Insomnia medication: Do published studies reflect the complete picture of efficacy and safety?

Selective publication can have a deleterious effect on evidence based medicine, health policy decision making and treatment guidelines. Using the European Public Assessment Reports (EPARs) as reference, this study examined selective publication and selective reporting of efficacy and safety of insomnia medication.EPARs of with three insomnia medications were used to identify all clinical trials that were performed between 1998 and 2007 for the purpose of registration in the EU. The matching publication for each trial was searched through a systematic literature search. Accuracy of information in the publications was examined by comparison to the information in the EPARs.Only 55% of the trials with insomnia medications identified in EPARs were published. Positive trials were approximately two times more likely to be published. The lag time from study completion to publication was shorter for the positive compared to the negative trials. Sample size did not correlate with publication of negative trials. The meta-analysis of the effect size of insomnia medication was 1.6 times larger in the published data compared to the complete data. While the primary end points of the trials were reported reliably in the publications, remarkable inconsistencies were detected in the reporting of the secondary end points, methods, results and, especially safety. In conclusion, selective publication and reporting lead to an overestimation of efficacy and underestimation of safety of insomnia products. Authors of treatment guidelines should be aware of this bias. EPARs/FDA reviews provide a more unbiased view of the benefit-risk balance of insomnia and other medications and hence these documents should be consulted by e.g. authors of meta-analyses and of treatment guidelines.     

Evaluation of clinical safety and tolerance of a Lactobacillus reuteri NCIMB 30242 supplement capsule: A randomized control trial

A significant number of human clinical trials have reported no adverse effects associated with consumption of Lactobacillus reuteri (L. reuteri). In the present study, the clinical safety and toxicology of oral ingestion of supplement capsules containing L. reuteri NCIMB 30242 was investigated. A randomized group of 131 subjects received a dose of 2.9 × 10⁹ CFU L. reuteri NCIMB 30242 capsules (n = 67) or placebo capsules (n = 64) twice daily for 9 weeks. Clinical chemistry and hematological parameters of safety were analyzed. The frequency, duration and intensity of adverse events (AE)s and clinical significance of safety parameters were recorded for both groups. No clinically significant differences between the probiotic capsule and placebo capsule treated groups were detected in either the blood clinical chemistry or hematology results. The frequency and intensity of AEs was similar in the two groups. These results demonstrate that administration of a twice daily dose of 2.9 × 10⁹ CFU was safe and well tolerated in the population evaluated over 9 weeks.     

Publication trends in chronic fatigue syndrome: comparisons with fibromyalgia and fatigue: 1995-2004

OBJECTIVE: In order to identify publishing patterns in chronic fatigue syndrome (CFS), we compared the annual number of peer review articles for CFS, fibromyalgia (FM), and non-CFS fatigue over a recent decade (1995-2004). METHOD: Citations were drawn from Ovid/Medline, PsychInfo, and the Journal of Chronic Fatigue Syndrome for peer review articles focusing on CFS, FM, and fatigue for each year of the decade ending in 2004. Statistics included chi-square, tests for differences in proportions, and regression-based curve estimation. RESULTS: The frequency of CFS peer review articles did not significantly change from the first half to the second half of the decade (1995-2004). By comparison, the output of both FM and fatigue articles significantly increased (P<.0001). A quadratic model (inverted U shape; P<.02) best fit the data for CFS annual publication frequency. By comparison, exponential models best fit the data for both FM (P<.0001) and fatigue (P<.0001) citations. The highest percentage of citations (15-16%) for both CFS and FM fell within the domains of diagnosis, physiopathology, and psychology. For fatigue, almost one third (31.4%) of the citations were focused on etiology, while psychology (11.5%) and physiopathology (10.4%) articles were the next most cited. Based on first-author affiliation, CFS articles were most likely to originate in the United States (37.7%), England (31.4%), and the Netherlands (4.9%). CONCLUSION: The output of CFS peer review articles has not increased over the past decade, while the number of FM and fatigue articles has increased substantially.     

Scientific papers presented at the European Congress of Radiology: a two-year comparison

The purpose of this report was to determine the rate at which abstracts orally presented at the European Congress of Radiology (ECR) 2001 were published in 2001–2005 Medline-indexed journals and to compare publication rates and factors with presentations at the ECR in two different periods (2001 and 2000). Absolute and relative publication rates (APR, RPR) and different publication-related factors were analysed. From 991 abstracts originating from 52 countries, 449 articles (APR 45%) were subsequently published in 125 journals, most frequently in European Radiology (n=79, 18%). Country of origin statistically (p<0.0001) influences subsequent publication of the abstract, with Germany having the highest number of presentations (n=300) and derived articles (n=175, RPR 58%) whereas Sweden had the highest RPR (82%). Interventional and physics studies had the highest RPR (59% and 58%, respectively). The ECR meeting has a very high and stable APR (ECR 2001: 45% vs ECR 2000: 47%), and the journal European Radiology had the larger number of related publications (18% RPR following ECR 2001 compared with 14% from ECR 2000). Germany had the highest number of presentations and publications for both meetings. The highest RPR for ECR 2001 was found in interventional and physics studies whereas chest and cardiac studies had the highest RPR for ECR 2000.     

When will I see you again? The fate of research findings from international wound care conferences*

Medical conferences provide a forum for the rapid dissemination of research directly to health professionals and academics. However, the published record of poster and oral presentations from these meetings is usually limited to abstracts. We aimed to assess how many wound studies presented as conference abstracts were eventually published in journals and to identify the factors that predicted publication. The study was a retrospective review. We identified abstracts relating to oral and poster presentation from two large wound conferences. Following data extraction from the abstracts, a systematic search was conducted to examine if the research was subsequently published as a journal article. A time-to-event analysis was conducted to assess predictive associations between features of the research reported in the conference abstracts and time to full publication. In total, 492 abstracts from two European wound care conferences were identified (467 after exclusions). Of the abstracts included, 60% (279) were for posters and 40% (188) were for oral presentations. Over half of the abstracts (53%) reported results from case studies or case series design. In total, only 57 (12%) of the abstracts included resulted in a related publication. Analysis suggested that those studies reporting positive findings were significantly more likely to be published (hazard ratio 1.79, P= 0.001, 95% CIs 1.26-2.55). Few studies presented as conference abstracts at these two wounds conferences were subsequently published. This may be because of the low methodological quality of studies accepted for poster or oral presentation.     

Fate of the abstracts presented at three Spanish clinical pharmacology congresses and reasons for unpublished research

Objectives To assess the publication rate of abstracts at 5 years after their presentation at three consecutive clinical pharmacology congresses and to examine the reasons relating to the lack of publication. Methods Oral and poster presentations from the congresses of the Spanish Society of Clinical Pharmacology (SSCP) in 1994, 1996, and 1998 were reviewed. Authors were contacted to determine the fate of their presented studies and the reasons for not publishing them. Publications of abstracts with unknown fate were searched the in PubMed database. Determinants of publication were examined by Cox regression. Results In all, 248 abstracts were analysed. The cumulative publication rate at 5 years was 26%, and the median time for publication was 18 months (range: 2–60). The European Journal of Clinical Pharmacology was the English language medical journal where most abstracts were published. The median impact factor of the articles published was 1.96 (range: 0.29–8.32). The author survey identified a lack of time (38.2%) and a lack of interest (33.3%) as the main reasons for failure to publish. The only predictor of an abstract’s publication was to be affiliated with a university department (hazard ratio: 1.98, 95% confidence interval: 1.20–3.27). Conclusions Only one-quarter of the abstracts presented at SSCP congresses were subsequently published. A lack of time and interest were the main reasons given for not submitting these presentations for publication. Authors, scientific societies and editorial boards should enhance publications as full papers in peer-reviewed journals of the abstracts presented at meetings.     

Transition from congress abstract to full publication for clinical trials presented at laser meetings

The present study aims to identify (1) what proportion of abstracts of clinical trials presented at The American Society for Laser Medicine and Surgery (ASLMS) annual meetings are published as full reports, (2) time to publication, and (3) factors that may predict the publication of research in peer-reviewed journals. Two investigators independently hand-searched all abstracts of the ASLMS meetings to identify all reports of clinical trials. Details of sample size, the country of origin, topic of research, type of presentation, type of laser, direction of outcome, and statistical significance were recorded for each abstract. To determine the full publication status of each study, The Cochrane Central Register of Controlled Trials, PubMed, and EMBASE was searched. A total of 198 abstracts were identified. Of these, 87 abstracts (44%) have been fully published. The average time from presentation at the meeting to full publication was 57 months (95% confidence interval = 52-61), and the estimated rate of abstracts published at 1, 2, and 4 years was 15, 30, and 38%, respectively. There is significant tendency for being fully published in high-power laser studies, with USA as country of origin, and orally presented. Our findings supports this opinion that conference abstracts can be an important source for systematic reviews and failure to identify trials presented in congresses might threaten the validity of systematic reviews.