A Trial Summary (TS) domain represents an essential part of standardizing study data for electronic submissions. In July 2016, the U.S. FDA issued version 3.1 of the Study Data Technical Conformance Guide, which advised including a TS domain to identify the study start date in the submission. In clinical studies, the study start date is earliest date of informed consent from any subject enrolled in the study, whereas nonclinical studies use the study initiation (protocol finalization) date. This article reviews the importance of the study start date and makes recommendations to help ensure a successful submission for current and legacy studies.
To determine if a complete Standard for the Exchange of Nonclinical Data (SEND) dataset is a requirement for inclusion in an eCTD (electronic Common Technical Document) submission, the study start date is the most crucial piece of information. As part of the CDER SBIA webinar series in October 2016, the FDA further clarified this stipulation. In short, this approach was introduced to "implement a process for rejection of submissions that do not conform to the required study data standards."1
More specifically referred to as "technical rejection criteria," the purpose of this initiative is to avoid Refuse to File (RTF)/ Refuse to Review (RTR) submissions, and instead, issue a rejection of a less severe nature. The technical rejection allows the sponsor to correct parts of the submission that failed a conformance validation rather than going back to square one and starting over.
For legacy studies started before December 17th, 2016 (NDA/BLA) or December 17, 2017 (IND), sponsors can avoid a technical conformance failure notice by doing one simple thing:
Include a TS file containing one row of information - the study start date - in .xpt format. Then, with the concise nature of this file, there will be no question as to the status of the study and inclusion/exclusion of SEND formatted data.
It is reasonable to think that for some time, sponsor's submissions will include a blend of studies that are in scope and legacy studies that are out of scope from a regulatory requirement standpoint. When the agency receives the submission, the TS files will be used to sort the studies within their system. Legacy studies will go to a "queue" with no further checks required. In-scope studies will go to a different "queue." Here, further evaluation of the define.xml and DM.xpt files will commence.
Example of the TS.xpt for legacy studies