Hierarchical levels of evidence based medicine are incorrect.

Background“Evidence based medicine insists on rigorous standards to appraise clinical interventions. Failure to apply the same rules to its own tools could be equally damaging” - Joseph L, Ioannidis JPA, Norma T, et al. The case of the misleading funnel plot BMJ 2006; 333:597.

Aims Hypothesis: Hierarchical levels of evidence based medicine are incorrect.

ObjectiveTo analyze the strength of evidence provided by different types of study designs: systematic reviews and meta-analysis, controlled clinical trials, and observational studies (case-control, cohort, and cross-sectional).

MethodsAnalysis of public databases (e.g., ClinicalTrials.gov, PubMed, ISI Web of Knowledge, Embase, and WHO ICTRP) according to the following variables: geographical locations, sponsors (i.e., industry and non-industry), study designs, conditions (diseases), and interventions (pharmacological and non-pharmacological).

Estimation of unpublished clinical trials according to the variables listed above.

Analysis of publication bias in systematic reviews and meta-analysis.

ResultsData and analysis supports the hypothesis in the title of this abstract.

ConclusionsHuman pharmacology is a non-linear science created by multiple variables at different levels of complexity:1. Drug effects at molecular and cellular levels: drug-receptor interaction (pharmacodynamics) and drug disposition (pharmacokinetics)

2. Effects of drugs on human health and disease: safety, efficacy, and effectiveness

3. Effects of drugs in the society: economical aspects (i.e., pharmacoeconomics), epidemiology (i.e., pharmacological surveillance), healthcare systems (i.e., definitions of essential medicines), over the counter availability of medicines, drug addiction, and many other variables.

Hierarchical levels of evidence-based medicine (EBM) are over-simplistic to understand complex relationships involved in human pharmacology. The first EBM article matching search terms in PubMed was published in 1992. The model of drug approval into the market, as well as our methods for appraisal of the evidence involving therapeutic interventions in humans, are supported by opinions instead of real data (i.e., evidence).Evidence-based medicine is not "evidence-based".

Referenceshttp://www.bmj.com/content/348/bmj.g3725/rr/762595http://dx.doi.org/10.6084/m9.figshare.1093997