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Summary: Being able to draw accurate conclusions from childhood obesity trials is important to make advances in reversing the obesity epidemic. However, obesity research sometimes is not conducted or reported to appropriate scientific standards. To constructively draw attention to this issue, we present 10 errors that are commonly committed, illustrate each error with examples from the childhood obesity literature, and follow with suggestions on how to avoid these errors. These errors are as follows: using self‐reported outcomes and teaching to the test; foregoing control groups and risking regression to the mean creating differences over time; changing the goal posts; ignoring clustering in studies that randomize groups of children; following the forking paths, subsetting, p‐hacking, and data dredging; basing conclusions on tests for significant differences from baseline; equating "no statistically significant difference" with "equally effective"; ignoring intervention study results in favor of observational analyses; using one‐sided testing for statistical significance; and stating that effects are clinically significant even though they are not statistically significant. We hope that compiling these errors in one article will serve as the beginning of a checklist to support fidelity in conducting, analyzing, and reporting childhood obesity research. [ABSTRACT FROM AUTHOR]

Most studies aiming to construct reference or standard charts use a cross-sectional design, collecting one measurement per participant. Reference or standard charts can also be constructed using a longitudinal design, collecting multiple measurements per participant. The choice of appropriate statistical methodology is important as inaccurate centiles resulting from inferior methods can lead to incorrect judgements about fetal or newborn size, resulting in suboptimal clinical care. Reference or standard centiles should ideally provide the best fit to the data, change smoothly with age (eg, gestational age), use as simple a statistical model as possible without compromising model fit, and allow the computation of Z-scores from centiles to simplify assessment of individuals and enable comparison with different populations. Significance testing and goodness-of-fit statistics are usually used to discriminate between models. However, these methods tend not to be useful when examining large data sets as very small differences are statistically significant even if the models are indistinguishable on actual centile plots. Choosing the best model from amongst many is therefore not trivial. Model choice should not be based on statistical considerations (or tests) alone as sometimes the best model may not necessarily offer the best fit to the raw data across gestational age. In this paper, we describe the most commonly applied methodologies available for the construction of age-specific reference or standard centiles for cross-sectional and longitudinal data: Fractional polynomial regression, LMS, LMST, LMSP, and multilevel regression methods. For illustration, we used data from the INTERGROWTH-21st Project, ie, newborn weight (cross-sectional) and fetal head circumference (longitudinal) data as examples. [ABSTRACT FROM AUTHOR]

This paper discusses the features of study design and methodological considerations for constructing reference centile charts for attained size, growth, and velocity charts with a focus on human growth charts used during pregnancy. Recent systematic reviews of pregnancy dating, fetal size, and newborn size charts showed that many studies aimed at constructing charts are still conducted poorly. Important design features such as inclusion and exclusion criteria, ultrasound quality control measures, sample size determination, anthropometric evaluation, gestational age estimation, assessment of outliers, and chart presentation are seldom well addressed, considered, or reported. Many of these charts are in clinical use today and directly affect the identification of at-risk newborns that require treatment and nutritional strategies. This paper therefore reiterates some of the concepts previously identified as important for growth studies, focusing on considerations and concepts related to study design, sample size, and methodological considerations with an aim of obtaining valid reference or standard centile charts. We discuss some of the key issues and provide more details and practical examples based on our experiences from the INTERGROWTH-21st Project. We discuss the statistical methodology and analyses for cross-sectional studies and longitudinal studies in a separate article in this issue. [ABSTRACT FROM AUTHOR]

Importance: The quality of reporting of randomized clinical trials is suboptimal. In an era in which the need for greater research transparency is paramount, inadequate reporting hinders assessment of the reliability and validity of trial findings. The Consolidated Standards of Reporting Trials (CONSORT) 2010 Statement was developed to improve the reporting of randomized clinical trials, but the primary focus was on parallel-group trials with 2 groups. Multi-arm trials that use a parallel-group design (comparing treatments by concurrently randomizing participants to one of the treatment groups, usually with equal probability) but have 3 or more groups are relatively common. The quality of reporting of multi-arm trials varies substantially, making judgments and interpretation difficult. While the majority of the elements of the CONSORT 2010 Statement apply equally to multi-arm trials, some elements need adaptation, and, in some cases, additional issues need to be clarified.Objective: To present an extension to the CONSORT 2010 Statement for reporting multi-arm trials to facilitate the reporting of such trials.Design: A guideline writing group, which included all authors, formed following the CONSORT group meeting in 2014. The authors met in person and by teleconference bimonthly between 2014 and 2018 to develop and revise the checklist and the accompanying text, with additional discussions by email. A draft manuscript was circulated to the wider CONSORT group of 36 individuals, plus 5 other selected individuals known for their specialist knowledge in clinical trials, for review. Extensive feedback was received from 14 individuals and, after detailed consideration of their comments, a final revised version of the extension was prepared.Findings: This CONSORT extension for multi-arm trials expands on 10 items of the CONSORT 2010 checklist and provides examples of good reporting and a rationale for the importance of each extension item. Key recommendations are that multi-arm trials should be identified as such and require clear objectives and hypotheses referring to all of the treatment groups. Primary treatment comparisons should be identified and authors should report the planned and unplanned comparisons resulting from multiple groups completely and transparently. If statistical adjustments for multiplicity are applied, the rationale and method used should be described.Conclusions and Relevance: This extension of the CONSORT 2010 Statement provides specific guidance for the reporting of multi-arm parallel-group randomized clinical trials and should help provide greater transparency and accuracy in the reporting of such trials. [ABSTRACT FROM AUTHOR]

OBJECTIVES: There is still little evidence to boldport routine dual antiplatelet therapy (DAPT) with P2Y12 antagonists following coronary artery bypass grafting (CABG). The Arterial Revascularization Trial (ART) was designed to compare 10-year survival after bilateral versus single internal thoracic artery grafting. We aimed to get insights into the effect of DAPT (with clopidogrel) following CABG on 1-year outcomes by performing a post hoc ART analysis. METHODS: Among patients enrolled in the ART (n = 3102), 609 (21%) and 2308 (79%) were discharged on DAPT or aspirin alone, respectively. The primary end-point was the incidence of major adverse cerebrovascular and cardiac events (MACCE) at 1 year including cardiac death, myocardial infarction, cerebrovascular accident and reintervention; safety end-point was bleeding requiring hospitalization. Propensity score (PS) matching was used to create comparable groups. RESULTS: Among 609 PS-matched pairs, MACCE occurred in 34 (5.6%) and 34 (5.6%) in the DAPT and aspirin alone groups, respectively, with no significant difference between the 2 groups [hazard ratio (HR) 0.97, 95% confidence interval (CI) 0.59-1.59; P = 0.90]. Only 188 (31%) subjects completed 1 year of DAPT, and in this subgroup, MACCE rate was 5.8% (HR 1.11, 95% CI 0.53-2.30; P = 0.78). In the overall sample, bleeding rate was higher in DAPT group (2.3% vs 1.1%; P = 0.02), although this difference was no longer significant after matching (2.3% vs 1.8%; P = 0.54). CONCLUSIONS: Based on these findings, when compared with aspirin alone, DAPT with clopidogrel prescribed at discharge was not associated with a significant reduction of adverse cardiac and cerebrovascular events at 1 year following CABG. [ABSTRACT FROM AUTHOR]

Background: Whether the use of the radial artery (RA) can improve clinical outcomes in coronary artery bypass graft surgery remains unclear. The ART (Arterial Revascularization Trial) was designed to compare survival after bilateral internal thoracic artery (BITA) over single left internal thoracic artery (SITA). In the ART, a large proportion of patients (≈20%) also received an RA graft instead of a saphenous vein graft (SVG). We aimed to investigate the associations between using the RA instead of an SVG to supplement SITA or BITA grafts and outcomes by performing a post hoc analysis of the ART.Methods: Patients enrolled in the ART (n=3102) were classified on the basis of conduits actually received (as treated). The analysis included 2737 patients who received an RA graft (RA group; n=632) or SVG only (SVG group; n=2105) in addition to SITA or BITA grafts. The primary end point was the composite of myocardial infarction, cardiovascular death, and repeat revascularization at 5 years. Propensity score matching and stratified Cox regression were used to compare the 2 strategies.Results: Myocardial infarction, cardiovascular death, and repeat revascularization cumulative incidence was 2.3% (95% confidence interval [CI], 1.1-3.4), 3.5% (95% CI, 2.1-5.0), and 4.4% (95% CI, 2.8-6.0) in the RA group and 3.4% (95% CI, 2.0-4.8), 4.0% (95% CI, 2.5-5.6), and 7.6% (95% CI, 5.5-9.7) in the SVG group, respectively. The composite end point was significantly lower in the RA group (8.8%; 95% CI, 6.5-11.0) compared with the SVG group (13.6%; 95% CI, 10.8-16.3; P=0.005). This association was present when an RA graft was used to supplement both SITA and BITA grafts (interaction P=0.62).Conclusions: This post hoc ART analysis showed that an additional RA was associated with lower risk for midterm major adverse cardiac events when used to supplement SITA or BITA grafts.Clinical Trial Registration: URL: https://www.situ.ox.ac.uk/surgical-trials/art. Unique identifier: ISRCTN46552265. [ABSTRACT FROM AUTHOR]

Incomplete and inadequate reporting is an avoidable waste that reduces the usefulness of research. The CONSORT (Consolidated Standards of Reporting Trials) Statement is an evidence-based reporting guideline that aims to improve research transparency and reduce waste. In 2008, the CONSORT Group developed an extension to the original statement that addressed methodological issues specific to trials of nonpharmacologic treatments (NPTs), such as surgery, rehabilitation, or psychotherapy. This article describes an update of that extension and presents an extension for reporting abstracts of NPT trials. To develop these materials, the authors reviewed pertinent literature published up to July 2016; surveyed authors of NPT trials; and conducted a consensus meeting with editors, trialists, and methodologists. Changes to the CONSORT Statement extension for NPT trials include wording modifications to improve readers' understanding and the addition of 3 new items. These items address whether and how adherence of participants to interventions is assessed or enhanced, description of attempts to limit bias if blinding is not possible, and specification of the delay between randomization and initiation of the intervention. The CONSORT extension for abstracts of NPT trials includes 2 new items that were not specified in the original CONSORT Statement for abstracts. The first addresses reporting of eligibility criteria for centers where the intervention is performed and for care providers. The second addresses reporting of important changes to the intervention versus what was planned. Both the updated CONSORT extension for NPT trials and the CONSORT extension for NPT trial abstracts should help authors, editors, and peer reviewers improve the transparency of NPT trial reports. [ABSTRACT FROM AUTHOR]

The selection of appropriate outcomes is crucial when designing clinical trials in order to compare the effects of different interventions directly. For the findings to influence policy and practice, the outcomes need to be relevant and important to key stakeholders including patients and the public, health care professionals and others making decisions about health care. It is now widely acknowledged that insufficient attention has been paid to the choice of outcomes measured in clinical trials. Researchers are increasingly addressing this issue through the development and use of a core outcome set, an agreed standardised collection of outcomes which should be measured and reported, as a minimum, in all trials for a specific clinical area.Accumulating work in this area has identified the need for guidance on the development, implementation, evaluation and updating of core outcome sets. This Handbook, developed by the COMET Initiative, brings together current thinking and methodological research regarding those issues. We recommend a four-step process to develop a core outcome set. The aim is to update the contents of the Handbook as further research is identified. [ABSTRACT FROM AUTHOR]

Background: The use of bilateral internal thoracic (mammary) arteries for coronary-artery bypass grafting (CABG) may improve long-term outcomes as compared with the use of a single internal-thoracic-artery plus vein grafts.Methods: We randomly assigned patients scheduled for CABG to undergo single or bilateral internal-thoracic-artery grafting in 28 cardiac surgical centers in seven countries. The primary outcome was death from any cause at 10 years. The composite of death from any cause, myocardial infarction, or stroke was a secondary outcome. Interim analyses were prespecified at 5 years of follow-up.Results: A total of 3102 patients were enrolled; 1554 were randomly assigned to undergo single internal-thoracic-artery grafting (the single-graft group) and 1548 to undergo bilateral internal-thoracic-artery grafting (the bilateral-graft group). At 5 years of follow-up, the rate of death was 8.7% in the bilateral-graft group and 8.4% in the single-graft group (hazard ratio, 1.04; 95% confidence interval [CI], 0.81 to 1.32; P=0.77), and the rate of the composite of death from any cause, myocardial infarction, or stroke was 12.2% and 12.7%, respectively (hazard ratio, 0.96; 95% CI, 0.79 to 1.17; P=0.69). The rate of sternal wound complication was 3.5% in the bilateral-graft group versus 1.9% in the single-graft group (P=0.005), and the rate of sternal reconstruction was 1.9% versus 0.6% (P=0.002).Conclusions: Among patients undergoing CABG, there was no significant difference between those receiving single internal-thoracic-artery grafts and those receiving bilateral internal-thoracic-artery grafts with regard to mortality or the rates of cardiovascular events at 5 years of follow-up. There were more sternal wound complications with bilateral internal-thoracic-artery grafting than with single internal-thoracic-artery grafting. Ten-year follow-up is ongoing. (Funded by the British Heart Foundation and others; ART Current Controlled Trials number, ISRCTN46552265 .). [ABSTRACT FROM AUTHOR]

Despite calls for guidelines on reporting statistical aspects of studies, most journals have still not included in their instructions for authors more than a paragraph or two about reporting statistical methods and results. However, given that many statistical errors concern basic statistics, a comprehensive - and comprehensible - set of reporting guidelines might improve how statistical analyses are documented. The SAMPL guidelines are designed to be included in a journal's Instructions for Authors. These guidelines tell authors, journal editors, and reviewers how to report basic statistical methods and results. Although these guidelines are limited to the most common statistical analyses, they are nevertheless sufficient to prevent most of the reporting deficiencies routinely found in scientific articles. [ABSTRACT FROM AUTHOR]

Contributing Reviewers: A peer-reviewed journal would not survive without the generous time and insightful comments of the reviewers, whose efforts often go unrecognized. Although final decisions are always editorial, they are greatly facilitated by the deeper technical knowledge, scientific insights, understanding of social consequences, and passion that reviewers bring to our deliberations. For these reasons, the Editors-in-Chief and staff of Trials warmly thank the 854 reviewers whose comments helped to shape the journal, for their invaluable assistance with review of manuscripts in Volume 16 (2015). [ABSTRACT FROM AUTHOR]

David Moher and Douglas Altman outline four potential interventions that may improve the quality of peer-reviewed medical research publications. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The Arterial Revascularization Trial (ART) is a randomized comparison of bilateral internal mammary artery (BIMA) versus single internal mammary artery (SIMA) grafting in coronary artery bypass graft (CABG) surgery and is one of the largest randomized trials of surgery ever conducted. ART is also one of the largest studies of contemporary CABG with a high proportion of off-pump surgeries (41%). The objective of this post hoc analysis was to evaluate the surgical process and 1-year outcomes for surgery performed on-pump compared with off-pump. METHODS: ART randomized 3102 patients with multivessel coronary artery disease (CAD) to SIMA or BIMA grafts to determine if BIMA grafts have an additional survival advantage at 10 years. The 1-year interim analysis showed an overall very low mortality and major morbidity rate irrespective of whether the procedure was with an SIMA or BIMA. The surgical process and 1-year outcomes were analysed according to whether surgery was performed on-pump or off-pump. RESULTS: Baseline variables were not statistically significantly different between on- and off-pump surgery within each treatment group after taking account of the effects of clustering by individual surgeons. At both 30 days and 1 year, there was a low incidence of death (1.2%, 2.3%), stroke (1.1%, 1.7%), myocardial infarction (MI) (1.4%, 1.9%), repeat revascularization (0.5%, 1.5%) and wound reconstruction (1.2%). A similar average number of grafts were performed with on- and off-pump surgery (median = 3), but the duration of surgery was 20-30 min and ventilation time ~2 h shorter with off-pump surgery. Blood loss and platelet transfusions were lower in the off-pump group, with no difference in the need for balloon pump or renal support. Sternal wound reconstruction was similar with off-pump surgery in the SIMA group (0.5 vs 0.6%) and lower with off-pump surgery in the BIMA group (1.4 vs 2.2%). Repeat revascularization was marginally higher in off-pump patients at 30 days (0.8 vs 0.3%) and at 1 year (1.7 vs 1.3%). CONCLUSIONS: The outcomes of contemporary CABG are excellent with low mortality, stroke, myocardial infarction and need for wound reconstruction and repeat revascularization whether performed on-pump or off-pump. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Revascularization in stable coronary artery disease (CAD) can be achieved through percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) depending on the anatomical pattern of CAD, comorbidities and patient preference. Recent studies in the USA, Canada and Australia show marked local variation in the PCI/CABG ratio that is unexplained by patient-related factors. This current study assesses the geographical variation in elective coronary revascularization interventions across England and discusses its appropriateness. METHODS: The rates and actual procedure numbers of total CABG, total PCIs and elective PCIs were collated for each of 151 primary care trusts (PCTs). The 'elective PCI/total CABG ratio' was taken as an indicator of elective coronary revascularization practices. The Index of Multiple Deprivation (IMD) for PCTs was taken as a marker of deprivation. RESULTS: In 2010/2011, the degree of variation in elective PCI/total CABG ratios across 151 PCTs in England was >13-fold (min = 0.36, max = 4.74, median = 1.19, interquartile range = 0.98, 1.73). The ratio was not correlated to the IMD 2010 rank of the PCTs (Spearman's P = 0.08, P = 0.36) and was not explained by the volume of interventions performed. CONCLUSIONS: Despite clear evidence-based guidelines for intervention, marked geographical variation in elective coronary revascularization practices also exists in England. This variation is unexplained by procedure volume or deprivation, suggesting the contribution of unwarranted influences which may include practitioner preference. To reduce this level of unwarranted variation, we suggest that all interventions should be underpinned by internationally recognized guidelines or approved by a multidisciplinary team approach (The Heart Team). [ABSTRACT FROM AUTHOR]

Background: Diagnosis is the traditional basis for decision-making in clinical practice. Evidence is often lacking about future benefits and harms of these decisions for patients diagnosed with and without disease. We propose that a model of clinical practice focused on patient prognosis and predicting the likelihood of future outcomes may be more useful. Discussion: Disease diagnosis can provide crucial information for clinical decisions that influence outcome in serious acute illness. However, the central role of diagnosis in clinical practice is challenged by evidence that it does not always benefit patients and that factors other than disease are important in determining patient outcome. The concept of disease as a dichotomous 'yes' or 'no' is challenged by the frequent use of diagnostic indicators with continuous distributions, such as blood sugar, which are better understood as contributing information about the probability of a patient's future outcome. Moreover, many illnesses, such as chronic fatigue, cannot usefully be labelled from a disease-diagnosis perspective. In such cases, a prognostic model provides an alternative framework for clinical practice that extends beyond disease and diagnosis and incorporates a wide range of information to predict future patient outcomes and to guide decisions to improve them. Such information embraces non-disease factors and genetic and other biomarkers which influence outcome. Summary: Patient prognosis can provide the framework for modern clinical practice to integrate information from the expanding biological, social, and clinical database for more effective and efficient care. [ABSTRACT FROM AUTHOR]

IMPORTANCE A persistent dilemma when performing meta-analyses is whether all available trials should be included in the meta-analysis. OBJECTIVES To compare treatment outcomes estimated by meta-analysis of all trials and several alternative analytic strategies: single most precise trial (ie, trial with the narrowest confidence interval), meta-analysis restricted to the 25%largest trials, limit meta-analysis (a meta-analysis model adjusted for small-study effect), and meta-analysis restricted to trials at low overall risk of bias. DATA SOURCES One hundred sixty-three meta-analyses published between 2008 and 2010 in high-impact-factor journals and between 2011 and 2013 in the Cochrane Database of Systematic Reviews: 92 (705 randomized clinical trials [RCTs]) with subjective outcomes and 71 (535 RCTs) with objective outcomes. DATA SYNTHESIS For each meta-analysis, the difference in treatment outcomes between meta-analysis of all trials and each alternative strategy, expressed as a ratio of odds ratios (ROR), was assessed considering the dependency between strategies. A difference greater than 30% was considered substantial. RORs were combined by random-effects meta-analysis models to obtain an average difference across the sample. An ROR greater than 1 indicates larger treatment outcomes with meta-analysis of all trials. Subjective and objective outcomes were analyzed separately. RESULTS Treatment outcomes were larger in the meta-analysis of all trials than in the single most precise trial (combined ROR, 1.13 [95% CI, 1.07-1.19]) for subjective outcomes and 1.03 (95% CI, 1.01-1.05) for objective outcomes). The difference in treatment outcomes between these strategies was substantial in 47 of 92 (51%) meta-analyses of subjective outcomes (meta-analysis of all trials showing larger outcomes in 40/47) and in 28 of 71 (39%) meta-analyses of objective outcomes (meta-analysis of all trials showing larger outcomes in 21/28). The combined ROR for subjective and objective outcomes was, respectively, 1.08 (95% CI, 1.04-1.13) and 1.03 (95% CI, 1.00-1.06) when comparing meta-analysis of all trials and meta-analysis of the 25%largest trials, 1.17 (95% CI, 1.11-1.22) and 1.13 (95% CI, 0.82-1.55) when comparing meta-analysis of all trials and limit meta-analysis, and 0.94 (95% CI, 0.86-1.04) and 1.03 (95% CI, 1.00-1.06) when comparing meta-analysis of all trials and meta-analysis restricted to trials at low risk of bias. CONCLUSIONS AND RELEVANCE Estimation of treatment outcomes in meta-analyses differs depending on the strategy used. This instability in findings can result in major alterations in the conclusions derived from the analysis and underlines the need for systematic sensitivity analyses. [ABSTRACT FROM AUTHOR]

: In a systematic review of cohort studies, Kerry Dwan and colleagues examine the evidence for selective reporting and discrepancies in analyses between journal publications and other documents for clinical trials. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]

The article discusses waste at all stages in medical research, particularly due to inadequate reporting, best documented in controlled trial reports but occurs in all types of studies. The authors recommend a change in the research rewards and regulations system to encourage improved and more complete reporting, and fund infrastructure development and maintenance in support of better reporting, linkage, and archiving of research elements.

Reports of randomized controlled trials (RCTs) inform the care of future patients and are especially important to clinicians and systematic reviewers. Readers should satisfy themselves that the study methods were sound. Clinicians should consider the relevance to their own patients, both benefits and harms, and absolute as well as relative effects. Trial reports should provide a clear, transparent, and complete report of what was done and what was found. Unfortunately, bad reporting of RCTs is common, which has serious consequences for clinical practice, research, policy making, and ultimately for patients. RCT reports should adhere to the CONSORT Statement, a minimum set of items that should be addressed. Authors, peer reviewers, and editors should all work to ensure that research reports maximize the value derived from the cost and effort of conducting a trial. [ABSTRACT FROM AUTHOR]

Background: A prognostic model should not enter clinical practice unless it has been demonstrated that it performs a useful role. External validation denotes evaluation of model performance in a sample independent of that used to develop the model. Unlike for logistic regression models, external validation of Cox models is sparsely treated in the literature. Successful validation of a model means achieving satisfactory discrimination and calibration (prediction accuracy) in the validation sample. Validating Cox models is not straightforward because event probabilities are estimated relative to an unspecified baseline function. Methods: We describe statistical approaches to external validation of a published Cox model according to the level of published information, specifically (1) the prognostic index only, (2) the prognostic index together with Kaplan-Meier curves for risk groups, and (3) the first two plus the baseline survival curve (the estimated survival function at the mean prognostic index across the sample). The most challenging task, requiring level 3 information, is assessing calibration, for which we suggest a method of approximating the baseline survival function. Results: We apply the methods to two comparable datasets in primary breast cancer, treating one as derivation and the other as validation sample. Results are presented for discrimination and calibration. We demonstrate plots of survival probabilities that can assist model evaluation. Conclusions: Our validation methods are applicable to a wide range of prognostic studies and provide researchers with a toolkit for external validation of a published Cox model. [ABSTRACT FROM AUTHOR]

Introduction: To evaluate the performance of QCancer® (Renal) for predicting the absolute risk of renal tract cancer in a large independent UK cohort of patients from general practice records. Materials and methods: Open cohort study to validate QCancer® (Renal) prediction model. Record from 365 practices from United Kingdom contributing to The Health Improvement Network (THIN) database. 2.1 million patients registered with a general practice surgery between 01 January 2000 and 30 June 2008, aged 30- 84 years (3.7 million person years) with 2283 renal tract cancer cases. Renal tract cancer was defined as incident diagnosis of renal tract cancer during the 2 years after study entry. Model discrimination was measured using the receiver operating characteristics derived area under the curve. Calibration plots examined the relationship between predicted and observed probabilities of undetected renal tract cancer. Results: The results from this independent and external validation of QCancer® (Renal) demonstrated good performance data on a large cohort of general practice patients. QCancer® (Renal) had very good discrimination with areas under the ROC curve of 0.92 and 0.95 for women and men respectively. QCancer® (Renal) was well calibrated across all tenths of risk and over all age ranges with predicted risks closely matching observed risks. QCancer® (Renal) explained 74.4% and 74.2% of the variation in men and women respectively. A limitation of our study is the recording of symptoms might be less complete, as patients with mild symptoms may not visit their general practitioner or not report mild symptoms. Conclusions: QCancer® (Renal) are useful tools to help in identifying undetected cases of undiagnosed renal tract cancer in primary care in the UK [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the performance of QCancer® (Gastro-Oesophageal) for predicting the risk of undiagnosed gastro-oesophageal cancer in an independent UK cohort of patients from general practice records. Design: Open cohort study to validate QCancer® (Gastro-Oesophageal) prediction model. Three hundred sixty-five practices from the United Kingdom contributing to The Health Improvement Network database. 2.1 million patients registered with a general practice surgery between 01 January 2000 and 30 June 2008, aged 30–84years (3.7 million person years) with 1766 gastro-oesophageal cancer cases. The outcome, gastro-oesophageal cancer was defined as incident diagnosis of gastro-oesophageal cancer during the 2years after study entry. Results: The results from this independent and external validation of QCancer® (Gastro-Oesophageal) demonstrated good performance data on a large cohort of general practice patients. QCancer® (Gastro-Oesophageal) had very good discrimination with c-statistics of 0.93 and 0.94 for women and men respectively. QCancer® (Gastro-Oesophageal) was well calibrated across all tenths of risk and over all age ranges with predicted risks closely matching observed risks. QCancer® (Gastro-Oesophageal) explained 74.4% and 75.6% of the variation in men and women respectively. Conclusions: QCancer® (Gastro-Oesophageal) is a useful tool to identify undiagnosed gastro-oesophageal cancer in primary care in the United Kingdom. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the performance of QCancer® (Gastro-Oesophageal) for predicting the risk of undiagnosed gastro-oesophageal cancer in an independent UK cohort of patients from general practice records. Design: Open cohort study to validate QCancer® (Gastro-Oesophageal) prediction model. Three hundred sixty-five practices from the United Kingdom contributing to The Health Improvement Network database. 2.1 million patients registered with a general practice surgery between 01 January 2000 and 30 June 2008, aged 30–84years (3.7 million person years) with 1766 gastro-oesophageal cancer cases. The outcome, gastro-oesophageal cancer was defined as incident diagnosis of gastro-oesophageal cancer during the 2years after study entry. Results: The results from this independent and external validation of QCancer® (Gastro-Oesophageal) demonstrated good performance data on a large cohort of general practice patients. QCancer® (Gastro-Oesophageal) had very good discrimination with c-statistics of 0.93 and 0.94 for women and men respectively. QCancer® (Gastro-Oesophageal) was well calibrated across all tenths of risk and over all age ranges with predicted risks closely matching observed risks. QCancer® (Gastro-Oesophageal) explained 74.4% and 75.6% of the variation in men and women respectively. Conclusions: QCancer® (Gastro-Oesophageal) is a useful tool to identify undiagnosed gastro-oesophageal cancer in primary care in the United Kingdom. [Copyright &y& Elsevier]

An extensive and growing number of reviews of the published literature demonstrate that health research publications have frequent deficiencies. Of particular concern are poor reports of randomised trials, which make it difficult or impossible for readers to assess how the research was conducted, to evaluate the reliability of the findings, or to place them in the context of existing research evidence. As a result, published reports of trials often cannot be used by clinicians to inform patient care or to inform public health policy, and the data cannot be included in systematic reviews. Reporting guidelines are designed to identify the key information that researchers should include in a report of their research. We describe the history of reporting guidelines for randomised trials culminating in the CONSORT Statement in 1996. We detail the subsequent development and extension of CONSORT and consider related initiatives aimed at improving the reliability of the medical research literature. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background: Individual participant data (IPD) meta-analyses that obtain "raw" data from studies rather than data typically adopt a "two-stage" approach to analysis whereby IPD within trials generate measures, which are combined using standard meta-analytical methods. Recently, a range of "one-stage" approaches which combine all individual participant data in a single meta-analysis have been suggested as providing a more powerful and flexible approach. However, they are more complex to implement and require statistical support. This study uses a dataset to compare "two-stage" and "one-stage" models of varying complexity, to ascertain whether results obtained from the approaches differ in a clinically meaningful way. Methods and Findings: We included data from 24 randomised controlled trials, evaluating antiplatelet agents, for the prevention of pre-eclampsia in pregnancy. We performed two-stage and one-stage IPD meta-analyses to estimate overall treatment effect and to explore potential treatment interactions whereby particular types of women and their babies might benefit differentially from receiving antiplatelets. Two-stage and one-stage approaches gave similar results, showing a benefit of using anti-platelets (Relative risk 0.90, 95% CI 0.84 to 0.97). Neither approach suggested that any particular type of women benefited more or less from antiplatelets. There were no material differences in results between different types of one-stage model. Conclusions: For these data, two-stage and one-stage approaches to analysis produce similar results. Although one-stage models offer a flexible environment for exploring model structure and are useful where across study patterns relating to types of participant, intervention and outcome mask similar relationships within trials, the additional insights provided by their usage may not outweigh the costs of statistical support for routine application in syntheses of randomised controlled trials. Researchers considering undertaking an IPD meta-analysis should not necessarily be deterred by a perceived need for sophisticated statistical methods when combining information from large randomised trials. [ABSTRACT FROM AUTHOR]

Objective To evaluate the performance of the QStatin scores for predicting the 5-year risk of developing acute renal failure, cataract, liver dysfunction and myopathy in men and women in England and Wales receiving statins. Design Prospective cohort study to evaluate the performance of four statin risk prediction models. Setting 364 practices in the UK contributing to The Health Improvement Network database. Participants 2.2 million patients aged 35e84 years registered with a general practice surgery between 1 January 2002 and 30 June 2008, with 2037 incident cases of acute renal failure, 25 692 incident cataract cases, 14 756 cases of liver dysfunction and 1209 incident cases of myopathy. Main outcome measures First recorded occurrence of acute renal failure, cataract, moderate or severe liver dysfunction and moderate or severe myopathic events as recorded in general practice records. Results Results from this independent and external validation of QStatin scores indicate that models predicting the 5-year statin risk of developing acute renal failure, cataracts and myopathy perform well with areas under the receiver operating characteristic curve ranging from 0.73 to 0.87. Calibration plots for the three models also indicated close agreement between observed and predicted risks. Poor performance was observed for the model predicting the 5-year statin risk of developing liver dysfunction with areas under the receiver operating characteristic curve of 0.64 and 0.60 for women and men, respectively. Conclusions QStatin scores for predicting the 5-year statin risk of developing acute renal failure, cataract and myopathy appear to be useful models with good discriminative and calibration properties. The model for predicting the 5-year statin risk of developing liver dysfunction appears to have limited ability to identify high-risk individuals and the authors caution against its use. [ABSTRACT FROM AUTHOR]

The article presents a study which provides detailed explanations on the checklist items in the Reporting Recommendations for Tumor Marker Prognostic Studies (REMARK). It is inferred that the recommendations were developed by the European Organization for Research and Treatment of Cancer and the National Cancer Institute. An overview on the proper method of reporting prognostic marker research is provided.

Background: Pre-publication peer review of manuscripts should enhance the value of research publications to readers who may wish to utilize findings in clinical care or health policy-making. Much published research across all medical specialties is not useful, may be misleading, wasteful and even harmful. Reporting guidelines are tools that in addition to helping authors prepare better manuscripts may help peer reviewers in assessing them. We examined journals' instructions to peer reviewers to see if and how reviewers are encouraged to use them. Methods: We surveyed websites of 116 journals from the McMaster list. Main outcomes were 1) identification of online instructions to peer reviewers and 2) presence or absence of key domains within instructions: on journal logistics, reviewer etiquette and addressing manuscript content (11 domains). Findings: Only 41/116 journals (35%) provided online instructions. All 41 guided reviewers about the logistics of their review processes, 38 (93%) outlined standards of behaviour expected and 39 (95%) contained instruction about evaluating the manuscript content. There was great variation in explicit instruction for reviewers about how to evaluate manuscript content. Almost half of the online instructions 19/41 (46%) mentioned reporting guidelines usually as general statements suggesting they may be useful or asking whether authors had followed them rather than clear instructions about how to use them. All 19 named CONSORT for reporting randomized trials but there was little mention of CONSORT extensions. PRISMA, QUOROM (forerunner of PRISMA), STARD, STROBE and MOOSE were mentioned by several journals. No other reporting guideline was mentioned by more than two journals. Conclusions: Although almost half of instructions mentioned reporting guidelines, their value in improving research publications is not being fully realised. Journals have a responsibility to support peer reviewers. We make several recommendations including wider reference to the EQUATOR Network online library (www.equator-network.org/). [ABSTRACT FROM AUTHOR]

The selection of appropriate outcomes or domains is crucial when designing clinical trials in order to compare directly the effects of different interventions in ways that minimize bias. If the findings are to influence policy and practice then the chosen outcomes need to be relevant and important to key stakeholders including patients and the public, health care professionals and others making decisions about health care. There is a growing recognition that insufficient attention has been paid to the outcomes measured in clinical trials. These issues could be addressed through the development and use of an agreed standardized collection of outcomes, known as a core outcome set, which should be measured and reported, as a minimum, in all trials for a specific clinical area. Accumulating work in this area has identified the need for general guidance on the development of core outcome sets. Key issues to consider in the development of a core outcome set include its scope, the stakeholder groups to involve, choice of consensus method and the achievement of a consensus. [ABSTRACT FROM AUTHOR]

The article analyzes several issues related to design, conduct, analysis, and reporting of randomised trials and the efficacy of the tool developed by the not-for-profit organization Cochrane Collaboration for assessing risk of bias so the research process can be made clearer and more accurate. It is reported that, the situation of underestimation or overestimation may arise in the presence of flaws in the design, conduct, analysis, and reporting. It is reported that, the tool developed by the organization covers six domains of bias including, selection bias, performance bias, and detection bias.

The STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) were published in five journals in 2001 and 2002. These guidelines, in the form of a checklist and explanations for use by authors and journal editors, were designed to improve reporting of acupuncture trials, particularly the interventions, thereby facilitating their interpretation and replication. Subsequent reviews of the application and impact of STRICTA have highlighted the value of STRICTA as well as scope for improvements and revision. To manage the revision process a collaboration between the STRICTA Group, the CONSORT Group and the Chinese Cochrane Centre was developed in 2008. An expert panel with 47 participants was convened that provided electronic feedback on a revised draft of the checklist. At a subsequent face-to-face meeting in Freiburg, a group of 21 participants further revised the STRICTA checklist and planned dissemination. The new STRICTA checklist, which is an official extension of CONSORT, includes 6 items and 17 subitems. These set out reporting guidelines for the acupuncture rationale, the details of needling, the treatment regimen, other components of treatment, the practitioner background and the control or compara-tor interventions. In addition, and as part of this revision process, the explanations for each item have been elaborated, and examples of good reporting for each item are provided. In addition, the word 'controlled' in STRICTA is replaced by 'clinical', to indicate that STRICTA is applicable to a broad range of clinical evaluation designs, including uncontrolled outcome studies and case reports. It is intended that the revised STRICTA checklist, in conjunction with both the main CONSORT statement and extension for non-pharmacological treatment, will raise the quality of reporting of clinical trials of acupuncture. [ABSTRACT FROM AUTHOR]

Logistic regression models are widely used in medicine for predicting patient outcome (prognosis) and constructing diagnostic tests (diagnosis). Multivariable logistic models yield an (approximately) continuous risk score, a transformation of which gives the estimated event probability for an individual. A key aspect of model performance is discrimination, that is, the model's ability to distinguish between patients who have (or will have) an event of interest and those who do not (or will not). Graphical aids are important in understanding a logistic model. The receiver-operating characteristic (ROC) curve is familiar, but not necessarily easy to interpret. We advocate a simple graphic that provides further insight into discrimination, namely a histogram or dot plot of the risk score in the outcome groups. The most popular performance measure for the logistic model is the c-index, numerically equivalent to the area under the ROC curve. We discuss the comparative merits of the c-index and the (standardized) mean difference in risk score between the outcome groups. The latter statistic, sometimes known generically as the effect size, has been computed in slightly different ways by several different authors, including Glass, Cohen and Hedges. An alternative measure is the overlap between the distributions in the outcome groups, defined as the area under the minimum of the two density functions. The larger the overlap, the weaker the discrimination. Under certain assumptions about the distribution of the risk score, the c-index, effect size and overlap are functionally related. We illustrate the ideas with simulated and real data sets. Copyright © 2010 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

In clinical measurement comparison of a new measurement technique with an established one is often needed to see whether they agree sufficiently for the new to replace the old. Such investigations are often analysed inappropriately, notably by using correlation coefficients. The use of correlation is misleading. An alternative approach, based on graphical techniques and simple calculations, is described, together with the relation between this analysis and the assessment of repeatability. [Copyright &y& Elsevier]

The STandards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) were published in five journals in 2001 and 2002. These guidelines, in the form of a checklist and explanations for use by authors and journal editors, were designed to improve reporting of acupuncture trials, particularly the interventions, thereby facilitating their interpretation and replication. Subsequent reviews of the application and impact of STRICTA have highlighted the value of STRICTA as well as scope for improvements and revision. To manage the revision process a collaboration between the STRICTA Group, the CONSORT Group, and the Chinese Cochrane Centre was developed in 2008. An expert panel with 47 participants was convened that provided electronic feedback on a revised draft of the checklist. At a subsequent face-to-face meeting in Freiburg, a group of 21 participants further revised the STRICTA checklist and planned dissemination. The new STRICTA checklist, which is an official extension of CONSORT, includes six items and 17 sub-items. These set out reporting guidelines for the acupuncture rationale, the details of needling, the treatment regimen, other components of treatment, the practitioner background, and the control or comparator interventions. In addition, and as part of this revision process, the explanations for each item have been elaborated, and examples of good reporting for each item are provided. In addition, the word 'controlled' in STRICTA is replaced by 'clinical,' to indicate that STRICTA is applicable to a broad range of clinical evaluation designs, including uncontrolled outcome studies and case reports. It is intended that the revised STRICTA, in conjunction with both the main CONSORT Statement and extension for nonpharmacologic treatment, will raise the quality of reporting of clinical trials of acupuncture. [ABSTRACT FROM AUTHOR]

The article focuses on the 2001 Consolidated Standards of Reporting Trials (CONSORT) statement, an updated guideline for report of randomised, group, parallel trials. It presents a chart that shows a checklist of information on the CONSORT 2010. It emphasises that CONSORT 2010 symbolises an evolving guideline, which requires perpetual reassessment and, if needed, some modifications.

The CONSORT (Consolidated Standards of Reporting Trials) statement is used worldwide to improve the reporting of randomized, controlled trials. Schulz and colleagues describe the latest version, CONSORT 2010, which updates the reporting guideline based on new methodological evidence and accumulating experience. [ABSTRACT FROM AUTHOR]

In this article the author discusses the attributes of Consolidated Standards of Reporting Trials 2010 (CONSORT 2010). He mentions that randomized controlled trials when properly designed and reported is important in the evaluation of health care interventions. He says that CONSORT 2010 provides guidance in reporting all controlled trials with the focus on the most common type. He also cites that with CONSORT 2010, a rigid structure for reporting randomized trials is again missed out.

Background Forest plots are graphical displays of findings of systematic reviews and meta-analyses. Little is known about the style and content of these plots and whether published plots maximize the graphic’s potential for information exchange. [ABSTRACT FROM PUBLISHER]

The article offers information on the Consolidated Standards of Reporting Trials (CONSORT) 2010, an updated guidelines for reporting parallel group randomized trials in Great Britain. The purpose of the CONSORT 2010 is elaborated. It traces the origins of CONSORT, beginning from the first CONSORT statement in 1996. Included in the updated CONSORT 2010 are the structured summary of trial design, methods, results and conclusions, the interventions for each group with sufficient details and method used to generate the random allocation sequence, among others. Additionally, the updated guidelines reportedly focuses on parallel randomized controlled trial.

The article offers information on the Consolidated Standards of Reporting Trials (CONSORT) 2010 Statement. It offers guidance for reporting all randomised controlled trials including individually randomised, two group and parallel trials. The CONSORT aims to improve the reporting of randomised controlled trials.

The CONSORT statement is used worldwide to improve the reporting of randomised controlled trials. Kenneth Schulz and colleagues describe the latest version, CONSORT 2010, which updates the reporting guideline based on new methodological evidence and accumulating experience. To encourage dissemination of the CONSORT 2010 Statement, this article is freely accessible on bmj.com and will also be published in the Lancet, Obstetrics and Gynecology, PLoS Medicine, Annals of Internal Medicine, Open Medicine, Journal of Clinical Epidemiology, BMC Medicine, and Trials. [ABSTRACT FROM AUTHOR]

The CONSORT statement is used worldwide to improve the reporting of randomised controlled trials. Kenneth Schulz and colleagues describe the latest version, CONSORT 2010, which updates the reporting guideline based on new methodological evidence and accumulating experience. To encourage dissemination of the CONSORT 2010 Statement, this article is freely accessible on bmj.com and will also be published in the Lancet, Obstetrics and Gynecology, PLoS Medicine, Annals of Internal Medicine, Open Medicine, Journal of Clinical Epidemiology, BMC Medicine, and Trials. [ABSTRACT FROM AUTHOR]

Background: The appropriate handling of missing covariate data in prognostic modelling studies is yet to be conclusively determined. A resampling study was performed to investigate the effects of different missing data methods on the performance of a prognostic model. Methods: Observed data for 1000 cases were sampled with replacement from a large complete dataset of 7507 patients to obtain 500 replications. Five levels of missingness (ranging from 5% to 75%) were imposed on three covariates using a missing at random (MAR) mechanism. Five missing data methods were applied; a) complete case analysis (CC) b) single imputation using regression switching with predictive mean matching (SI), c) multiple imputation using regression switching imputation, d) multiple imputation using regression switching with predictive mean matching (MICE-PMM) and e) multiple imputation using flexible additive imputation models. A Cox proportional hazards model was fitted to each dataset and estimates for the regression coefficients and model performance measures obtained. Results: CC produced biased regression coefficient estimates and inflated standard errors (SEs) with 25% or more missingness. The underestimated SE after SI resulted in poor coverage with 25% or more missingness. Of the MI approaches investigated, MI using MICE-PMM produced the least biased estimates and better model performance measures. However, this MI approach still produced biased regression coefficient estimates with 75% missingness. Conclusions: Very few differences were seen between the results from all missing data approaches with 5% missingness. However, performing MI using MICE-PMM may be the preferred missing data approach for handling between 10% and 50% MAR missingness. [ABSTRACT FROM AUTHOR]

Background: There is no consensus on the most appropriate approach to handle missing covariate data within prognostic modelling studies. Therefore a simulation study was performed to assess the effects of different missing data techniques on the performance of a prognostic model. Methods: Datasets were generated to resemble the skewed distributions seen in a motivating breast cancer example. Multivariate missing data were imposed on four covariates using four different mechanisms; missing completely at random (MCAR), missing at random (MAR), missing not at random (MNAR) and a combination of all three mechanisms. Five amounts of incomplete cases from 5% to 75% were considered. Complete case analysis (CC), single imputation (SI) and five multiple imputation (MI) techniques available within the R statistical software were investigated: a) data augmentation (DA) approach assuming a multivariate normal distribution, b) DA assuming a general location model, c) regression switching imputation, d) regression switching with predictive mean matching (MICE-PMM) and e) flexible additive imputation models. A Cox proportional hazards model was fitted and appropriate estimates for the regression coefficients and model performance measures were obtained. Results: Performing a CC analysis produced unbiased regression estimates, but inflated standard errors, which affected the significance of the covariates in the model with 25% or more missingness. Using SI, underestimated the variability; resulting in poor coverage even with 10% missingness. Of the MI approaches, applying MICE-PMM produced, in general, the least biased estimates and better coverage for the incomplete covariates and better model performance for all mechanisms. However, this MI approach still produced biased regression coefficient estimates for the incomplete skewed continuous covariates when 50% or more cases had missing data imposed with a MCAR, MAR or combined mechanism. When the missingness depended on the incomplete covariates, i.e. MNAR, estimates were biased with more than 10% incomplete cases for all MI approaches. Conclusion: The results from this simulation study suggest that performing MICE-PMM may be the preferred MI approach provided that less than 50% of the cases have missing data and the missing data are not MNAR. [ABSTRACT FROM AUTHOR]

The article proposes recommendations for the assessment of surgery based on a description of the surgical development process. It discusses stages in the development and assessment of surgical innovations such as innovation, development, exploration, assessment, and long-term study, or the IDEAL model. The authors believe that surgical science can be improved and progress in surgical care and interventions is expected to become safer, more efficient, and better. Recommendations of the British Medical Research Council (MRC) for the assessment of complex interventions are also discussed.

Systematic reviews and meta-analyses are essential to summarize evidence relating to efficacy and safety of health care interventions accurately and reliably. The clarity and transparency of these reports, however, is not optimal. Poor reporting of systematic reviews diminishes their value to clinicians, policy makers, and other users. Since the development of the QUOROM (QUality Of Reporting Of Meta-analysis) Statement--a reporting guideline published in 1999--there have been several conceptual, methodological, and practical advances regarding the conduct and reporting of systematic reviews and meta-analyses. Also, reviews of published systematic reviews have found that key information about these studies is often poorly reported. Realizing these issues, an international group that included experienced authors and methodologists developed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses) as an evolution of the original QUOROM guideline for systematic reviews and meta-analyses of evaluations of health care interventions. The PRISMA Statement consists of a 27-item checklist and a four-phase flow diagram. The checklist includes items deemed essential for transparent reporting of a systematic review. In this Explanation and Elaboration document, we explain the meaning and rationale for each checklist item. For each item, we include an example of good reporting and, where possible, references to relevant empirical studies and methodological literature. The PRISMA Statement, this document, and the associated Web site (www .prisma-statement.org) should be helpful resources to improve reporting of systematic reviews and meta-analyses. [ABSTRACT FROM AUTHOR]