Dataset Information

Rates of Discontinuation and Nonpublication of Head and Neck Cancer Randomized Clinical Trials.

ABSTRACT:

Importance

Randomized clinical trials (RCTs) play an important role in clinical decision-making, and discontinuation or nonpublication of these trials are causes of great concern. The extent of discontinued or unpublished RCTs about head and neck cancer remains unclear.

Objective

To assess the rate of discontinuation or nonpublication of RCTs involving patients with head and neck cancer. This objective was measured by observing 3 domains: discontinuation of trial, nonpublication of trial data, and feasibility of contacting trial investigators of aforementioned trials.

Evidence review

For this study, the sample was derived using the ClinicalTrials.gov advanced search feature on March 18, 2019, to locate completed and discontinued RCTs pertaining to head and neck cancer registered before this date. Trials were analyzed to identify reasons for trial discontinuation and publication status of each trial. If publication status or reason for trial discontinuation was not allocated through the systematic search of ClinicalTrials.gov, the corresponding author was emailed to determine publication status.

Findings

After exclusions, 130 RCTs were included. Of these trials, 92 (70.8%) were completed and 38 (29.2%) were discontinued for various reasons. The most common reason for discontinuation of trials was committee recommendations. Of the 130 analyzed trials, 67 (51.5%) were published in a peer-reviewed journal and 63 (48.5%) were unpublished trials. Of the 92 completed trials, 55 (59.8%) were published and 37 (40.2%) remained unpublished 3 or more years after trial completion. Trials funded by other sources (private, nonprofit, or the National Institutes of Health) were more likely to reach publication than industry-funded RCTs (unadjusted odds ratio, 4.3 [95% CI, 1.3-14.0]; adjusted odds ratio, 4.1 [95% CI, 1.2-14.3]).

Conclusions and relevance

Of RCTs in head and neck cancer, 29.2% were discontinued and 40.2% completed trials never reached publication. The findings suggest that needs exist for RCT guidance of head and neck cancer. The reporting of reasons for trial discontinuation appears to be lacking, and trial publication rates were low. This study is relevant to many physicians and researchers because it identifies potential sources of decreased research productivity and ethics.

SUBMITTER: Johnson AL

PROVIDER: S-EPMC6990718 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Rates of Discontinuation and Nonpublication of Head and Neck Cancer Randomized Clinical Trials.

Johnson Austin L AL Fladie Ian I Anderson J Michael JM Lewis David M DM Mons Bradley R BR Vassar Matt M

JAMA otolaryngology-- head & neck surgery 20200201 2

<h4>Importance</h4>Randomized clinical trials (RCTs) play an important role in clinical decision-making, and discontinuation or nonpublication of these trials are causes of great concern. The extent of discontinued or unpublished RCTs about head and neck cancer remains unclear.<h4>Objective</h4>To assess the rate of discontinuation or nonpublication of RCTs involving patients with head and neck cancer. This objective was measured by observing 3 domains: discontinuation of trial, nonpublication o ...[more]

PMID: 31876933

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Project description:BackgroundWe previously found that 25% of 1,017 randomized clinical trials (RCTs) approved between 2000 and 2003 were discontinued prematurely, and 44% remained unpublished at a median of 12 years follow-up. We aimed to assess a decade later (1) whether rates of completion and publication have increased; (2) the extent to which nonpublished RCTs can be identified in trial registries; and (3) the association between reporting quality of protocols and premature discontinuation or nonpublication of RCTs.Methods and findingsWe included 326 RCT protocols approved in 2012 by research ethics committees in Switzerland, the United Kingdom, Germany, and Canada in this metaresearch study. Pilot, feasibility, and phase 1 studies were excluded. We extracted trial characteristics from each study protocol and systematically searched for corresponding trial registration (if not reported in the protocol) and full text publications until February 2022. For trial registrations, we searched the (i) World Health Organization: International Clinical Trial Registry Platform (ICTRP); (ii) US National Library of Medicine (ClinicalTrials.gov); (iii) European Union Drug Regulating Authorities Clinical Trials Database (EUCTR); (iv) ISRCTN registry; and (v) Google. For full text publications, we searched PubMed, Google Scholar, and Scopus. We recorded whether RCTs were registered, discontinued (including reason for discontinuation), and published. The reporting quality of RCT protocols was assessed with the 33-item SPIRIT checklist. We used multivariable logistic regression to examine the association between the independent variables protocol reporting quality, planned sample size, type of control (placebo versus other), reporting of any recruitment projection, single-center versus multicenter trials, and industry versus investigator sponsoring, with the 2 dependent variables: (1) publication of RCT results; and (2) trial discontinuation due to poor recruitment. Of the 326 included trials, 19 (6%) were unregistered. Ninety-eight trials (30%) were discontinued prematurely, most often due to poor recruitment (37%; 36/98). One in 5 trials (21%; 70/326) remained unpublished at 10 years follow-up, and 21% of unpublished trials (15/70) were unregistered. Twenty-three of 147 investigator-sponsored trials (16%) reported their results in a trial registry in contrast to 150 of 179 industry-sponsored trials (84%). The median proportion of reported SPIRIT items in included RCT protocols was 69% (interquartile range 61% to 77%). We found no variables associated with trial discontinuation; however, lower reporting quality of trial protocols was associated with nonpublication (odds ratio, 0.71 for each 10% increment in the proportion of SPIRIT items met; 95% confidence interval, 0.55 to 0.92; p = 0.009). Study limitations include that the moderate sample size may have limited the ability of our regression models to identify significant associations.ConclusionsWe have observed that rates of premature trial discontinuation have not changed in the past decade. Nonpublication of RCTs has declined but remains common; 21% of unpublished trials could not be identified in registries. Only 16% of investigator-sponsored trials reported results in a trial registry. Higher reporting quality of RCT protocols was associated with publication of results. Further efforts from all stakeholders are needed to improve efficiency and transparency of clinical research.

Project description:BACKGROUND:Clinical trials are key to advancing evidence-based medical research. The medical research literature has identified the impact of publication bias in clinical trials. Selective publication for positive outcomes or nonpublication of negative results could misdirect subsequent research and result in literature reviews leaning toward positive outcomes. Digital health trials face specific challenges, including a high attrition rate, usability issues, and insufficient formative research. These challenges may contribute to nonpublication of the trial results. To our knowledge, no study has thus far reported the nonpublication rates of digital health trials. OBJECTIVE:The primary research objective was to evaluate the nonpublication rate of digital health randomized clinical trials registered in ClinicalTrials.gov. Our secondary research objective was to determine whether industry funding contributes to nonpublication of digital health trials. METHODS:To identify digital health trials, a list of 47 search terms was developed through an iterative process and applied to the "Title," "Interventions," and "Outcome Measures" fields of registered trials with completion dates between April 1, 2010, and April 1, 2013. The search was based on the full dataset exported from the ClinlicalTrials.gov database, with 265,657 trials entries downloaded on February 10, 2018, to allow publication of studies within 5 years of trial completion. We identified publications related to the results of the trials through a comprehensive approach that included an automated and manual publication-identification process. RESULTS:In total, 6717 articles matched the a priori search terms, of which 803 trials matched our latest completion date criteria. After screening, 556 trials were included in this study. We found that 150 (27%) of all included trials remained unpublished 5 years after their completion date. In bivariate analyses, we observed statistically significant differences in trial characteristics between published and unpublished trials in terms of the intervention target condition, country, trial size, trial phases, recruitment, and prospective trial registration. In multivariate analyses, differences in trial characteristics between published and unpublished trials remained statistically significant for the intervention target condition, country, trial size, trial phases, and recruitment; the odds of publication for non-US-based trials were significant, and these trials were 3.3 (95% CI 1.845-5.964) times more likely to be published than US-based trials. We observed a trend of 1.5 times higher nonpublication rates for industry-funded trials. However, the trend was not statistically significant. CONCLUSIONS:In the domain of digital health, 27% of registered clinical trials results are unpublished, which is lower than nonpublication rates in other fields. There are substantial differences in nonpublication rates between trials funded by industry and nonindustry sponsors. Further research is required to define the determinants and reasons for nonpublication and, more importantly, to articulate the impact and risk of publication bias in the field of digital health trials.

Project description:IntroductionPatient adherence to therapy in clinical practice is often low, and the difference between efficacy measured in clinical trials and effectiveness in clinical practice is probably a function of discontinuation of therapy because of lack of efficacy or because of unmanageable or intolerable adverse events. Discontinuation is frequently measured in clinical trials but is not usually described in detail in published reports, often because of limitations in the size of publications. By contrast, company clinical trial reports include much more detail.MethodsWe examined company clinical trial reports of trials involving etoricoxib in four musculoskeletal conditions: osteoarthritis, rheumatoid arthritis, chronic low back pain and ankylosing spondylitis. Information was available from 18 randomized trials (10,143 patients) lasting 4 to 12 weeks (one 4 weeks, three 6 weeks, one 8 weeks and seven 12 weeks) and from three trials with a mean duration of about 80 weeks (34,695 patients). These clinical trial reports contain over 73,000 pages of information.ResultsOver 12 weeks, lack of efficacy and adverse event discontinuations were similar between osteoarthritis, rheumatoid arthritis and back pain, with lack of efficacy discontinuation rates some three times higher than for adverse events. All-cause and lack of efficacy discontinuations were lower with etoricoxib (all doses combined) and traditional nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) than with placebo, although NSAIDs produced higher rates of clinical adverse events and gastrointestinal discontinuations than did placebo. Etoricoxib had fewer discontinuations than NSAIDs for lack of efficacy, clinical adverse events, and laboratory and gastrointestinal adverse events, but with more discontinuations because of hypertension and oedema. Comparison with two similar meta-analyses of other cyclo-oxygenase-2 selective inhibitors (more than 80,000 patients in total) revealed consistency between analyses.ConclusionExamining discontinuation data from clinical trials, even when the numbers of patients are very large, does not necessarily predict what will happen in the real world, where clinical effectiveness may differ from clinical efficacy assessed in trials. Data from these analyses appears to agree with findings from real world practice.

Project description:BackgroundCurrent treatment for head and neck cancers (HNCs) have led to an improved survival. However, the sequelae of cancer treatment often result in trismus, or reduced mouth opening. The purpose of this report is to identify interventional studies for trismus management in HNC patients.MethodsA search of PubMed, Embase, Cumulated Index to Nursing and Allied Health Literature, and the Cochrane Library was conducted in March 2020 for randomized controlled trials (RCTs) involving interventions for trismus for head and neck cancer within 10 years. Intervention could involve the use of an exercise regime, jaw rehabilitation device, technological device, medication or massage therapy. The primary outcome was the measurement of mouth opening.ResultsEleven RCTs involving a total of 685 patients with HNC were included. Six RCTs evaluated the effectiveness of a jaw mobilization device with exercises; there was no significant benefit of an exercise regime with a jaw mobilization device either initiated before, during or after treatment compared to no exercise. Two RCTs compared 2 intervention groups that involved exercises only, with 1 study assessing the benefit of weekly supervised physical therapy with gum chewing and another evaluating the benefit of immediate (1-2 days) versus delayed (7-10 days) initiation of exercise post-surgery; there was no significant difference between groups in either study. One RCT that recruited only patients with trismus demonstrated that an exercise regime in combination with low-level laser therapy or low-intensity ultrasound had superior results in mouth opening measurements compared to exercise alone. Two RCTs compared intervention groups with and without follow-up reminders; both studies showed a significant improvement in mouth opening measurements in groups with follow-up reminders.ConclusionThis systematic review did not convey a clear consensus as to optimal intervention for trismus in HNC patients. A variety of exercise regimens and jaw rehabilitation devices appear to have comparable effectiveness. However, efforts focused on increasing adherence to a particular intervention protocol may positively impact mouth opening measures in head and neck cancer patients. Also, low-level laser therapy and low-intensity ultrasound coupled with exercise may be beneficial for patients with trismus.

Dataset Information

Rates of Discontinuation and Nonpublication of Head and Neck Cancer Randomized Clinical Trials.

Importance

Objective

Evidence review

Findings

Conclusions and relevance

Publications

Rates of Discontinuation and Nonpublication of Head and Neck Cancer Randomized Clinical Trials.

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