An evaluation of the quality of statistical design and analysis of published medical research: results from a systematic survey of general orthopaedic journals.

BACKGROUND: The application of statistics in reported research in trauma and orthopaedic surgery has become ever more important and complex. Despite the extensive use of statistical analysis, it is still a subject which is often not conceptually well understood, resulting in clear methodological flaws and inadequate reporting in many papers. METHODS: A detailed statistical survey sampled 100 representative orthopaedic papers using a validated questionnaire that assessed the quality of the trial design and statistical analysis methods. RESULTS: The survey found evidence of failings in study design, statistical methodology and presentation of the results. Overall, in 17% (95% confidence interval; 10-26%) of the studies investigated the conclusions were not clearly justified by the results, in 39% (30-49%) of studies a different analysis should have been undertaken and in 17% (10-26%) a different analysis could have made a difference to the overall conclusions. CONCLUSION: It is only by an improved dialogue between statistician, clinician, reviewer and journal editor that the failings in design methodology and analysis highlighted by this survey can be addressed.

Specific in vivo binding of activator of G protein signalling 1 to the Gbeta1 subunit.

Activator of G protein signalling 1 (AGS1) is a Ras-like protein that affects signalling through heterotrimeric G proteins. Previous in vitro studies suggest that AGS1 can bind to G(alpha)-GDP subunits and promote nucleotide exchange, leading to activation of intracellular signalling pathways. This model is consistent with in vivo evidence demonstrating that AGS1 activates both G(alpha)- and G(betagamma)-dependent pathways in the absence of ligand. However, it does not easily explain how AGS1 blocks G(betagamma)-dependent, but not G(alpha)-dependent, signalling following receptor activation. We have used yeast two hybrid analysis and co-immunoprecipitation studies in mammalian cells to demonstrate a direct interaction between AGS1 and the G(beta1) subunit of heterotrimeric G proteins. The interaction is specific for G(beta1) and involves the cationic region of AGS1 and the C-terminal region of G(beta1). Possible implications of this novel interaction for the activity of AGS1 are discussed.