Abstract: Methods of designing a hybrid clinical trial including an external control arm (ECA) study located in at least one site, to support a randomized clinical trial (RCT) study for a treatment of a condition are disclosed. A Mahalanobis distance value is calculated based on a point comprising a set of values corresponding to a first plurality of feature variables corresponding to at least one ECA candidate; and a distribution of points comprising a set of values corresponding to the first plurality of feature variables of each of a plurality of RCT participants that have received the treatment. ECA candidates may be excluded as ECA participants if they are deemed outliers based on the Mahalanobis distance value. Recruitment is dynamically adjusted into at least one ECA participant site database by comparing sets of feature variables in at least one ECA participant site database to corresponding sets of feature variables in the RCT participant database.