Article

A call for transparent reporting to optimize the predictive value of preclinical research.

National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland 20892, USA.
Nature (Impact Factor: 42.35). 10/2012; 490(7419):187-91. DOI: 10.1038/nature11556
Source: PubMed

ABSTRACT The US National Institute of Neurological Disorders and Stroke convened major stakeholders in June 2012 to discuss how to improve the methodological reporting of animal studies in grant applications and publications. The main workshop recommendation is that at a minimum studies should report on sample-size estimation, whether and how animals were randomized, whether investigators were blind to the treatment, and the handling of data. We recognize that achieving a meaningful improvement in the quality of reporting will require a concerted effort by investigators, reviewers, funding agencies and journal editors. Requiring better reporting of animal studies will raise awareness of the importance of rigorous study design to accelerate scientific progress.

Full-text

Available from: Oswald Steward, May 31, 2015
2 Followers
 · 
213 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Despite multiple publications on potential therapies for neuromuscular diseases (NMD) in cell and animal models only a handful reach clinical trials. The ability to prioritise drug development according to objective criteria is particularly critical in rare diseases with large unmet needs and a limited numbers of patients who can be enrolled into clinical trials. TREAT-NMD Advisory Committee for Therapeutics (TACT) was established to provide independent and objective guidance on the preclinical and development pathway of potential therapies (whether novel or repurposed) for NMD. We present our experience in the establishment and operation of the TACT. TACT provides a unique resource of recognized experts from multiple disciplines. The goal of each TACT review is to help the sponsor to position the candidate compound along a realistic and well-informed plan to clinical trials, and eventual registration. The reviews and subsequent recommendations are focused on generating meaningful and rigorous data that can enable clear go/no-go decisions and facilitate longer term funding or partnering opportunities. The review process thereby acts to comment on viability, de-risking the process of proceeding on a development programme. To date TACT has held 10 review meeting and reviewed 29 program applications in several rare neuromuscular diseases: Of the 29 programs reviewed, 19 were from industry and 10 were from academia; 15 were for novel compounds and 14 were for repurposed drugs; 16 were small molecules and 13 were biologics; 14 were preclinical stage applications and 15 were clinical stage applications. 3 had received Orphan drug designation from European Medicines Agency and 3 from Food and Drug Administration. A number of recurrent themes emerged over the course of the reviews and we found that applicants frequently require advice and education on issues concerned with preclinical standard operating procedures, interactions with regulatory agencies, formulation, repurposing, clinical trial design, manufacturing and ethics. Over the 5 years since its establishment TACT has amassed a body of experience that can be extrapolated to other groups of rare diseases to improve the community’s chances of successfully bringing new rare disease drugs to registration and ultimately to market.
    Orphanet Journal of Rare Diseases 04/2015; 10(1):49. DOI:10.1186/s13023-015-0258-1 · 3.96 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Matrix degradation is central to tumor pathogenesis. Enzymes that degrade extracellular matrix are abundant in tumors. But which out of the complex mixture of cells that form a tumor produces them? Surprisingly, several hundred studies devoted to this question have provided confusion rather than clarity. Our analysis of these studies identifies likely reasons as to why this may be the case, which has implications for the broader issue of research reproducibility.
    The Journal of Cell Biology 04/2015; 209(2):195-198. DOI:10.1083/jcb.201501034 · 9.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The effect that sponsorship has on publication rates or overall effect estimates in animal studies is unclear, though methodological biases are prevalent in animal studies of statins and there may be differences in efficacy estimates between industry and non-industry sponsored studies. In the present analysis, we evaluated the impact of funding source on publication bias in animal studies estimating the effect of statins on atherosclerosis and bone outcomes. We conducted two independent systematic reviews and meta-analyses identifying animal studies evaluating the effect of statins on reducing the risk of atherosclerosis outcomes (n = 49) and increasing the likelihood of beneficial bone outcomes (n = 45). After stratifying the included studies within each systematic review by funding source, three separate analyses were employed to assess publication bias in these meta-analyses-funnel plots, Egger's Linear Regression, and the Trim and Fill methods. We found potential evidence of publication bias, primarily in non-industry sponsored studies. In all 3 assessments of publication bias, we found evidence of publication bias in non-industry sponsored studies, while in industry-sponsored studies publication bias was not evident in funnel plots and Egger's regression tests. We also found that inadequate reporting of sponsorship in animal studies is still exceedingly common. In meta-analyses assessing the effects of statins on atherosclerosis and bone outcomes in animal studies, we found evidence of publication bias, though small numbers of industry-sponsored studies limit the interpretation of the trim-and-fill results. This publication bias is more prominent in non-industry sponsored studies. Industry and non-industry funded researchers may have different incentives for publication. Industry may have a financial interest to publish all preclinical animal studies to maximize the success of subsequent trials in humans, whereas non-industry funded academics may prefer to publish high impact statistically significant results only. Differences in previously published effect estimates between industry- and non-industry sponsored animal studies may be partially explained by publication bias.
    BMC Medical Research Methodology 03/2015; 15(1). DOI:10.1186/s12874-015-0008-z · 2.17 Impact Factor