Outcomes for patients with the same disease treated inside and outside of randomized trials: a systematic review and meta-analysis

Open access

Limitations

Although 68% of the studies included here employed identical follow-up protocols for both “insiders” and “outsiders,” some studies did not explicitly state whether “outsiders” included all eligible patients or only those for whom data could be obtained. If “outsiders” are more likely to become lost to follow-up, in part because they have died or suffered other adverse events, true trial advantages might be missed.

Conclusion

We found no evidence to support either clinically important harm or clinically important benefit when patients’ illnesses were managed inside or outside an RCT. These results can inform discussions between clinicians and the patients to whom they are offering entry into peer-reviewed, ethically conducted RCTs. These results are also relevant to the policies, procedures and actions of institutions, ethics committees and granting agencies that permit and support the execution of RCTs.

Our findings and conclusions are only as good as the publication base of relevant RCTs, and we look forward to the day when the proposals of Vickers160 and Altman and Cates161 are fully realized, with all trials registered and reported and with raw trial data made readily available. When that day arrives, our study should be repeated to determine the validity of the conclusions reached here.