On November 29th, CDISC released updated versions of SDTM and ADaM, including standardized structures for medical devices and new non-compartmental analysis data.

Moving to new versions of standards is always a challenge and requires planning. Pinnacle 21's subject matter experts Trevor Mankus and Michael Beers summarized key changes and answered industry questions in this webinar and the discussion below, so you can better prepare to up-version your study data.

ADaM Medical Devices (ADaMIG-MD)

The device-level analysis dataset (ADDL) plays a similar rule as the ADSL dataset, except that the identifier of interest is the device rather than the subject. It’s the source for device-level variables, such as device-specific demographics, characteristic, and treatment timing variables. In practice, you can use the ADDL dataset in the same way as ADSL, in that you can merge data with any other dataset containing the device identifier.

Note: ADDL might not be required in a simple one-device-per-subject study because the device characteristics could be accommodated in ADSL. However, if a clinical study involves multiple devices per subject or multiple subjects per device, an ADDL dataset becomes required. However, even when it is not required, programmers may choose to create an ADDL dataset for all trials in which medical devices are analyzed, to be consistent.

While ADSL is required for pharmaceutical and biologic studies, it is required for medical device studies only when subject information is collected and is to be analyzed.

ADaM Non-compartmental Analysis (ADNCA)

The input data format for NCA must associate subject drug concentrations over time with study drug dosing. It should support the exclusion of specific records and subjects and provide other supporting information as needed. While the input data typically comes from the Pharmacokinetics Concentrations (PC) domain, you may use multiple CDISC source datasets to populate ADNCA based on the analysis need. Outside of the SDTM PC domain, ADaM sources are expected to be the most common and used sometimes with other sources to create this dataset. All data sources used must be submitted to regulatory bodies. The NCA dataset structure can also be leveraged for pharmacodynamics (PD) analysis where the primary dataset source is not PC. In that case, it is assumed that the relevant traceability variables and domain references will be included in place of PC.

The output from NCA is the PK parameter calculation per subject. These calculations are based on the specific dosing regimen, collection schedule, and the objectives associated with parameter calculations. These outputs are then typically reported in the SDTM Pharmacokinetics Parameters (PP) domain.

Support in P21 Software

Our P21 subject matter experts are working to write and test Validation Rules to support these new standards. One challenge is the new concepts that are now used to decide when Rules should fire (e.g., SubClass). Once we have finalized the Rules themselves, we will publish them under a new Engine. Changes will be documented in detail within the Metadata Release Notes (MRNs).

Recommendation for Up-versioning

Generally, for any studies that will be included in a submission to a regulatory agency over 2022–2023, it is likely a good idea to use a currently supported version of the standard, such as SDTM-IG 3.3. For longer-term studies, up-versioning to the new SDTM-IG 3.4 may be safe, depending on how long-term, in anticipation of its being added at some point to the Data Standards Catalog.

There is typically a significant delay between publication by CDISC and ability to use in an agency submission. For example, here is the timeline from SDTM-IG 3.3's being published, to being able to use it in a submission, to being required to use it:

• 2018-11-20 Published by CDISC
• 2020-07-07 Added to the FDA’s Data Standards Catalog
• 2021-03-15 Support Begins (FDA)
• 2023-03-15 Requirement Begins (FDA)

From publication by CDISC to the mere ability to use it (“support”) in an FDA submission, the delay was over two years. This doesn’t necessarily mean that it will be the same for SDTM-IG 3.4—this timeline for the previous version simply illustrates the possible delay.

Note: Due to the flexibility of the ADaM standard (compared to SDTM) and backwards compatibility, you can likely up-version to new versions of ADaM-IG, but state that it is an older, supported version of ADaM-IG in the define.xml and Reviewer’s Guide, and still be compliant.

If you have any concerns, it is a good idea to check with FDA eDATA (cder-edata@fda.hhs.gov or cber-edata@fda.hhs.gov or cdrh.datastandards@fda.hhs.gov), or even your regulatory review division, for guidance on how to handle studies in your submission.

Handling Data Previously Mapped to the MO (Morphology) Domain

Section 6.3.6 of SDTM-IG 3.4 includes an update on the decommissioning of the MO domain, including the history of the decision-making that led to the update. There is guidance for updating mapping of data that you may have been using the MO domain for. The SDTM-IG defines body-system domains that should be used instead of the MO domain, such as:

• CV (Cardiovascular System Findings)
• MK (Musculoskeletal System Findings)
• NV (Nervous System Findings)
• OE (Ophthalmic Examinations)
• RP (Reproductive System Findings)
• RE (Respiratory System Findings)
• UR (Urinary System Findings)

These domains were introduced in the previous version of the SDTM Implementation Guide: SDTM-IG 3.3. Although SDTM-IG 3.3 states, “For data prepared using a version of the SDTMIG that includes both the MO domain and body system-based physiology/morphology domains, morphology findings may be represented in either the MO domain or in a body system based physiology/morphology domain,” we recommend simply moving to the appropriate body system domains now and leaving the MO domain behind.

If we missed any burning questions or topics, check out the full webinar and slide deck to see if we covered it. If you still have other questions, please feel free to contact us!