Is This Clinical Trial Fully Registered? — A Statement from the International Committee of Medical Journal Editors

DeAngelis, Catherine D.; Drazen, Jeffrey M.; Frizelle, Frank; Huang, Chunming; Hoey, John; Horton, Richard; Kotzin, Sheldon; Lainé, Christine; Marušić, Ana; Overbeke, A. John P.M.; Schroeder, Torben V.; Sox, Harold C.; Weyden, Martin B Van Der

doi:10.1056/nejme058127

Cited by 279 publications

(161 citation statements)

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“…Do these findings cast doubt on the utility of clinical trial registration as a tool to increase the transparency of clinical research? It seems probable that standards of adequacy for trial registration have not been sufficient [12,13], and stricter enforcement of registration standards as well as new laws requiring minimal outcomes reporting may improve the utility of clinical trial registration to reduce publication bias and selective outcomes reporting.…”

Section: Discussionmentioning

confidence: 99%

Reporting of Negative Randomized Trials in Three Major Medical Journals

Brooks¹,

Bowles²,

Jamieson³

et al. 2013

IJCM

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Context: In recent years there has been increasing interest on publication bias and on initiatives to decrease bias, including trial registration. Objective: To test whether there has been an increase in reports of randomized control trials (RCT's) with negative outcomes in major journals and to identify factors associated with these reports. Design: Retrospective review of reports of RCT's published in the Journal of the American Medical Association, The Lancet and the New England Journal of Medicine before (2002-'03, pre-registration era) and after (2007-'08, registration era) the institution of mandatory trial registration. Main Outcome Measure: The primary outcome was the proportion of RCT reports with negative outcomes compared across the two eras. Secondary outcome includes other factors affecting publication. Results: We identified 917 reports of RCT's published in the two study eras. No publications in the pre-registration era reported trial registration compared with 94.4% in the registration era (p < 0.001). There was a non-significant increase in negative trials from the pre-registration to the registration era (29.1% vs. 34.1%, p = 0.10, OR 1.26, 95% CI 0.96 -1.67). Study characteristics associated with negative outcomes include trials of drugs (OR 1.62, 95% CI 1.08 -2.43), procedures or devices (OR 2.08, 95% CI 1.29 -3.35), explicit identification of a single primary endpoint (OR 1.70, 95% CI 1.40 -2.47), and increasing sample size (OR 3.08, 95% CI 1.78 -5.34). Non-inferiority study design was associated with a decreased likelihood of a negative outcome (OR 0.13, 95% CI 0.05 -0.31). Conclusions:The proportion of published RCT reports with negative outcomes in three major medical journals has not significantly increased since the mandatory clinical trial registration policy. The observed prevalence of negative trials is associated with increases in sample size and greater specificity in trial endpoints.

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Section: Discussionmentioning

confidence: 99%

Reporting of Negative Randomized Trials in Three Major Medical Journals

Brooks¹,

Bowles²,

Jamieson³

et al. 2013

IJCM

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“…Trial registration was not compulsory at that time, as this was prior to the publication of the International Committee of Medical Journal Editors demanding such [13]. The protocol was not submitted to the human subject committee, as no strong evidence documenting an advantage of high-flux membranes existed at that time.…”

Section: Methodsmentioning

confidence: 99%

Effect of Membrane Permeability on Cardiovascular Risk Factors and β2m Plasma Levels in Patients on Long-Term Haemodialysis: A Randomised Crossover Trial

Chazot

Kirchgessner²,

Pham³

et al. 2015

Nephron

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Survival of haemodialysis (HD) patients is influenced by many factors. Mortality is mainly of cardiovascular (CV) origin and related to both traditional and nontraditional CV risk factors. Low plasma Beta2-microglobulin (β2m) levels are associated with improved HD patient survival. HD session times that are longer than the conventional 4 h (i.e., extended dialysis) provide better middle molecule clearance and are also associated with a survival advantage. In this crossover randomised trial, we investigated the effect of membrane flux on CV risk factors and on β2m plasma levels in patients treated with extended dialysis. Dialysis session duration was between 5 and 8 h for all patients. Patients were randomly assigned to the treatment sequences low-flux/high-flux dialysis versus high-flux/low-flux dialysis in a crossover design after a 3-month run-in period, with each phase lasting 9 months. Of the initially enrolled 168 patients, 155 patients started the study after the run-in period, 117 patients completed Phase 1, and 83 patients completed the whole study. Lp(a), homocystein, LDL cholesterol, HDL cholesterol and serum albumin were comparable in the low-flux and high-flux treatments. The average β2m level was 43.3 ± 11.1 mg/l at the end of the low-flux phase. Independent of sequence assignation, average β2m was significantly lower at the end of the high-flux phase (27.5 ± 76.0 mg/l, p < 0.0001 versus end of low-flux phase). Both phosphate and nPNA were significantly lower at the end of the high-flux phase compared to the low-flux phase (p = 0.045 and p = 0.002, respectively). Inclusion of those patients who completed Phase 1 and who dropped out of the study during Phase 2 did not significantly change the results. In conclusion, this study did not find an influence of high-flux filters on several traditional CV risk factors in a population of HD patients treated with extended dialysis. However, high-flux filters are necessary to optimise middle molecule clearance and reduce the β2m level.

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“…This has been a focus in both clinical trials and in systematic reviews of interventions, where specific strategies (eg, prospective trial design registration3 and the Cochrane Collaboration systematic review strategy) have been implemented to improve reliability. While guidelines for the conduct and reporting of observational studies and systematic reviews of these have been developed, the impact of suboptimal reporting has been less well defined.…”

Section: Commentarymentioning

confidence: 99%

Prognostic value of CRP in stable coronary artery disease unclear due to a variety of biases in existing studies, therefore no clinical practice recommendations can be made

Perkovic

Huxley²

2010

Evid Based Med

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ContextIndividuals with cardiovascular disease (CVD) are at high risk for further cardiovascular events. Further risk stratifi cation in these individuals could allow more precise targeting of invasive tests (eg, cardiac stress tests, angiograms) as well as interventions (blood pressure or lipid lowering, antithrombotics, revascularisation, etc) aiming to reduce subsequent risk but which also confer risk, inconvenience and costs to the individual and/or the healthcare system. Better methods of risk stratifi cation are therefore of great interest.C reactive protein (CRP) is an infl ammatory marker associated with risk in people without CVD. 1 The review by Hemingway and colleagues aimed to consolidate the available evidence assessing CRP as a risk marker in people with coronary artery disease and to assess whether there was evidence of bias affecting the results. MethodsThis study is a systematic review of prospective observational studies reporting the association between CRP and death or CVD identifi ed from Medline and Embase. Studies were selected if participants had stable coronary artery disease, and were excluded if they measured CRP during admissions for acute coronary syndromes or revascularisation, as assessed by three reviewers. The outcomes assessed were clearly defi ned: coronary events, cardiovascular events and death. A random effects meta-analysis was performed, with additional sensitivity analyses to identify biases potentially affecting the results. Interestingly, the authors did not refer to the MOOSE guidelines 2 for systematic reviews of observational studies, although they were mostly followed. FindingsEighty-three studies including information on 6485 events among 61 485 patients were identifi ed, most of which did poorly on quality assessment. Overall, individuals in the top third of the CRP distribution had double the risk of an event compared with those in the lower third (HR 1.97, 95% CI 1.78 to 2.17), but there was evidence of considerable heterogeneity between studies (I 2 =79.5) and publication bias (Egger's test, p=0.001). Only 13 studies adjusted for conventional risk factors and the pooled estimate from those was 1.65 (95% CI 1.39 to 1.96). In some models adjusting for publication bias, the relationship was no longer statistically signifi cant. These fi ndings strongly support the notion that any true relationship between CRP and the risk of adverse outcomes in people with stable coronary disease has been overstated, and the value of measuring CRP in this population remains to be proven. Commentary on: Hemingway H, Philipson P, Chen R, et al. Evaluating the quality of research into a single prognostic biomarker: a systematic review and meta-analysis of 83 studies of C-Reactive protein in stable coronary artery disease. PLoS Med 2010;7:e1000286.

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Is This Clinical Trial Fully Registered? — A Statement from the International Committee of Medical Journal Editors

Cited by 279 publications

References 1 publication

Reporting of Negative Randomized Trials in Three Major Medical Journals

Reporting of Negative Randomized Trials in Three Major Medical Journals

Effect of Membrane Permeability on Cardiovascular Risk Factors and β2m Plasma Levels in Patients on Long-Term Haemodialysis: A Randomised Crossover Trial

Prognostic value of CRP in stable coronary artery disease unclear due to a variety of biases in existing studies, therefore no clinical practice recommendations can be made

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