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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]

Rationale, aims and objectives Clinical nurse specialists ( CNSs) are major providers of transitional care. This paper describes a systematic review of randomized controlled trials ( RCTs) evaluating the clinical effectiveness and cost-effectiveness of CNS transitional care. Methods We searched 10 electronic databases, 1980 to July 2013, and hand-searched reference lists and key journals for RCTs that evaluated health system outcomes of CNS transitional care. Study quality was assessed using the Cochrane Risk of Bias and Quality of Health Economic Studies tools. The quality of evidence for individual outcomes was assessed using the Grading of Recommendations Assessment, Development and Evaluation ( GRADE) tool. We pooled data for similar outcomes. Results Thirteen RCTs of CNS transitional care were identified ( n = 2463 participants). The studies had low ( n = 3), moderate ( n = 8) and high ( n = 2) risk of bias and weak economic analyses. Post-cancer surgery, CNS care was superior in reducing patient mortality. For patients with heart failure, CNS care delayed time to and reduced death or re-hospitalization, improved treatment adherence and patient satisfaction, and reduced costs and length of re-hospitalization stay. For elderly patients and caregivers, CNS care improved caregiver depression and reduced re-hospitalization, re-hospitalization length of stay and costs. For high-risk pregnant women and very low birthweight infants, CNS care improved infant immunization rates and maternal satisfaction with care and reduced maternal and infant length of hospital stay and costs. Conclusions There is low-quality evidence that CNS transitional care improves patient health outcomes, delays re-hospitalization and reduces hospital length of stay, re-hospitalization rates and costs. Further research incorporating robust economic evaluation is needed. [ABSTRACT FROM AUTHOR]

Objectives To design and evaluate the effectiveness of a pre-notification leaflet about research to increase recruitment to a randomized controlled trial (RCT). Methods A methodological, two-arm, RCT was conducted, embedded within an existing cohort RCT (REFORM). Participants were randomized for the embedded trial, using a 1:2 ratio (intervention : control) before being randomized for REFORM. Controls received a trial recruitment pack. The intervention group received an additional pre-notification leaflet 2-3 weeks before the recruitment pack. Primary and secondary analyses were conducted using relative risk, the Cox proportional hazards model and incremental cost-effectiveness ratios. Results Of the 1436 intervention group participants, 73 (5.1%) were randomized into the REFORM trial compared with 126 (4.4%) of the 2878 control group participants. The associated relative risk (1.16) was not statistically significant [95% confidence interval (CI) 0.88-1.56]. Return rate was not significantly increased (relative risk 1.10, 95% CI 0.92-1.28) nor time to return decreased (hazard ratio: 1.11, 95% CI 0.93-1.33). Incremental cost-effectiveness ratios indicated the intervention may be cost-effective if the true estimate of effect was close to the upper bound of the associated 95% CI. Conclusion Pre-notification for potential trial participants demonstrated a small difference to randomization (0.7% difference) and return rates (1.1% difference) in favour of the intervention. Results should however be interpreted with caution as CIs for these estimates cross the point of no effect. Nevertheless, this research enhances existing evidence for pre-notification to increase recruitment rates, with further development and assessment of this potentially cost-effective intervention being recommended. [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives Our aim was to evaluate the effectiveness of a Post-it® note to increase response rates and shorten response times to a 4-month postal follow-up questionnaire sent to participants taking part in the Collaborative Care in Screen-Positive Elders (CASPER) trials. Method Our trial was a two-arm randomized controlled trial comparing response rates to questionnaires with a printed Post-it® note (intervention) and without (control), nested in multi centred randomized controlled trials of older people with varying levels of depressive symptoms; the CASPER+ and CASPER Self Help for those At Risk of Depression (SHARD) trials. A total of 611 participants were eligible and randomized. The primary outcome was response rates, secondary outcomes were time to response and need for a reminder. Results Of 297 participants, 266 (89.6%) returned their 4-month questionnaire in the post-it note arm, compared with 282 of 314 participants (89.8%) in the control arm (OR = 0.97, 95% CI: 0.57, 1.65, P = 0.913). There were no statistically significant differences in time to respond or the need to be sent a reminder. Patients with a major depressive episode were more likely to return questionnaires with post-it notes ( P of interaction = .019). Conclusion There was no significant difference in response rates, time to response, or the need for a reminder between the intervention and control at 4-month follow up for older people with depressive symptoms. However, there was a significant interaction between the Post-it® note group and level of depression. [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 This study aimed to evaluate the relative effectiveness of electronic and postal reminders for increasing adherence to the quality assurance programme for the international normalized ratio ( INR) point-of-care testing ( POCT) device in primary care. Methods All 213 family practices that use the Elective Laboratory of the Capital Region, Denmark, and regularly conduct INR POCT were randomly allocated into two similarly sized groups. During the 4-month intervention, these practices were sent either computer reminders ( Com Rem) or computer-generated postal reminders ( Postal) if they did not perform a split test to check the quality of their INR POCT for each calendar month. The adherence of the practices was tracked during the subsequent 8 months subdivided into two 4-month periods both without intervention. Outcomes were measures of split test procedure adherence. Results Both interventions were associated with an increase in adherence to the split test procedure - a factor 6.00 [95% confidence interval (CI) 4.46-7.72] and 8.22 [95% CI 5.87-11.52] for ComRem and Postal, respectively - but there is no evidence that one of the interventions was more effective than the other. In the Com Rem group, the expected number of split tests (out of four) was 2.54 (95% CI 2.33-2.76) versus 2.44 (95% CI 2.24-2.65) in the Postal group, P = 0.14. There was a slight decrease in adherence over the two follow-ups, but neither intervention was better than the other in achieving a lasting improvement in adherence. Conclusion Computer reminders are as efficient as postal reminders in increasing adherence to a quality assurance programme for the INR POCT device in primary care. [ABSTRACT FROM AUTHOR]

Rationale, aims and objectives Frequent use and serious adverse effects related to non-steroidal anti-inflammatory drugs ( NSAIDs) underscore the need to raise patient awareness about potential risks. Partial success of patient- or provider-based interventions has recently led to interest in combined approaches focusing on both patient and physician. This research tested a shared decision-making intervention for increasing patient-reported awareness of NSAID risk. Methods A group randomized trial was performed in Alabama from 2005 to 2007. Intervention group doctor practices received continuing medical education ( CME) about NSAIDs and patient activation tools promoting risk assessment and communication during visits. Comparison group doctor practices received only CME. Cross-sectional data were collected before and after the intervention. Generalized linear latent and mixed models with logistic link tested relationships among the intervention, study phase, intervention by study phase interaction and patient-reported awareness of risks with either prescription or over-the-counter ( OTC) NSAIDs. Results Three hundred and forty-seven patients at baseline and 355 patients at follow-up participated in this study. The intervention [adjusted odds ratio ( AOR) = 0.74, P = 0.248], follow-up study phase ( AOR = 1.31, P = 0.300) and intervention by study phase interaction ( AOR = 0.98, P = 0.942) were not significantly associated with patient-reported awareness of any prescription NSAID risk. Follow-up study phase was associated with increased odds of reporting any OTC NSAID risk awareness ( AOR = 2.99, P < 0.001), but the patient activation intervention and intervention by study phase interaction were not significantly associated with patient-reported awareness of any OTC NSAID risk ( AOR = 0.98, P = 0.929; AOR = 0.87, P = 0.693, respectively). Conclusions Our point-of-care intervention encouraging shared decision making did not increase NSAID risk awareness. [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]

Background The Cochrane Collaboration is strongly encouraging the use of a newly developed tool, the Cochrane Collaboration Risk of Bias Tool (CCRBT), for all review groups. However, the psychometric properties of this tool to date have yet to be described. Thus, the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity, in comparison with the Effective Public Health Practice Project Quality Assessment Tool (EPHPP). Methods Both tools were used to assess the methodological quality of 20 randomized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain. Each study assessment was completed independently by two reviewers using each tool. We analysed the inter-rater reliability of each tool's individual domains, as well as final grade assigned to each study. Results The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade. In contrast, the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade. Of interest, no agreement between the two tools was evident in their final grade assigned to each study. Although both tools were developed to assess 'quality of the evidence', they appear to measure different constructs. Conclusions Both tools performed quite differently when evaluating the risk of bias or methodological quality of studies in knowledge translation interventions for cancer pain. The newly introduced CCRBT assigned these studies a higher risk of bias. Its psychometric properties need to be more thoroughly validated, in a range of research fields, to understand fully how to interpret results from its application. [ABSTRACT FROM AUTHOR]

Rationale Attrition is a threat to the validity of randomized trials. Few randomized studies have been conducted within randomized trials to test methods of reducing attrition. Aim To test whether using yellow post-it notes on follow-up questionnaires in the ATLAS treatment trial for neck pain reduces attrition. Method Nested trial within a trial. ATLAS participants were randomized to have their 6-month follow-up questionnaire have a 3′ yellow post-it note with a handwritten message encouraging return of questionnaire. Results 499 participants were independently randomized using simple allocation to receive the post-it notes or not. Two hundred fifteen of the 256 (84.0%) participants in the intervention group returned their questionnaire compared with 205 of the 243 (84.4%) in the control group. There was no difference in time to response. Conclusion Yellow post-it notes do not enhance questionnaire return rates for participants in a randomized trial of neck pain. [ABSTRACT FROM AUTHOR]