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Rationale, aims and objectives Open-label extension (OLE) studies following blinded randomized controlled trials (RCTs) of pharmaceuticals are increasingly being carried out but do not conform to regulatory standards and questions surround the validity of their evidence. OLE studies are usually discussed as a homogenous group, yet substantial differences in study design still meet the definition of an OLE. We describe published papers reporting OLE studies focussing on stated objectives, design, conduct and reporting. Method A search of Embase and Medline databases for 1996 to July 2008 revealed 268 papers reporting OLE studies that met our eligibility criteria. A random sample of 50 was selected for detailed review. Results Over 80% of the studies had efficacy stated as an objective. The most common methods of allocation at the start of the OLE were for all RCT participants to switch to one active treatment or for only participants on the new drug to continue, but in three studies all participants were re-randomized at the start of the OLE. Eligibility criteria and other selection factors resulted in on average of 74% of participants in the preceding RCT(s) enrolling in the OLE and only 57% completed it. Conclusions Published OLE studies do not form a homogenous group with respect to design or retention of participants, and thus the validity of evidence from an OLE should be judged on an individual basis. The term 'open label' suggests bias through lack of blinding, but slippage in relation to the sample randomized in the preceding RCT may be the more important threat to validity. [ABSTRACT FROM AUTHOR]

Background Colorectal cancer (CRC) is one of the most common types of cancer in European countries and associated with a high mortality rate. A 16% relative risk reduction (RRR) of mortality was found in a meta-analysis based on four randomized controlled trials (RCT) on CRC screening. The aim of this paper was to scrutinize these trials for potential biases and assess their influence on the screening trials. Methods The four RCTs were reviewed based on the principles of 'Critical Appraisal of the Medical Literature'. Principal investigators of the four RCTs were contacted to clarify uncertainties in their study. Data were collected from The Danish Data Archives. Authors of the Cochrane review were contacted. Results Six biases were identified, of which five favour screening. Three of the biases identified were specific to CRC screening: type of diagnostic method, place of surgery and diagnostic delay. Conclusion The 16% RRR in CRC mortality found in the updated Cochrane review's meta-analysis is overestimated. [ABSTRACT FROM AUTHOR]

Rationale, aims, and objectives Long-term exposure to glucocorticoids can cause adverse drug reactions of long latency ( ADRLLs), including glucocorticoid-induced diabetes mellitus ( GID). Providers can monitor for GID using the glycosylated haemoglobin blood ( HbA1C) test. This study examined the utility of decisional support to improve HbA1C-based screening for GID. US veterans were identified as chronic users of oral glucocorticoids (>120 days of oral glucocorticoids in the last 2 years). The primary care providers caring for these patients were the target of the intervention. Providers were randomized to receive automatic HbA1C orders for their patients receiving chronic glucocorticoid or usual care. Methods This study was a pilot two-arm, group-randomized, controlled trial ( n = 12 providers, n = 38 patients). Data collection occurred from 5 May 2013 until 10 January 2014. A pharmacist generated the order for an HbA1C through the electronic medical record. The time between the intervention start date and the date on which an HbA1C order was signed were compared using Cox proportional and hierarchical linear regression. Results The time to sign HbA1C orders (mean 12.0 days for the intervention arm; 104.0 days for control arm) was associated with significant differences favouring the intervention [ HR (Hazard Ratio) 50.2, P < 0.001, confidence interval ( CI) 6.3 to 398.7]. For the intervention group, 95% of orders were signed, whereas only 12% of control providers signed orders (odds ratio 150, P < 0.001, CI 12.4 to 1812.9). Conclusions The results of this study strongly suggest that the clinical pharmacist-triggered order intervention is effective. This method of computerized decisional support may be useful in improving screening for GID and ADRLLs. [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives Systematic reviews, meta-analyses and clinical guidelines (reviews) are intended to inform clinical practice, and in this sense can be thought of as scientific truthmakers. High-quality controlled trials should align to this truth, and method quality markers should predict truth status. We sought to determine in what way controlled trial quality relates to scientific truth, and to determine predictive utility of trial quality and bibliographic markers. Method A sample of reviews in rehabilitation medicine was examined. Two scientific truth dimensions were established based on review outcomes. Quality and bibliographic markers were extracted from associated trials for use in a regression analysis of their predictive utility for trial truth status. Probability analysis was undertaken to examine judgments of future trial truth status. Results Of the 93 trials included in contemporaneous reviews, overall, n = 45 (48%) were true. Randomization was found more in true trials than false trials in one truth dimension ( P = 0.03). Intention-to-treat analysis was close to significant in one truth dimension ( P = 0.058), being more commonly used in false trials. There were no other significant differences in quality or bibliographic variables between true and false trials. Regression analysis revealed no significant predictors of trial truth status. Probability analysis reported that the reasonable chance of future trials being true was between 2 and 5%, based on a uniform prior. Conclusions The findings are at odds with what is considered gold-standard research methods, but in line with previous reports. Further work should focus on scientific dynamics within healthcare research and evidence-based practice constructs. [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives The accurate reporting of the trial methodology and results is essential for accurate judgement on the quality of the research. This review aims to assess the impact of the adequacy of allocation concealment on treatment effect estimates. Methods A search was performed in MEDLINE (via the Ovid platform) to identify all randomized controlled trials ( RCTs) indexed in January 2011 within its set of 'core clinical journals'. Meta-regression was undertaken on a subset of two arm trials to quantify the association between adequacy of allocation concealment and effect size. Results Adequate allocation concealment methods were used in 27% ( n = 23) of included trials. There was insufficient information given in 68% ( n = 58) of trials to make a judgement on allocation concealment. Meta-regression showed that there was a trend, not statistically significant, towards a smaller effect size between adequacy of allocation concealment and effect sizes. Conclusion This review highlighted that research needs to be reported to a higher standard and there are many trials reporting poor methods of allocation concealment within the small sample of trials included in this review. [ABSTRACT FROM AUTHOR]