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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.  No other Nicotine replacement products were allowed to be used.  

The subject regular cigarettes were not supplied by the sponsor, and not considered a study product by the sponsor.  The sponsor reported the cigarettes used in the in the SU domain.  The SU domain is not shown here, but an example is shown in xxxxxx. 

Since the data in Exposure as collected would be practically identically to the summarized EX domain, the sponsor did not submit the EC domain.  A Product Accountability domain was submitted to represent dispensed and returned amounts, but this data was not used in determining exposure. It was used by the sponsor when reviewing the exposure data for each subject. This DA domain is not shown here.    

Note, the sponsor 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 domain represented the amount of product used, the total amount amount of liquid product ( including all is components) used from each cartridge and the associated nicotine pharmaceutical strength of each cartridge. The sponsored 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 exposer from the cartridges per day.    

Since the data in Exposure as collected would be practically identically to the summarized EX domain, the sponsor did not submit the EC domain.  The DA domain was used to capture the amount of nicotine dispensed and returned for each cartridge. 

Note, the sponsor unblinded the study before creating the EX domain. The unblinded product name is used in EXTRT.  

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.   

...

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

DOSEU  - QUID is not included in CT.