Comparison of Treatment Effect Estimates for Pharmacological Randomized Controlled Trials Enrolling Older Adults Only and Those including Adults: A Meta-Epidemiological Study

Context Older adults are underrepresented in clinical research. To assess therapeutic efficacy in older patients, some randomized controlled trials (RCTs) include older adults only. Objective To compare treatment effects between RCTs including older adults only (elderly RCTs) and RCTs including all adults (adult RCTs) by a meta-epidemiological approach. Methods All systematic reviews published in the Cochrane Library (Issue 4, 2011) were screened. Eligible studies were meta-analyses of binary outcomes of pharmacologic treatment including at least one elderly RCT and at least one adult RCT. For each meta-analysis, we compared summary odds ratios for elderly RCTs and adult RCTs by calculating a ratio of odds ratios (ROR). A summary ROR was estimated across all meta-analyses. Results We selected 55 meta-analyses including 524 RCTs (17% elderly RCTs). The treatment effects differed beyond that expected by chance for 7 (13%) meta-analyses, showing more favourable treatment effects in elderly RCTs in 5 cases and in adult RCTs in 2 cases. The summary ROR was 0.91 (95% CI, 0.77–1.08, p = 0.28), with substantial heterogeneity (I2 = 51% and τ2 = 0.14). Sensitivity and subgroup analyses by type-of-age RCT (elderly RCTs vs RCTs excluding older adults and vs RCTs of mixed-age adults), type of outcome (mortality or other) and type of comparator (placebo or active drug) yielded similar results. Conclusions The efficacy of pharmacologic treatments did not significantly differ, on average, between RCTs including older adults only and RCTs of all adults. However, clinically important discrepancies may occur and should be considered when generalizing evidence from all adults to older adults

Effect of editors’ implementation of CONSORT guidelines on the reporting of abstracts in high impact medical journals: interrupted time series analysis

Objective To investigate the effect of the CONSORT for Abstracts guidelines, and different editorial policies used by five leading general medical journals to implement the guidelines, on the reporting quality of abstracts of randomised trials

Meta-Analysis of a Complex Network of Non-Pharmacological Interventions: The Example of Femoral Neck Fracture

Background Surgical interventions raise specific methodological issues in network meta-analysis (NMA). They are usually multi-component interventions resulting in complex networks of randomized controlled trials (RCTs), with multiple groups and sparse connections. Purpose To illustrate the applicability of the NMA in a complex network of surgical interventions and to prioritize the available interventions according to a clinically relevant outcome. Methods We considered RCTs of treatments for femoral neck fracture in adults. We searched CENTRAL, MEDLINE, EMBASE and ClinicalTrials.gov up to November 2015. Two reviewers independently selected trials, extracted data and used the Cochrane Collaboration’s tool for assessing the risk of bias. A group of orthopedic surgeons grouped similar but not identical interventions under the same node. We synthesized the network using a Bayesian network meta-analysis model. We derived posterior odds ratios (ORs) and 95% credible intervals (95% CrIs) for all possible pairwise comparisons. The primary outcome was all-cause revision surgery. Results Data from 27 trials were combined, for 4,186 participants (72% women, mean age 80 years, 95% displaced fractures). The median follow-up was 2 years. With hemiarthroplasty (HA) and total hip arthroplasty (THA) as a comparison, risk of surgical revision was significantly higher with the treatments unthreaded cervical osteosynthesis (OR 8.0 [95% CrI 3.6–15.5] and 5.9 [2.4–12.0], respectively), screw (9.4 [6.0–16.5] and 6.7 [3.9–13.6]) and plate (12.5 [5.8–23.8] and 7.8 [3.8–19.4]). Conclusions In older women with displaced femoral neck fractures, arthroplasty (HA and THA) is the most effective treatment in terms of risk of revision surgery

Quality of Reporting of Bioequivalence Trials Comparing Generic to Brand Name Drugs: A Methodological Systematic Review

BACKGROUND: Generic drugs are used by millions of patients for economic reasons, so their evaluation must be highly transparent. OBJECTIVE: To assess the quality of reporting of bioequivalence trials comparing generic to brand-name drugs. METHODOLOGY/PRINCIPAL FINDINGS: PubMed was searched for reports of bioequivalence trials comparing generic to brand-name drugs between January 2005 and December 2008. Articles were included if the aim of the study was to assess the bioequivalency of generic and brand-name drugs. We excluded case studies, pharmaco-economic evaluations, and validation dosage assays of drugs. We evaluated whether important information about funding, methodology, location of trials, and participants were reported. We also assessed whether the criteria required by the Food and Drug Administration (FDA) and the European Medicine Agency (EMA) to conclude bioequivalence were reported and that the conclusions were in agreement with the results. We identified 134 potentially relevant articles but eliminated 55 because the brand-name or generic drug status of the reference drug was unknown. Thus, we evaluated 79 articles. The funding source and location of the trial were reported in 41% and 56% of articles, respectively. The type of statistical analysis was reported in 94% of articles, but the methods to generate the randomization sequence and to conceal allocation were reported in only 15% and 5%, respectively. In total, 65 articles of single-dose trials (89%) concluded bioequivalence. Of these, 20 (31%) did not report the 3 criteria within the limits required by the FDA and 11 (17%) did not report the 2 criteria within the limits required by the EMA. CONCLUSIONS/SIGNIFICANCE: Important information to judge the validity and relevance of results are frequently missing in published reports of trials assessing generic drugs. The quality of reporting of such trials is in need of improvement

Influence of trial sample size on treatment effect estimates: meta-epidemiological study

Objective To assess the influence of trial sample size on treatment effect estimates within meta-analyses. Design Meta-epidemiological study. Data sources 93 meta-analyses (735 randomised controlled trials) assessing therapeutic interventions with binary outcomes, published in the 10 leading journals of each medical subject category of the Journal Citation Reports or in the Cochrane Database of Systematic Reviews. Data extraction Sample size, outcome data, and risk of bias extracted from each trial. Data synthesis Trials within each meta-analysis were sorted by their sample size: using quarters within each meta-analysis (from quarter 1 with 25% of the smallest trials, to quarter 4 with 25% of the largest trials), and using size groups across meta-analyses (ranging from <50 to ≥1000 patients). Treatment effects were compared within each meta-analysis between quarters or between size groups by average ratios of odds ratios (where a ratio of odds ratios less than 1 indicates larger effects in smaller trials). Results Treatment effect estimates were significantly larger in smaller trials, regardless of sample size. Compared with quarter 4 (which included the largest trials), treatment effects were, on average, 32% larger in trials in quarter 1 (which included the smallest trials; ratio of odds ratios 0.68, 95% confidence interval 0.57 to 0.82), 17% larger in trials in quarter 2 (0.83, 0.75 to 0.91), and 12% larger in trials in quarter 3 (0.88, 0.82 to 0.95). Similar results were obtained when comparing treatment effect estimates between different size groups. Compared with trials of 1000 patients or more, treatment effects were, on average, 48% larger in trials with fewer than 50 patients (0.52, 0.41 to 0.66) and 10% larger in trials with 500-999 patients (0.90, 0.82 to 1.00). Conclusions Treatment effect estimates differed within meta-analyses solely based on trial sample size, with stronger effect estimates seen in small to moderately sized trials than in the largest trials

Interpretation of Results of Studies Evaluating an Intervention Highlighted in Google Health News: A Cross-Sectional Study of News

Background Mass media through the Internet is a powerful means of disseminating medical research. We aimed to determine whether and how the interpretation of research results is misrepresented by the use of “spin” in the health section of Google News. Spin was defined as specific way of reporting, from whatever motive (intentional or unintentional), to emphasize that the beneficial effect of the intervention is greater than that shown by the results. Methods We conducted a cross-sectional study of news highlighted in the health section of US, UK and Canada editions of Google News between July 2013 and January 2014. We searched for news items for 3 days a week (i.e., Monday, Wednesday, and Friday) during 6 months and selected a sample of 130 news items reporting a scientific article evaluating the effect of an intervention on human health. Results In total, 78% of the news did not provide a full reference or electronic link to the scientific article. We found at least one spin in 114 (88%) news items and 18 different types of spin in news. These spin were mainly related to misleading reporting (59%) such as not reporting adverse events that were reported in the scientific article (25%), misleading interpretation (69%) such as claiming a causal effect despite non-randomized study design (49%) and overgeneralization/misleading extrapolation (41%) of the results such as extrapolating a beneficial effect from an animal study to humans (21%). We also identified some new types of spin such as highlighting a single patient experience for the success of a new treatment instead of focusing on the group results. Conclusions Interpretation of research results was frequently misrepresented in the health section of Google News. However, we do not know whether these spin were from the scientific articles themselves or added in the news

Applicability and generalisability of published results of randomised controlled trials and non-randomised studies evaluating four orthopaedic procedures: methodological systematic review

Objective To compare the reporting of essential applicability data from randomised controlled trials and non-randomised studies evaluating four new orthopaedic surgical procedures

Development and evaluation of a pedagogical tool to improve understanding of a quality checklist: a randomised controlled trial.

OBJECTIVE: The aim of this study was to develop and evaluate a pedagogical tool to enhance the understanding of a checklist that evaluates reports of nonpharmacological trials (CLEAR NPT). DESIGN: Paired randomised controlled trial. PARTICIPANTS: Clinicians and systematic reviewers. INTERVENTIONS: We developed an Internet-based computer learning system (ICLS). This pedagogical tool used many examples from published randomised controlled trials to demonstrate the main coding difficulties encountered when using this checklist. Randomised participants received either a specific Web-based training with the ICLS (intervention group) or no specific training. OUTCOME MEASURES: The primary outcome was the rate of correct answers compared to a criterion standard for coding a report of randomised controlled trials with the CLEAR NPT. RESULTS: Between April and June 2006, 78 participants were randomly assigned to receive training with the ICLS (39) or no training (39). Participants trained by the ICLS did not differ from the control group in performance on the CLEAR NPT. The mean paired difference and corresponding 95% confidence interval was 0.5 (-5.1 to 6.1). The rate of correct answers did not differ between the two groups regardless of the CLEAR NPT item. Combining both groups, the rate of correct answers was high or items related to allocation sequence (79.5%), description of the intervention (82.0%), blinding of patients (79.5%), and follow-up schedule (83.3%). The rate of correct answers was low for items related to allocation concealment (46.1%), co-interventions (30.3%), blinding of outcome assessors (53.8%), specific measures to avoid ascertainment bias (28.6%), and intention-to-treat analysis (60.2%). CONCLUSIONS: Although we showed no difference in effect between the intervention and control groups, our results highlight the gap in knowledge and urgency for education on important aspects of trial conduct

Data capture by digital pen in clinical trials: A qualitative and quantitative study.

International audienceOBJECTIVES: To investigate the use of the digital pen (DP) system to collect data in a clinical trial. To assess the accuracy of the system in this setting. DESIGN: Qualitative study based on semistructured interviews and a focus group. Quantitative study comparing the DP system and a double manual data-entry system in accuracy of acquiring data by variable type (tick boxes, dates, numbers, letters). SETTING: An ongoing randomised multicentric clinical trial in tertiary care in France. PARTICIPANTS: 27 investigators involved in the trial (anaesthetists) who did or did not include patients, 4 study monitors and the study coordinator. RESULTS: Six key findings emerged: 1) the DP system was easy to use; its utilisation was intuitive, even for investigators inexperienced in informatics; 2) despite its portability, the DP was not always used in front of patients; 3) the DP system did not affect patient recruitment; 4) most of the technical problems of the system occurred during setup (compatibility, password access, antivirus software); 5) the main advantage was quickness of data availability for the study coordination staff and the main hindrance was the extra time required for online verification; and 6) all investigators were ready to use the system again. The investigators had to check 16% of data obtained by the DP system during the verification step. There is no relevant difference between the number of errors for the DP and the double manual data-entry systems: 8/5022 versus 6/5022 data entries. 5 out of 8 DP-system failures were due to the intelligent character recognition system. CONCLUSION: The DP system has a good acceptability among all investigators in a clinical setting, whether they are experienced with computers or not, and a good accuracy, as compared with double manual data entry