20130411_Public comments on SDTM updates

Report
DISCUSSION: SDTM UPDATES
MARCH 2013
Public comments
Comments were requested from CDISC for the new and updated domains for
SDTM v3.1.4 Batch 1 :
• RD - Reproduction Details /
RP – Reproductive System Findings
•
•
•
•
IS - Immunogenicity Specimen Assessment
SR - Skin Response
EX - Exposure
EC - Exposure as Collected
Overview of the comments:
Most comments were about :
Label inconsistencies, Incorrect Type, CORE and Controlled Term/Codelist/Format information
Spelling errors
Controlled Terminology updates
Questions
Suggestions
Public comments
Update : EX / EC domain
IG v 3.1.4, batch 1
Comments (EXOCCUR/EXREASND):
EX domain is an Interventions domain and therefore --PRESP, --OCCUR, --STAT
and --REASND are already available, they were only excluded from EX because
according to the current Implementation Guide page 85:
‘EX should contain only medications received’ - as this concept is now
changed, it's making sense to allow these variables in EX and fill
them as in all other domains.
Public comments
Update : EX / EC domain
IG v 3.1.4, batch 1
Comments (EXOCCUR/EXREASND):
• Also the SDTMIG V3.1.2 section 4.1.5.7 should be updated to document the use
of a --REASND in combination with an --OCCUR=N. The table listed in this section is
used by many electronic compliance checking tools as the set of allowed
situations. It should be clearly stated that for EX/EC an exception is to be made.
(Please note I refered to the SDTMIG V3.1.2 as there is not yet an updated
version of this part of the IG available)
Public comments
Update : EX / EC domain
IG v 3.1.4, batch 1
Comments (EXOCCUR/EXREASND):
- In every other SDTM domain, REASND is used for the reason that an
observation was not made. In findings domains, this is the reason a test was not
done. In events domains, this is the reason that a question about a pre-specified
event was not asked. In other interventions domains, this is the reason that a
question about a pre-specified intervention was not asked. REASND is populated when
STAT=NOT DONE.
EXSTAT/EXREASND
In this proposal, REASND would be populated when OCCUR = N.
If it is desired to record the reason why a dose was not given, then a new variable
for "reason not given" (or some such) should be created, instead of overloading the
existing variable REASND. Even if we don't foresee using REASND for its original
purpose in EX, this proposal would create a domain-specific exception to the general
mapping of REASND to BRIDG, complicating the process of mapping future
BRIDG-based SHARE content to SDTM.
Public comments
Update : EX / EC domain
IG v 3.1.4, batch 1
Comments (EC Domain):
It's also good to have the CRF collected dose/units and the protocol specified ones,
but in my opinion it would be a lot easier to introduce something like Standard Dose
and Standard Units like in the Finding domains, and there the dosage and units as
specified in the protocol.
The original collected dosage and unit can be kept in EXDOSE and EXDOSU.
That would be more clear than making two very similar domains
and linking them via RELREC.
Public comments
Update : EX / EC domain
IG v 3.1.4, batch 1
Comments (EC Domain):
Another argument for the EC/EX solution was that the values from EC can be
summarized in EX to support analysis. In my opinion this should not be part of
SDTM - as SDTM is usually not preparing tables for analysis but should reflect
the CRF data as entered, sure some values are derived as well but to put one whole
domain which is only derived and summarizing/pooling treatment data is maybe
not what SDTM was intended for, for me that sounds more like ADaM.
Update : EX / EC domain
IG v 3.1.4, batch 1
It is indicated that EXVAMT will be deprecated, but it is not clear to me what replaces
it. There are no examples showing collected doses based on a preparation step
such as an infusion where study drug is diluted to a certain
concentration in a vehicle such as saline.
Public comments
Update : RD domain
IG v 3.1.4, batch 1
Comments :
In the NCI Terminology Codelists there is a RP (Reproductive System Findings) domain
assigned, why did it change to RD ?
The Response:
It was decided by CDISC that this domain will be renamed to RP
(Reproductive System Findings) as per CDISC controlled terminology.
Public comments
Update : RD domain
IG v 3.1.4, batch 1
Comments :
• “Why RDSTDTC is not spelled out in the list of variables, given that one might
want to know when a particular ‘finding’ occurred. What's being collected is
RDDTC, the collection date. For some ‘tests’, like PREGNT, it is important to
know when a pregnancy began, not simply the collection date. Reconsider this
as a findings class.”
The Response:
RDDTC is the date of the reproductive finding and should not be confused
with the collection date relative to when it was recorded on a CRF.
Public comments
Update : RD domain
IG v 3.1.4, batch 1
Control Terminology Suggestions:
RDTESTCD – PREGSTAT / RDTEST- Pregnancy Status
RDTESTCD - EARLYTRM / RDTEST - Early Termination
RDTESTCD – LIVEBRTH / RDTEST- Live Birth
PREGSTAT -PREGNANCY ONGOING, LIVE BIRTH, STILLBIRTH, EARLY
TERMINATION
EARLYTRM - SPONTANEOUS ABORTION, THERAPEUTIC ABORTION,
ELECTIVE ABORTION, OTHER
LIVEBRTH - NORMAL, BIRTH DEFECT, OTHER
The Response:
Suggestions for controlled terminology should be send to the NCI EVS
for consideration upon the release of the domain in provisional
status.
Public comments
Update : IS and SR domains
IG v 3.1.4, batch 1
Public comments
Update : IS and SR domains
IG v 3.1.4, batch 1
Comments:
• IS needs controlled terminology. Many of the tests used as examples are
existing LBTESTCD codes - either existing terminology e.g. HCAB or extensible e.g.
as in Example 3. Will they be copied from LBTESTCD terms? Will they then be
removed from LBTESTCD terminology?
• Will ALL Serology and Immunology tests now reside in this domain rather
than LAB? How about VIROLOGY? Can you provide a list of tests which will
move? I think this needs clear guidance as the definition of
serology/immunology in relation to specific testing can be rather vague.
Defining the CAT for each LBTESTCD/ISTEST would be helpful.
• Please explain why you don't have an upper limit of quantitation. We have
serology data that requires this
.
Public comments
Update : IS and SR domains
IG v 3.1.4, batch 1
Comments:
• I am concerned about moving categories of data out of LAB into their own
domain. Generally all the categories fit well within the existing LAB domain
and may only need a few extra variables. My preference would have been to keep
serology and immunology and viral within LAB but add extra optional
variables to LAB e.g. ISLLOQ & ASSAYV with examples of how to use them.
Dividing the data up too much leads to problems when people have different
opinions as to whether this data is immunology or virology or biomark. We end
up having the same data in different dataset domains due to study team
preference. Does LAB just end up being haem, chem and urine?
•
ISTEST:
Immunoglobulin E is given as an example in the CDISC notes and HCAB
in example 1. These are already a lab test codes. Will ISTESTCD/ISTEST share same
codelist as LB? If so, how will users know whether to report results in LB vs IS?
Does purpose of test determine domain to use?
• Any specific reason why the data from IS can't be included in
LB, differentiated by LBCAT?
Public comments
Summary of comments on v3.1.4 batch 1:
For the EX/EC/IS domains a lot more thought should go in there so that there is no duplication
of information and a review of the quality of work to be reviewed by users should be done.
Non-standard variables
Non-standard variables
Update : Non-standard variables
IG v 3.1.4, batch 2
Biggest Concerns:
•
•
•
Dataset Size
Validation
Cost Impact
NSVs in standard domains
Update : Non-standard variables
IG v 3.1.4, batch 2
Permitting NSVs in parent domain will likely produce
datasets that are very wide and sparse in the NSV columns.
SuppQual increases the overall complexity of SDTM. SDTM
isn’t easy to understand and explain. Jettisoning the
SuppQual would make it a lot more appealing.
While SAS v5 XPORT files remain as the transport
mechanism, sparse datasets will result in big files, which the
US FDA openly complains
Separating data that belongs together in two datasets is
confusing. Given that SuppQual is transposed it is even
more confusing
Reviewing wide datasets is very unlikely to improve review
efficiency as mentioned in section 3.
Data transparency would be increased if extra variables
were allowed.
There is also the issue of additional file size that is sure to
occur from the NSVs being included in the datasets, which
flies in the face of often repeated comments from CDER that
we should not have dataset files that area "too big". Most of
the records will likely not even have data for many of these
NSVs, yet they will have the variables and the character
spacing for them. The increase of the file size (for all files
with Supplemental Variables) should be carefully weighed
against the benefit of the "ease of use" by only some
reviewers.
"Please develop this. This would make the SDTM datasets
more operationally useful, which is likley to lead to better
transparency.
More information is needed. Varied examples in the IG
would be helpful."
NSVs in standard domains
Update : Non-standard variables
IG v 3.1.4, batch 2
No. While this may address some challenges, it will create
others, and we think that therapeutic area development is
an overriding priority.
The compliance-checking is a particularly worrisome
prospect. How can a dataset be standard if it isn't?
If CDISC flips their fundamental constructs around as they
did when moving from v2 to v3, especially when this is
purely a matter of preference, I, and others, will throw up
my hands in disgust and question the validity of the CDISC
"standard".
Compiling NSVs into SUPPXX domain structure requires
complex programming and subsequent QC algorithms.
Programming and data review is more cumbersome and
time consuming in SUPPXX structure. Much time is spent by
sponsors programming teams removing NSV data from the
original source parent domain where it is collected and
moving it to the SUPPXX domain. Then again for internal
data review sponsors must put the data back to the parent
domain where it logically should be reviewed from.
Working on studies, when reviewing data
and confirming NSV's, it was found best to
have them linked to the parent domain.
NSVs in standard domains
Update : Non-standard variables
IG v 3.1.4, batch 2
At GSK we have invested millions of dollars and several
years into developing an SDTM-compliant submission data
development system. The creation of SUPP datasets are
embedded into this system and are an integral part of the
what defines the standard. Everyone knows that SUPP
datasets can be transposed and merged for operational
purposes. The existence of a standard is supposed to
protect sponsors from having to adapt to various user
preferences. To change SDTM to make it "optional" to
include NSV in the main domain dataset will mean that
reviewers will request it, so GSK would by necessity be
forced to redesign our data creation and compliancechecking systems at great expense.
Companies with existing SuppQual infrastructure or
companies that derive revenue by managing SuppQual for
other companies will be advocating to keep the SuppQual
paradigm.
The SuppQual paradigm favours larger companies that can
provide the infrastructure and staff to handle the increased
complexity associate with SuppQual operations
The current SuppQual convention ignores the fact that not
all data is ultimately submitted to the FDA so the SuppQual
costs are incurred without benefit. Given the rate of failure
in pharmaceutical development this doesn’t seem optimal.
NSVs in standard domains
Update : Non-standard variables
IG v 3.1.4, batch 2
For organizations that have already invested significant
resources into developing a system to handle raw data at
the operational level and then create SDTM compliant data,
there would be an obvious negative impact. These
organizations have already found a way to collect and clean
the data, then separate the non-standard data into
SUPPQUAL sets. If this proposal eliminates the SUPPQUAL,
the investment of resources is lost.
This is not however the only potential cost. Dependent upon
how the proposal is developed, for all organizations the
potential exists that adding NSV data to the standardized
domains will require study level custom programming to
draw these in the ADaM data. (As SDTM stands, NSV data is
100% predictable – values always appear as QVAL,
transposed varnames are always in QNAM, etc.) Creating
standardized programming to build analysis datasets is
easier in the current model.
Dropping the use of SuppQuals in favour of using NSVs is a
very good idea for the following reasons:
Maintaining the infrastructure to transpose and merge
SuppQual variables for operational, non-submission
business use case is substantial. With the current standard
extra costs are incurred not matter which paradigm a
pharmaceutical company chooses.
• The cost of converting operational, wide data sets to strict
SDTM with SuppQual is expensive.
• The cost of converting strict SDTM with SuppQual to
operational, wide data sets is expensive.
NSVs in standard domains
Update : Non-standard variables
IG v 3.1.4, batch 2
We are not in favour of the proposed change. We do think
that there would be a heavy cost impact because of the
work that would need to be undertaken to change existing
standards as implemented by industry. We feel that the
change is not backwards compatible with existing work. The
impact to validation via OpenCDISC or other tools should
also be considered. The possibility that this will open the
door to the inclusion of more derived variables in SDTM
data is also a concern
NSVs in standard domains
Update : Non-standard variables
IG v 3.1.4, batch 2
No. Roche's "operational" SDTM datasets include NSVs.
Roche has a standard procedure to separate the operational
datasets into parent and supplemental qualifier domains
and create study metadata (define.xml).
As SDTM exists today, the SUPPQUAL supports collection of
standardized data. Using the SUPP- - to extend the standard
requires additional effort. Sponsors are incentivized to look
for existing variables that meet each purpose or to find
related datasets (e.g., FA) to contain data. Should a sponsor
find no other way to meet the standards, sponsors are more
likely to create a review process to justify the deviation from
accepted industry standards. (To properly build a SUPP- domain for submission requires planning, programming
resources, QC effort, etc.) By simplifying the ability to add
non-standard data, this proposal increases the temptation
to work outside the established standards and possibly
negate the gains provided.
Yes. Roche has queried members of TBI and the consensus
support this proposal. Roche would like to see this proposal
prioritized and expediently pushed through the SDS
development process. Given the resource requirements of
the TA standards development, Roche encourages CDISC to
explore alternate resourcing methods. For example, could
this proposal be formalized as part of an FDA/PhUSE
project?
This will also be much easier to use the variables in ADaM.
Consequently, we at BI support this proposal of keeping
NSVs in the parent domain with clear rules such as standard
variable prefixes (ie) SP_NSV. This would help streamline
SDTM dataset creation and subsequent data review.
Any Comments ?

similar documents