Questions for CDISC

Questions for CDISC

On 7th June 2016 the CDISC UK Network held a face-to-face meeting which included breakout sessions where any issues related to the implementation of CDISC standards could be discussed. Several questions arose from these sessions. We were able to answer some of these questions among the UK Network. Below are the questions that we were not able to answer ourselves, or where we thought that clarification was required. We would be grateful if you could take a look at these questions. We appreciate that it may not necessarily be possible to give clear-cut answers. We will be grateful for any feedback that you are able to give.

Q1. Suppose that there is an SDTM domiandomain containing a character result --STRESC which gets converted to a numeric result --STRESN. This gets mapped to AVAL in an ADaM dataset, but all results below some threshold get mapped to zero. The character result --STRESC is also needed in the ADaM dataset. --STRESC cannot be put into AVALC without causing a validation failure because AVAL and AVALC would not be one-to-one. Is it acceptable to copy --STRESC (retaining the name of the SDTM variable) into the ADaM dataset in this case, even though it is quite similar in meaning to AVALC?

Q2. ADaM IG is not very clear about the meanings of the concepts ‘visit’,’timepoint’ and ’window’. E.g. in the notes for AVISIT and ATPT these words are frequently used but without a definition. In ADaM IG1.1 there is some clarification about the use of the AVISIT and ATPT variables, but it is still not very easy to understand what the intended use of the ATPT variable is, especially since the notes on AVISIT say that AVISIT doesn’t need to correspond to SDTM VISIT. One question that arose related to this is whether it is acceptable to include time-of-day information (e.g. 1 hour, 5 hour, 10 minutes) in the AVISIT variable, so that it takes the form of e.g. Day 1, 2 hour? Or is it better to have both an AVISIT and an ATPT variable so that AVISIT contains the day information, Day 1 in this example, and ATPT contains the hour information, e.g. 2 hours?

Q3. --CLSIG variables are mentioned in a short paragraph in SDTM IG 3.2 section 4.1.5.5 and also referred to in 6.3 EG Assumptions point 4, 6.3 LB Assumptions point 3, 6.3 VS Assumptions point 3.

What is the intended meaning and purpose of the --CLSIG variable? How should they be mapped to ADaM?

Two possible ways of mapping to ADaM arose: first by just bringing in the --CLSIG variable from the SDTM and adding it to the ADaM, or by holding the clinical significance in an AVALCATx variable. The problem with the 2nd method is that if for some reason, we have 2 high results where 1 is clinically significant and the other is not, we have seen validator errors because there is not a 1-1 map between AVAL and AVALCATx.

Q4. Related to Q3, ADaM IG 1.1 hints (but is not at all clear) that AVALCATx should be a function of AVAL/AVALC and PARAMCD (either one-to-one or many-to-one), i.e. the value of AVALCATx should be determined by the values of PARAMCD and AVAL/AVALC, but nothing else. Is this correct?

Q5. Sponsors find it useful to split up some terminology codelists so that they are more useful in particular contexts, e.g. the NCI codelists for units is very large, but in any given SDTM domain only a small number of units are likely to be relevant. However in define.xml it seems that the whole unit codelist must be referred to by any column where this is the defined codelist. Is there any way of splitting up e.g. the unit codelist in define.xml and still having it validate correctly?

Questions for FDA CDER

On 7th June 2016 the CDISC UK Network held a face-to-face meeting which included breakout sessions where any issues related to the implementation of CDISC standards could be discussed. Several questions arose from these sessions. We were able to answer some of these questions among the UK Network, others have been passed onto CDISC, but a few seemed more appropriate for CDER. We would be grateful if you could take a look at these questions. We appreciate that it may not necessarily be possible to give clear-cut answers. We will be grateful for any feedback that you are able to give.

Q1. If the client require the treatments to be given as abbreviations, or letters (e.g. Drug A 250 mg = A) as per the Study Analysis Plan, is it acceptable to use these abbreviations in the treatment variables in the ADSL and subsequent ADaMs (TRTxxP/TRTP/TRTSEQP), or is it preferred to have the actual drug name and dose information in these treatment variables and create the abbreviations in the software that produces the Tables/Figures/Listings?

Q2. The Mapping of the Treatment Emergent Flag in SDTM – in light of the latest FDA technical conformance guide: CDER Common Data Standards Issues Document (version 1.1/December 2011) says that a treatment emergent flag should be included in AE. See page 8 of:

http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/FormsSubmissionRequirements/ElectronicSubmissions/UCM254113.pdf

FDA Technical Conformance Guide (March 2016) says that there is no variable in the AE domain that indicates if an AE was “treatment-emergent”, and that all AEs should be included in the AE domain regardless of whether they are treatment emergent. No mention is made of including a “treatment-emergent” flag. See page 17 of: http://www.fda.gov/downloads/ForIndustry/DataStandards/StudyDataStandards/UCM384744.pdf

What is the rationale for removing discussion of this variable? Is use of this variable still acceptable? If use of this variable has been dropped, please consider reinstating it.

Q3. Before making a submission to CDER, it would be ideal to be able to validate the submission using exactly the same set of validation rules that CDER will use when the data is received, so that any errors can be fixed before submission.

Under section 4b at the URL: http://www.fda.gov/ForIndustry/DataStandards/StudyDataStandards/ucm2005545.htm

There is a set of validation rules. It is not clear which version(s) of SDTM these apply to. Presumably these rules will change over time as SDTM changes over time. How will these rules be version controlled? How do these rules relate to the rules provided by validation software, such as the Pinnacle 21 validator?

Are these rules the only SDTM validation rules that CDER use on incoming data, or are they a subset of a more comprehensive set of rules?

In future would it be possible for CDER to move towards incorporating references to complete validation rule sets for each version of each data standard into the data standards catalog linked to under section 1 of the URL above?