AEREL and AEACN in Trials with Multiple Study Drugs 

Problem:  

See JJPharmaStdAEForm.  How do we map AEREL and AEACN when we have multiple study drugs? 

SDTM Guidance: 

Per SDTMIG 3.1.2, section 4.1.2.8.3, we have two basic options: 

• Record a value of “MULTIPLE” for AEREL and AEACN.  Put specific responses for each drug in 
SUPPAE. 
• Record the “primary” response in the standard variables (AEREL, AEACN); record responses for 
other drug(s) in SUPPAE 

In either case, we can create “meaningful” SUPPAE variables if we wish.  

CRF Considerations: 

• Trial may be open label so study drugs are named specifically on CRF. 
o  See Sample CRF 1.  This study had 4 named drugs, two (CNTO328 & Velcade) are J&J 
products. 
• Trial may be blinded so study drugs are not specifically named.   
o See Sample CRF 2 for a study with J&J product vs placebo plus a second named product. 
o See Sample CRF 3 for a CRF which uses descriptors other than drug name (note this 
predates the J&J std CRFs).  In this study, subjects received a study injection (J&J 
product or placebo) and an oral study drug (non‐J&J product or placebo).  Both the 
injection and oral drug were considered to be study drugs per protocol. 
• CRF prompts change over the life cycle of the product.  Early studies might use a JNJ number; 
later studies might use generic name. 

Proposal from DISCO Programming Representatives 

• As much as possible, we would like consistent use of variables within a compound to facilitate 
program reuse, dataset integration, and generally to avoid error or confusion. 
• When multiple agents are designated as study drugs and the protocol indicates (or study team 
determines) that a response for AE causality (relationship) and/or action taken must be 
collected for each study drug, the AEREL and/or AEACN variables will be populated with 
‘MULTIPLE.’    
• Separate variables, AERELxy and/or AEACNxy,  will be created in SUPPAE for each study drug as 
follows: 
o x will be populated with ‘S’ for the J&J product (‘S’ refers to ‘sponsor’) or ‘O’ for non‐J&J 
products (‘O’ refers to ‘other drug’).  
o For J&J drugs, y will be populated with ‘1’ for the primary study drug.  This is generally 
clear from the protocol and compound development plan that it is supporting.   
 

o If an additional J&J drug(s) is part of a multidrug regimen, then y will be assigned 
sequentially within the trial (‘2’,’3’, etc). 
o For non‐J&J products, y values will be assigned sequentially (‘1’, ‘2’, ‘3’) based on the 
treatment regimen described for the trial. 
• As an example, consider a trial with golimumab (J&J drug)  vs placebo in combination with 
methotrexate and prednisone (non‐J&J drugs): 
o AEREL and AEACN would be populated with ‘MULTIPLE’ 
o AERELS1 and AEACNS1 would store responses for golimumab/placebo 
o AERELO1 and AEACNO1 would store responses for methotrexate 
o AERELO2 and AEACNO2 would store responses for prednisone 
• Consistent labels for SUPPAE variables will be used across compounds and trials.  IDS will use the 
metadata comment field to indicate the applicable study drug based on the protocol treatment 
regimen. 
o Continuing the example above: 

Variable  Label  Comment 

AERELS1  Causality ‐ Sponsor Study Treatment 1  Sponsor study treatment 1 = golimumab or 
placebo 
AEACNS1  Action Taken ‐ Sponsor Study  Sponsor study treatment 1 = golimumab or 
Treatment 1  placebo 
AERELO1  Causality ‐ Other Study Treatment 1  Other study treatment 1 = methotrexate  
AEACNO1  Action Taken ‐ Other  Study Treatment  Other study treatment 1 = methotrexate  
1 
AERELO2  Causality ‐ Other Study Treatment 2  Other study treatment 2 = prednisone  
AEACNO2  Action Taken ‐ Other  Study Treatment  Other study treatment 2 = prednisone  
2 
 

• IDS will determine appropriate AERELxy and AEACNxy variables to use based on the protocol 
with input from the trial team as needed.  IDS will populate the metadata Comment field to 
provide clear documentation of the meaning of each variable. 
 • For an additional example, consider the hypothetical development plan for a J&J product called JNJ12345 given as an injection: 
o Trial 1: Open label JNJ12345  
o Trial 2: Blinded JNJ12345 vs placebo 
o Trial 3: Blinded JNJ12345/placebo + aspirin 
o Trial 4: Blinded JNJ12345/NonJJdrug + aspirin/placebo 
o Trial 5: Blinded JNJ12345/placebo + prednisone 
o Prior to the development of the trial 6 protocol, JNJ12345 is given a generic compound name: abcdef 
o Trial 6: Blinded study injection (abcdef or placebo) + blinded oral study drug (aspirin or placebo) 
 
Variable /  Trial 1*  Trial 2*  Trial 3*  Trial 4*  Trial 5*  Trial 6* 
Label 
AEREL / Causality  <CRF  <CRF  MULTIPLE / ‐  MULTIPLE / ‐  MULTIPLE / ‐  MULTIPLE / ‐ 
response> / ‐  response> / ‐ 
AEACN / Action Taken with Study  <CRF  <CRF  MULTIPLE / ‐  MULTIPLE / ‐  MULTIPLE / ‐  MULTIPLE / ‐ 
Treatment  response> / ‐  response> / ‐ 
AERELS1 / Causality ‐ Sponsor  ‐  ‐  <CRF response> /  <CRF response> /  <CRF response> /  <CRF response> / 
Study Treatment 1  Sponsor study  Sponsor study treatment  Sponsor study  Sponsor study 
treatment 1 =  1 = JNJ12345 or  treatment 1 =  treatment 1 = 
JNJ12345 or  NonJJdrug  JNJ12345 or Placebo  abcdef or Placebo 
Placebo 
AEACNS1 / Action Taken ‐  ‐  ‐  <CRF response> /  <CRF response> /  <CRF response> /  <CRF response> / 
Sponsor Study Treatment 1  Sponsor study  Sponsor study treatment  Sponsor study  Sponsor study 
treatment 1 =  1 = JNJ12345 or  treatment 1 =  treatment 1 = 
JNJ12345 or  NonJJdrug  JNJ12345 or Placebo  abcdef or Placebo 
Placebo 
AERELO1 / Causality ‐ Other  ‐  ‐  <CRF response> /  <CRF response> / Other  <CRF response> /  <CRF response> / 
Study Treatment 1  Other study  study treatment 1 =  Other study  Other study 
treatment 1 =  Aspirin or Placebo  treatment 1 =  treatment 1 = 
Aspirin  Prednisone  Aspirin or Placebo 
AEACNO1/ Action Taken ‐ Other   ‐  ‐  <CRF response> /  <CRF response> / Other  <CRF response> /  <CRF response> / 
Study Treatment 1  Other study  study treatment 1 =  Other study  Other study 
treatment 1 =  Aspirin or Placebo  treatment 1 =  treatment 1 = 
Aspirin  Prednisone  Aspirin or Placebo 
 

* For each trial, the table indicates how the variable will be populated (‘‐‘ if not used and not included on dataset) and the content of the 
metadata Comment column (‘‐‘ if not applicable)  
 Page 1 of 2

Sample CRF 1
Subject: Subject
Page: Adverse Events

If AE reported 'Yes', describe below using medical

terminology

Click Add Entry to add a record

Currently viewing line 1 of 1.

Click here to return to Complete View.

Sequence Number [Calculated]

Adverse Event

Start Date of Event (dd MMM yyyy) ...

Start Time of Event (24-hr clock) :

Toxicity Grade by CTCAE V3.0 j1 n

k
l
m
n j2 n
k
l
m j3 n
k
l
m j4 n
k
l
m j5
k
l
m

Action taken regarding CNTO328 ...

Action taken regarding Velcade ...

Action taken regarding Melphalan ...

Action taken regarding Prednisone ...

Was this infusion-related reaction associated with n Yes m

j
k
l
m n No
j
k
l
CNTO328?

Was this infusion-related reaction associated with j Yes n

k
l
m
n j No
k
l
m
Velcade?

Relation to CNTO328 ...

Relation to Velcade ...

Relation to Melphalan ...

Relation to Prednisone ...

Outcome ...

If "Recovered/ Resolved," specify Recovery Date ...

(dd MMM yyyy)

http://ispec.eadv.na.jnj.com/iSpec/ui/temp/AE_1238703729705_second.html 4/2/2009
 Page 2 of 2

If "Recovered/Resolved," specify Recovery Time :

(24-hour clock)

Is this a serious adverse event? j Yes n

k
l
m
n j No
k
l
m

Close Preview

http://ispec.eadv.na.jnj.com/iSpec/ui/temp/AE_1238703729705_second.html 4/2/2009
 Sample CRF 2
Adverse Events

Adverse Event

Was this a serious

adverse event?

Seriousness
(Check all that apply)

*An important medical event that may not result in death, be life-threatening, or require
hospitalization may be considered a serious adverse event when, based on appropriate
medical judgment, it may jeopardize the subject or may require medical or surgical
intervention to prevent one of the other outcomes listed.

Event Type

Onset Date - - (dd-MMM-yyyy)

Onset Time : (hh:mm 24 Hour Clock)

Resolution Date - - (dd-MMM-yyyy)

Resolution Time : (hh:mm 24 Hour Clock)

OR

Toxicity Grade

Relationship to
CNTO 95 / Placebo

Relationship to DTIC

Action taken with

CNTO 95 / Placebo

Action taken with DTIC

Adverse Events - W0 through Unblinding Sample CRF 3

Adverse Event

Was this a serious

adverse event?

Seriousness
(Check all that apply)

*Is an important medical event that, while it may not result in death or be immediately
life-threatening or require/prolong hospitalization, may jeopardize the subject and/or may
require medical or surgical intervention to prevent one of the outcomes listed.

Onset Date - - (dd-MMM-yyyy)

Onset Time : (hh:mm 24 Hour Clock)

Resolution Date - - (dd-MMM-yyyy)

- OR -

Intensity

Related to Trial
Procedure

If related to trial
procedure is yes,
specify procedure

Relationship to
subcutaneous study
agent

Relationship to oral
study agent

Action taken with

subcutaneous study
agent

Action taken with oral

study agent

Infection

If yes, was infection

treated with oral or
parenteral antibiotics?

Was this event a

subcutaneous study
agent injection site
reaction?
Specify subcutaneous
study agent injection
site