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In this study, subjects were randomized to 1 of 3 nicotine dosage levels. At the baseline visit (week 0), they received an ENDS device that used 0, 8, or 24 mg/ml nicotine liquid. Self-reported daily cigarette consumption was recorded for each day of the study for 4 weeks. The subjects were supplied replacement nicotine cartridges at each weekly visit. The applicant used an e-diary to track when cartridges were inserted and removed, and the daily number of cigarettes smoked. Subjects used their normal brand of cigarettes; these were not supplied by the applicant, and are not considered a study product. Each cartridge was 8 mL. No other nicotine replacement products were allowed to be used. Multiple cartridges were dispensed at a visit.   

The applicant represented the cigarettes used in the SU domain. After the first visit, the number of cigarettes smoked for each day of the study were represented. If no cigarettes were smoked,(although "0" records are typically not included), 0 was recorded as the data was collected. Only a few rows are shown.    

Dataset wrap

Questions: 

Exposure collect may be be used to provided information on the amount of product used, or the amount of product used and the associated nicotine content. 

  1. Product used can be reflect in the number of the product used -number of cigarettes, number of patch, etc.   

      2.  Additionally, some sponsor may be interested in the amount of nicotine in the product itself. 

      3. The actual exposure to nicotine is typically analyzed using biomarkers,  measuring actual nicotine exposure from self-reported use can be challenging. 

The sponsor needs to decide what level of exposure information is needed for the particular study. 

EC was developed to allow the collection of exposure data as typically the actual exposure amount may be blinded. 

EX would at a minimal be provided. It is recognized that  EX is a derived domain. Some sponsor find it easier to report the collected data and the derived EX data to clearly provided exposure data with the tracking to what was collected.   In many cases, the derivation for EX, may just  be the unblinding of the product, and sponsor decide not to show the EC because the derivation used for EX is obvious.  Some  other details may be defined in an ADaM  dataset.  For example, the estimated daily nicotine exposure may based on self-reported may be provided. Since, thee are estimates, they are typically not reported in EX.     

We would like to develop some examples to try to  illustrated some common ways to provide this data that others can follow.             

We looked at ENDS- we collect amount of product used. We know the amount of e-liquid contained in the product when pre-filled containers are used. We also know the concentration of nicotine in the e-liquid. The study analysis plan decide what is of interest in the study     

We looked at SDTM and would like to discuss options for representing  this information. First , we looked at the derived EX dataset.  

EX would report the unblinded exposure to e-nicotine liquid. 

1) The dose may be the actual volume of liquid used over the interval represented in the dates, or that x containers were used, or weight of the container etc.   

This  EX dataset attempts to provide all the basic information.   

...

INHALED
Dataset wrap
NameEX
EXENDTC
Dataset2
RowSTUDYIDDOMAINUSUBJID
EXSEQ
SUSEQ
EXTRT
SUTRT
EXDOSE
SUCAT
EXDOSU
SUDOSE
EXROUTE
SUDOSU
ECVAMT
SUDOSFRQ
EXVAMTU
EXPSTRGEXPSTRGEXSTDTC
SUSTDTCSUENDTC
1TENDS01
EX
SU
10001 
TEN010011
e-nicotine liquid1CONTAINER
CIGARETTESTOBACCO6
mL
CIGARETTE
8
QD
mg/mL
2020-06-272020-
07
06-
01
27
2TENDS01
EC
SU
10001 
TEN010012
e-nicotine liquid 
CIGARETTESTOBACCO1
CONTAINERINHALED6.7mL8mg/mL
CIGARETTEQD2020-
07
06-
01
282020-
07
06-
05
28
3TENDS01
EC
SU
10001 
TEN010013
e-nicotine liquid  1CONTAINERINHALED8mL8mg/mL
CIGARETTESTOBACCO0CIGARETTEQD2020-
07
06-
05
292020-
07
06-
104TENDS01EC100021e-nicotine liquid  1CONTAINERINHALED5mL36mg/mL2020-09-012020-09-075TENDS01EC10002 2e-nicotine liquid 1CONTAINERINHALED7mL36mg/mL2020-09-072020-09-146TENDS01EC10002 3e-nicotine liquid 1CONTAINERINHALED8mL36mg/mL2020-09-142020-09-217TENDS01EC10002 4e-nicotine liquid 1CONTAINERINHALED6mL36mg/mL2020-09-212020-09-288TENDS01EC10002 5e-nicotine liquid 1CONTAINERINHALED7mL36mg/mL2020-09-282020-09-319TENDS01EC10002 6e-nicotine liquid 1CONTAINERINHALED8mL36mg/mL2020-10-312020-10-0810TENDS01EC10002 7e-nicotine liquid 1CONTAINERINHALED6.7mL36mg/mL2020-10-082020-10-1511TENDS01EC10002 8e-nicotine liquid 1CONTAINERINHALED5.5mL36mg/mL2020-10-152020-10-22

Various options exist . This example however, exclude the amount of product used. This could be shown in EC.   

In this case, i get the volume used from DA and derive this. 

RowSTUDYIDDOMAINUSUBJIDEXSEQEXTRTEXDOSEEXDOSUEXROUTEEXPSTRGEXPSTRGEXSTDTCEXENDTC1TENDS01EX10001 1e-nicotine liquid7mLINHALED8mg/mL2020-06-272020-07-012TENDS01EC10001 2e-nicotine liquid 6mL INHALED8mg/mL2020-07-012020-07-053TENDS01EC10001 3e-nicotine liquid  7mL INHALED8mg/mL2020-07-052020-07-104TENDS01EC100021e-nicotine liquid  6mL INHALED36mg/mL2020-09-012020-09-075TENDS01EC10002 2e-nicotine liquid 5mL INHALED36mg/mL2020-09-072020-09-146TENDS01EC10002 3e-nicotine liquid 8mL INHALED36mg/mL2020-09-142020-09-217TENDS01EC10002 4e-nicotine liquid 8mL INHALED36mg/mL2020-09-212020-09-288TENDS01EC10002 5e-nicotine liquid 8mL INHALED36mg/mL2020-09-282020-09-319TENDS01EC10002 6e-nicotine liquid 8mL INHALED36mg/mL2020-10-312020-10-0810TENDS01EC10002 7e-nicotine liquid 7mL INHALED36mg/mL2020-10-082020-10-1511TENDS01EC10002 8e-nicotine liquid 7mL INHALED36mg/mL2020-10-152020-10-22 Panel

Use container such as a cartridge or tank.  Hence used CT of container  to be generic. 

DOSEU  - QUID is not included in CT. 

CANCan Dosing UnitA dosing measurement based on the can unit.(NCI)Can Dosing Unit
CONTAINERContainer Dosing UnitA dosing measurement based on the container unit.(NCI)Container Dosing Unit
CIGARCigar Dosing UnitA dosing measurement based on the cigar unit.
CIGARETTECigarette Dosing UnitA dosing measurement based on the cigarette unit.
PUFFPuff Dosing UnitA means of delivering a defined dose of a therapeutic aerolized solution into either the upper or lower respiratory tract. Metered-dose inhalers or spray pumps are devices that provide a puff dose for delivery into either the oral or the nasal cavity.(NCI)
CARTRIDGECartridge Dosing UnitA dosing measurement based on the cartridge unit.(NCI)

More unit codes as well- PACK, PACKAGE, CIGAR, Cigarettes. POUCH,  

  1. When the EC domain is implemented in conjunction with the EX domain, EXVAMT and EXVAMTU would not be used in EX; collected values instead would be represented in ECDOSE and ECDOSU (and ECVAMT and ECVAMTU as needed).

     

Use container such as a cartridge or tank.  Hence used CT of container  to be generic. 

DOSEU  - QUID is not included in CT. 

...

CONTAINERContainer Dosing UnitA dosing measurement based on the container unit.(NCI)Container Dosing Unit
CIGARCigar Dosing UnitA dosing measurement based on the cigar unit.
CIGARETTECigarette Dosing UnitA dosing measurement based on the cigarette unit.
PUFFPuff Dosing UnitA means of delivering a defined dose of a therapeutic aerolized solution into either the upper or lower respiratory tract. Metered-dose inhalers or spray pumps are devices that provide a puff dose for delivery into either the oral or the nasal cavity.(NCI)
CARTRIDGECartridge Dosing UnitA dosing measurement based on the cartridge unit.(NCI)

More unit codes as well- PACK, PACKAGE, CIGAR, Cigarettes. POUCH,  

29

The DA domain was used to represent dispensed and returned amounts. The ENDS product used in the study was assigned a product identifier (VAPE-Z27), and each cartridge had a uniquely assigned number. This unique number was represented in DAREFID. Multiple cartridges were dispensed at weekly visits, and each cartridge was tracked. At each weekly visit, all previously dispensed cartridges were returned and new cartridges dispensed. Cartridges were replaced at each visit. DADTC are the visit dates when the cartridge was returned or dispensed. Cartridges not used were recorded as having the full volume returned.     

Dataset wrap
Dataset2
RowSTUDYIDDOMAINUSUBJIDDASEQSPTOBIDDAREFIDDATESTCDDATESTDACATDAORRESDAORRESUDASTRESCDASTRESNDASTRESUVISITNUMDADTC
1TENDS01DATEN01001

1

VAPE-Z27CRT8754DISPAMTDispensed AmountSTUDY PRODUCT8mL88mL12020-06-26
2TENDS01DATEN01001

2

VAPE-Z27CRT8768DISPAMTDispensed AmountSTUDY PRODUCT8mL88mL12020-06-26
3TENDS01DATEN01001

3

VAPE-Z27CRT8769DISPAMTDispensed AmountSTUDY PRODUCT8mL88mL12020-06-26
4TENDS01DATEN01001

4

VAPE-Z27CRT8754RETAMTReturned AmountSTUDY PRODUCT2mL22mL22020-07-06
2TENDS01DATEN01001

5

VAPE-Z27CRT8768RETAMTReturned AmountSTUDY PRODUCT1.6mL1.61.6mL22020-07-06
3TENDS01DATEN01001

6

VAPE-Z27CRT8769RETAMTReturned AmountSTUDY PRODUCT8mL88mL22020-07-06
5TENDS01DATEN01001

7

VAPE-Z27CRT9756DISPAMTDispensed AmountSTUDY PRODUCT8mL88mL22020-07-06
6TENDS01DATEN01001

8

VAPE-Z27CRT9756RETAMTReturned AmountSTUDY PRODUCT1mL11mL32020-07-10

Because the data in EC would be practically identical to the summarized EX domain, the applicant did not submit the EC domain. The applicant unblinded the study before creating the EX domain. The unblinded product name is provided in EXTRT; here, a dummy name is used for the tobacco product.

The applicant used an e-diary to collect the start and end date of the insertion and removal date of each cartridge in the ENDS device. For simplicity, in this example the actual times of insertion/removal were not collected, although this may often be collected.    

The total amount of liquid product used from each cartridge was determined using the data in the DA domain. The associated nicotine pharmaceutical strength of each cartridge was known. The applicant used this information in the analysis. The summaries included in the analysis were the estimated number of cartridges used per week, and the estimated nicotine exposure from the cartridges per day.    

Dataset wrap
Nameex

 In this study, subjects were randomized to one of three 24-week conditions.  At the baseline visit, they receiving either an ENDS  device that used  0, 8 or 36 mg/ml nicotine liquid . Self-reported daily cigarette consumption  were measured at all study visits  (Weeks 1, 2, 4, 8, 12, ). The subjects were supplied replacement nicotine cartridges.  The sponsor used an electronic diary application to track when the cartridge were replaced, and the daily number of cigarettes smoked.  The subject used their normal brand cigarettes , and these were not supplied by the sponsor. Each cartridge was 8 mL.  

Vapes, vaporizers, vape pens, hookah pens, electronic cigarettes (e-cigarettes or e-cigs), e-cigars, and e-pipes are some of the many tobacco product terms used to describe electronic nicotine delivery systems (ENDS). These products use an “e-liquid” that usually contains nicotine derived from tobacco, as well as flavorings, propylene glycol, vegetable glycerin, and other ingredients. The liquid is heated to create an aerosol that the user inhales.

Since, the subject regular cigarettes were not supplied by the sponsor, the sponsor elected to report this data as a Concomitant medication, in the CM domain. The ENDS device exposure use was represented in EC.        

 

INHALED
Dataset wrap
NameEC
ECENDTC
Dataset2
RowSTUDYIDDOMAINUSUBJID
ECSEQECTRTECDOSEECDOSUECROUTEECVAMTECVAMTECSTDTC
EXSEQSPTOBIDEXREFIDEXTRTEXDOSEEXDOSUEXDOSFRMEXROUTEEXPSTRGEXPSTRGUEXSTDTCEXENDTC
1TENDS01
EC
EX
10001 
TEN010011VAPE-Z27CRT8754Nicotine e-
nicotine liquid 		1CONTAINER
liquid6mLCARTRIDGERESPIRATORY (INHALATION)8mg/mL2020-06-
27
262020-07-01
2TENDS01
EC
EX
10001 
TEN010012VAPE-Z27CRT8768Nicotine e-
nicotine liquid 1CONTAINER
liquid6.4mLCARTRIDGERESPIRATORY (INHALATION)
INHALED
8mg/mL2020-07-012020-07-
05
06
3TENDS01
EC
EX
10001 
TEN010013VAPE-Z27CRT9756Nicotine e-
nicotine liquid  1CONTAINER
liquid7mLCARTRIDGERESPIRATORY (INHALATION)
INHALED
8mg/mL2020-07-062020-07
-05
-10
3TENDS01EXTEN010014VAPE-Z27CRT9778Nicotine e-liquid8mLCARTRIDGERESPIRATORY (INHALATION)8mg/mL2020-07-102020-07-14
4TENDS01
EC
EX
10002
TEN100021VAPE-Z27CRT8000Nicotine e-
nicotine liquid 1CONTAINERINHALED8
liquid5mLCARTRIDGERESPIRATORY (INHALATION)0mg/mL2020-09-012020-09-07
5TENDS01
EC
EX
10002 
TEN100022VAPE-Z27CRT9006Nicotine e-
nicotine liquid 1CONTAINERINHALED8
liquid7mLCARTRIDGERESPIRATORY (INHALATION)0mg/mL2020-09-072020-09-14
6TENDS01
EC
EX
10002 
TEN100023VAPE-Z27CRT9008Nicotine e-
nicotine liquid 1CONTAINERINHALED8
liquid8mLCARTRIDGERESPIRATORY (INHALATION)0mg/mL2020-09-142020-09-21
7TENDS01
EC
EX
10002 
TEN100024VAPE-Z27CRT9017Nicotine e-
nicotine liquid 1CONTAINERINHALED8
liquid6mLCARTRIDGERESPIRATORY (INHALATION)0mg/mL2020-09-212020-09-28
8TENDS01
EC
EX
10002 
TEN100025VAPE-Z27CRT9089Nicotine e-
nicotine liquid 1CONTAINERINHALED8
liquid7mLCARTRIDGERESPIRATORY (INHALATION)0mg/mL2020-09-282020-09-31
9TENDS01
EC
EX
10002 
TEN100026VAPE-Z27CRT9128Nicotine e-
nicotine liquid 1CONTAINERINHALED8
liquid8mLCARTRIDGERESPIRATORY (INHALATION)0mg/mL2020-10-312020-10-08
10TENDS01
EC
EX
10002 
TEN100027VAPE-Z27CRT6868Nicotine e-
nicotine liquid 1CONTAINERINHALED8
liquid6.7mLCARTRIDGERESPIRATORY (INHALATION)0mg/mL2020-10-082020-10-15
11TENDS01
EC
EX
10002 
TEN100028VAPE-Z27CRT7868Nicotine e-
nicotine liquid 1CONTAINERINHALED8
liquid5.5mLCARTRIDGERESPIRATORY (INHALATION)0mg/mL2020-10-152020-10-22

EX would report the unblinded exposure to e-nicotine liquid. 

1) The dose may be the actual volume of liquid used over the interval represented in the dates, or that 1 container was used, or xxx. 

2. IF amount of product used ( Numer of pouches, number of cigarettes, etc then we may be able to use VAMT, and Pharmaceutical strength to provide more details. 

...