ABSTRACT
In clinical trials, it is not uncommon to issue protocol amendments during the conduct of a clinical trial due to various reasons such as slow enrollment and/or safety concerns. For slow enrollment, the investigator may modify the entry (inclusion/exclusion) criteria in order to expedite patient enrollment in a timely fashion. On the other hand, during the conduct of a clinical trial, it is possible that additional safety information may become available. This additional safety information may come either from similar clinical trials conducted simultaneously or from publications newly published in leading medical journals. With this additional safety information, protocol amendment is necessarily issued for patient protection. For good clinical practice (GCP), before protocol amendments can be issued, description, rationales, and clinical/statistical justiŒcation regarding the changes made should be provided to ensure the validity and integrity of the clinical trial. As a result of the changes or modiŒcations, the original target patient population under study could have become a similar but different patient population. If the changes or modiŒcations are made frequently during the conduct of the trial, the target patient population is in fact a moving target patient population. This raises the controversial issue regarding the validity of the statistical inference drawn based on data collected before and after protocol amendment.
