Current Controlled Trials: an opportunity to help improve the quality of clinical research

Some problems with the quality of controlled clinical trials can be addressed by following these procedures: registering all trials at inception; using systematic reviews to inform the design of new studies; posting and obtaining feedback on preprints; reporting all well conducted trials, regardless of their results; reducing biased and inefficient assessment of reports submitted for publication; publishing sufficiently detailed reports; linking trial reports to relevant external information; providing readier access to reports; and reviewing and amending reports after initial publication. The launch of a new range of electronic journals by Current Controlled Trials offers an opportunity to contribute to progress in these ways

Castleman disease and lymphocytic interstitial pneumonia: a complex diagnostic and management challenge

No abstract available

Should there be greater use of preprint servers for publishing reports of biomedical science?

Vitek Tracz and Rebecca Lawrence declare the current journal publishing system to be broken beyond repair. They propose that it should be replaced by immediate publication followed by transparent peer review as the starting place for more open and efficient reporting of science. While supporting this general objective, we suggest that research is needed both to understand why biomedical scientists have been slow to take up preprint options, as well as to assess the relative merits of this and other alternatives to journal publishing

Focus on sharing individual patient data distracts from other ways of improving trial transparency

The International Committee of Medical Journal Editors (ICMJE) recently reiterated its commitment to improving trial transparency by sharing individual patient data from randomised trials.1 2 But, although sharing individual patient data contributes to transparency, it is not sufficient by itself. Trial transparency requires a data sharing package, which begins with trial registration and contains other elements such as protocols, summary results, and other trial materials. Valuable as sharing individual patient data can be,3 discussion about it has hijacked the broader conversation about data sharing and trial transparency.4-6 For example, we identified 76 articles published in the six leading general medical journals that had “data” and “sharing” in their title and were about clinical trials. In 64 (84%) articles, the content was focused on individual patient data and did not mention any of the other components of trial transparency (see appendix on bmj.com). Much of the discussion has focused on the complexities and practical problems associated with sharing individual patient data and on the processes and systems needed for responsible data sharing.6-9 However, many of the data sharing activities that are needed for trial transparency are not complex. We believe that trying to solve the complex issues around availability of individual patient data should not eclipse or distract from a more pressing problem: the unavailability of even summary data and protocols from all controlled trials. Current estimates are that around 85% of research is avoidably “wasted” because of design flaws, poor conduct, non-publication, and poor reporting.10 Focusing efforts and attention on making individual patient data accessible might paradoxically exacerbate this waste in research. We argue that simpler and more cost efficient activities should be prioritised.</p

Seventy-Five Trials and Eleven Systematic Reviews a Day: How Will We Ever Keep Up?

Hilda Bastian and colleagues examine the extent to which critical summaries of clinical trials can be used by health professionals and the public

Educational interventions to improve people's understanding of key concepts in assessing the effects of health interventions: a systematic review

Abstract Background Health information is readily accessible but is of variable quality. General knowledge about how to assess whether claims about health interventions are trustworthy is not common, so people’s health decisions can be ill-informed, unnecessarily costly and even unsafe. This review aims to identify and evaluate studies of educational interventions designed to improve people’s understanding of key concepts for evaluating claims about the effects of health interventions. Methods/Design We searched multiple electronic databases and sources of grey literature. Inclusion criteria included all study types that included a comparison, any participants (except health professionals or health professional students) and educational interventions aimed at improving people’s understanding of one or more of the key concepts considered necessary for assessing health intervention claims. Knowledge and/or understanding of concepts or skills relevant to evaluating health information were our primary outcome measures. Secondary outcomes included behaviour, confidence, attitude and satisfaction with the educational interventions. Two authors independently screened search results, assessed study eligibility and risk of bias and extracted data. Results were summarised using descriptive synthesis. Results Among 24 eligible studies, 14 were randomised trials and 10 used other study designs. There was heterogeneity across study participants, settings and educational intervention type, content and delivery. The risk of bias was high in at least one domain for all randomised studies. Most studies measured outcomes immediately after the educational intervention, with few measuring later. In most of the comparisons, measures of knowledge and skills were better among those who had received educational interventions than among controls, and some of these differences were statistically significant. The effects on secondary outcomes were inconsistent. Conclusions Educational interventions to improve people’s understanding of key concepts for evaluating health intervention claims can improve people’s knowledge and skills, at least in the short term. Effects on confidence, attitude and behaviour are uncertain. Many of the studies were at moderate or greater risk of bias. Improvements in study quality, consistency of outcome measures and measures of longer-term effects are needed to improve confidence in estimates of the effects of educational interventions to improve people’s understanding of key concepts for evaluating health intervention claims. Systematic review registration PROSPERO CRD4201603310

The quality of reports of medical and public health research from Palestinian institutions:A systematic review

Research reports are the most common way to communicate research findings for target readerships. Complete, accurate and transparent reporting of research studies facilitates dissemination, interpretation, translation and replication of research findings. Inadequate reporting has major consequences for clinicians, researchers, policy makers and ultimately patients. It impairs critical assessment of the validity, relevance and trustworthiness of research and so impedes its use in practice. It also limits the usability of study findings by other researchers conducting systematic reviews and meta-analyses and building on or replicating studies. In addition, inadequate reporting is one of the key contributors to avoidable waste in biomedical research. Researchers thus have an ethical obligation to research participants, funding organisations and society as a whole to report their findings in ways that are of use in practice and policy makin

Erratum to ‘Combining bioinformatics, cheminformatics, functional genomics and whole organism approaches for identifying epigenetic drug targets in Schistosoma mansoni’:[IJP Drugs Drug Resist. 8 (2018) 559–570]

Schistosomiasis endangers the lives of greater than 200 million people every year and is predominantly controlled by a single class chemotherapy, praziquantel (PZQ). Development of PZQ replacement (to combat the threat of PZQ insensitivity/resistance arising) or combinatorial (to facilitate the killing of PZQ-insensitive juvenile schistosomes) chemotherapies would help sustain this control strategy into the future. Here, we re-categorise two families of druggable epigenetic targets in Schistosoma mansoni, the histone methyltransferases (HMTs) and the histone demethylases (HDMs). Amongst these, a S. mansoni Lysine Specific Demethylase 1 (SmLSD1, Smp_150560) homolog was selected for further analyses. Homology modelling of SmLSD1 and in silico docking of greater than four thousand putative inhibitors identified seven (L1 – L7) showing more favourable binding to the target pocket of SmLSD1 vs Homo sapiens HsLSD1; six of these seven (L1 – L6) plus three structural analogues of L7 (L8 – L10) were subsequently screened against schistosomula using the Roboworm anthelmintic discovery platform. The most active compounds (L10 - pirarubicin > L8 – danunorubicin hydrochloride) were subsequently tested against juvenile (3 wk old) and mature (7 wk old) schistosome stages and found to impede motility, suppress egg production and affect tegumental surfaces. When compared to a surrogate human cell line (HepG2), a moderate window of selectivity was observed for the most active compound L10 (selectivity indices - 11 for schistosomula, 9 for juveniles, 1.5 for adults). Finally, RNA interference of SmLSD1 recapitulated the egg-laying defect of schistosomes co-cultivated in the presence of L10 and L8. These preliminary results suggest that SmLSD1 represents an attractive new target for schistosomiasis; identification of more potent and selective SmLSD1 compounds, however, is essential. Nevertheless, the approaches described herein highlight an interdisciplinary strategy for selecting and screening novel/repositioned anti-schistosomals, which can be applied to any druggable (epigenetic) target encoded by the parasite's genome. Keywords: Anthelmintic drug discovery, Neglected tropical diseases, Schistosoma mansoni, Epigenetics, Lysine specific demethylas