The role of systematic data reviews in safety assessment of infant nutrition.

To make informed, evidence-based decisions regarding whether a given intervention is necessary, information about its benefits as well as harms is needed. Systematic reviews are always at the top of the evidence hierarchy. In general, the methodology for conducting systematic reviews of benefits and safety/harms overlaps. While systematic reviews of randomized controlled trials (RCTs) are sufficient for providing information regarding the efficacy and short-term safety aspects of these trials, they may be insufficient for providing adequate information about long-term safety and consequences. To adequately address harms, systematic reviews should include evidence from both RCTs and non-RCTs. The inclusion of the latter is to be considered particularly for addressing rare adverse effects, long-term adverse effects, or outcomes that were unknown at the time the RCTs were performed.