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Journal ArticleDOI

Trial Publication after Registration in ClinicalTrials.Gov: A Cross-Sectional Analysis

TL;DR: Joseph Ross and colleagues examine publication rates of clinical trials and find low rates of publication even following registration in Clinicaltrials.gov.
Abstract: Background ClinicalTrials.gov is a publicly accessible, Internet-based registry of clinical trials managed by the US National Library of Medicine that has the potential to address selective trial publication. Our objectives were to examine completeness of registration within ClinicalTrials.gov and to determine the extent and correlates of selective publication.

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Citations
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Journal ArticleDOI
09 Jan 2013-BMJ
TL;DR: The SPIRIT 2013 Explanation and Elaboration paper provides important information to promote full understanding of the checklist recommendations and strongly recommends that this explanatory paper be used in conjunction with the SPIRit Statement.
Abstract: High quality protocols facilitate proper conduct, reporting, and external review of clinical trials. However, the completeness of trial protocols is often inadequate. To help improve the content and quality of protocols, an international group of stakeholders developed the SPIRIT 2013 Statement (Standard Protocol Items: Recommendations for Interventional Trials). The SPIRIT Statement provides guidance in the form of a checklist of recommended items to include in a clinical trial protocol. This SPIRIT 2013 Explanation and Elaboration paper provides important information to promote full understanding of the checklist recommendations. For each checklist item, we provide a rationale and detailed description; a model example from an actual protocol; and relevant references supporting its importance. We strongly recommend that this explanatory paper be used in conjunction with the SPIRIT Statement. A website of resources is also available (www.spirit-statement.org). The SPIRIT 2013 Explanation and Elaboration paper, together with the Statement, should help with the drafting of trial protocols. Complete documentation of key trial elements can facilitate transparency and protocol review for the benefit of all stakeholders.

3,108 citations

Journal ArticleDOI
TL;DR: Three main actions are warranted: academic institutions and funders should reward investigators who fully disseminate their research protocols, reports, and participant-level datasets, and standards for the content of protocols and full study reports should be rigorously developed and adopted for all types of health research.

668 citations

Journal ArticleDOI
TL;DR: The structure and contents of the results database are summarized, an update of relevant policies are provided, and how the data can be used to gain insight into the state of clinical research are shown.
Abstract: BACKGROUND The ClinicalTrials.gov trial registry was expanded in 2008 to include a database for reporting summary results. We summarize the structure and contents of the results database, provide an update of relevant policies, and show how the data can be used to gain insight into the state of clinical research. METHODS We analyzed ClinicalTrials.gov data that were publicly available between September 2009 and September 2010. RESULTS As of September 27, 2010, ClinicalTrials.gov received approximately 330 new and 2000 revised registrations each week, along with 30 new and 80 revised results submissions. We characterized the 79,413 registry and 2178 results of trial records available as of September 2010. From a sample cohort of results records, 78 of 150 (52%) had associated publications within 2 years after posting. Of results records available publicly, 20% reported more than two primary outcome measures and 5% reported more than five. Of a sample of 100 registry record outcome measures, 61% lacked specificity in describing the metric used in the planned analysis. In a sample of 700 results records, the mean number of different analysis populations per study group was 2.5 (median, 1; range, 1 to 25). Of these trials, 24% reported results for 90% or less of their participants. CONCLUSIONS ClinicalTrials.gov provides access to study results not otherwise available to the public. Although the database allows examination of various aspects of ongoing and completed clinical trials, its ultimate usefulness depends on the research community to submit accurate, informative data.

632 citations

Journal ArticleDOI
03 Jan 2012-BMJ
TL;DR: Pattern of publication of clinical trials funded by US National Institutes of Health in peer reviewed biomedical journals indexed by Medline is reviewed to review patterns of publication in the biomedical literature, as determined through Medline searches, the last of which was performed in June 2011.
Abstract: Objective To review patterns of publication of clinical trials funded by US National Institutes of Health (NIH) in peer reviewed biomedical journals indexed by Medline. Design Cross sectional analysis. Setting Clinical trials funded by NIH and registered within ClinicalTrials.gov (clinicaltrials.gov), a trial registry and results database maintained by the US National Library of Medicine, after 30 September 2005 and updated as having been completed by 31 December 2008, allowing at least 30 months for publication after completion of the trial. Main outcome measures Publication and time to publication in the biomedical literature, as determined through Medline searches, the last of which was performed in June 2011. Results Among 635 clinical trials completed by 31 December 2008, 294 (46%) were published in a peer reviewed biomedical journal, indexed by Medline, within 30 months of trial completion. The median period of follow-up after trial completion was 51 months (25th-75th centiles 40-68 months), and 432 (68%) were published overall. Among published trials, the median time to publication was 23 months (14-36 months). Trials completed in either 2007 or 2008 were more likely to be published within 30 months of study completion compared with trials completed before 2007 (54% (196/366) v 36% (98/269); P Conclusions Despite recent improvement in timely publication, fewer than half of trials funded by NIH are published in a peer reviewed biomedical journal indexed by Medline within 30 months of trial completion. Moreover, after a median of 51 months after trial completion, a third of trials remained unpublished.

336 citations

Journal ArticleDOI
TL;DR: Characteristics of drug trials listed in ClinicalTrials.gov are described and those funded by industry were less likely to be published within 2 years of study completion and were more likely to report positive outcomes than were trials funded by other sources.
Abstract: This study examined associations between the funding sources of 546 registered trials of drugs in 5 commonly prescribed classes and published outcomes that favored the new intervention over the con...

295 citations


Cites background from "Trial Publication after Registratio..."

  • ...Tracking the existence of clinical trials and a priori primary outcome measures provides the potential to monitor the selective publication of trials and trial results (5, 6)....

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  • ...Concern remains that certain data, including descriptions of primary outcomes, are insufficiently detailed, but the use of these trial records already allows identification of inconsistencies between data elements reported in the registry and those reported in the final article (5, 6)....

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References
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Journal ArticleDOI
TL;DR: Patients and providers should consider the potential for serious adverse cardiovascular effects of treatment with rosiglitazone for type 2 diabetes mellitus as well as the availability of outcome data for myocardial infarction and death from cardiovascular causes.
Abstract: �Rosiglitazone was associated with a significant increase in the risk of myocardial infarction and with an increase in the risk of death from cardiovascular causes that had borderline significance. Our study was limited by a lack of access to original source data, which would have enabled time-to-event analysis. Despite these limitations, patients and providers should consider the potential for serious adverse cardiovascular effects of treatment with rosiglitazone for type 2 diabetes.

4,570 citations


"Trial Publication after Registratio..." refers background in this paper

  • ...Similarly unpublished clinical trials of rosiglitazone [3] identified from a company-maintained website and of erythropoiesis-stimulating agents [4] and antidepressants [5] found among data submitted to the FDA revealed important efficacy and safety information to be missing from the medical literature....

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  • ...Other evidence concerning selective publication is anecdotal, such as the absence of 6 mo of trial data from a key publication describing the efficacy of celecoxib [25,26], the delay of publication for two early trials of rofecoxib until after the medication was withdrawn from the market [27–29], and the aforementioned studies of rosiglitazone [3], erythropoiesis-stimulating agents [4], and antidepressants [5]....

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Journal ArticleDOI
13 Sep 2000-JAMA
TL;DR: In this study, celecoxib, at dosages greater than those indicated clinically, was associated with a lower incidence of symptomatic ulcers and ulcer complications combined, as well as other clinically important toxic effects, compared with NSAIDs at standard dosages.
Abstract: ContextConventional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a spectrum of toxic effects, notably gastrointestinal (GI) effects, because of inhibition of cyclooxygenase (COX)-1. Whether COX-2–specific inhibitors are associated with fewer clinical GI toxic effects is unknown.ObjectiveTo determine whether celecoxib, a COX-2–specific inhibitor, is associated with a lower incidence of significant upper GI toxic effects and other adverse effects compared with conventional NSAIDs.DesignThe Celecoxib Long-term Arthritis Safety Study (CLASS), a double-blind, randomized controlled trial conducted from September 1998 to March 2000.SettingThree hundred eighty-six clinical sites in the United States and Canada.ParticipantsA total of 8059 patients (≥18 years old) with osteoarthritis (OA) or rheumatoid arthritis (RA) were enrolled in the study, and 7968 received at least 1 dose of study drug. A total of 4573 patients (57%) received treatment for 6 months.InterventionsPatients were randomly assigned to receive celecoxib, 400 mg twice per day (2 and 4 times the maximum RA and OA dosages, respectively; n = 3987); ibuprofen, 800 mg 3 times per day (n = 1985); or diclofenac, 75 mg twice per day (n = 1996). Aspirin use for cardiovascular prophylaxis (≤325 mg/d) was permitted.Main Outcome MeasuresIncidence of prospectively defined symptomatic upper GI ulcers and ulcer complications (bleeding, perforation, and obstruction) and other adverse effects during the 6-month treatment period.ResultsFor all patients, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.76% vs 1.45% (P = .09) and 2.08% vs 3.54% (P = .02), respectively. For patients not taking aspirin, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.44% vs 1.27% (P = .04) and 1.40% vs 2.91% (P = .02). For patients taking aspirin, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 2.01% vs 2.12% (P = .92) and 4.70% vs 6.00% (P = .49). Fewer celecoxib-treated patients than NSAID-treated patients experienced chronic GI blood loss, GI intolerance, hepatotoxicity, or renal toxicity. No difference was noted in the incidence of cardiovascular events between celecoxib and NSAIDs, irrespective of aspirin use.ConclusionsIn this study, celecoxib, at dosages greater than those indicated clinically, was associated with a lower incidence of symptomatic ulcers and ulcer complications combined, as well as other clinically important toxic effects, compared with NSAIDs at standard dosages. The decrease in upper GI toxicity was strongest among patients not taking aspirin concomitantly.

3,213 citations

Journal ArticleDOI
TL;DR: The presence of publication bias in a cohort of clinical research studies is confirmed and it is suggested that conclusions based only on a review of published data should be interpreted cautiously, especially for observational studies.

2,800 citations


"Trial Publication after Registratio..." refers background in this paper

  • ...Many studies have attempted to evaluate the extent of selective publication in the biomedical literature and found similarly low rates of publication [5,12–24], although none have used, to our knowledge, as large and as broadly representative a registry as ClinicalTrials....

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Journal ArticleDOI
TL;DR: A systematic literature search found that among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published, and the increase in effect size ranged from 11 to 69% for individual drugs and was 32% overall.
Abstract: Background Evidence-based medicine is valuable to the extent that the evidence base is complete and unbiased. Selective publication of clinical trials — and the outcomes within those trials — can lead to unrealistic estimates of drug effectiveness and alter the apparent risk–benefit ratio. Methods We obtained reviews from the Food and Drug Administration (FDA) for studies of 12 antidepressant agents involving 12,564 patients. We conducted a systematic literature search to identify matching publications. For trials that were reported in the literature, we compared the published outcomes with the FDA outcomes. We also compared the effect size derived from the published reports with the effect size derived from the entire FDA data set. Results Among 74 FDA-registered studies, 31%, accounting for 3449 study participants, were not published. Whether and how the studies were published were associated with the study outcome. A total of 37 studies viewed by the FDA as having positive results were published; 1 stu...

2,176 citations


"Trial Publication after Registratio..." refers background or result in this paper

  • ...Similarly unpublished clinical trials of rosiglitazone [3] identified from a company-maintained website and of erythropoiesis-stimulating agents [4] and antidepressants [5] found among data submitted to the FDA revealed important efficacy and safety information to be missing from the medical literature....

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  • ...Given the documented presence of outcome reporting bias among trials studied in other settings [5,12,13], the potential impact of ClinicalTrials....

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  • ...Other evidence concerning selective publication is anecdotal, such as the absence of 6 mo of trial data from a key publication describing the efficacy of celecoxib [25,26], the delay of publication for two early trials of rofecoxib until after the medication was withdrawn from the market [27–29], and the aforementioned studies of rosiglitazone [3], erythropoiesis-stimulating agents [4], and antidepressants [5]....

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Journal ArticleDOI
29 May 2003-BMJ
TL;DR: Investigating whether funding of drug studies by the pharmaceutical industry is associated with outcomes that are favourable to the funder and whether the methods of trials funded by pharmaceutical companies differ from the methods in trials with other sources of support found systematic bias favours products which are made by the company funding the research.
Abstract: Objective To investigate whether funding of drug studies by the pharmaceutical industry is associated with outcomes that are favourable to the funder and whether the methods of trials funded by pharmaceutical companies differ from the methods in trials with other sources of support Methods Medline (January 1966 to December 2002) and Embase (January 1980 to December 2002) searches were supplemented with material identified in the references and in the authors' personal files Data were independently abstracted by three of the authors and disagreements were resolved by consensus Results 30 studies were included Research funded by drug companies was less likely to be published than research funded by other sources Studies sponsored by pharmaceutical companies were more likely to have outcomes favouring the sponsor than were studies with other sponsors (odds ratio 405; 95% confidence interval 298 to 551; 18 comparisons) None of the 13 studies that analysed methods reported that studies funded by industry was of poorer quality Conclusion Systematic bias favours products which are made by the company funding the research Explanations include the selection of an inappropriate comparator to the product being investigated and publication bias

1,917 citations


"Trial Publication after Registratio..." refers result in this paper

  • ...However, we also found significantly different publication rates among study types and primary sponsors, consistent with prior research [11]....

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