As with other types of research, the limitations of this systematic review are important to recognize. These can be divided into 2 groups, those relating to generalizability of the results and those relating to methodology within the scope of this review. The generalizability of the results are limited by the scope of the Key Questions and inclusion criteria and by the generalizability of the studies included. Most studies included narrowly defined populations of patients who met strict criteria for case definition, had few comorbidities, and used few or no concomitant medications. Minorities, older patients, and the most seriously ill patients were underrepresented.

Methodological limitations of the review within the defined scope included the exclusion of studies published in languages other than English and lack of a specific search for unpublished studies.