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The study attempts to investigate the nature and frequency of distortion of interpretation of trial results or to distract the reader from statistically nonsignificant results for primary outcomes in published reports of randomized controlled trials (RCTs) with statistically nonsignificant results for primary outcomes. The results indicate that in the case of such RCTs, the reporting and interpretation of findings was found to be very often inconsistent with the results.

A study was conducted to compare the primary outcomes of registered trials with those reported in published trials and to determine whether primary outcome reporting bias favored significant outcomes. Results indicated that selective outcome reporting was prevalent in comparison of primary outcomes of registered randomized controlled trials (RCTs).

An adapted Consolidated Standards of Reporting Trials (CONSORT) checklist for reporting noninferiority and equivalence trials is presented and illustrative examples and explanations for those items amended from the original CONSORT checklist are provided. The intent is to improve reporting of noninferiority and equivalence trials, enabling readers to assess the validity of their results and conclusions.

An attempt is made to examine the extent and nature of outcome reporting bias in a cohort of randomized trials. The conclusion states that the reporting of trial outcomes is biased and inconsistent with protocols.

Most medical researchers who do a factorial clinical trial are performing them appropriately and only use them for treatments that do not interact. This was the conclusion of researchers who analyzed 33 reports of 29 factorial trials. A factorial clinical trial is one that evaluates more than one treatment.

Some authors of scientific papers do not allow a person who specializes in statistics to review their paper, according to a survey of 704 authors. Even when they do, they may not include the name of the statistician in the list of authors and contributors., Context: Investigation of the nature and frequency of statistician involvement in medical research and its relation to the final editorial decision. Methods: Authors of original research articles who submitted to BMJ and Annals of Internal Medicine from May through August 2001 were sent a short questionnaire at the time of manuscript submission. Authors were asked if they received assistance from a person with statistical expertise, the nature of any such contribution, and reasons why, if no statistical input was received. Results: The response rate was 75% (704/943); methodological input was reported for 514(73%) of these papers. In 435 papers (85%), such input was provided by biostatisticians or epidemiologists and, if deemed significant, was typically associated with authorship. A total of 33 of 122 methodologists (27%) whose main contribution started at the analysis stage received neither acknowledgment nor authorship. Research without methodological assistance was more likely to be rejected without review (71% vs 57%; [chi square]=10.6; P=.001) and possibly less likely to be accepted for publication (7% vs 11%; [chi square]=2.37; P=.12). Conclusions: Statistical input to medical research is widely recommended but inconsistently obtained. Individuals providing such expertise are often not involved until the analysis of data and many go unrecognized by either authorship or acknowledgment.

Inadequate concealment of patient treatment allocation during randomized, controlled trials appears to lead to unreliable results. Randomized, controlled trials are used to evaluate drug therapy or other treatments. Thirty-three meta-analyses of the design of 250 controlled trials were analyzed. In 79 trials researchers judged that adequate steps were taken to conceal treatment allocation from participants. In 21 trials, inadequate steps were taken and in 150 trials researchers were unable to determine if steps to conceal treatment allocation were adequate. Significantly larger estimates of treatment effects occurred in trials in which concealment was unclear or inadequate than in trials judged to have provided adequate concealment. When evaluating studies, researchers should carefully assess whether biases in comparison groups exist., Objective. - To determine if inadequate approaches to randomized controlled trial design and execution are associated with evidence of bias in estimating treatment effects. Design. - An observational study in which we assessed the methodological quality of 250 controlled trials from 33 meta-analyses and then analyzed, using multiple logistic regression models, the associations between those assessments and estimated treatment effects. Data Sources. - Meta-analyses from the Cochrane Pregnancy and Childbirth Database. Main Outcome Measures. - The associations between estimates of treatment effects and inadequate allocation concealment, exclusions after randomization, and lack of double-blinding. Results. - Compared with trials in which authors reported adequately concealed treatment allocation, trials in which concealment was either inadequate or unclear (did not report or incompletely reported a concealment approach) yielded larger estimates of treatment effects (P

Editors and peer reviewers of medical reports will need to become more aware of innovations in statistical methodology, which are being used more quickly in medical journals. The transfer of statistical innovations from statistical journals to medical journals happened much faster in the 1970s and 1980s, although it still takes roughly four to six years for such methods to become widely used in medical journals after their introduction. Authors of reports should supply reference or support information to editors and peer reviewers to help them scrutinize statistical findings in a more enlightened manner. Statistical specialists may need to be used by medical journals to review trials and reports for publication. Postgraduate medical education should focus greater attention on innovative statistical methods. A proper understanding of the latest statistical methods will allow editors and peer reviewers to make more informed decisions., Objective.--To investigate the speed of the transfer of new statistical methods into the medical literature and, on the basis of current data, to predict what methods medical journal editors should expect to see in the next decade. Design.--Influential statistical articles were identified and the time pattern of citations in the medical literature was ascertained. In addition, longitudinal studies of the statistical content of articles in medical journals were reviewed. Main Outcome Measures.--Cumulative number of citations in medical journals of each article in the years after publication. Results.--Annual citations show some evidence of decreasing lag times between the introduction of new statistical methods and their appearance in medical journals. Newer technical innovations still typically take 4 to 6 years before they achieve 25 citations in the medical literature. Few methodological advances of the 1980s seem yet to have been widely cited in medical journals. Longitudinal studies indicate a large increase in the use of more complex statistical methods. Conclusions.--Time trends suggest that technology diffusion has speeded up during the last 30 years, although there is still a lag of several years before medical citations begin to accrue. Journals should expect to see more articles using increasingly sophisticated methods. Medical journals may need to modify reviewing procedures to deal with articles using these complex new methods. (JAMA. 1994;272:129-132)

Selection for enrollment in clinical trials dealing with obstetrics and gynecology appears to be less than random. A study of four medical journals dealing with obstetrics and gynecology from 1990 to 1991 revealed 206 supposedly randomized clinical trials. However, 68% of the reports did not specify the method used to achieve proper randomization, and 77% did not specify the method used to achieve proper allocation concealment. Only 9% of the reports presented necessary evidence of both randomization and concealment. Differences in group sizes between the test groups and the control groups were less than would normally occur by chance, suggesting a manipulation of the allocation process. Proper randomization is a necessary means of ensuring the validity of test results. Any manipulation of the process can lead to inaccurate and biased information., Objective.--To assess the methodologic quality of approaches used to allocate participants to comparison groups in randomized controlled trials f rom one medical specialty. Design.--Survey of published, parallel group randomized controlled trials. Data Sources.--All 206 reports with allocation described as randomized from the 1990 and 1991 volumes of four journals of obstetrics and gynecology. Main Outcome Measures.--Direct and indirect measures of the adequacy of randomization and baseline comparisons. Results.--Only 32% of the reports described an adequate method for generating a sequence of random numbers, and only 23% contained information showing that steps had been taken to conceal assignment until the point of treatment allocation. A mere 9% described both sequence generation and allocation concealment. In reports of trials that had apparently used unrestricted randomization, the differences in sample sizes between treatment and control groups were much smaller than would be expected due to chance. In reports of trials in which hypothesis tests had been used to compare baseline characteristics, only 2% of reported test results were statistically significant, lower than the expected rate of 5%. Conclusions.--Proper randomization is required to generate unbiased comparison groups in controlled trials, yet the reports in these journals usually provided inadequate or unacceptable information on treatment allocation. Additional analyses suggest that nonrandom manipulation of comparison groups and selective reporting of baseline comparisons may have occurred. (JAMA. 1994;272:125-128)

Journal editors can do much to improve the quality of research reports before publication. In addition to peer review, editors can create standards that all authors must meet when writing research reports., The aim of medical research is to advance scientific knowledge and hence--directly or indirectly--lead to improvements in the treatment and prevention of disease. Each research project should continue systematically from previous research and feed into future research. Each project should contribute beneficially to a slowly evolving body of research. A study should not mislead; otherwise it could adversely affect clinical practice and future research. In 1994 I observed that research papers commonly contain methodological errors, report results selectively, and draw unjustified conclusions. Here I revisit the topic and suggest how journal editors can help.

The International Committee of Medical Journal Editors should investigate fraud and misconduct on the part of medical editors with the same vigor that they investigate such misdeeds on the part of manuscript authors. Most journals have been afraid to address such matters for fear of legal complications. The establishment of an International Medical Scientific Press Council would help codify proper editorial conduct and procedure. Journals could agree to uphold certain standards and abide by agreed upon investigation procedures set forth by the council. Authors would be able to direct their grievances toward the council, which would hear appeals and address grievances as necessary. A monitoring of editorial behavior is as necessary as the peer review of manuscripts to ensure the editorial integrity of medical journals., Serious abuse of editorial power is rarely publicized, but evidence that it occurs is accumulating. Authors who believe that they have been dealt with unfairly have little possibility of a hearing of their complaint, and cases cannot easily be publicized because of fears of legal action. We describe briefly three cases in which the alleged misdeeds indicate that there were legitimate questions that needed answers. In the first case, an editor republished a previously published article without the authors' permission (but stated the opposite), attacked it in an accompanying editorial, and then denied the authors the right of reply. The other cases concerned a commissioned review article that was plagiarized and an editor with an undisclosed vested interest. An appeal process is needed for authors who think that they are victims of editorial abuse of power. We suggest that the international Committee of Medical Journal Editors turn its attention to editorial misconduct and explore possible procedures for allowing authors' grievances to be heard and for possible sanctions if complaints are upheld. An International Medical Scientific Press Council might be established to produce a code of conduct for editors and a corresponding taxonomy of inappropriate editorial behavior. (JAMA. 1994;272:166-167)

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]

The CONSORT (Consolidated Standards of Reporting Trials) Statement aims to improve the reporting of randomized controlled trials (RCTs); however, it lacks guidance on the reporting of patient-reported outcomes (PROs), which are often inadequately reported in trials, thus limiting the value of these data. In this article, we describe the development of the CONSORT PRO extension based on the methodological framework for guideline development proposed by the Enhancing the Quality and Transparency of Health Research (EQUATOR) Network. Five CONSORT PRO checklist items are recommended for RCTs in which PROs are primary or important secondary end points. These recommendations urge that the PROs be identified as a primary or secondary outcome in the abstract, that a description of the hypothesis of the PROs and relevant domains be provided (ie, if a multidimensional PRO tool has been used), that evidence of the PRO instrument's validity and reliability be provided or cited, that the statistical approaches for dealing with missing data be explicitly stated, and that PRO-specific limitations of study findings and generalizability of results to other populations and clinical practice be discussed. Examples and an updated CONSORT flow diagram with PRO items are provided. It is recommended that the CONSORT PRO guidance supplement the standard CONSORT guidelines for reporting RCTs with PROs as primary or secondary outcomes. Improved reporting of PRO data should facilitate robust interpretation of the results from RCTs and inform patient care. [ABSTRACT FROM AUTHOR]

The CONSORT (Consolidated Standards of Reporting Trials) Statement, which includes a checklist and a flow diagram, is a guideline developed to help authors improve the reporting of the findings from randomized controlled trials. It was updated most recently in 2010. Its primary focus is on individually randomized trials with 2 parallel groups that assess the possible superiority of one treatment compared with another. The CONSORT Statement has been extended to other trial designs such as cluster randomization, and recommendations for noninferiority and equivalence trials were made in 2006. In this article, we present an updated extension of the CONSORT checklist for reporting noninferiority and equivalence trials, based on the 2010 version of the CONSORT Statement and the 2008 CONSORT Statement for the reporting of abstracts, and provide illustrative examples and explanations for those items that differ from the main 2010 CONSORT checklist. The intent is to improve reporting of noninferiority and equivalence trials, enabling readers to assess the reliability of their results and conclusions. [ABSTRACT FROM AUTHOR]

Context Selective reporting of outcomes within published studies based on the nature or direction of their results has been widely suspected, but direct evidence of such bias is currently limited to case reports. Objective To study empirically the extent and nature of outcome reporting bias in a cohort of randomized trials. Design Cohort study using protocols and published reports of randomized trials approved by the Scientific-Ethical Committees for Copenhagen and Frederiksberg, Denmark, in 1994-1995. The number and characteristics of reported and unreported trial outcomes were recorded from protocols, journal articles, and a survey of trialists. An outcome was considered incompletely reported if insufficient data were presented in the published articles for meta-analysis. Odds ratios relating the completeness of outcome reporting to statistical significance were calculated for each trial and then pooled to provide an overall estimate of bias. Protocols and published articles were also compared to identify discrepancies in primary outcomes. Main Outcome Measures Completeness of reporting of efficacy and harm outcomes and of statistically significant vs nonsignificant outcomes; consistency between primary outcomes defined in the most recent protocols and those defined in published articles. Results One hundred two trials with 122 published journal articles and 3736 outcomes were identified. Overall, 50% of efficacy and 65% of harm outcomes per trial were incompletely reported. Statistically significant outcomes had a higher odds of being fully reported compared with nonsignificant outcomes for both efficacy (pooled odds ratio, 2.4; 95% confidence interval [CI], 1.4-4.0) and harm (pooled odds ratio, 4.7; 95% CI, 1.8-12.0) data. In comparing published articles with protocols, 62% of trials had at least 1 primary outcome that was changed, introduced, or omitted. Eighty-six percent of survey responders (42/49) denied the existence of unreported outcomes despite clear... [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article related to reporting of noninferiority and equivalence clinical trials.

The article analyzes a sample of systematic review abstracts to examine the nature and degree of any deficiencies in reporting. Results reveal that 77 of 182 abstracts failed to describe the direction of intervention effect in words, and just 22 described the size in words. In 34 of the abstracts, the direction of effect could only be determined by interpreting numerical results. In 43 of the abstracts, the direction of effect was not reliably determined.

The article presents a research letter entitled "Constraints on Publication Rights in Industry-Initiated Clinical Trials."

Presents a letter to the editor questioning the conclusion of Dr. Fonarow and colleagues' risk model for in-hospital mortality in acutely decompensated heart failure.

A letter and a response to a letter to the editor is presented which discussed the inappropriate use of statistically nonsignificant results in public reports of randomized controlled trials.

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.

Importance: While guidance on statistical principles for clinical trials exists, there is an absence of guidance covering the required content of statistical analysis plans (SAPs) to support transparency and reproducibility., Objective: To develop recommendations for a minimum set of items that should be addressed in SAPs for clinical trials, developed with input from statisticians, previous guideline authors, journal editors, regulators, and funders., Design: Funders and regulators (n = 39) of randomized trials were contacted and the literature was searched to identify existing guidance; a survey of current practice was conducted across the network of UK Clinical Research Collaboration-registered trial units (n = 46, 1 unit had 2 responders) and a Delphi survey (n = 73 invited participants) was conducted to establish consensus on SAPs. The Delphi survey was sent to statisticians in trial units who completed the survey of current practice (n = 46), CONSORT (Consolidated Standards of Reporting Trials) and SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guideline authors (n = 16), pharmaceutical industry statisticians (n = 3), journal editors (n = 9), and regulators (n = 2) (3 participants were included in 2 groups each), culminating in a consensus meeting attended by experts (N = 12) with representatives from each group. The guidance subsequently underwent critical review by statisticians from the surveyed trial units and members of the expert panel of the consensus meeting (N = 51), followed by piloting of the guidance document in the SAPs of 5 trials., Findings: No existing guidance was identified. The registered trials unit survey (46 responses) highlighted diversity in current practice and confirmed support for developing guidance. The Delphi survey (54 of 73, 74% participants completing both rounds) reached consensus on 42% (n = 46) of 110 items. The expert panel (N = 12) agreed that 63 items should be included in the guidance, with an additional 17 items identified as important but may be referenced elsewhere. Following critical review and piloting, some overlapping items were combined, leaving 55 items., Conclusions and Relevance: Recommendations are provided for a minimum set of items that should be addressed and included in SAPs for clinical trials. Trial registration, protocols, and statistical analysis plans are critically important in ensuring appropriate reporting of clinical trials.