治験概要ドメインで FDA 申請をスピードアップ

試験データを標準化するうえで不可欠な治験概要(TS:Trial Summary)ドメインですが、 FDA は2016年7月、試験データ技術的適合ガイド (Study Data Technical Conformance Guide) の 3.1 版を発行し、申請の際に研究開始日を特定する TS ドメインを含めるよう指示しました。治験においては、最初に被験者から出されたインフォームドコンセントの日付が研究開始日、非臨床研究の場合は研究に着手した日(プロトコルの最終決定日)が研究開始日となります。この記事では研究開始日の重要性を取り上げ、進行中あるいはこれまでの研究における申請を成功させるためのアドバイスを提供します。

Checking conformance to the standards

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.

Reviewing your legacy studies

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.

Handling blended studies

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

Reference:

  1. CDER Small Business and Industry Assistance (CDER SBIA) Webinar – Study Data Standards in eCTD: What You Need to Know about the New Technical Rejection Criteria. Presented October 12, 2016.