Under-reporting of Adverse Events in the Biomedical Literature

Purpose: To address the under-reporting of research results, with emphasis on the underreporting/distorted reporting of adverse events in the biomedical research literature.Design/methodology/approach: A four-step approach is used:(1) To identify the characteristics of literature that make it adequate to support policy;(2) to show how each of these characteristics becomes degraded to make inadequate literature;(3) to identify incentives to prevent inadequate literature; and(4) to show policy implications of inadequate literature.Findings: This review has provided reasons for, and examples of, adverse health effects of myriad substances(1) being under-reported in the premiere biomedical literature, or(2) entering this literature in distorted form. Since there is no way to gauge the extent of this under/distorted-reporting, the quality and credibility of the ‘premiere’ biomedical literature is unknown. Therefore, any types of meta-analyses or scientometric analyses of this literaturewill have unknown quality and credibility. The most sophisticated scientometric analysis cannot compensate for a highly flawed database.Research limitations: The main limitation is in identifying examples of under-reporting. There are many incentives for under-reporting and few dis-incentives.Practical implications: Almost all research publications, addressing causes of disease, treatments for disease, diagnoses for disease, scientometrics of disease and health issues, and other aspects of healthcare, build upon previous healthcare-related research published. Many researchers will not have laboratories or other capabilities to replicate or validate the published research, and depend almost completely on the integrity of this literature. If the literature is distorted, then future research can be misguided, and health policy recommendations can be ineffective or worse.Originality/value: This review has examined a much wider range of technical and nontechnical causes for under-reporting of adverse events in the biomedical literature than previous studies.

Russian clinical research policy does not guarantee results availability

AIM: To investigate results availability from clinical studies enrolling Russian subjects and Russian clinical research policy.METHODS: We analyzed Russian legislation and ethical regulations about drug and devices approval,clinical research registration and the results availability.In August 2012,we searched International Clinical Trials Registry Platform and clinicaltrials.gov to find all registered studies that had an investigational site in the territory of the Russian Federation.To find publication status,we searched the Pub Med and Scirus bibliographical databases with trial registration number to find journal publications of the registered studies.RESULTS: We identified 2062 registered research protocols comprising 2017 international and 45 protocols sponsored by the Russian funding agencies.The number of the studies enrolling Russian subjects increased dramatically from three studies in 2002 to 252 studies in 2012.Most studies(92%) were funded exclusively by industry,were interventions(94.6%),examined drugs(87%) and enrolled exclusively adults(86%) of both genders(89%).Only 383(19%) of multinational studies and two(4.4%) of exclusively Russian studies werepublished.Posting of patient outcomes was available for 16% of the trials that recruited trial participants in the Russian territory including one study funded exclusively by Russian sponsors.Investigators terminated 99 studies of 38111 participants and did not provide the results in clinicaltrials.gov or in published manuscripts.Federal laws require clinical study registration and conflict of interest disclosure.However,routine monitoring of compliance to clinical research policy is not available.CONCLUSION: Russian legislation does not guarantee the availability of clinical research results.Russian legislation should mandate transparent evidence- based market approval of the drugs and devices.

Sirtuins are not conserved longevity genes

It is central to biology that sequence conservation suggests functional conservation.Animal longevity is an emergent property of selected traits that integrates capacities to perform physical and mental functions after reproductive maturity.Though the yeast SIR2 gene was nominated as a longevity gene based on extended replicative longevity of old mother cells,this is not a selected trait:SIR2 is selected against in chronological aging and the direct targets of SIR2 in replicative lifespan are not conserved.Though it would be difficult to imagine how a gene that advantages 1 in 5 million yeast cells could have anticipated causes of aging in animals,overexpression of SIR2 homologs was tested in invertebrates for longevity.Because artifactual positive results were reported years before they were sorted out and because it was not known that SIR2 functions as a pro-aging gene in yeast chronological aging and in flies subject to amino acid deprivation,a global pursuit of longevity phenotypes was driven by a mixture of framing bias,confirmation bias,and hype.Review articles that propagate these biases are so rampant that few investigators have considered how weak the case ever was for sirtuins as longevity genes.Acknowledging that a few positive associations between sirtuins and longevity have been identified after thousands of person-years and billions of dollars of effort,we review the data and suggest rejection of the notions that sirtuins(i)have any specific connection to lifespan in animals and(ii)are primary mediators of the beneficial effects of NAD repletion.