SEND 4.0 is almost upon us. Here’s why you will want to review it, and what you need to know to make your review as efficient as possible!
The latest version is about to be released for public review, and this is our chance to really understand what’s changing—and, just as importantly, to comment on it. It’s expected there’ll only be a single public review window, so this is likely the only opportunity we’ll have to influence changes we’ll all eventually need to adopt. Some of these updates could affect how data are recorded and the systems used to manage them, so I’d strongly recommend reviewing the document to make sure your data can be represented as intended.
SEND Implementation Guide v4.0 is, without question, the biggest change I’ve seen to the standard in the 15(ish) years I’ve been involved. The scale of change really shouldn’t be underestimated. The scope of data is expanding significantly, with more study types and results being standardized, and almost all existing SEND domains are changing too. That means major knock-on effects for data we’ve been producing in SEND for years.
While I’d always encourage a full cover-to-cover read, I know time is often limited. So below is a quick guide to the scope of the changes, to help you focus on the areas most likely to impact your organisation. I’d suggest starting there, identifying what matters most to you, and then diving deeper into those sections.
‘til next time,
-Marc
Overview of scope of the most significant changes:
What’s changing
1. Immune System Data Standardisation
We have introduction of new domains to support immunogenicity and immune cell characterisation.
Key changes
- New Immunogenicity Specimen (IS) domain for antigen‑specific immune responses.
- New Cell Phenotyping (CP) domain for characterisation of immune cell populations.
- Expanded use of LB for immune mediators (e.g. cytokines, complement).
- Clear decision logic on how immune data flows across LB, IS, and CP.
Impact
- Enables standardisation of data types previously submitted in non-standard formats.
- Significant impact for organisations running immunology, biologics, vaccines, or cell‑based assays.
2. New Findings Domains (Expanded Test Coverage)
2.1 Nervous System Tests (NV)
What’s changing
New NV domain for neurological and neurobehavioral assessments.
Includes
Functional Observational Battery (FOB), Motor activity, coordination, reflexes, sensory function etc
Impact
Expands the standardisation of safety pharmacology to include CNS test.
2.2 Skin Test Results (SK)
What’s changing
New SK domain for dermal irritation and skin-related assessments.
Includes
Quantitative (e.g. wheal diameter) and qualitative (e.g. erythema, edema) results.
Notes
Studies where the same‑subject is both treated and its own control, remain out of scope.
2.3 Ophthalmic Evaluations (OE)
What’s changing
New OE domain for ophthalmic examinations beyond routine clinical signs.
Includes
Pupillometry, tonometry, specialized eye exams.
Notes
Routine eye observations remain in CL.
Studies where the same‑subject is both treated and its own control, remain out of scope.
2.4 Pharmacokinetic Input (PI) Domain
What’s changing
New PI domain introduced between PC and PP.
Purpose
Stores adjusted concentration values used to derive PK parameters, including:
- Omits values not included in the analysis
- Replaces BLQ / ALQ text with substitute values
Impact
Major conceptual shift in how TK/PK derivations are represented.
May requires changes to PK workflows and reporting.
2.5 Scoring Scales (SX)
What’s changing
New SX domain to fully describe scoring scales used across findings domains.
Key rule
If a scoring scale is used, the entire scale must be represented in SX, even if results use controlled terminology.
Impact
Improves interpretability but requires additional dataset generation and linkage.
3. Updates to existing domains
3.1 Exposure Domain (EX) Updates
What’s changing
Multiple new EX variables added:
EXGRPID, EXOCCUR, EXREASOC, EXLAT, EXDIR, EXFAST
EXDOSFRQ removed.
Clear requirement to include:
- Missed doses
- All planned administrations
- Non-occurrences
Impact
Structural changes to dosing data representation.
3.2 Microscopic Findings (MI) Expansion
What’s changing
Expanded scope to include:
- Carcinogenic studies
- Sexual maturity
- Reproductive cycle phase
- Targeted staining
- Follow-up macroscopic examination
Controlled terminology additions:
- Sexual maturity status
- Reproductive cycle phase
- Result modifiers, specimen condition, methods
3.3 Baseline & Timing Changes
What’s changing
Baseline flag (–BLFL) removed
Improved baseline interpretation via:
- New variables across findings domains
- Explicit inclusion of study phase elements
- Improved representation for studies with multiple baselines (e.g. Latin square studies)
3.4 Domain Deprecations & Removals
What’s changing
Deprecated domains:
- Tumor Findings (TF)
- Body Weight Gain (BG)
3.5 Age Representation Changes
What’s changing
Move from text-based age ranges (AGETXT) to structured numeric values to improve precision and cross-study analysis.
4. Other Domains
4.1 Non-Standard Variables (NS)
What’s changing
SUPP– domains replaced with NS.
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