A Taxpayer-Funded Clinical Trials Registry and Results Database

It already exists within the US Food and Drug Administration, argues a former clinical reviewer of psychotropic drugs at the FD

Is It Always Unethical to Use a Placebo in a Clinical Trial?

Background to the debate: Placebos are used in trials to conceal whether a treatment is being given or not and hence to control for the psychosomatic effects of offering treatment. Placebo-controlled trials are controversial. Critics of such trials argue that if a proven effective therapy exists, a placebo should not be used. But proponents argue that placebo trials are still crucial to prove the efficacy and safety of many treatments

Reporting of conflicts of interest from drug trials in Cochrane reviews:cross sectional study

Objectives To investigate the degree to which Cochrane reviews of drug interventions published in 2010 reported conflicts of interest from included trials and, among reviews that reported this information, where it was located in the review documents. Design Cross sectional study. Data sources Cochrane Database of Systematic Reviews. Selection criteria Systematic reviews of drug interventions published in 2010 in the Cochrane Database of Systematic Reviews, with review content classified as up to date in 2008 or later and with results from one or more randomised controlled trials. Results Of 151 included Cochrane reviews, 46 (30%, 95% confidence interval 24% to 38%) reported information on the funding sources of included trials, including 30 (20%, 14% to 27%) that reported information on trial funding for all included trials and 16 (11%, 7% to 17%) that reported for some, but not all, trials. Only 16 of the 151 Cochrane reviews (11%, 7% to 17%) provided any information on trial author-industry financial ties or trial author-industry employment. Information on trial funding and trial author-industry ties was reported in one to seven locations within each review, with no consistent reporting location observed. Conclusions Most Cochrane reviews of drug trials published in 2010 did not provide information on trial funding sources or trial author-industry financial ties or employment. When this information was reported, location of reporting was inconsistent across reviews

Dynamical Solutions to the Horizon and Flatness Problems

We discuss in some detail the requirements on an early-Universe model that solves the horizon and flatness problems during the epoch of classical cosmology ($t\ge t_i\gg 10^{-43}\sec$). We show that a dynamical resolution of the horizon problem requires superluminal expansion (or very close to it) and that a truly satisfactory resolution of the flatness problem requires entropy production. This implies that a proposed class of adiabatic models in which the Planck mass varies by many orders of magnitude cannot fully resolve the flatness problem. Furthermore, we show that, subject to minimal assumptions, such models cannot solve the horizon problem either. Because superluminal expansion and entropy production are the two generic features of inflationary models, our results suggest that inflation, or something very similar, may be the only dynamical solution to the horizon and flatness problems.Comment: 17 page

Reporting of Conflicts of Interest in Meta-analyses of Trials of Pharmacological Treatments

Context Disclosure of conflicts of interest (COIs) from pharmaceutical industry study funding and author-industry financial relationships is sometimes recommended for randomized controlled trials (RCTs) published in biomedical journals. Authors of meta-analyses, however, are not required to report COIs disclosed in original reports of included RCTs. Objective To investigate whether meta-analyses of pharmacological treatments published in high-impact biomedical journals report COIs disclosed in included RCTs. Data Sources and Study Selection We selected the 3 most recent meta-analyses of patented pharmacological treatments published January 2009 through October 2009 in each general medicine journal with an impact factor of at least 10; in high-impact journals in each of the 5 specialty medicine areas with the greatest 2008 global therapeutic sales (oncology, cardiology, respiratory medicine, endocrinology, and gastroenterology); and in the Cochrane Database of Systematic Reviews. Data Extraction Two investigators independently extracted data on disclosed study funding, author-industry financial ties, and author employment from each meta-analysis, from RCTs included in each meta-analysis, and on whether meta-analyses reported disclosed COIs of included RCTs. Results Of 29 meta-analyses reviewed, which included 509 RCTs, only 2 meta-analyses (7%) reported RCT funding sources; and 0 reported RCT author-industry ties or employment by the pharmaceutical industry. Of 318 meta-analyzed RCTs that reported funding sources, 219 (69%) were industry funded; and 91 of 132 (69%) that reported author financial disclosures had 1 or more authors with pharmaceutical industry financial ties. In 7 of the 29 meta-analyses reviewed, 100% of included RCTs had at least 1 form of disclosed COI (pharmaceutical industry funding, author-industry financial ties, or employment), yet only 1 of these 7 meta-analyses reported RCT funding sources, and 0 reported RCT author-industry ties or employment. Conclusion Among a group of meta-analyses of pharmacological treatments published in high-impact biomedical journals, information concerning primary study funding and author COIs for the included RCTs were only rarely reported. JAMA. 2011;305(10):1008-1017 www.jama.co

Novel methods to deal with publication biases: secondary analysis of antidepressant trials in the FDA trial registry database and related journal publications

Objective To assess the performance of novel contour enhanced funnel plots and a regression based adjustment method to detect and adjust for publication biases

Spin in RCTs of anxiety medication with a positive primary outcome:A comparison of concerns expressed by the US FDA and in the published literature

OBJECTIVES: This study aimed to determine the presence of spin in papers on positive randomised clinical trials (RCTs) of antidepressant medication for anxiety disorders by comparing concerns expressed in the Food and Drug Administration (FDA) reviews with those expressed in the published paper. METHODS: For every positive anxiety medication trial with a matching publication (n=41), two independent reviewers identified the concerns raised in the US FDA reviews and those in the published literature. Spin was identified when concerns or limitations were expressed by the FDA (about the efficacy of the study drug) but not in the corresponding published paper. Concerns mentioned in the papers but not by the FDA were scored as ‘non-FDA’ concerns. FINDINGS: Only six out of 35 (17%) of the FDA concerns pertaining to drug efficacy were reported in the papers. Two papers mentioned a concern that fit the FDA categories, but was not mentioned in the corresponding FDA review. Eighty-seven non-FDA concerns were counted, which often reflected general concerns or concerns related to the study design. CONCLUSIONS: Results indicate the presence of substantial spin in the clinical trial literature on drugs for anxiety disorders. In papers describing RCTs on anxiety medication, the concerns raised by the authors differed from those raised by the FDA. Published papers mentioned a large number of generic concerns about RCTs, such as a lack of long-term research and limited generalisability, while they mentioned few concerns about drug efficacy. These results warrant the promotion of independent statistical review, reporting of patient-level data, more study of spin, and an increased expectation that authors report FDA concerns