Extreme prematurity is the leading cause of death among children under 5 years of age. Currently, there is no treatment for bronchopulmonary dysplasia (BPD), the most common complication of extreme ...prematurity. Experimental studies in animal models of BPD suggest that mesenchymal stromal cells (MSCs) are lung protective. To date, no systematic review and meta‐analysis has evaluated the preclinical evidence of this promising therapy. Our protocol was registered with Collaborative Approach to Meta‐Analysis and Review of Animal Data from Experimental Studies prior to searching MEDLINE (1946 to June 1, 2015), Embase (1947 to 2015 Week 22), Pubmed, Web of Science, and conference proceedings (1990 to present) for controlled comparative studies of neonatal animal models that received MSCs or cell free MSC‐derived conditioned media (MSC‐CM). Lung alveolarization was the primary outcome. We used random effects models for data analysis and followed the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses reporting guidelines. We screened 990 citations; 25 met inclusion criteria. All used hyperoxia‐exposed neonatal rodents to model BPD. MSCs significantly improved alveolarization (Standardized mean difference of −1.330, 95% confidence interval CI −1.724, −0.94, I2 69%), irrespective of timing of treatment, source, dose, or route of administration. MSCs also significantly ameliorated pulmonary hypertension, lung inflammation, fibrosis, angiogenesis, and apoptosis. Similarly, MSC‐CM significantly improved alveolarization, angiogenesis, and pulmonary artery remodeling. MSCs, tested exclusively in hyperoxic rodent models of BPD, show significant therapeutic benefit. Unclear risk of bias and incomplete reporting in the primary studies highlights nonadherence to reporting standards. Overall, safety and efficacy in other species/large animal models may provide useful information for guiding the design of clinical trials. Stem Cells Translational Medicine 2017;6:2079–2093
MSCs in pre‐clinical bronchopulmonary dysplasia (BPD). In this first‐ever systematic review and meta‐analysis, when tested exclusively in hyperoxic rodent models of BPD, mesenchymal stromal cells significantly improved several outcome measures, although with a high degree of heterogeneity, unclear risk of bias, poor reporting and potential publication bias; underscoring the need to fix methodological flaws by rigorously implementing reporting standards such as Animal Research: Reporting of In Vivo Experiments (ARRIVE) guidelines, thereby ensuring successful clinical translation of this promising therapy.
With the exponential growth of published systematic reviews (SR), there is a high potential for overlapping and redundant duplication of work. Prospective protocol registration gives the opportunity ...to assess the added value of a new study or review, thereby potentially reducing research waste and simultaneously increasing transparency and research quality. The PROSPERO database for SR protocol registration was launched 10 years ago. This study aims to assess the proportion SRs of intervention studies with a protocol registration (or publication) and explore associations of SR characteristics with protocol registration status.
PubMed was searched for SRs of human intervention studies published in January 2020 and January 2021. After random-stratified sampling and eligibility screening, data extraction on publication and journal characteristics, and protocol registration status, was performed. Both descriptive and multivariable comparative statistical analyses were performed.
A total of 357 SRs (2020: n = 163; 2021: n = 194) were included from a random sample of 1267 publications. Of the published SRs, 38% had a protocol. SRs that reported using PRISMA as a reporting guideline had higher odds of having a protocol than publications that did not report PRISMA (OR 2.71; 95% CI: 1.21 to 6.09). SRs with a higher journal impact factor had higher odds of having a protocol (OR 1.12; 95% CI 1.04 to 1.25). Publications from Asia had a lower odds of having a protocol (OR 0.43; 95% CI 0.23 to 0.80, reference category = Europe). Of the 33 SRs published in journals that endorse PROSPERO, 45% did not have a protocol. Most SR protocols were registered in PROSPERO (n = 129; 96%).
We found that 38% of recently published SRs of interventions reported a registered or published protocol. Protocol registration was significantly associated with a higher impact factor of the journal publishing the SR and a more frequent self-reported use of the PRISMA guidelines. In some parts of the world, SR protocols are more often registered or published than others. To guide strategies to increase the uptake of SR protocol registration, further research is needed to gain understanding of the benefits and informativeness of SRs protocols among different stakeholders.
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With the growing movement to engage patients in research, questions are being asked about who is engaging patients and how they are being engaged. Internationally, research groups are supporting and ...funding patient-oriented research studies that engage patients in the identification of research priorities and the design, conduct and uptake of research. As we move forward, we need to know what meaningful patient engagement looks like, how it benefits research and clinical practice, and what are the barriers to patient engagement?We conducted a review of the published literature looking for trials that report engaging patients in the research. We included both randomized controlled trials and non-randomized comparative trials. We looked at these trials for important study characteristics, including how patients were engaged, to better understand the practices used in trials. Importantly, we also discuss the number of trials reporting patient engagement practices relative to all published trials. We found that very few trials report any patient engagement activities even though it is widely supported by many major funding organizations. The findings of our work will advance patient-oriented research by showing how patients can be engaged and by stressing that patient engagement practices need to be better reported.
Patient-Oriented Research (POR) is research informed by patients and is centred on what is of importance to them. A fundamental component of POR is that patients are included as an integral part of the research process from conception to dissemination and implementation, and by extension, across the research continuum from basic research to pragmatic trials J Comp Eff Res 2012, 1:181-94, JAMA 2012, 307:1587-8. Since POR's inception, questions have been raised as to how best to achieve this goal.We conducted a systematic review of randomized controlled trials and non-randomized comparative trials that report engaging patients in their research. Our main goal was to describe the characteristics of published trials engaging patients in research, and to identify the extent of patient engagement activities reported in these trials.
The MEDLINE®, EMBASE®, Cinahl, PsycINFO, Cochrane Methodology Registry, and Pubmed were searched from May 2011 to June 16th, 2016. Title, abstract and full text screening of all reports were conducted independently by two reviewers. Data were extracted from included trials by one reviewer and verified by a second. All trials that report patient engagement for the purposes of research were included.
Of the 9490 citations retrieved, 2777 were reviewed at full text, of which 23 trials were included. Out of the 23 trials, 17 were randomized control trials, and six were non-randomized comparative trials. The majority of these trials (83%, 19/23) originated in the United States and United Kingdom. The trials engaged a range of 2-24 patients/ community representatives per study. Engagement of children and minorities occurred in 13% (3/23) and 26% (6/23) of trials; respectively. Engagement was identified in the development of the research question, the selection of study outcomes, and the dissemination and implementation of results.
The prevalence of patient engagement in patient-oriented interventional research is very poor with 23 trials reporting activities engaging patients. Research dedicated to determining the best practice for meaningful engagement is still needed, but adequate reporting measures also need to be defined.
AbstractBackgroundIn the scientific literature, “spin” refers to reporting practices that make the study findings appear more favorable than results justify. The practice of “spin” or ...misrepresentation and overinterpretation may lead to an imbalanced and unjustified optimism in the interpretation of study results about performance of putative biomarkers. We aimed to classify spin (i.e., misrepresentation and overinterpretation of study findings) in recent clinical studies evaluating the performance of biomarkers in ovarian cancer. MethodsWe searched PubMed systematically for all evaluations of ovarian cancer biomarkers published in 2015. Studies eligible for inclusion reported the clinical performance of prognostic, predictive, or diagnostic biomarkers. ResultsOur search identified 1,026 studies; 326 studies met all eligibility criteria, of which we evaluated the first 200 studies. Of these, 140 (70%) contained one or more form of spin in the title, abstract, or main-text conclusion, exaggerating the performance of the biomarker. The most frequent forms of spin identified were (1) other purposes of biomarker claimed not investigated (65; 32.5%); (2) mismatch between intended aim and conclusion (57; 28.5%); and (3) incorrect presentation of results (40; 20%). ConclusionOur study provides evidence of misrepresentation and overinterpretation of finding in recent clinical evaluations of ovarian cancer biomarkers.
To estimate the effect of an intervention compared to the usual peer-review process on reducing spin in the abstract’s conclusion of biomedical study reports.
We conducted a two-arm, parallel-group ...RCT in a sample of primary research manuscripts submitted to BMJ Open. The authors received short instructions alongside the peer reviewers’ comments in the intervention group. We assessed the presence of spin (primary outcome), types of spin, and wording change in the revised abstract’s conclusion. Outcome assessors were blinded to the intervention assignment.
Of the 184 manuscripts randomized, 108 (54 intervention, 54 control) were selected for revision and could be evaluated for the presence of spin. The proportion of manuscripts with spin was 6% lower (95% CI: 24% lower to 13% higher) in the intervention group (57%, 31/54) than in the control group (63%, 34/54). The wording of the revised abstract’s conclusion was changed in 34/54 (63%) manuscripts in the intervention group and 26/54 (48%) in the control group. The four prespecified types of spin involved (i) selective reporting (12 in the intervention group vs. 8 in the control group), (ii) including information not supported by evidence (9 vs. 9), and (iii) interpretation not consistent with the study results (14 vs. 18), and (iv) unjustified recommendations for practice (5 vs. 11).
These short instructions to authors did not have a statistically significant effect on reducing spin in revised abstract conclusions, and based on the confidence interval, the existence of a large effect can be excluded. Other interventions to reduce spin in reports of original research should be evaluated.
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•First randomized controlled trial of an editorial intervention to reduce spin.•Intervention implemented in a real editorial setting at a general medical journal.•Authors asked to remove four prominent forms of spin in their abstract conclusion.•Evaluated spin in 108 manuscripts by blinded assessors and in duplicate.•Short instructions to authors did not have a large impact on reducing spin in abstract conclusions.
The objective of this study was to identify potential trial characteristics associated with reported treatment effect estimates in randomized trials of testosterone therapy in adult men.
This is a ...meta-epidemiological study. MEDLINE was searched for meta-analyses of randomized trials of testosterone therapy in men published between 2008 and 2018. Data on trial characteristics were extracted independently by two reviewers. The impact of trial characteristics on reported treatment effects was investigated using a two-step meta-analytic approach.
We identified 132 randomized trials, included in 19 meta-analyses, comprising data from 10,725 participants. None of the investigated design characteristics, including year of publication, sample size, trial registration status, center status, regionality, funding source, and conflict of interest were statistically significantly associated with reported treatment effects of testosterone therapy in men. Although trials rated at high risk of bias overall reported treatment effects that were 21% larger compared with trials rated at low risk of bias overall, the 95% confidence interval included the null (ratio of odds ratio: 0.79, 95% confidence interval: 0.60 to 1.03).
The present study found no clear evidence that trial characteristics are associated with treatment effects in randomized trials of testosterone therapy in men. To establish stronger evidence about the treatment effects of testosterone therapy in men, future randomized trials should not only be adequately designed but also transparently reported.
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•First meta-research study investigating bias in randomized trials of testosterone therapy.•Analysis of 132 randomized trials, included in 19 meta-analyses, comprising data from 10,725 participants.•No clear evidence that trial characteristics are associated with treatment effects in randomized trials of testosterone therapy in men.•Results indicate the importance of adequately designing and transparently reporting clinical trials.
To develop a framework to identify and evaluate spin practices and its facilitators in studies on clinical prediction model regardless of the modeling technique.
We followed a three-phase consensus ...process: (1) premeeting literature review to generate items to be included; (2) a series of structured meetings to provide comments discussed and exchanged viewpoints on items to be included with a panel of experienced researchers; and (3) postmeeting review on final list of items and examples to be included. Through this iterative consensus process, a framework was derived after all panel's researchers agreed.
This consensus process involved a panel of eight researchers and resulted in SPIN-Prediction Models which consists of two categories of spin (misleading interpretation and misleading transportability), and within these categories, two forms of spin (spin practices and facilitators of spin). We provide criteria and examples.
We proposed this guidance aiming to facilitate not only the accurate reporting but also an accurate interpretation and extrapolation of clinical prediction models which will likely improve the reporting quality of subsequent research, as well as reduce research waste.
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