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I think all of us were haunted by the “levels of evidence pyramid” in our pharmacy school days.  As you move up the pyramid, the quality of evidence increases. Systematic reviews are summaries of evidence pertaining to a specific clinical question.  They collect results from case control studies, cohort studies, animal studies and randomized controlled studies to give an overall trend. Generally, randomized controlled trials are thought of as the gold standard of clinical trials.
Cohort and case control studies are both observational in nature, meaning subjects are not randomized to exposure or non-exposure.  I always mixed up these types of studies, so I've included some schematics trying to explain them. Case reports and series are reports of a single patient or very small groups of patients that something interesting happens to.   There are no control groups and these generally tend to be descriptive in nature.



As shown in the pyramid, these tend to be considered the bottom of the barrel in terms of robustness of information. There appeared to be case reports and animal studies that supported an interaction between methotrexate and beta-lactam antibiotics.  Patients ranged in age from 8-50 years of age and concurrent antibiotics included amoxicillin, piperacillin-tazobactam, ceftazadime, oxacillin and mezlocillin. Animal studies in rabbits and monkeys showed that penicillin and piperacillin both decreased elimination of methotrexate while the cephalosporin ceftriaxone did not appear to affect eliminiation. In our case, it was clear that there was room for more research in this area, as we were unable to find anything more than case reports and animal studies.  Stay tuned for next entry with tricks to appraisal of information! However, in practice, finding evidence that would qualify as being “ideal research” is difficult.  I know that, in pediatrics, we are usually not fortunate enough to have prospective, randomized, double blind studies for every clinical question so it becomes important to realize the differences in the types of studies that can be done.


Essentially, a meta-analysis is a type of systemic review that combines the results of all available trails as if they were one large study.  This increases sample size, which can be especially useful for disease states that are not common leading to many studies with small sample sizes. In prospective studies, you identify patients with and without the risk factor of interest and follow them to see if they develop the outcome of interest in the future (i.e.
Although expert opinion is generally well informed (these are, after all, experts in whatever field they are voicing their opinion about), these tend to be based on anecdotal evidence and are especially susceptible to bias from whoever is writing them.



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