Sample size calculations for randomized clinical trials published in anesthesiology journals: a comparison of 2010 versus 2016.

PURPOSE: Although every randomized clinical trial (RCT) needs participants, determining the ideal number of participants that balances limited resources and the ability to detect a real effect is difficult. Focussing on two-arm, parallel group, superiority RCTs published in six general anesthesiology journals, the objective of this study was to compare the quality of sample size calculations for RCTs published in 2010 vs 2016. METHODS: Each RCT's full text was searched for the presence of a sample size calculation, and the assumptions made by the investigators were compared with the actual values observed in the results. Analyses were only performed for sample size calculations that were amenable to replication, defined as using a clearly identified outcome that was continuous or binary in a standard sample size calculation procedure. RESULTS: The percentage of RCTs reporting all sample size calculation assumptions increased from 51% in 2010 to 84% in 2016. The difference between the values observed in the study and the expected values used for the sample size calculation for most RCTs was usually > 10% of the expected value, with negligible improvement from 2010 to 2016. CONCLUSION: While the reporting of sample size calculations improved from 2010 to 2016, the expected values in these sample size calculations often assumed effect sizes larger than those actually observed in the study. Since overly optimistic assumptions may systematically lead to underpowered RCTs, improvements in how to calculate and report sample sizes in anesthesiology research are needed.

The degree of adherence to CONSORT reporting guidelines for the abstracts of randomised clinical trials published in anaesthesia journals: A cross-sectional study of reporting adherence in 2010 and 2016.

BACKGROUND: Abstracts are intended to be concise summaries of the entire randomised clinical trial (RCT). Despite their importance, few studies have examined the reporting quality of abstracts in the anaesthesiology literature. OBJECTIVES: To examine the quality of RCT abstract reporting according to the CONSORT for Abstracts guidelines and determine whether recommended items omitted from the abstract were present in the body of the article. DESIGN: A cross-sectional study of RCTs. SETTING: This study was performed at the University of Western Ontario and University Hospital, London Health Sciences Centre. PARTICIPANTS: All RCTs meeting inclusion criteria that were published in 2010 or 2016 in six general anaesthesiology journals (Anaesthesia, Anesthesia & Analgesia, Anesthesiology, British Journal of Anaesthesia, Canadian Journal of Anesthesia and European Journal of Anaesthesiology). MAIN OUTCOME MEASURES: The 16 checklist items from the CONSORT for Abstracts statement were used to create a convenience score as a proxy for RCT abstract reporting quality, with each criterion measured as being reported in abstract, not reported in abstract but reported in full-text article, or not reported in abstract or full-text article. RESULTS: Of the 395 RCTs identified, 219 were published in 2010 and 176 were published in 2016. Out of the maximum possible score of 16, the median abstract score increased from 4 points [interquartile range (IQR): 3 to 5] in 2010 to 6 points [IQR: 5 to 8] in 2016. Although most checklist items showed improvement from 2010 to 2016, around 75% of RCTs in 2016 met fewer than half of the 16 items with no RCTs reporting all 16 items in the abstract. A majority of the RCTs had the information present in the full-text. In 2016, only 71 out of 176 (40%) of RCTs reported outcomes conforming to the CONSORT guidelines (with an effect size and a confidence interval around the effect size) in the Abstract. CONCLUSION: Abstracts for many anaesthesiology RCTs are incomplete selective summaries of the entire article.

Comparison of Registered and Reported Outcomes in Randomized Clinical Trials Published in Anesthesiology Journals.

BACKGROUND: Randomized clinical trials (RCTs) provide high-quality evidence for clinical decision-making. Trial registration is one of the many tools used to improve the reporting of RCTs by reducing publication bias and selective outcome reporting bias. The purpose of our study is to examine whether RCTs published in the top 6 general anesthesiology journals were adequately registered and whether the reported primary and secondary outcomes corresponded to the originally registered outcomes. METHODS: Following a prespecified protocol, an electronic database was used to systematically screen and extract data from RCTs published in the top 6 general anesthesiology journals by impact factor (Anaesthesia, Anesthesia & Analgesia, Anesthesiology, British Journal of Anaesthesia, Canadian Journal of Anesthesia, and European Journal of Anaesthesiology) during the years 2007, 2010, 2013, and 2015. A manual search of each journal's Table of Contents was performed (in duplicate) to identify eligible RCTs. An adequately registered trial was defined as being registered in a publicly available trials registry before the first patient being enrolled with an unambiguously defined primary outcome. For adequately registered trials, the outcomes registered in the trial registry were compared with the outcomes reported in the article, with outcome discrepancies documented and analyzed by the type of discrepancy. RESULTS: During the 4 years studied, there were 860 RCTs identified, with 102 RCTs determined to be adequately registered (12%). The proportion of adequately registered trials increased over time, with 38% of RCTs being adequately registered in 2015. The most common reason in 2015 for inadequate registration was registering the RCT after the first patient had already been enrolled. Among adequately registered trials, 92% had at least 1 primary or secondary outcome discrepancy. In 2015, 42% of RCTs had at least 1 primary outcome discrepancy, while 90% of RCTs had at least 1 secondary outcome discrepancy. CONCLUSIONS: Despite trial registration being an accepted best practice, RCTs published in anesthesiology journals have a high rate of inadequate registration. While mandating trial registration has increased the proportion of adequately registered trials over time, there is still an unacceptably high proportion of inadequately registered RCTs. Among adequately registered trials, there are high rates of discrepancies between registered and reported outcomes, suggesting a need to compare a published RCT with its trial registry entry to be able to fully assess the quality of the study. If clinicians base their decisions on evidence distorted by primary outcome switching, patient care could be negatively affected.

Myocardial Hypertrophic Remodeling and Impaired Left Ventricular Function in Mice with a Cardiac-Specific Deletion of Janus Kinase 2.

The Janus kinase (JAK) system is involved in numerous cell signaling processes and is highly expressed in cardiac tissue. The JAK isoform JAK2 is activated by numerous factors known to influence cardiac function and pathologic conditions. However, although abundant, the role of JAK2 in the regulation or maintenance of cardiac homeostasis remains poorly understood. Using the Cre-loxP system, we generated a cardiac-specific deletion of Jak2 in the mouse to assess the effect on cardiac function with animals followed up for a 4-month period after birth. These animals had marked mortality during this period, although at 4 months mortality in male mice (47%) was substantially higher compared with female mice (30%). Both male and female cardiac Jak2-deleted mice had hypertrophy, dilated cardiomyopathy, and severe left ventricular dysfunction, including a marked reduction in ejection fractions as assessed by serial echocardiography, although the responses in females were somewhat less severe. Defective cardiac function was associated with altered protein levels of sarcoplasmic reticulum calcium-regulatory proteins particularly in hearts from male mice that had depressed levels of SERCA2 and phosphorylated phospholamban. In contrast, SERCA2 was unchanged in hearts of female mice, whereas phosphorylated phospholamban was increased. Our findings suggest that cardiac JAK2 is critical for maintaining normal heart function, and its ablation produces a severe pathologic phenotype composed of myocardial remodeling, heart failure, and pronounced mortality.

When Is Evidence Enough Evidence? A Systematic Review and Meta-Analysis of the Trabectome as a Solo Procedure in Patients with Primary Open-Angle Glaucoma.

The purpose of this systematic review and meta-analysis was to examine the availability of evidence for one of the earliest available minimally invasive glaucoma surgery (MIGS) procedures, the Trabectome. Various databases were searched up to December 20, 2016, for any published studies assessing the use of the Trabectome as a solo procedure in patients with primary open-angle glaucoma (POAG). The standardized mean differences (SMD) were calculated for the change in intraocular pressure (IOP) and number of glaucoma mediations used at 1-month, 6-month, and 12-month follow-up. After screening, three studies and one abstract with analyzable data were included. The meta-analysis showed statistically significant reductions in IOP and number of glaucoma medications used at all time points. Though the Trabectome as a solo procedure appears to lower IOP and reduces the number of glaucoma medications, more high-quality studies are required to make definitive conclusions. The difficulty of obtaining evidence may be one of the many obstacles that limit a full understanding of the potential safety and/or efficacy benefits compared to standard treatments. The time has come for a thoughtful and integrated approach with stakeholders to determine optimal access to care strategies for our patients.