Embed Size (px)
Citation preview
Nancy Brucken has been a statistical programmer in the pharmaceutical industry for over 25 years, is a member of the inVentiv Health Data Standards group, and currently co-leads the ADQRS team. She is a proud graduate of Marietta College, and a devout Ohio State Buckeyes fan.
Karin LaPann has been a SAS programmer for over 25 years. She is the co-lead of ADQRS team. In the past 4 years, Karin has moved to standards work and is the ADaM Standards lead at Shire. She is a graduate of Middlebury College in VT, and Drexel University in PA.
1
Nancy Brucken, inVentiv HealthKarin LaPann, Shire
3
4
5
Pharma Company
6
7
Pharma Company
Computer-Assisted New
Drug Application
(CANDA)
8
Clinical Data Interchange Standards Consortium
“CDISC is a 501(c)(3) global, nonprofit charitable organization that develops data standards to streamline clinical research and enable connections to healthcare.”
Mission Statement: The CDISC mission is to develop and support global, platform-independent data standards that enable information system interoperability to improve medical research and related areas of healthcare.
9
Regulatory agencies (FDA, PMDA) Pharmaceutical companies Clinical research organizations (CROs) Hospital research centers Universities Government agencies (NCI)
10
Clinical Data Acquisition Standards Harmonization (CDASH) Study Data Tabulation Model (SDTM) Analysis Data Model (ADaM) Standard for Exchange of Nonclinical Data (SEND)
11
Clinical Data Acquisition Standards Harmonization (CDASH)
Study Data Tabulation Model (SDTM) Analysis Data Model (ADaM)
Standard for Exchange of Nonclinical Data (SEND)
12
June 2004- Study Data Tabulation Model (SDTM) v1.0 standard released
July 2004- Study Data Tabulation Model Implementation Guide (SDTMIG) v3.1 standard released
July 2004- FDA references use of SDTM in submissions in the Study Data Specifications for the Electronic Common Technical Document
SDTM provides a standard for representing clinical study data as collected
13
Organized by type of data collected
Current version is SDTM v1.5 and SDTMIG v3.2
14
AEDM MH
LB VS
QS EXCM
SDTM = data as collected
but……
Statisticians need to modify for analysis purposes:◦ Missing data imputation◦ Additional derived variables◦ Analysis visit windows◦ Combine data from multiple domains
15
December 2009- ADaM Model v2.0 and ADaM Implementation Guide v1.0 released
2 main dataset models◦ ADSL = Subject-Level Analysis Dataset◦ BDS = Basic Data Structure 1 or more records per subject per analysis parameter per analysis timepoint
Structure driven by analysis requirements Current version is ADaMIG v1.1, with the addition of models for
occurrence data (OCCDS) and time-to-event analyses (ADTTE)
16
17
ADSL ADLB
ADAE
ADGDSSF
ADGAD7
ADQRS
18
CDISC Definition of Questionnaires:
“Questionnaires are named, stand-alone measures designed to provide an assessment of a concept. Questionnaires have a defined standard structure, format, and content; consist of conceptually related items that are typically scored; and have documented methods for administration and analysis. Questionnaires consist of defined questions with a defined set of potential answers. Most often, questionnaires have as their primary purpose the generation of a quantitative statistic to assess a qualitative concept.”
19
Questionnaires◦ Set of related questions combined in some manner to produce one or more
scores, which are then analyzed.
Ratings ◦ Classification or ranking of someone or something based on a comparative
assessment of their quality, standard, or performance.
Scales◦ Defined by a set of criteria that makes up a single measurement.
20
Functional Tests (FT)
Clinical Classifications
(RS)
Ratings and Scales
Oversee development of standards for collection and storage of questionnaires, ratings and scales
◦ Help select specific version(s) of instruments to be used◦ Obtain copyright permission, if not public domain◦ Determine standard variable names and values◦ Annotate sample data collection instrument◦ Determine any assumptions required for using data◦ Coordinate reviews by regulatory agencies, CDISC Standards Review
Council and general public (new step under discussion)◦ Publish standard in CDISC catalog
21
22
23
Where do requests for new QRS standards come from?
24
CDISC Therapeutic Area Standard Team Sponsor Companies
See the QRS page on the CDISC website: https://www.cdisc.org/foundational/qrs
CDISC Operating Procedure COP 017 outlines the steps for creation of a new standard (note that this COP is currently under revision, so watch the QRS page for an updated version)
Complete list of all published QRS supplements available on the QRS page of the CDISC website◦ All supplements in progress will also be added to the list shortly◦ Check this first, to see if a standard already exists!
25
I’ve collected all of this questionnaire data- what do I do with it now?
26
Move existing SDTM QRS data forward into standardized analysis datasets via ADaM supplements
Concentrate primarily on questionnaires in the QS domain, since their analysis is generally more complex
Prioritize by FDA and TA needs first Define datasets for use in a variety of analyses
27
28
Max length of 8 characters, must begin with ‘AD’ Remaining 6 characters used to identify instrument (no need
to include QS, RS, FT) as clearly as possible◦ ADGDSSF = “GDS Short Form Analysis Dataset”
QS origin is documented within Define.xml
29
Variable DescriptionPARAMCD • Transferred from QSTESTCD
• Scale scores use same root as QSTESTCD name plus additional letters e.g., GDS02TOT for total score
PARAM • Description of PARAMCD• Transferred from QSTEST, or descriptive of derivation
PARCAT1 • Recognized instrument name transferred from QSCAT• Identical for derived and collected parameters from the same instrument
PARCAT2 • Associated questionnaire sub-scale name or subcategory, if applicable
30
Variable Description
AVAL • Transferred from QSSTRESN for individual items• Derived in new rows for scale and sub-scale scores
AVALC • Store if needed for analysis or displaysQSORRES • Can be kept for traceability from SDTM
• Contains original character string as collected• Null for derived records
31
Keep the original QS records in the analysis dataset, with QSTEST and QSTESTCD copied into PARAM and PARAMCD
Keep records for any sub-scale and/or total scores included in QS Create separate records for calculated scores (e.g., may be recalculated because of
missing value imputation) in addition to operational score records from SDTM Create new PARAMCD using the same QSTESTCD root, plus additional characters
representing the specific sub-scale or total score (i.e. GDS02 to GDS02TOT) ABLFL (analysis baseline flag) and ANLzzFL (analysis flags) should be set only on
sub-scale and total score records, or on individual question records analyzed separately
CHG and BASE should only be computed for records that will be analyzed, not for every individual question
32
For each questionnaire, decide whether to include responses to all questions in the ADQRS data sets, or only summary records being analyzed
Regulatory agencies (FDA) have expressed a preference for including both the individual questions and summary records in the same dataset.
However, large datasets may take longer to process. A compromise is to create the full dataset, containing all individual and summary
records, and then create summary records in a separate dataset for the analysis Document all questionnaire scoring instructions in define.xml, along with all
imputation rules used for missing values.
33
34
SUBJID PARAMCD PARCAT1 QSORRES QSSTRESC QSSTRESN AVAL
0001 GDS0201 GDSSF Yes 0 0 00001 GDS0202 GDSSF Yes 1 1 10001 GDS0203 GDSSF No 0 0 00001 GDS0204 GDSSF Yes 1 1 1... ... ... ... ... ... ...0001 GDS0215 GDSSF No 0 0 00001 GDS02TOT GDSSF 10
35
In the SDTM QRS instructions for GDSSF, the scoring is already reversed for certain questions, so that total score is simply the sum of the responses.
Note that GDS02TOT row contains AVAL but not QSORRES, QSSTRESC or QSSTRESN, as it is a derived score.
Variable Where Type CT or Format
Source/ Derivation
AVAL PARAMCD NE "GDS02TOT" (GDS02-Total Score)
Num QS.QSSTRESN (Analysis Value is the standardizednumeric result copied in from SDTM)
AVAL PARAMCD EQ "GDS02TOT" (GDS02-Total Score)
Num 1) Sum of QS.QSSTRESN for QS.QSTESTCD in ('GDS0201‘ - 'GDS0215') if no questions are missing
2) If <=5 missing then AVAL is 15*(Sum of QS.QSSTRESN for QS.QSTESTCD in ('GDS0201'-'GDS0215')/ # non-missing questions
3) If more than 5 responses are missing, do not calculate a total score, and do not create a total score record.
36
Drug A (N=nnn)_________________________________
Drug B (N=nnn)___________________________________
TimepointValue at Visit Change from Baseline Value at Visit Change from Baseline
BASELINEn nn nnMean(SD)
xx.x(xx.x)
xx.x(xx.x)
Median xx.x xx.xMin - max xx.x - xx.x xx.x - xx.x
VISIT 1n nn nn nn nnMean(SD)
xx.x(xx.x)
xx.x(xx.x)
xx.x(xx.x)
xx.x(xx.x)
Median xx.x xx.x xx.x xx.xMin - Max xx.x - xx.x xx.x - xx.x xx.x - xx.x xx.x - xx.x....VISIT xn nn nn nn nnMean(SD)
xx.x(xx.x)
xx.x(xx.x)
xx.x(xx.x)
xx.x(xx.x)
Median xx.x xx.x xx.x xx.xMin - Max xx.x - xx.x xx.x - xx.x xx.x - xx.x xx.x - xx.x
37
38
Starting to see benefits of standards◦ Easier exchanging data between companies◦ FDA JumpStart process and technical rejection criteria leading to faster
review times Over 130 QRS supplements published so far Nearing completion of first ADQRS supplement Need more volunteers to develop ADQRS Supplements under
the guidance of the ADQRS sub-team
39
Update SDTM COP 017 to incorporate regulatory, CDISC Standards Review Council and public review of new QRS supplements
Develop online format for supplements instead of current Word/PDF files
Create ADaM supplement template for use in developing additional supplements
Develop ADaM equivalent of SDTM COP 017, enabling supplement development by other teams
Register Controlled Terminology terms for PARAM/PARAMCD with NCI team
Identify more high priority questionnaires for ADQRS supplements
40
Name: Nancy BruckenOrganization: InVentiv HealthCity, State ZIP: Ann Arbor, MIWork Phone: 734-887-0255E-mail: [email protected]
Name: Karin LaPannOrganization: Shire PharmaceuticalsAddress: 500 Shire WayCity, State ZIP: Lexington, MA 02421 Work Phone: 617-610-2361E-mail: [email protected]
41
42
