evidence - based medicine ( ebm ) has been defined as the  integration of best research evidence with clinical expertise and patient values  .
the first historical descriptions of ebm date back to the beginning of 1990s , when the work of gordon guyatt , david sackett and others established the emerging methodologies of ebm , .
the main products of ebm are evidence - based guidelines ( ebgs ) ,  systematically developed statements to assist practitioner and patient decision about appropriate health care for specific clinical circumstances  .
costs , ethical concerns in placebo - controlled trials , publication bias and a real risk of reductionism are the most emphasized limitations of ebm . in order to overcome these limitations and improve ebgs quality standards , different societies ( among which the world health organization , who ) produced guidelines for guidelines developers .
preliminary steps for guideline development are evaluation of priority settings , composition of an expert panel , management of conflicts of interests , determination of appropriate group processes , of important outcomes   and of which evidences have to be included .
then developers have to produce synthesis and presentation of evidences , exposing criteria for grading evidence and recommendations , integrating when possible values ( e.g. ethical considerations ) and consumer involvement .
next , considerations of cost - effectiveness , affordability and resource implications , of equity , applicability , transferability and adaptation   should be included .
the final steps are the report of guidelines recommendations , the dissemination and implementation of guidelines   and their evaluation .
the appraisal of guidelines for research and evaluation ( agree ) instrument was a validated , easy - to - use , and transparent tool , which was internationally developed and widely accepted .
it was developed through a process of item generation , selection and scaling , field - testing and refinement .
the final version of the instrument contained 23 items grouped into six domains : scope and purpose , stakeholder involvement , rigor of development , clarity and presentation , applicability , and editorial independence . despite the good review of the agree instruments , two important limitations are present : although it can be used to compare clinical practice guidelines , agree instrument does not set a threshold to classify them as good or bad , and it does not assess the quality of the evidence supporting the recommendations .
level of evidences and grade of recommendations in fact do not necessarily correlate , since the first is a measure of scientific strength and the latter of clinical utility .
recently , an improved version of the agree , i.e. the agree ii instrument , has been released , , partly overcoming the previous limitations . indeed , the introduction of the new item assessing the description of strengths and limitation of the body of evidences can be considered as a precursor for clinical validity or appropriateness of the recommendations .
the authors recognize the value of this point , in fact they state that the agree consortium is targeting this area as its next priority for further study in the agree a3 initiative . in our opinion , correlating level with grade could be a valid way to integrate the agree ii instrument and quickly display the internal consistence of ebgs .
the guidelines for the treatment of bone metastases by the italian society for medical oncology ( aiom ) are based on : european society for medical oncology ( esmo ) guidance on the use of bisphosphonates in solid tumors   and on the management of aromatase inhibitor - associated bone loss ; cochrane network reviews ; critical review of the literature updated to june 2009 .
the topics covered by the aiom guidelines are use of bisphosphonates in metastatic cancers ; use of bisphosphonates in the prevention and treatment of cancer treatment induced bone loss ; safety of bisphosphonates use ; treatment of bone metastases pain ; role of bisphosphonates in specific settings ; role of orthopedic surgery in bone metastases ; role of radiotherapy in bone metastases .
level of evidences ( i  vi ) and grade of recommendations ( a  e ) were provided according to the recommendations of the italian centre for the evaluation of the efficacy of health assistance coordinated by the italian national health institute ( istituto superiore di sanit ) and are presented in table 1 .
we performed an analysis of levels of evidence and respective grades of recommendations of the guidelines for treatment of bone metastases by aiom .
spearman 's rank correlation coefficient was calculated per each topic of the guidelines , a p value < 0.05 was considered statistically significant .
the final correlation was performed using a linear regression model ( graphpad prims version 5.04 , la jolla california usa ) ; linear r value was reported to weight the results and a p value < 0.05 was considered statistically significant .
the results of our analysis showed a statistically significant correlation between the levels of evidence and the grades of recommendation in the following topics : use of bisphosphonates in metastatic cancers ( p<0.01 ) ; use of bisphosphonates in the prevention and treatment of cancer treatment induced bone loss ( p<0.01 ) ; safety of bisphosphonates use ( p<0.05 ) ; role of bisphosphonates in specific settings ( p<0.01 ) ; role of orthopedic surgery in bone metastases ( p<0.0001 ) ; role of radiotherapy in bone metastases ( p<0.01 ) .
finally , a statistically significant correlation was also found considering all the levels of evidence and grades of recommendation together regardless of the division in topics ( r=0.4454 , p<0.0001 ; fig .
ebgs represent a milestone for modern evidence - based clinical practice ; they indeed substantially improve clinical care .
nevertheless , ebgs frequently vary widely in quality , , thus their evaluation is of critical importance . among several evaluation tools ,
the agree instrument is the most widely used , even though it has known limitations , i.e. the impossibility to classify ebgs as good or bad and to assess the quality of the evidences supporting the recommendations . in order to overcome these limitations
, we performed an analysis of levels of evidence and respective grades of recommendations of the guidelines for treatment of bone metastases by aiom . in six out of seven topics ,
moreover , a statistically significant correlation was also found considering all the levels of evidence and grades of recommendation together regardless of the division in topics .
these results indicate that the authors of the guidelines worked scientifically with a correct approach and that these guidelines are likely to be adherent with modern medical literature .
however , we can not exclude that a significant correlation for some topics could be due to low levels of evidences from medical literature and consequent low grades of recommendations .
moreover , the lack of concordance in specific items could also derive from the impossibility for the physicians to prescribe a specific drug in a specific setting ( i.e. low grade of recommendation ) due to the delayed approval by regulatory agencies ( e.g. fda , ema ) even in presence of adequate scientific literature ( i.e. high level of evidence ) .
the critical evaluation of ebgs is an underestimated issue in current clinical practice . moreover , specific methodological aspects for the evaluation of ebgs are of increasing interest in the medical oncology community .
here we provide clinicians with a quick tool to evaluate the internal consistence of ebgs .
further analysis should confirm the reliability of this method , which could be easily implemented in future ebgs .
 modern clinical practice relies on evidence - based medicine ( ebm ) and evidence - based guidelines ( ebgs ) . 
 the critical evaluation of ebgs value is therefore an essential step to further improve clinical practice . in our opinion , 
 correlating levels of evidence and grades of recommendation can be an easy tool to quickly display internal consistence of ebgs . 
Introduction
Material and methods
Results
Discussion