Restoring invisible and abandoned trials: a call for people to publish the findings.
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ABSTRACT:
SUBMITTER: Doshi P
PROVIDER: S-EPMC3685516 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionGabapentin (Neurontin) is prescribed widely for conditions for which it has not been approved by regulators, including certain neuropathic pain conditions. There is limited evidence that gabapentin is safe and effective for the treatment of neuropathic pain. Published trial reports, and systematic reviews based on published trial reports, mislead patients and providers because information about gabapentin's harms has been published only partly. We confirmed that trials conducted by the drug developer have been abandoned, and we plan to conduct a restoration with support from the Restoring Invisible and Abandoned Trials Support Centre (https://restoringtrials.org/).Methods and analysisIn this study, we will analyse and report the harms that were observed in six trials of gabapentin, which have not been reported publicly (eg, in journal articles). We will use clinical study reports and individual participant data to identify and report the harms observed in each individual trial and to summarise the harms observed across all six trials. We will report all adverse events observed in the included trials by sharing deidentified data and summary tables on the Open Science Framework (https://osf.io/w8puv/). Additionally, we will produce a summary report that describes differences between the randomised groups in each trial and across trials for prespecified harms outcomes.Ethics and disseminationWe will use secondary data. This study was determined to be exempt from Institutional Review Board (IRB) review (protocol #1910607198).
| S-EPMC8246349 | biostudies-literature
Project description:The last 50 years have seen an impressive development of mathematical methods for the analysis and processing of digital images, mostly in the context of photography, biomedical imaging and various forms of engineering. The arts have been mostly overlooked in this process, apart from a few exceptional works in the last 10 years. With the rapid emergence of digitisation in the arts, however, the arts domain is becoming increasingly receptive to digital image processing methods and the importance of paying attention to this therefore increases. In this paper we discuss a range of mathematical methods for digital image restoration and digital visualisation for illuminated manuscripts. The latter provide an interesting opportunity for digital manipulation because they traditionally remain physically untouched. At the same time they also serve as an example for the possibilities mathematics and digital restoration offer as a generic and objective toolkit for the arts.
| S-EPMC6559148 | biostudies-literature
Project description:BACKGROUND:Growing evidence suggests that prolonged uninterrupted sitting can be detrimental to health. Much sedentary behaviour research is reliant on self-reports of sitting time, and sitting-reduction interventions often focus on reducing motivation to sit. These approaches assume that people are consciously aware of their sitting time. Drawing on Action Identification Theory, this paper argues that people rarely identify the act of sitting as 'sitting' per se, and instead view it as an incidental component of more meaningful and purposeful typically-seated activities. METHODS:Studies 1 and 2 explored whether people mentioned sitting in written descriptions of actions. Studies 3-5 compared preferences for labelling a typically desk-based activity as 'sitting' versus alternative action identities. Studies 6 and 7 used card-sort tasks to indirectly assess the prioritisation of 'sitting' relative to other action descriptions when identifying similar actions. RESULTS:Participants rarely spontaneously mentioned sitting when describing actions (Studies 1-2), and when assigning action labels to a seated activity, tended to offer descriptions based on higher-order goals and consequences of action, rather than sitting or other procedural elements (Studies 3-5). Participants primarily identified similarities in actions based not on sitting, but on activities performed while seated (e.g. reading; Studies 6-7). CONCLUSION:'Sitting' is a less accessible cognitive representation of seated activities than are representations based on the purpose and implications of seated action. Findings suggest that self-report measures should focus on time spent in seated activities, rather than attempting to measure sitting time via direct recall. From an intervention perspective, findings speak to the importance of targeting behaviours that entail sitting, and of raising awareness of sitting as a potential precursor to attempting to reduce sitting time.
| S-EPMC6790031 | biostudies-literature
Project description:BackgroundTo identify published letters to the editor (LTE) written in response to randomized controlled trials (RCTs), determine the topics addressed in the letters, and to examine if these topics were affected by the characteristics and results of the RCTs.MethodsComparative cross-sectional study of a representative sample of RCTs from a set of high-impact medical journals (BMJ, Lancet, NEJM, JAMA, and Annals of Internal Medicine). RCTs and their published LTE were searched from these 5 journals in 2007. Data were collected on RCTs and their characteristics (author affiliation, funding source, intervention, and effect on the primary outcome) and the topics addressed in published LTE related to these RCTs. Analysis included chi-square and regression analysis (RCT characteristics) and thematic analysis (LTE topics).ResultsOf 334 identified RCTs, 175 trials had at least one LTE. Of these, 381 published LTE were identified. Most RCTs, tested drug interventions (68%), were funded by government (54%) or industry (33%), and described an intervention that had a positive impact on the primary outcome (62%). RCT authors were primarily affiliated with an academic centre (78%). Ninety percent of the 623 LTE topics concerned methodological issues regarding the analysis, intervention, and population in the RCT. There was a significant association between funding source and impact on outcomes (p?=?0.002) or type of intervention tested (p?=?0.001) in these trials. Clinical and "Other" LTE topics were more likely to be published in response to a government funded RCT (p?=?0.005 and p?=?0.033, respectively); no other comparisons were significant.ConclusionsThis study showed that most LTE are about methodological topics, but found little evidence to support that these topics are affected by the characteristics or results of the RCTs. The lack of association may be explained by editorial censorship as a small proportion of LTE that are submitted are actually published.
| S-EPMC3852599 | biostudies-literature
Project description:The recent FDA approval of two drugs, pirfenidone and nintedanib, for the treatment of idiopathic pulmonary fibrosis (IPF) has fueled interest in the development of additional drugs to treat the disease or its major clinical complications including cough and acute exacerbations. Since 2015, there are at least a dozen active interventional studies that are testing the efficacy of novel pharmacotherapies, exercise or stem cells in modifying the disease process in IPF. Additionally, there are combinatorial studies evaluating the effectiveness of pirfenidone or nintedanib in combination with other agents. However, there remains an urgent need for clinical trials to prospectively evaluate the efficacy of existing drugs with promising retrospective data, such as proton pump inhibitors (PPIs), in IPF. Several retrospective cohorts have provided tantalizing data supporting the beneficial effect of PPIs in patients with well-defined IPF. This review provides the general outlook of pharmacotherapies in IPF, and highlights preclinical and retrospective clinical data to make a case for randomized controlled clinical trials of PPIs in IPF.
| S-EPMC5966555 | biostudies-literature
Project description:In response to the pressing need for more efficacious and safer therapeutics for endometriosis, there have been numerous reports in the last decade of positive results from animal and in vitro studies of various compounds as potential therapeutics for endometriosis. A handful of these have undergone phase II/III clinical trials. Since the announcement of the International Committee of Medical Journal Editors that mandated registration as a prerequisite for publication, 57 endometriosis-related clinical trials have been registered at ClinicalTrials.gov, an Internet-based public depository for information on drug studies. Among them, 25 are listed as completed, and 2 as suspended. There are 15 completed phase II/III trials, which evaluated the efficacy of various promising compounds. Yet only three of the 15 trials (20%) have published their results. The remaining 12 (80%) studies so far have not published their findings. We argue that this apparent lack of transparency will actually not benefit the trial sponsors or the public, and will ultimately prove detrimental to research efforts attempting to develop more efficacious and safer therapeutics for endometriosis. Thus we call for more transparency of clinical trials on endometriosis.
| S-EPMC4102915 | biostudies-literature
Project description:Common ALL (cALL) is the most frequent entity of childhood ALL and carries an early pre-B cell phenotype. Expression patterns of 25 pediatric cALL samples were analyzed by use of high-density DNA microarrays HG-U133A. Leukemic patients’ bone marrow samples were compared to sorted B cells from cord blood of healthy donors expressing CD19 and CD10 surface antigens. Differential gene expression profiling of pediatric cALL versus non-malignant tissues enabled the identification of aberrantly expressed genes in malignant cells, facilitating discrimination of leukemic from normal cells and possibly revealing specific disease mechanisms. Principal component analysis clearly distinguished leukemia samples from normal controls. Significance analysis of microarrays revealed 487 genes significantly up-regulated, and 572 down-regulated genes in leukemic cells. A comparison to previous publications investigating genetically defined subsets of cALL revealed 465 genes previously not associated with cALL. Interestingly, terminal deoxynucleotidyl-transferase (DNTT) as well as in the context of cALL unknown genes, were found to be the strongest predictive genes for the malignant phenotype signifying the diagnostic value of our approach.
2012-06-30 | GSE34670 | GEO
Project description: Not available
| S-EPMC1463958 | biostudies-literature
Project description:ObjectivesAn increasing number of abandoned clinical trials have forestalled efforts to advance the evidence base for the treatment of mood and anxiety disorders in children and adolescents. With this in mind, we sought to present and validate a Bayesian approach for the reanalysis of summary data in abandoned clinical trials and to review and re-evaluate available pharmacokinetic, tolerability, and efficacy data from two large, randomized controlled trials of buspirone in pediatric patients with generalized anxiety disorder (GAD).MethodsProspective, randomized, parallel-group controlled trials of buspirone in pediatric patients with GAD as well as associated pharmacokinetic studies were identified and data were extracted. In addition to descriptive statistics, marginal posterior densities for each variable of interest were determined and a Monte Carlo pseudosample was generated with random draws obtained from the Student's t-distribution to assess, with inferential statistics, differences in variables of interest.ResultsBuspirone was evaluated in one flexibly dosed (N?=?227) and one fixed-dose (N?=?341) trial in children and adolescents aged 6-17 years with a primary diagnosis of GAD. With regard to improvement in the sum of the Columbia Schedule for Affective Disorders and Schizophrenia GAD items, buspirone did not separate from placebo in the fixed-dose trial at low (95% CI: -0.78 to 2.39, p?=?0.32) or high dose (95% CI: -0.87 to 1.87, p?=?0.47) nor did it separate from placebo in the flexibly dosed study (95% CI: -0.3 to 1.9, p?=?0.15). Drop out as a result of a treatment-emergent adverse event was significantly greater in buspirone-treated patients compared to placebo (p?=?0.011). Side effects were consistent with the known profile of buspirone with lightheadedness occurring more frequently in buspirone-treated patients (p?<?0.001).ConclusionsBuspirone is well tolerated in pediatric patients with GAD, although two randomized controlled trials were underpowered to detect small effect sizes (Cohen's d?<?0.15). Finally, Bayesian approaches may facilitate re-examination of data from abandoned clinical trials.
| S-EPMC5771537 | biostudies-literature
Project description:ObjectivesThe HIV epidemic in India is concentrated in key populations such as people who inject drugs (PWID). New HIV infections are high among young PWID (≤30 years of age), who are hard to engage in services. We assessed perspectives of young PWID to guide development of youth-specific services.SettingWe conducted focus group discussions (FGDs) with PWID and staff at venues offering services to PWID in three Indian cities representing historical and emerging drug use epidemics.ParticipantsPWID were eligible to participate if they were between 18 and 35 years, had initiated injection as adolescents or young adults and knew adolescent PWID in their networks. 43 PWID (81% male, 19% female) and 10 staff members participated in FGDs. A semistructured interview guide was used to elicit participants' narratives on injection initiation experiences, barriers to seeking harm reduction services, service delivery gaps and recommendations to promote engagement. Thematic analysis was used to develop an explanatory model for service engagement in each temporal stage across the injection continuum.ResultsInjection initiation followed non-injection opioid dependence. Lack of services for non-injection opioid dependence was a key gap in the preinjection initiation phase. Lack of knowledge and reliance on informal sources for injecting equipment were key reasons for non-engagement in the peri-injection phase. Additionally, low-risk perception resulted in low motivation to seek services. Psychosocial and structural factors shaped engagement after established injection. Housing and food insecurity, and stigma disproportionately affected female PWID while lack of confidential adolescent friendly services impeded engagement by adolescent PWID.ConclusionsDevelopment of youth-specific services for young PWID in India will need to address unique vulnerabilities and service gaps along each stage of the injection continuum. Scaling-up of tailored services is needed for young female PWID and adolescents, including interventions that prevent injection initiation and provision of confidential harm reduction services.
| S-EPMC8458355 | biostudies-literature