To increase transparency in research, the International Committee of Medical Journal Editors required, in 2005, prospective registration of clinical trials as a condition to publication. However, many trials remain unregistered or retrospectively registered. We aimed to assess the association between trial prospective registration and treatment effect estimates. Methods This is a meta-epidemiological study based on all Cochrane reviews published between March 2011 and September 2014 with meta-analyses of a binary outcome including three or more randomised controlled trials published after 2006. We extracted trial general characteristics and results from the Cochrane reviews. For each trial, we searched for registration in the report’s full text, contacted the corresponding author if not reported and searched ClinicalTrials.gov and the International Clinical Trials Registry Platform in case of no response. We classified each trial as prospectively registered (i.e. registered before the start date); retrospectively registered, distinguishing trials registered before and after the primary completion date; and not registered. Treatment effect estimates of prospectively registered and other trials were compared by the ratio of odds ratio (ROR) (ROR <1 indicates larger effects in trials not prospectively registered). Results We identified 67 meta-analyses (322 trials). Overall, 225/322 trials (70 %) were registered, 74 (33 %) prospectively and 142 (63 %) retrospectively; 88 were registered before the primary completion date and 54 after. Unregistered or retrospectively registered trials tended to show larger treatment effect estimates than prospectively registered trials (combined ROR = 0.81, 95 % CI 0.65–1.02, based on 32 contributing meta-analyses). Trials unregistered or registered after the primary completion date tended to show larger treatment effect estimates than those registered before this date (combined ROR = 0.84, 95 % CI 0.71–1.01, based on 43 contributing meta-analyses). Conclusions Lack of trial prospective registration may be associated with larger treatment effect estimates.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"A new study published in the journal Anesthesiology suggests that computer-assisted individualized hemodynamic management is a promising strategy to minimize hypotension during certain surgeries. Intraoperative hypotension is common but can increase the risk of postoperative complications. During surgery, individualized hemodynamic management can help mitigate hypotension and decrease such complications. In this strategy, clinicians use both intravenous fluids and vasopressors to maintain mean arterial pressure and blood volume near a patient’s personalized baseline. Despite its reported success, this approach requires constant monitoring and adjustment, which can be particularly challenging during complex and prolonged surgeries. Automated systems that can deliver either vasopressors or fluids have recently been developed, but a single closed-loop system that can deliver both with minimal clinician intervention isn’t yet available..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

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.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Real-world data and real-world evidence are terms widely used in the field of health care. In fact, various stakeholders are showing increasing interest in using real world data and real world evidence. Pharmaceutical companies, for example, use real world data for various purposes—from the early stages of development to post-launch. One hot topic focuses on using real world data and real world evidence to support regulatory decision making to deliver drugs faster to patients with high medical needs. This has been the subject of active discussion in the US, Europe, Japan and other countries, leading to regulatory reform and improvement of the implementation environment. However, there are barriers to the regulatory acceptance and use of both real world data and real world evidence. Real world data should be evaluated not only for quality but also for data relevance. There is a lack of universally accepted methodological criteria..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

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.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"A new study published in _The American Journal of Sports Medicine_ suggests that adding more shoulder-strengthening exercise to current nonoperative care protocols for subacromial impingement does _not _improve outcomes. Nonoperative care including physical therapy is the first-line treatment for subacromial impingement, also known as shoulder impingement. Although shoulder strengthening is important for recovery, the current exercise protocols don’t always provide sufficient relief. In addition, decompression surgery is no longer recommended for refractory cases, leaving patients with fewer options and increasing the need for better nonoperative care. To determine whether more shoulder-strengthening exercise might help patients achieve relief, the study’s authors randomly divided 200 patients with chronic shoulder pain due to impingement into a control group and an intervention group. The patients in the control group received normal nonoperative care..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Low blood pressure, or hypotension, is common during surgery. Because hypotensive events are associated with worse outcomes, reducing the frequency, depth, and duration of intraoperative hypotension might be a way to help patients. Commercially available hypotension prediction algorithms can help physicians prevent potentially dangerous bouts of low blood pressure. But it’s unknown how effective they are. To address this question, researchers with the Cleveland Clinic tested a prediction algorithm in a pilot randomized controlled trial. The trial found no difference in hypotension in patients using the algorithm versus unguided controls. In the trial, which included 214 non-cardiac surgical patients, about half had care from practitioners using the algorithm, which is based on arterial pressure waveform features. The algorithm provides the probability of hypotension as an index ranging from 0 to 100, with 85 serving as an alert..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

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.

This resource is a video abstract of a research paper created by Research Square on behalf of its authors. It provides a synopsis that's easy to understand, and can be used to introduce the topics it covers to students, researchers, and the general public. The video's transcript is also provided in full, with a portion provided below for preview:

"Crohn’s disease causes chronic inflammation of the gastrointestinal (GI) tract Although its cause is not fully understood, abnormal activation of the GI immune system toward the gut microbiota could be playing a role In addition, the high number of pro-inflammatory bacteria found in the intestinal microbiota of Crohn’s patients could be triggering this abnormal immune response A recent pilot trial is the first to evaluate the use of Fecal Microbiota Transplantation (FMT) in maintaining remission in Crohn’s patients The authors found a higher rate of steroid-free remission in Crohn’s patients treated with FMT As well as improved lesions and inflammatory biomarkers Although further studies on a larger patient population are needed The results of this pilot trial are promising for the many patients suffering from Crohn’s disease..."

The rest of the transcript, along with a link to the research itself, is available on the resource itself.

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.