Adverse Experiences (AE)

In tobacco product studies, the Adverse Events (AE) domain is used for representing adverse experiences. The FDA's PMTA rule defines adverse experience as any unfavorable physical or psychological effect in a person that is temporally associated with the use of or exposure to a tobacco product, whether or not the person uses the tobacco product, and whether or not the effect is considered to be related to the use of or exposure to the tobacco product. In consultation with regulatory authorities, applicants may extend or limit the scope of collection (e.g., collecting pre-exposure experiences related to trial conduct, not collecting events that are assessed as study endpoints). It is the applicant's responsibility to define an event and the appropriate collection period for events. This definition may vary based on product characterization and reporting of product safety. In consultation with regulatory authorities, applicants may extend or limit the scope of event collection. Adverse events may be captured either as free text or via a prespecified list of terms.

Example

This is an example of a CRF used to collect all adverse experiences that occurred after informed consent was obtained. Adverse experiences were collected using free text. The CRF was designed to allow the applicant to use either AEENRF or AEENRTPT to represent an event that was ongoing. 

This example CRF has 2 sections: Section 1 collects whether a subject experienced any adverse experiences, while section 2 collects a record/row for each adverse experience. 

 This is the metadata specifications for Section 1 and 2 of the CRF

CDASH AE Metadata Specifications

Section 1 

Order	Question Text	Prompt	Case Report Form Completion Instructions	Type	Collection Variable	Tabulation Target	Mapping Instructions	Controlled Terminology CodeList Name	Permissible Values	Pre-Populated Value
1	Were there any adverse experiences?	Any Adverse Experiences	Indicate if the subject experienced any adverse experiences. If Yes, include the appropriate details where indicated on the CRF.	Text	AEYN	N/A		(NY)	Yes; No

 Section 2  

Order	Question Text	Prompt	Case Report Form Completion Instructions	Type	Collection Variable	Tabulation Target	Mapping Instructions	Controlled Terminology CodeList Name	Permissible Values	Pre-Populated Value
2	What is the category of the adverse experience?	Adverse Experiences Category	Record the adverse experience category, if not pre-printed on the CRF.	Text	AECAT	AECAT				Applicant Defined
3	What is the subcategory of the adverse experience?	Adverse Experience Subcategory	Record the adverse experience subcategory, if not pre-printed on the CRF.	Text	AESCAT	AESCAT				Applicant Defined
4	What is the adverse experience identifier?	AE Number	If collected on the CRF, the applicant may insert instructions to ensure each record has a unique identifier.	Integer	AESPID	AESPID
5	What is the adverse experience term?	Adverse Experiences	Record only 1 diagnosis, sign, or symptom per line (e.g., nausea and vomiting should not be recorded in the same entry, but as 2 separate entries). Using accepted medical terminology, enter the diagnosis (if known); otherwise, enter a sign or symptom.	Text	AETERM	AETERM
6	What is the adverse experience start date?	Start Date	Record the start date of the Adverse Experience using this format (DD-MON-YYYY).	Date	AESTDAT	AESTDTC
7	Is the adverse experience ongoing?	Ongoing	Indicate if the adverse experience has not resolved at the time of data collection; leave the End Date blank.	Text	AEONGO	AEENRTPT; AEENRF	AEENRTPT/ AEENRF	(NY)	Yes
8	What was the adverse experience end date?	End Date	Record the date that the AE resolved using this format (DD-MON-YYYY). If the AE is ongoing, leave the field blank.	date	AEENDAT	AEENDTC
9	What is the severity of the adverse experience?	Severity	The reporting physician/healthcare professional will assess the severity of the experience using applicant-defined categories. This assessment is subjective, and the reporting physician/healthcare professional should use medical judgment to compare the reported AE to similar type experiences observed in clinical practice. Severity is not equivalent to seriousness.	Text	AESEV	AESEV		(AESEV)	MILD; MODERATE; SEVERE
10	Was the adverse experience serious?	Serious	Assess if an adverse experience should be classified as serious based on the criteria defined in the protocol.	Text	AESER	AESER		(NY)	Yes; No
11	Did the adverse experience result in death?	Death	Record whether the serious adverse experience resulted in death.	Text	AESDTH	AESDTH		(NY)	Yes; No
12	Was the adverse experience life-threatening?	Life Threatening	Record whether the serious adverse experience is life-threatening.	Text	AESLIFE	AESLIFE		(NY)	Yes; No
13	Did the adverse experience result in initial or prolonged hospitalization for the subject?	Hospitalization (initial or prolonged)	Record whether the serious adverse experience resulted in an initial or prolonged hospitalization.	Text	AESHOSP	AESHOSP		(NY)	Yes; No
14	Did the adverse experience result in disability or permanent damage?	Disability or Permanent Damage	Record whether the serious adverse experience resulted in a persistent or significant disability or incapacity.	Text	AESDISAB	AESDISAB		(NY)	Yes; No
15	Was the adverse experience associated with a congenital anomaly or birth defect?	Congenital Anomaly or Birth Defect	Record whether the serious adverse experience was associated with congenital anomaly or birth defect.	Text	AESCONG	AESCONG		(NY)	Yes; No
16	Did the adverse experience require intervention to prevent permanent impairment or damage resulting from the use of a medical product?	Needs Intervention to Prevent Impairment	Record whether the serious adverse experience required intervention to prevent permanent impairment or damage due to the use of a medical product.	Text	AESINTV	SUPPAE.QVAL		(NY)	Yes; No
17	Was the adverse experience a medically important event not covered by other "serious" criteria?	Other Serious (Important Medical Events)	Record whether the serious adverse experience is an important medical event, which may be defined in the protocol or in the investigator brochure.	Text	AESMIE	AESMIE		(NY)	Yes; No
18	Was this adverse experience related to study product?	Relationship to Study Product	Indicate if the cause of the adverse experience was related to the study product and cannot be reasonably explained by other factors (e.g., subject's clinical state, concomitant therapy, other interventions).	Text	AEREL	AEREL			NOT RELATED; UNLIKELY RELATED; POSSIBLY RELATED; RELATED
19	What action was taken with the study product?	Action Taken with Study Product	Record changes made to the study product resulting from the adverse experience.	Text	AEACN	AEACN		(TPACN)	DRUG WITHDRAWN; DOSE REDUCED; DOSE INCREASED; DOSE NOT CHANGED; UNKNOWN; NOT APPLICABLE
20	What other action was taken?	Other Action Taken	Record all other action(s) taken resulting from the adverse experience that are unrelated to study product given because of this adverse experience.	Text	AEACNOTH	AEACNOTH
21	What is the action taken with a device?	Action Taken with Device	Record any action taken with a device as the result of the adverse experience. The device may or may not be a device under study.	Text	AEACNDEV	AEACNDEV		(DEACNDEV)	DEVICE REPLACED: BATTERY REPLACED:CALIBRATION;  REPROGRAMMING
22	What is the outcome of this adverse experience?	Outcome	Record the appropriate outcome of the experience in relation to the subject's status.	Text	AEOUT	AEOUT		(OUT)	FATAL;NOT RECOVERED/ NOT RESOLVED;RECOVERED/RESOLVED; RECOVERED/RESOLVED WITH SEQUELAE;  RECOVERING/RESOLVING; UNKNOWN
23	Was this adverse experience related to a device?	Relationship of Experience to Device	Record the relationship of the adverse experience to device	Text	AERLDEV	AERLDEV			NOT RELATED; UNLIKELY RELATED; POSSIBLY RELATED; RELATED

 

This SDTM dataset illustrates data collected on the example AE CRF. This SDTM dataset used AENRTPT. For more information, see Section 2.8.7.6, Representing References and Relative Timing.

AEs were coded using MedDRA, and the applicant’s procedures include the possibility of modifying the reported term to aid in coding. The CRF was structured so that seriousness category variables (e.g., AESDTH, AESHOSP) were checked only when AESER is answered “Y.” In this study, the study reference period started at the start of product exposure. Three AEs were reported for this subject. This SDTM dataset used AEENRF to represent ongoing events. Expected variables (e.g., AELLT, AELLTCD, AEPT, AEPTCD, AEHLT, AEHLTCD, AEHLGT, AEHLCTCD, AEBDSYCD, AESOC, AESOCCD) are not included to save space.  

The applicant also collected information about whether the event was associated with a device. These subjects did not have any device-related issues. See Section 3.3.3.4, Tobacco Product Events and Malfunctions, for an example of device-related events.  

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Rows 1-2:	Show examples of modifying the reported term for coding purposes, with the modified term in AEMODIFY. These adverse events were not serious, so the seriousness criteria variables are null. Note that for the event in row 2, AESTDY = "1". Day 1 was the day product was started; the AE start and end times, as well as dates, were collected to allow comparison of the AE timing to the start of product.
Row 3:	Shows an example of the overall seriousness question AESER answered with "Y" and the relevant corresponding seriousness category variables (AESHOSP and AESLIFE) answered "Y". The other seriousness category variables are left blank. This row also shows AEENRF being populated because the AE was marked as “Continuing” as of the end of the study reference period for the subject.

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Row	STUDYID	DOMAIN	SPDEVID	USUBJID	AESEQ	AETERM	AEMODIFY	AEDECOD	AEBODSYS	AESEV	AESER	AEACN	AEACNDEV	AEREL	AERLDEV	AEOUT	AESCONG	AESDISAB	AESDTH	AESHOSP	AESLIFE	AESMIE	AECONTRT	EPOCH	AESTDTC	AEENDTC	AESTDY	AEENDY	AEENRF
1	ABC123	AE		ABC123-0001	1	POUNDING HEADACHE	HEADACHE	Headache	Nervous system disorders	SEVERE	N	NOT APPLICABLE		DEFINITELY NOT RELATED		RECOVERED/RESOLVED							Y	PRODUCT EXPOSURE	2006-10-14	2006-10-18	2	5
2	ABC123	AE		ABC123-0001	2	BACK PAIN FOR 6 HOURS	BACK PAIN	Back pain	Musculoskeletal and connective tissue disorders	MODERATE	N	DOSE REDUCED		PROBABLY RELATED		RECOVERED/RESOLVED							N	PRODUCT EXPOSURE	2006-10-13T13:05	2006-10-13T19:00	1	1
3	ABC123	AE		ABC123-0002	1	INFLUENZA	Influenza	Influenza	Infections and infestations	SEVERE	Y	PRODUCT WITHDRAWN		PROBABLY NOT RELATED		RECOVERING/RESOLVING				Y	Y		Y	PRODUCT EXPOSURE	2006-02-26		12		AFTER

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