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Regulatory Landscape

Clinical study data is defined by the FDA as information about a person in a clinical trial, that may include information, details of medical treatment, descriptions of the participant’s progress, and other relevant information. In early studies, this same information is captured for animals and is called nonclinical study data. The FDA requires that submission of IND (for studies starting after Dec. 17, 2017), NDA, ANDA, BLA (for studies starting after Dec. 17, 2016) and any subsequent submissions to those applications, should comply with data standards at the time of the study’s start date.

The standard data formats supported by the FDA are:

  • CDISC Standard for Exchange of Nonclinical Data (SEND) for nonclinical data
  • CDISC Study Data Tabulation Model (SDTM) for clinical data
  • CDISC Analysis Data Model (ADaM) for analysis of clinical data
  • CDISC Case Report Tabulation Data Definition Specification (Define-XML) for the metadata that accompany SEND, SDTM, and ADaM datasets

In Addition, Therapeutic Areas (TA) standards are constantly under development as a joint effort between CDISC consortium, the FDA and additional collaborators with an aim to provide guidance on data standardization for specific medical conditions. The TA standards include guidance relating to the domains and datasets that should be used when collecting data, what variables should be used to represent data items, definitions of SUPP variables and data relations across domains. In addition, examples of annotated CRFs may be provided as guidance for annotation as well as table shells and sample analysis datasets.

Currently the FDA supports TA standards for the following areas: Chronic Hepatitis C, Diabetes, Dyslipidemia, Diabetic Kidney Disease, Ebola, Kidney Transplant, Malaria, QT Studies, Rheumatoid Arthritis and Tuberculosis.

In addition to the above-mentioned data standards, submissions to CBER are recommended to be accompanied by a Study Data Standardization Plan (SDSP) that outlines the anticipated structure of the standardized data submissions. The SDSP is used for early communication between the Sponsor and the CBER reviewer (mostly the RPM – Regulatory Project Manager) regarding their CDISC submission plan, and may also be used as a reference during IND meetings. The SDSP includes the expected CDISC data submission structures (i.e. SDTM and ADaM datasets, information regarding the ISS and ISE formation, traceability, supplemental qualifiers, standard version, etc.). Another important consideration is related to customized domains, for which the sponsor is expected to consult with CBER prior to any use of such domain.

Recently, the FDA has published a new version of the Technical Conformance Guide (TCG), outlining additional criteria for the submission of module 4 and module 5 sections to be effective post a 30 day notice from the FDA. The FDA has defined that every study pertaining to these sections must be accompanied with SDTM TS (Trial Summary), DM (Demographics) domains and define.xml (for sections in module 4 and 5) and also ADaM ADSL (Analysis Data Subject Level) domain for Module 5 sections.

Study data requirements for regulatory clinical data submissions based on CDISC data standards are gradually being adopted and supported by the FDA as the only acceptable data submission standard. The use of such standards requires up to date professional knowledge and technical know-how, together with vast experience relating to the implementation and validation of these standards in various clinical data study designs and different therapeutic areas.