FDA Requirements for Providing Datasets for Nonclinical Studies in SEND Format

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The CDISC Standard for the Exchange of Nonclinical Data (SEND) provides the structure and implementation rules for the submission of computer readable datasets. SEND is one of the required standards for data submission to the U.S. Food and Drug Administration (FDA) and specifies a way to collect and present nonclinical data in a consistent format. The overall package consists of several components, but the focus is on individual study endpoint data which are typically mapped to datasets in domains with several variables in each study dataset.

Data Standards

SEND is evolving with input from sponsors and various stakeholders. FDA continues to implement data standards for study data through the acceptance of the SDTM and ADaM standards for clinical data and the SEND standard for non-clinical data. FDA mandated that all studies started on or after December 17, 2016 are required to use the data standards listed in the FDA Data Standards Catalog or the application may receive a refuse-to-file action. FDA also plans to implement a process to check adherence to the rejection criteria at the time of application submission and validation, and will notify the applicant if the submission is rejected.

As a result of the growing trends for new versions, the SEND implementation guides continue to add domains to the standard. FDA is still strict about rejecting submissions if they do not contain the specific SEND dataset (usually endpoints) or SEND package along with its companion transformation file. The SENDIG notes that the following domains generally form the foundation of each SEND package: TS, TX, DM, and EX, along with at least one endpoint-related domain dataset (such as BW for body weights); however, the list of domains will be specific to each package and what data were collected.

Below is an example set of files for a simple submission with body weights and clinical observations:

  • xml – to describe what is in the submission, such as the columns, comments about the columns, data types, Controlled Terminology used, and so on.
  • define-1-0-0.xsl – a static file which allows a visual presentation of the information in the define.xml file when opened with a browser.
  • xpt – Trial Summary (TS) dataset, which provides high-level details about every study. (Note: All .xpt files with the correct file tags). A TS dataset must be included for each study, even if the study started prior to December 17, 2016, and non-clinical legacy data in PDF format should be submitted along with a TS dataset.
  • xpt – Trial Arms dataset, which provides a specification of the sequence of planned treatment-related events in the study.
  • xpt – Trial Elements dataset, which provides a listing of the treatment-related events in the study used in Trial Arms.
  • xpt – Trial Sets dataset, which provides group information.
  • xpt – Demographics dataset, which provides a listing of the animals on study in Module 4, section 4.2.
  • xpt – Exposure dataset, which provides dosing information.
  • xpt – Body Weights dataset, which provides body weight results collected on study.
  • xpt – Clinical Observations dataset, which provides clinical observation results collected on study.
  • An nSDRG (Nonclinical Study Data Reviewer’s Guide).

Additonally, the following is also generally needed:

  • A cover letter (e.g., summarizing what’s in the submission, reiterating some of the information provided when initiating the submission process, etc.)

nSDRG

Nonclinical Study Data Reviewers Guide (nSDRG) is a document which is meant to aid the reader in understanding the SEND dataset in the context of the study report. The Technical Conformance Guide published by the FDA states that it is “recommended as an integral part of a standards-compliant study data submission.” While the content and the proper format of an nSDRG are not mandated, FDA has provided some expectations in the Technical Conformance Guide. It also helps the reviewers to understand and identify the list of domains in need of improvement for future scopes. On these and other potential issues, FDA continues to collaborate with sponsors through a PhUSE working group to modify SEND to meet the nonclinical reviewers’ needs for future development.

SEND Dataset Variables

The “Core” column in the SENDIG clearly talks about each variable and whether to include the variable in the dataset. It is good practice to include Req (a.k.a., ‘required,’ meaning not nullable) and Exp (a.k.a. ‘expected,’ meaning with or without data, but should have a good reason if not populated). Perm (a.k.a. ‘permissible,’ meaning can be excluded from the dataset if you do not collect it, i.e., either/or) if you have data to report in them in the domain dataset.

Inclusion of Pre-test/Stock Animals in the SEND Dataset

The animals included in a SEND dataset should be consistent with the animals included in the study data report. Generally, this means including pre-test/stock animals if they have been assigned to a test treatment group and have study data collected.

Submission Types and Study Art Timing with Examples

Submission Types and Study Start Timing with examples

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Author: Mahumood Hameed

Mahumood Sahul Hameed, MSc is a CDSIC standards Subject Matter Expert/Certified Senior Statistical Programmer in the Clinical Trial Transparency and Disclosure Team. His work is centered on developing and integrating innovative statistical approaches to Data Anonymization and Risk assessment methodologies. Broadly, Mahumood’s works on advanced data analysis utilizes data mining techniques and designs and produces complex statistical models to address a variety of business opportunities for the organization. Within data sharing policy, Mahumood develops complicated algorithms and uses advanced analytic tools to develop and evaluate a broad spectrum of analytics for large data sets. He co-leads several leadership teams to identify and analyze business problems in the areas of submission to the agency. Mahumood also co-leads in developing the platform to generate the safety and efficacy reports for various submission based on SAP and requirement from Medical writers. He also co-authored standard operating procedures for various submissions, contributed to manuscript writing and review, and generated recommendations regarding statistical methods and analyses.

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