How and When to Use Toxicity Variables

Introduction

If the safety analysis will report adverse events, clinical events, or laboratory grading according to a standard toxicity grading scale (e.g., Common Terminology Criteria for Adverse Events, CTCAE), then analysis toxicity variables should be implemented. These toxicity variables may be copied directly from SDTM as predecessor variables or they may be imputed or assigned based on the statistical analysis plan and sponsor requirements.

Advice/Instructions/Guidance 

The ADaMIG provides standard toxicity grading variables and their numeric counterparts. For mapping of parameters that have grading in only one direction, ATOXGR and BTOXGR can be used. 

• ATOXGR: toxicity grade of AVAL or AVALC that may be based on --TOXGR in SDTM, imputed, or assigned 
• ATOXGRN: numeric value of toxicity grade 
• BTOXGR: ATOXGR of the baseline record indicated by ABLFL 
• BTOXGRN: numeric value of baseline toxicity grade 

ATOXGRN and BTOXGRN may be copied directly from --TOXGR in SDTM and have values such as 1, 2, 3, 4, and 5. Alternatively, ATOXGR and BTOXGR may be assigned values based on reporting requirements and have values like "Mild", "Moderate", "Severe", "Life-threatening", and "Death". For studies that involve the analysis of lab values graded separately for low and high values, bidirectional mapping is needed and is out of scope for this article.

Example 

The parameters in this example were only graded in the low direction, using the unidirectional toxicity variables discussed in this article. The sponsor chose to assign toxicity values of "Grade 1" to "Grade 5". In the first row, hemoglobin has a value of 9.6 g/dL at visit 1 and 10.5 g/dL at baseline. Using the CTCAE grading scale, this corresponds to an analysis toxicity grading of grade 2 at visit 1 and baseline toxicity grading of grade 1. In the second row, albumin has a value of 3 g/dL at visit 1, which corresponds to an analysis toxicity grading of Mild. The baseline value is 4.2 g/dL, graded as None. While grade 0 is not defined by CTCAE criteria, the value of grade 0 is assigned in this example for analysis purposes.

References and Resources

ADaMIG v1.3, Sections 3.3.7, 4.9 

US Department of Health and Human Services Cancer Therapy Evaluation Program. Common Terminology Criteria for Adverse Events (CTCAE) v6.0 (MedDRA 28.0). Published July 22, 2025. Accessed August 19, 2026. 

US Food and Drug Administration. Pilot OCE/OOD Standard Safety Data Requests v1.3. Published February 2021. Accessed August 19, 2026.