluate the extent to which authors have complied with this policy by analyzing Data Availability Statements from 47,593 papers published in PLOS ONE between March 2014 (when the policy went into effect) and May 2016. Our analysis shows that compliance with the policy has increased, with a significant decline over time in papers that did not include a Data Availability Statement. However, only about 20% of statements indicate that data are deposited in a repository, which the PLOS policy states is the preferred method. More commonly, authors state that their data are in the paper itself or in the supplemental information, though it is unclear whether these data meet the level of sharing required in the PLOS policy. These findings suggest that additional review of Data Availability Statements or more stringent policies may be needed to increase data sharing.

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 (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 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.

There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias. In this essay, I discuss the implications of these problems for the conduct and interpretation of research.

Irreproducibility of preclinical biomedical research has gained recent attention. It is suggested that requiring authors to complete a checklist at the time of manuscript submission would improve the quality and transparency of scientific reporting, and ultimately enhance reproducibility. Whether a checklist enhances quality and transparency in reporting preclinical animal studies, however, has not been empirically studied. Here we searched two highly cited life science journals, one that requires a checklist at submission (Nature) and one that does not (Cell), to identify in vivo animal studies. After screening 943 articles, a total of 80 articles were identified in 2013 (pre-checklist) and 2015 (post-checklist), and included for the detailed evaluation of reporting methodological and analytical information. We compared the quality of reporting preclinical animal studies between the two journals, accounting for differences between journals and changes over time in reporting. We find that reporting of randomization, blinding, and sample-size estimation significantly improved when comparing Nature to Cell from 2013 to 2015, likely due to implementation of a checklist. Specifically, improvement in reporting of the three methodological information was at least three times greater when a mandatory checklist was implemented than when it was not. Reporting the sex of animals and the number of independent experiments performed also improved from 2013 to 2015, likely from factors not related to a checklist. Our study demonstrates that completing a checklist at manuscript submission is associated with improved reporting of key methodological information in preclinical animal studies.