Unresolved issues with noninferiority pragmatic trials: Results of a literature survey.

Specification of margins, adherence, and analytic population require careful consideration to prevent bias toward the alternative in noninferiority pragmatic trials. Although separate guidance has been developed for noninferiority and pragmatic trials, it is not compatible with conducting a noninferiority pragmatic trial. Hence, these trials should probably not be done in their current format without developing new guidelines.