SDTM AE assumptions

In consultation with regulatory authorities, applicants may extend or limit the scope of adverse event collection. The events included in the AE dataset should be consistent with the protocol requirements. Adverse events may be captured either as free text or via a prespecified list of terms.

1. AETERM captures the verbatim term collected for the event. It is the topic variable for the AE dataset. AETERM is a required variable and must have a value.
2.  AEMODIFY is a permissible variable and should be included if the applicant’s procedure permits modification of a verbatim term for coding. The modified term is listed in AEMODIFY. The variable should be populated as per the applicant’s procedures.
3. AEDECOD is the preferred term derived by the applicant from the coding dictionary. It is a required variable and must have a value. It is expected that the reported term (AETERM) will be coded using a standard dictionary such as MedDRA.
4. AEBODSYS is the system organ class (SOC) from the coding dictionary associated with the adverse event by the applicant. This value may differ from the primary SOC designated in the coding dictionary's standard hierarchy. TOBA-640 - Getting issue details... STATUS

1. AECAT and AESCAT should not be redundant with the domain code or dictionary classification provided by AEDECOD and AEBODSYS (i.e., they should provide a different means of defining or classifying AE records). AECAT and AESCAT are intended for categorizations that are defined in advance. For example, an applicant may have a CRF page for AEs of special interest and another page for all other AEs. AECAT and AESCAT should not be used for after-the-fact categorizations such as "clinically significant." In cases where a category of AEs of special interest resembles a part of the dictionary hierarchy (e.g., "CARDIAC EVENTS"), the categorization represented by AECAT and AESCAT may differ from the categorization derived from the coding dictionary.
2. AEGRPID may be used to link (or associate) different records together to form a block of related records at the subject level within the AE domain.

1. Adverse events are generally collected in 2 different ways, either by recording free text or using a prespecified list of terms. In the latter case, the solicitation of information on specific adverse events may affect the frequency at which they are reported; therefore, the fact that a specific adverse event was solicited may be of interest to reviewers. An AEPRESP value of “Y” is used to indicate that the event in AETERM was prespecified on the CRF.
2. If it is important to know which adverse events from a prespecified list were not reported as well as those that did occur, these data should be submitted in a Findings class dataset such as Findings About Events and Interventions. A record should be included in that Findings dataset for each prespecified adverse-event term. Records for adverse events that actually occurred should also exist in the AE dataset with AEPRESP set to “Y.”
3. If a study collects both prespecified adverse events and free-text events, the value of AEPRESP should be “Y” for all prespecified events and null for events reported as free text. AEPRESP is a permissible field and may be omitted from the dataset if all adverse events were collected as free text.
4. When adverse events are collected with the recording of free text, a record may be entered into the applicant’s data management system to indicate “no adverse events” for a specific subject. For these subjects, do not include a record in the AE submission dataset to indicate that there were no events. Records should be included in the submission AE dataset only for adverse events that have actually occurred.

1. Relative timing assessment “Ongoing” is common in the collection of AE information. AEENRF may be used when this relative timing assessment is made coincident with the end of the study reference period for the subject represented in the Demographics (DM) dataset (RFENDTC). AEENRTPT with AEENTPT may be used when "Ongoing" is relative to another date (e.g., the final safety follow-up visit date).
2. Additional timing variables (e.g., AEDTC) may be used when appropriate.

1. Actions other than concomitant treatments are recorded in:

   • AEACN, only for actions taken with study product
   • AEACNDEV, for actions with a device
   • AEACNOTH, for actions that do not involve product or a device

1. If categories of serious events are collected secondarily to a leading question the values of the variables that capture reasons an event is considered serious (e.g., AESCAN, AESCONG) may be null. On the other hand, if the CRF is structured so that a response is collected for each seriousness category, all category variables (e.g., AESDTH, AESHOSP) would be populated and AESER would be derived.

2.  The serious categories “Involves cancer” (AESCAN) and “Occurred with overdose” (AESOD) are not part of the ICH definition of a serious adverse event, but these categories are available for use in studies conducted under guidelines that existed prior to the FDA’s adoption of the ICH definition.
3. When a description of "Other Medically Important Serious Adverse Events" category is collected on a CRF, applicants should place the description in the SUPPAE dataset using the standard supplemental qualifier name code AESOSP.
4. In studies using toxicity grade according to a standard toxicity scale such as the Common Terminology Criteria for Adverse Events v3.0 (CTCAE), published by the National Cancer Institute (NCI; available at https://ctep.cancer.gov/protocoldevelopment/), AETOXGR should be used instead of AESEV. In most cases, either AESEV or AETOXGR is populated but not both. There may be cases when an applicant may need to populate both variables.
5. The structure of the AE domain is 1 record per adverse event per subject. It is the applicant's responsibility to define an event. This definition may vary based on the applicant's requirements for characterizing and reporting product safety and is usually described in the protocol. For example, the applicant may submit 1 record that covers an adverse event from start to finish. Alternatively, if there is a need to evaluate AEs at a more granular level, an applicant may submit a new record when severity, causality, or seriousness changes or worsens. By submitting these individual records, the applicant indicates that each is considered to represent a different event. The tabulation dataset structure may differ from the structure at the time of collection. For example, an applicant might collect data at each visit in order to meet operational needs, but submit records that summarize the event and contain the highest level of severity, causality, seriousness, and so on. Examples of dataset structure include:
   1. One record per adverse event per subject for each unique event. Multiple adverse event records reported by the investigator are submitted as summary records “collapsed” to the highest level of severity, causality, seriousness, and the final outcome.
   2. One record per adverse event per subject. Changes over time in severity, causality, or seriousness are submitted as separate events. Alternatively, these changes may be submitted in a separate dataset based on the Findings About Events and Interventions model.
   3. Other approaches may also be reasonable as long as they meet the applicant's safety evaluation requirements and each submitted record represents a unique event.