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Control for confounding is crucial in causal observational studies. However, the modelling of continuous confounders has not received much attention. This is probably because in causal research the focus is [...]

Missing data are a frequently encountered problem in epidemiologic and clinical research. (1,2) One approach is to include in the analysis only those participants without missing observations (complete or available [...]

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.

PRISMA Statement Systematic reviews and meta-analyses have become increasingly important in health care. Clinicians read them to keep up to date with their field, (1,2) and they are often used [...]

Randomized trials have traditionally been broadly categorized as either an effectiveness trial or an efficacy trial, although we prefer the terms "pragmatic" and "explanatory." Schwartz and Lellouch described these 2 [...]

Background: Composite end points are common in clinical trials. Objective: To describe how composite outcomes are used, constructed, and reported in cardiovascular trials and to evaluate the contribution of individual end points to the composite estimate of effect in those trials. Design: Review of 2-group, parallel-design, randomized cardiovascular trials that used composite end points and were published in 14 clinical journals from 1 January 2000 to 1 January 2007. Setting: Published randomized trials in cardiovascular medicine and surgery. Participants: Two-group, parallel-design trials published in 14 leading general medical, cardiology, and cardiothoracic surgery journals from 1 January 2000 to 1 January 2007. Measurements: The types and numbers of individual events included in the composite outcome and P values and risk estimates for the composite outcome. Results: Of 304 trials published that used composite outcomes, 221 (73%) reported a composite primary outcome and 83 (27%) reported a composite secondary outcome. Composite outcomes comprised a median of 3 (interquartile range, 3 to 4) individual outcomes; death was the most common individual outcome. The total number of individual events and the total number of events represented by the composite outcome differed in 79% of trials. P values for composite outcomes were less than 0.050 more frequently than they were 0.050 or greater. Death as an individual end point made a relatively minimal contribution to estimates of effect summarized by the trials' composite end points, whereas revascularization made a greater contribution. Limitation: All-cause and cardiovascular mortality were not distinguished, and the findings might not apply to trials in other fields. Conclusion: Composite outcomes in cardiovascular trials are frequent and commonly comprise 3 to 4 individual end points that vary in clinical significance. Discrepancies between the total number of individual events in a trial and those reported for composite outcomes are common. Individual outcomes do not contribute equally to composite measures, so the overall estimate of effect for a composite measure cannot be assumed to apply equally to each of its individual outcomes.

Adequate reporting of randomized, controlled trials (RCTs) is necessary to allow accurate critical appraisal of the validity and applicability of the results. The CONSORT (Consolidated Standards of Reporting Trials) Statement, a 22-item checklist and flow diagram, is intended to address this problem by improving the reporting of RCTs. However, some specific issues that apply to trials of non-pharmacologic treatments (for example, surgery, technical interventions, devices, rehabilitation, psychotherapy, and behavioral intervention) are not specifically addressed in the CONSORT Statement. Furthermore, considerable evidence suggests that the reporting of nonpharmacologic trials still needs improvement. Therefore, the CONSORT group developed an extension of the CONSORT Statement for trials assessing nonpharmacologic treatments. A consensus meeting of 33 experts was organized in Paris, France, in February 2006, to develop an extension of the CONSORT Statement for trials of nonpharmacologic treatments. The participants extended 11 items from the CONSORT Statement, added 1 item, and developed a modified flow diagram. To allow adequate understanding and implementation of the CONSORT extension, the CONSORT group developed this elaboration and explanation document from a review of the literature to provide examples of adequate reporting. This extension, in conjunction with the main CONSORT Statement and other CONSORT extensions, should help to improve the reporting of RCTs performed in this field.

Because of censoring, standard methods of plotting individual survival times are invalid. Therefore, graphic display of time-to-event data usually takes the form of a Kaplan--Meier survival plot. Kaplan--Meier plots, however, make differences between groups seem larger than they really are. To overcome these limitations, we developed a technique for producing scatter plots with survival data and applied it to data from a randomized trial of patients with renal cancer. As of June 21, 2001, 25 of the 347 patients with kidney cancer in the Medical Research Council RE01 randomized treatment trial for whom data were available had been censored, and the remainder had died. Values of the censored survival times were imputed by assuming a log-normal distribution in survival times and by drawing a random sample given that that each patient with censored data survived at least to the point of censoring. The combined original and imputed data were then examined by use of dot plots and scatter plots. In the RE01 trial, median survival of patients treated with interferon was 3.0 months (95% confidence interval = 0.3 to 5.5 months) Ionger than that in patients treated with medroxyprogesterone acetate. The Kaplan--Meier analysis showed clear separation between treatment groups and between prognostic groups. In contrast, comparisons of individual observed and imputed survival times between groups of patients showed considerable overlap and gave a more realistic idea of the modest between-group differences than Kaplan--Meier comparisons. These graphs of the distribution of survival times for individuals in each study group, which are simple to produce, may usefully complement Kaplan--Meier plots.

Much biomedical research is observational. The reporting of such research is often inadequate, which hampers the assessment of its strengths and weaknesses and of a study's generalizability. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Initiative developed recommendations on what should be included in an accurate and complete report of an observational study. We defined the scope of the recommendations to cover 3 main study designs: cohort, case-control, and cross-sectional studies. We convened a 2-day workshop in September 2004, with methodologists, researchers, and journal editors, to draft a checklist of items. This list was subsequently revised during several meetings of the coordinating group and in e-mail discussions with the larger group of STROBE contributors, taking into account empirical evidence and methodological considerations. The workshop and the subsequent iterative process of consultation and revision resulted in a checklist of 22 items (the STROBE Statement) that relate to the title, abstract, introduction, methods, results, and discussion sections of articles. Eighteen items are common to all 3 study designs and 4 are specific for cohort, case-control, or cross-sectional studies. A detailed Explanation and Elaboration document is published separately and is freely available at www.annals.org and on the Web sites of PLoS Medicine and Epidemiology. We hope that the STROBE Statement will contribute to improving the quality of reporting of observational studies.

Despite years of research and hundreds of reports on tumor markers in oncology, the number of markers that have emerged as clinically useful is pitifully small. Often, initially reported studies of a marker show great promise, but subsequent studies on the same or related markers yield inconsistent conclusions or stand in direct contradiction to the promising results. It is imperative that we attempt to understand the reasons that multiple studies of the same marker lead to differing conclusions. A variety of methodologic problems have been cited to explain these discrepancies. Unfortunately, many tumor marker studies have not been reported in a rigorous fashion, and published articles often lack sufficient information to allow adequate assessment of the quality of the study or the generalizability of study results. The development of guidelines for the reporting of tumor marker studies was a major recommendation of the National Cancer Institute-European Organisation for Research and Treatment of Cancer (NCI-EORTC) First International Meeting on Cancer Diagnostics in 2000. As for the successful CONSORT initiative for randomized trials and for the STARD statement for diagnostic studies, we suggest guidelines to provide relevant information about the study design, preplanned hypotheses, patient and specimen characteristics, assay methods, and statistical analysis methods. In addition, the guidelines suggest helpful presentations of data and important elements to include in discussions. The goal of these guidelines is to encourage transparent and complete reporting so that the relevant information will be available to others to help them to judge the usefulness of the data and understand the context in which the conclusions apply.

In response to overwhelming evidence and the consequences of poor-quality reporting of randomized, controlled trials (RCTs), many medical journals and editorial groups have now endorsed the CONSORT (Consolidated Standards of Reporting Trials) statement, a 22-item checklist and flow diagram. Because CONSORT primarily aimed at improving the quality of reporting of efficacy, only 1 checklist item specifically addressed the reporting of safety. Considerable evidence suggests that reporting of harms-related data from RCTs also needs improvement. Members of the CONSORT Group, including journal editors and scientists, met in Montebello, Quebec, Canada, in May 2003 to address this problem. The result is the following document: the standard CONSORT checklist with 10 new recommendations about reporting harms-related issues, accompanying explanation, and examples to highlight specific aspects of proper reporting. We hope that this document, in conjunction with other CONSORT-related materials (www.consort-statement.org), will help authors improve their reporting of harms-related data from RCTs. Better reporting will help readers critically appraise and interpret trial results. Journals can support this goal by revising Instructions to Authors so that they refer authors to this document.

Abstract Background: The reporting of outcomes within published randomized trials has previously been shown to be incomplete, biased and inconsistent with study protocols. We sought to determine whether outcome reporting [...]

Reports of cluster randomised trials require additional information to allow readers to interpret them accurately The effective reporting of randomised controlled trials has received useful attention in recent years. Many [...]

Summary points Inconsistency of studies' resets in a meta-analysis reduces the confidence of recommendations about treatment Inconsistency is usually assessed with a test for heterogeneity, but problems of power can [...]

Abstract Objective To determine the validity of adjusted indirect comparisons by using data from published meta-analyses of randomised trials. Design Direct comparison of different interventions in randomised trials and adjusted [...]

A discussion of blinding in medical research is presented, including definitions and clarifications of the different types of blinding. In medical research, blinding means that either the patient, the doctor, or both, do not know whether the patient is receiving the treatment or a placebo.

Background: The use of complex statistical models to adjust for confounding is common in medical research. Objective: To determine the frequency and adequacy of adjustment for confounding in medical articles. Design: Cross-sectional survey. Setting: 34 scientific medical journals with a high impact factor. Measurements: Frequency of reporting on methods used to adjust for confounding in 537 original research articles published in January 1998. Results: Of the 537 articles, 169 specified that adjustment for confounding was used. In 1 paper in 10, it was unclear which statistical method was used or for which variables adjustment was made. In 45% of papers, it was not clear how multicategory or continuous variables were treated in the analysis. Inadequate reporting was less frequent if an author was affiliated with a department of statistics, epidemiology, or public health and if articles were published in journals with a high impact factor. Conclusions: Details of methods used to adjust for confounding are frequently not reported in original research articles.

The number needed to treat (NNT) is a useful way of reporting the results of randomised controlled trials.[1] In a trial comparing a new treatment with a standard one, the [...]

Introduction Although local circumstances must always be taken into account, it is acknowledged that as far as possible clinical practice should be guided by rigorous evidence from large trials or [...]

In meta-analyses of clinical trials comparing a treated group with a control group it has been common to ask whether the treatment benefit varies according to the underlying risk of [...]

Abstract Objectives To evaluate the efficacy of low and medium dose aspirin therapy after coronary surgery by using an indirect comparison meta-analysis. Data sources Systematic literature search of Medline, Embase, [...]

Misuse of statistics in medical and sports science research is common and may lead to detrimental consequences to healthcare. Many authors, editors and peer reviewers of medical papers will not have expert knowledge of statistics or may be unconvinced about the importance of applying correct statistics in medical research. Although there are guidelines on reporting statistics in medical papers, a checklist on the more general and commonly seen aspects of statistics to assess when peer-reviewing an article is needed. In this article, we propose a CHecklist for statistical Assessment of Medical Papers (CHAMP) comprising 30 items related to the design and conduct, data analysis, reporting and presentation, and interpretation of a research paper. While CHAMP is primarily aimed at editors and peer reviewers during the statistical assessment of a medical paper, we believe it will serve as a useful reference to improve authors’ and readers’ practice in their use of statistics in medical research. We strongly encourage editors and peer reviewers to consult CHAMP when assessing manuscripts for potential publication. Authors also may apply CHAMP to ensure the validity of their statistical approach and reporting of medical research, and readers may consider using CHAMP to enhance their statistical assessment of a paper.

Abstract Objective--To assess the methodological quality of approaches to blinding and to handling of exclusions as reported in randomised trials from one medical specialty. Design--Survey of published, parallel group randomised [...]

We are all familiar with using single items of patient data such as age or smoking history to help in making difficult clinical decisions.[1] Prognostic models are more complex tools [...]

Purpose To assess the adherence of stroke randomised controlled trials to Consolidated Standards Of Reporting Trials reporting guidelines and investigate the factors that are associated with completeness of reporting.Method We took a random sample from the Cochrane Stroke Group's Trial Register of transient ischaemic attack or stroke randomised controlled trials, published in English in 1997–2016 inclusive. Two reviewers assessed the published report of the final primary results of stroke randomised controlled trials with a 10-point truncated Consolidated Standards Of Reporting Trials reporting checklist to investigate adherence over time, univariable associations and independent associations with total Consolidated Standards Of Reporting Trials reporting score in a multiple linear regression model.Findings In this random sample of 177 stroke randomised controlled trials, the mean score on the truncated Consolidated Standards Of Reporting Trials checklist was 5.8 (SD 2.2); reporting improved from 1997–2000 (4.9 SD 2.0) to 2001–2009 (5.8 SD 2.1) and to 2010–2016 (6.8 SD 2.1). A higher Consolidated Standards Of Reporting Trials score was independently associated with publication during epochs following a revision of Consolidated Standards Of Reporting Trials reporting guidelines (p < 0.001), journal endorsement of the Consolidated Standards Of Reporting Trials reporting guideline at the time of randomised controlled trial publication (p < 0.001) and modified journal impact factor using median citation distribution (p = 0.012).Discussion Stroke randomised controlled trial reporting to Consolidated Standards Of Reporting Trials standards has improved over time, but could be better.Conclusion Journal endorsement and enforcement of Consolidated Standards Of Reporting Trials reporting guidelines could further improve the reporting of stroke randomised controlled trials. Systematic review registration:Registered with PROSPERO (CRD42017072193).

We have previously explained why random allocation of treatments is a required design feature of controlled trials[1] and explained how to generate a random allocation sequence.[2] Here we consider the [...]

Summary points Systematic reviews are applicable to all types of research design, and studies of prognostic variables are an important additional area where appropriate methodology should be applied Prognostic variables [...]

This is the first in a series of four articles Summary points Empirical studies show that inadequate quality of trials may distort the results from systematic reviews and meta-analyses The [...]

Overwhelming evidence now indicates that the quality of reporting of randomized, controlled trials (RCTs) is less than optimal. Recent methodologic analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects. Such systematic error is seriously damaging to RCTs, which boast the elimination of systematic error as their primary hallmark. Systematic error in RCTs reflects poor science, and poor science threatens proper ethical standards. A group of scientists and editors developed the CONSORT (Consolidated Standards of Reporting Trials) statement to improve the quality of reporting of RCTs. The statement consists of a checklist and flow diagram that authors can use for reporting an RCT. Many leading medical journals and major international editorial groups have adopted the CONSORT statement. The CONSORT statement facilitates critical appraisal and interpretation of RCTs by providing guidance to authors about how to improve the reporting of their trials. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the CONSORT statement. The meaning and rationale for each checklist item are presented. For most items, at least one published example of good reporting and, where possible, references to relevant empirical studies are provided. Several examples of flow diagrams are included. The CONSORT statement, this explanatory and elaboration document, and the associated Web site (http://www.consort-statement.org) should be helpful resources to improve reporting of randomized trials. Ann Intern Med. 2001;134:663-694. www.annals.org