CDISC SDTM Implementation Guide (Version 3.2)

1 Introduction¶

1.1 Purpose¶

This document comprises the CDISC Version 3.2 (V3.2) Study Data Tabulation Model Implementation Guide for Human Clinical Trials (SDTMIG), which has been prepared by the Submissions Data Standards (SDS) team of the Clinical Data Interchange Standards Consortium (CDISC) . Like its predecessors, V3.2 is intended to guide the organization, structure, and format of standard clinical trial tabulation datasets submitted to a regulatory authority such as the US Food and Drug Administration (FDA) . V3.2 supersedes all prior versions of the Study Data Tabulation Model Implementation Guide for Human Clinical Trials (SDTMIG).

The SDTMIG should be used in close concert with the current version of the CDISC Study Data Tabulation Model (SDTM, available at http://www.cdisc.org/sdtm)that describes the general conceptual model for representing clinical study data that is submitted to regulatory authorities and should be read prior to reading the SDTMIG. V3.2 provides specific domain models, assumptions, business rules, and examples for preparing standard tabulation datasets that are based on the SDTM.

Tabulation datasets, which are electronic listings of individual observations for a subject that comprise the essential data reported from a clinical trial, are one of four types of data currently submitted to the FDA along with patient profiles, listings, and analysis files. By submitting tabulations that conform to the standard structure, sponsors may benefit by no longer having to submit separate patient profiles or listings with a product marketing application. SDTM datasets are not intended to fully meet the needs supported by analysis datasets, which will continue to be submitted separately in addition to the tabulations. Since July 2004, the FDA has referenced use of the SDTM in the Study Data Specifications for the Electronic Common Technical Document, available at http://www.fda.gov/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/.

The availability of standard submission data will provide many benefits to regulatory reviewers. Reviewers can be trained in the principles of standardized datasets and the use of standard software tools, and thus be able to work with the data more effectively with less preparation time. Another benefit of the standardized datasets is that they will support 1) the FDA's efforts to develop a repository for all submitted trial data, and 2) a suite of standard review tools to access, manipulate, and view the tabulations. Use of these data standards is also expected to benefit industry by streamlining the flow of data from collection through submission, and facilitating data interchange between partners and providers. Note that the SDTM represents an interchange standard, rather than a presentation format. It is assumed that tabulation data will be transformed by software tools to better support viewing and analysis.

This document is intended for companies and individuals involved in the collection, preparation, and analysis of clinical data that will be submitted to regulatory authorities.

1.2 Organization of this Document¶

This document is organized into the following sections:

�� Section 1 -Introduction , provides an overall introduction to the V3.2 models and describes changes from prior versions.
�� Section 2 -Fundamentals of the SDTM , recaps the basic concepts of the SDTM, and describes how this implementation guide should be used in concert with the SDTM.
�� Section 3 – Submitting Data in Standard Format , explains how to describe metadata for regulatory submissions, and how to assess conformance with the standards.
�� Section 4 – Assumptions for Domain Models , describes basic concepts, business rules, and assumptions that should be taken into consideration before applying the domain models.

CDISC SDTM Implementation Guide (Version 3.2)

�� Section 5 – Models for Special-Purpose Domains , describes special-purpose domains, including Demographics, Comments, Subject Visits, and Subject Elements.
�� Section 6 – Domain Models Based on the General Observation Classes , provides specific metadata models based on the three general observation classes, along with assumptions and example data.
�� Section 7 -Trial Design Datasets , provides specific metadata models, assumptions, and examples.
�� Section 8 – Representing Relationships and Data , describes how to represent relationships between separate domains, datasets, and/or records, and information to help sponsors determine where data belongs in the SDTM.
�� Appendices provide additional background material and describe other supplemental material relevant to implementation.

1.3 Relationship to Prior CDISC Documents¶

This document, together with the SDTM, represents the most recent version of the CDISC Submission Data Domain Models. Since all updates are intended to be backward compatible the term "V3.x" is used to refer to Version 3.1 and all subsequent versions. The most significant changes since the prior version, V3.1.3, include:

��Conversion of SDTMIG from a single document to a PDF Portfolio, or a collection of multiple files assembled into an integrated PDF unit. Not all PDF viewers can display a PDF portfolio, but any PDF viewer which supports Flash should display the PDF portfolio as intended. The "At A Glance" file offers a few options.
��Breakup of Sections 5 and 6 into Domain or topic documents (one per domain or one per set of specialty domains)
�� For the individual Domain Documents, the numbering schema has been replaced by a clear and consistent organization with smaller sub-sections such as "Description/Overview", "Specification", "Assumptions", and "Examples"; this approach will enable: 1.
1. Domains to be listed in alphabetical order (by their two-letter domain code)
2. Group related domains into single document where it makes sense to describe them together (e.g., Microbiology domains MS and MB, Pharmacokinetics domains PP and PC)
3. Insert new domains in the future without having to renumber those from previous releases
��Cross-referencing of Sections, sub-sections, assumptions, examples, appendices have all been harmonized with the following format:

o Section/Appendix-number: sub-section-number, [segment header], title

where [segment header] may be a named example or assumption title is the actual title of the document, section or sub-section being referenced

��An enhanced Exposure (EX) domain in Section 6.1
��The following new domains in Section 6.1 -Interventions: Exposure as Collected (EC) and Procedures (PR)
��The following new domain in Section 6.2 -Events: Healthcare Encounters (HO)
�� The following new domains in Section 6.3 Findings: 1.
1. Death Details (DD)
2. Immunogenicity Domain: Immunogenicity Specimen Assessment (IS)
3. Microscopic Findings (MI)
4. Morphology (MO)
5. Reproductive System Findings (RP)
6. Subject Status (SS)
��The following new Immunogenicity domain: Section 6.4 – Skin Response (SR)
��A complete re-design of Section 7, where In the same way that Sections 5 & 6 have been turned into a collection of more granular documents, each describing a single domain, or a collection of related ones, Section 7 is now a set of smaller documents that better organizes the Trial Design datasets
��The following new domain in Section 7 -Trial Design: Trial Disease Assessment (TD)
��Updated Controlled Terminology for applicable variables across all domains, if available.

CDISC SDTM Implementation Guide (Version 3.2)

��Reduction of Appendix C to contain only Trial Summary Codes and Supplemental Qualifiers Name Codes ; this is being done as CDISC Terminology is centrally managed by the CDISC Controlled Terminology Team, and up-to-date CDISC Terminology information is best found at the NCI Enterprise Vocabulary Serviceswebsite
��Removed the References column from all domain models specifications.

A detailed list of changes between versions is provided in Appendix E -** Revision History**.

V3.1 was the first fully implementation-ready version of the CDISC Submission Data Standards that was directly referenced by the FDA for use in human clinical studies involving drug products. However, future improvements and enhancements such as V3.2 will continue to be made as sponsors gain more experience submitting data in this format. Therefore, CDISC will be preparing regular updates to the implementation guide to provide corrections, clarifications, additional domain models, examples, business rules, and conventions for using the standard domain models. CDISC will produce further documentation for controlled terminology as separate publications, so sponsors are encouraged to check the CDISC website (http://www.cdisc.org/terminology ) frequently for additionalinformation. See Section 4: 4.1.3, Coding and Controlled Terminology Assumptions for the most up-to-date information on applying Controlled Terminology.

1.4 How to Read this Implementation Guide¶

This SDTM Implementation Guide (SDTMIG) is best read online, so the reader can benefit from the many hyperlinks included to both internal and external references. The following guidelines may be helpful in reading this document:

��First, read the SDTM to gain a general understanding of SDTM concepts.
��Next, read Sections 1-3 of this document to review the key concepts for preparing domains and submitting data to regulatory authorities. Refer to the Glossary in Appendix B -Glossary And Abbreviations as necessary.
��Read the Section 4 -Assumptions For Domain Models.
��Review Section 5 – Models For Special-Purpose Domains and Section 6 – Domain Models Based On The General Observation Classes in detail, referring back to Assumptions as directed (hyperlinks are provided). Note the implementation examples for each domain to gain an understanding of how to apply the domain models for specific types of data.
��Read Section 7 -Trial Design Datasets to understand the fundamentals of the Trial Design Model and consider how to apply the concepts for typical protocols. New extensions to the trial design model will be published separately on the CDISC website.
��Review Section 8 -Representing Relationships and Data to learn advanced concepts of how to express relationships between datasets, records and additional variables not specifically defined in the models.
��Finally, review the Appendices as appropriate. Appendix C – Controlled Terminology , in particular, describes how CDISC Terminology is centrally managed by the CDISC Controlled Terminology Team; efforts are made at publication time to ensure all SDTMIG domain/dataset specification tables and/or examples reflect the latest CDISC Terminology; users, however, should frequently refer to Appendix C – Controlled Terminology as CDISC terminology is updated on a quarterly.

1.5 Submitting Comments¶

Comments on this document can be submitted through the CDISC Discussion Forum.