In a previous post, I discussed the importance of proper use of CDISC Controlled Terminology (CDISC CT) in SDTM. However, the CDISC-CT is not the only submission terminology you need to be familiar with when building SDTM datasets to be submitted to the FDA (and similarly to the PMDA). As per the FDA Data Standards Catalog, when submitting datasets to the agency, you need to follow not only the CDISC standards (SDTM, ADAM, define-xml and CDISC-CT) but also a number of other submission terminologies. For example, this is the case of MedDRA when your SDTM package contains Adverse Events data, or WHO Drug Dictionary for Medications, but there are also a number of other submission terminologies you need to apply, particularly in the TS – Trial Summary Dataset.
A number of presentations and papers have been published discussing TS domain and clarify requirements that are not always fully clear in the SDTM IG or in the agencies Technical Conformance Guide.
In this blog, I focus on TS and discuss some specific parameters that you need to submit in TS using various “external” dictionaries, and help you understand how to find the correct term (and code).
Let us start with the ones mentioned in the FDA Data Standards Catalog.
UNII (Unique Ingredient Identifiers)
This a system used to classify and code “active ingredients” that are administered to investigational subjects in a study, and it is maintained by the FDA. In TS, UNII should be used when providing values for the following parameters:
TRT (Investigational Therapy or Treatment)
CURTRT (Current Therapy or Treatment)
COMPTRT (Comparative Treatment Name)
MED-RT (Medication Reference Terminology)
This a system used to classify and code Pharmacological Classes and it is maintained by the Department of Veterans Affairs/Veterans Health Administration. It is the successor of NDF-RT (Veterans Health Administration’s National Drug File). In TS, the parameter PCLAS (Pharmacological Class) should be submitted using the MED-RT classification system.
SNOMED CT (Systematized Nomenclature of Medicine)
While MedDRA is the standard to report adverse events to regulatory agencies and it is now systematically applied in all phases of clinical trials, SNOMED CT provides broad coverage of clinical medicine, including findings, diseases, and procedures, and is used in electronic medical records. SNOMED is used in TS to classify and code the following parameters:
INDIC (Trial Disease/Condition Indication)
TDIGRP (Diagnosis Group)
DUNS (Data Universal Numbering System)
This is a unique nine-digit identifier assigned to all businesses required to register with the US Federal Government. This should be used when sponsor entity name is provided in TS through TSPARMCD=SPONSOR.
Where to search for the appropriate term and code
A good way of searching for the most appropriate term and code is the NCI Term Browser. This is your “gateway”, among many, for MED-RT and SNOMED.
Once you select the “classification system” you want to browse and after accepting the “copyright/license statement, through the “Search” field you can browse for your term. For example, when I search for “Multiple Sclerosis”, I get 26 results from which I select “Progressive multiple sclerosis”, the exact indication of my study. I get the details shown in the screenshot below, where “Progressive multiple sclerosis” will be the term to be used in TSVAL, and “816984002” is the code to be stored in TSVALCD.
For UNII, the FDA Substance Registration System (SRS) can be browsed through a search field, similar to what I have described for the NCI portal. For example, the following screenshot is the result of my search for “ACETIL ACID” (TSVAL with TSVALCD=48U6WC1H35).
From the same portal, you can also download the full list in a text file and you can then copy it to the appropriate folder for Pinnacle21 validation (although, for both Enterprise and Community version 3.x, Pinnacle21 performs regular automatic update for you).
The SRS is also a part of openFDA, an Elasticsearch-based API that serves public FDA data about nouns like drugs, devices, and foods; if you are a developer, you may consider accessing SRS data directly through the openFDA API.
DUNS Number can be also searched in an FDA SRO List (Significantly Regulated Organizations) portal.
Of course, the sponsor is responsible for the accuracy of the information stored in TS, so the main recommendation is to get the full TS reviewed by the sponsor. Correct identification of “Sponsor Identity” in the DUNS system or understanding which Pharmaceutical Class a treatment belongs to, could be challenging for most of us.
Use the link in the reference below for more tips and tricks on how to correctly retrieve terms and codes, to be stored in TS.
Angelo Tinazzi is Senior Director, Statistical Programming, Clinical Data Standards and Clinical Data Submission at Cytel. He is a well- published and recognized expert in statistical programming with over 20 years' experience in clinical research. The application of CDISC standards in different therapeutic areas is part of his core expertise since 2003 in particular in the context of data submission to health authorities such as the FDA and PMDA.
Angelo is an authorized CDISC instructor and member of the CDISC ADaM Team as well as the CDISC European Committee where he also manages the Italian-speaking CDISC User Network.