The first article is on issues that can limit the ability to generalize data from randomized trials and systematic reviews into clinical practice.

Subsequent articles will reflect common clinician concerns about subgroups, meta-analyses, and risk.

Oxford University's Peter Rothwell, author of the first article, says: "(Randomized Clinical Trials) and systematic reviews cannot be expected to produce results that are directly relevant to all patients and all settings, but to be externally valid they should at least be designed and reported in a way that allows patients and clinicians to judge to whom they can reasonably be applied."

Among his recommendations are further research into the external validity of RCTs, particularly in relation to the measured treatment effect, and stricter requirements for the external validity of RCTs submitted to pharmaceutical licensing authorities.