Analysis Data Reviewer’s
Guide
TEVA Sweden AB
Protocol: BFS-AS-70001
Study BFS-AS-70001
Version 1.0 : Date-21 OCT 2015
Revision History
Date
13-DEC-2018
Version
0.1
Summary
Draft
Analysis Data Reviewer’s Guide
Contents
1.
Introduction........................................................................................................................................... 4
1.1
Purpose.......................................................................................................................................... 4
1.2
Acronyms ...................................................................................................................................... 4
1.3
Study Data Standards and Dictionary Inventory ........................................................................... 4
1.4
Source Data Used for Analysis Dataset Creation ......................................................................... 4
2.
Protocol Description ................................................................. Ошибка! Закладка не определена.
2.1
Protocol Number and Title................................................ Ошибка! Закладка не определена.
2.2
Protocol Design in Relation to ADaM Concepts .......................................................................... 5
3.
Analysis Considerations Related to Multiple Analysis Datasets .......................................................... 5
3.1
Comparison of SDTM and ADaM Content .................................................................................. 5
3.2
Core Variables .................................................................. Ошибка! Закладка не определена.
3.3
Treatment Variables ...................................................................................................................... 8
3.4
Subject Issues that Require Special Analysis Rules ..................................................................... 8
3.5
Use of Visit Windowing, Unscheduled Visits, and Record Selection .......................................... 8
3.6
Imputation/Derivation Methods .................................................................................................... 8
4.
Analysis Data Creation and Processing Issues ......................... Ошибка! Закладка не определена.
4.1
Split Datasets .................................................................... Ошибка! Закладка не определена.
4.2
Data Dependencies............................................................ Ошибка! Закладка не определена.
4.3
Intermediate Datasets ........................................................ Ошибка! Закладка не определена.
4.4
Variable Conventions........................................................ Ошибка! Закладка не определена.
5.
Analysis Dataset Descriptions .................................................. Ошибка! Закладка не определена.
5.1
Overview ........................................................................... Ошибка! Закладка не определена.
5.2
Analysis Datasets .............................................................. Ошибка! Закладка не определена.
5.2.1
ADSL – Subject-Level Analysis Dataset .................. Ошибка! Закладка не определена.
6.
Data Conformance Summary.................................................... Ошибка! Закладка не определена.
6.1
Conformance Inputs .......................................................... Ошибка! Закладка не определена.
6.2
Issues Summary ................................................................ Ошибка! Закладка не определена.
7.
Submission of Programs ........................................................... Ошибка! Закладка не определена.
8.
Appendix................................................................................... Ошибка! Закладка не определена.
1. Introduction
1.1 Purpose
This document provides context for the analysis datasets and terminology that benefit from additional
explanation beyond the Data Definition document (define.xml). In addition, this document provides a
summary of ADaM conformance findings.
1.2 Acronyms
Standard industry acronyms ( CDISC , ADaM and SDTM except MedDRA) are used.
1.3 Study Data Standards and Dictionary Inventory
This ADRG assumes that SDTM is used as input to the creation of analysis datasets and that the analysis
datasets adhere to the ADaM standard to the largest extent possible.
Standard or Dictionary
SDTM
ADaM
Versions Used
SDTM IG v3.2
Data Definitions
ADaM Implementation Guide v1.0
define.xml v2.0
Controlled Terminology
CDISC SDTM Controlled Terminology, 2017-09-29
1.4 Source Data Used for Analysis Dataset Creation
ADaM data sets are created by using SDTM version 3.2 but time variables in ADSL are created from the
raw data sets.
2. Protocol Description
2.1 Protocol Number and Title
Protocol Number : BFS-AS-70001
Protocol Title
: Evaluation of device handling for Spiromax®, Easyhaler®,and Turbuhaler
among Swedish healthy volunteers
Protocol Versions : Version 1.0 21 OCT 2015
2.2 Protocol Design in Relation to ADaM Concepts
This is a single-site , single-visit , cross-over study assessing device mastery, handling errors
and device preference with three inhaler devices, Spiromax®, Easyhaler® and Turbuhaler ®.
The study subjects are adult (≥ 18 years) Swedish individuals, who are currently not using any
inhaler for treatment of asthma, chronic obstructive lung disease (COPD), or other diseases.
Empty devices without active substance or excipients will be used for the study.
The subjects will be recruited by using among other, advertisement and participation will be
voluntary.
Total of 110 study subjects will be randomly assigned to test Spiromax®, Easyhaler®, and
Turbuhaler® devices in random order. Each device is tested in two steps: a) intuitive device use
(no instructions, step 1), all the inhalers b) device use after reading PIL (step 2), all the inhalers.
The subjects will be recorded and trained health care professional (HCP) will assess device use
in each step, record errors based on the device-specific handling error checklists (DSHEC) that
are developed from the package leaflet instructions for each device, as well as errors from a
predetermined device-independent inhalation error checklist (DIIEC) developed for errors during
and after inhalation. Device preference is measured using a device preference questionnaire
(DPQ) after participants have completed the two steps with three different devices.
3. Analysis Considerations Related to Multiple Analysis Datasets
3.1 Comparison of SDTM and ADaM Content

Are data for screen failures, including data for run-in screening (for example, SDTM values of
ARMCD=’SCRNFAIL’, or ‘NOTASSGN’) included in ADaM datasets ?
Two screen failures are reported in the study and it included in ADSL data set but it is absent
in ADQS data set for the analysis purpose.

Is data taken from an ongoing study ?
No. This is a final locked database.
3.2 Core Variables
Core variables are those that are represented across all/most analysis datasets.
Variable Name
Variable Description
STUDYID
Study Identifier
USUBJID
Unique Subject Identifier
SUBJID
Subject Identifier for the Study
SITEID
Study Site Identifier
GRPID
Group ID
COUNTRY
Country
AGE
Age
AGEU
Age Units
BRTHDT
Birth Date
SEX
Sex
SEXN
Sex (N)
RACE
Race
RACEN
Race (N)
EDUQUAL
Education Qualification
GROUP
Group
GROUPN
Group (N)
SCRNFFL
Screen Failure Flag
ENRLFL
Enrolled Population Flag
COMPFL
Compilation Flag
ARM
Description of Planned Arm
ARMCD
Planned Arm Code
TRT01P
Planned Treatment for Period 01
TRT01PN
Planned Treatment for Period 01 (N)
TRT01A
Actual Treatment for Period 01
TRT01AN
Actual Treatment for Period 01 (N)
TRT02P
Planned Treatment for Period 02
TRT02PN
Planned Treatment for Period 02 (N)
TRT02A
Actual Treatment for Period 02
TRT02AN
Actual Treatment for Period 02 (N)
TRT03P
Planned Treatment for Period 03
TRT03PN
Planned Treatment for Period 03 (N)
TRT03A
Actual Treatment for Period 03
TRT03AN
Actual Treatment for Period 03 (N)
TRTSEQP
Planned Sequence of Treatments
TRTSEQA
Actual Sequence of Treatments
TMSPRFL1
Total Mastery in using Spiromax at step1
TMTURFL1
Total Mastery in using Turbuhaler at step1
TMESYFL1
Total Mastery in using Easyhaler at step1
MSPRFL1
Mastery in using Spiromax at step1
MTURFL1
Mastery in using Turbuhaler at step1
MESYFL1
Mastery in using Easyhaler at step1
MSPRFL2
Mastery in using Spiromax at step2
MTURFL2
Mastery in using Turbuhaler at step2
MESYFL2
Mastery in using Easyhaler at step2
ATMESY2
Time taken in using Easyhaler at step2
ATMSPR1
Time taken in using Spiromax at step1
ATMSPR2
Time taken in using Spiromax at step2
ATMTUR1
Time taken in using Turbuhaler at step1
ATMTUR2
Time taken in using Turbuhaler at step2
ATMESY1
Time taken in using Easyhaler at step1
AVISIT
Analysis Visit
AVISITN
Analysis Visit (N)
PARAM
Parameter
PARAMCD
Parameter Code
PARAMN
Parameter (N)
PARCAT1
Parameter Category 1
PARCAT2
Parameter Category 2
AVALC
Analysis Value (C)
TRTP
Planned Treatment
TRTA
Actual Treatment
QSGRPID
Group ID
3.3 Treatment Variables
ARM versus TRTxxP
 Are the values of ARM equivalent in meaning to values of TRTxxP?
Yes.
ACTARM versus TRTxxA
 If TRTxxA is used, then are the values of ACTARM equivalent in meaning to values of TRTxxA?
Yes , since planned and actual treatment are same, TRTxxA variables are not used.
Use of ADaM Treatment Variables in Analysis
 Are both planned and actual treatment variables used in analyses?
Planned treatment variables are only used in analyses.
3.4 Subject Issues that Require Special Analysis Rules





Did subjects receive the wrong treatment entirely compared to assigned randomization?
No.
Did subjects receive the wrong treatment and/or wrong dose at least once, but not entirely from
what was expected per the assigned randomization?
No.
Did subjects have incorrectly defined randomization strata?
No.
Did subjects switch sites?
No. Here we have only one site.
Were there any protocol deviators that handled differently in the analysis than what was expected
per the definitions in the SAP?
No.
All the subjects were treated under the same analysis rule.
3.5 Use of Visit Windowing, Unscheduled Visits, and Record Selection
 Was windowing used in one or more analysis datasets?
No visit windowing was done in the analysis datasets.
 Were unscheduled visits used in any analyses?
The study has only one visit. There is no unscheduled visit.
3.6 Imputation/Derivation Methods
No imputation of data was done during the analysis.
4. Analysis Data Creation and Processing Issues
4.1 Source Data Used for ADaM Creation
The source data for the ADaM data sets were the combination of SDTM version 3.2 and non SDTM
clinical data base. Time variables in the ADSL data sets are created from non standardized data sets.
4.2 Split data sets
There is no size issue related to the data sets . Therefore no need to split the data sets .
4.3 Data dependencies
Planned and actual treatment variables in ADQS are derived from ADSL. The core variables in both data
sets are derived from SDTM data sets.
4.4 Intermediate data sets
No intermediate analysis datasets were created in this trial.
4.5 Variable Conventions
5. Analysis dataset descriptions
5.1 Overview

Do the analysis datasets support all protocol- and statistical analysis plan-specified objectives?
Yes, all protocol and statistical analysis plan specified objectives are supported by the analysis
datasets.

Do the submission datasets include screen failures?
ADSL data set includes screen failures
Primary
Objective
Class
PK/PD
Dataset Label
Baseline or
other patient
characteristics
Dataset
Safety
Efficacy
5.2 ADaM Domains
ADSL
Subject-Level Analysis
Dataset
ADQS
Questionnaire analysis Data
ADSL
BDS
X
X
X
X
Structure
One record per
subject
One record per
subject per
parameter per
analysis visit
5.2.1 ADSL – Subject Level Analysis Data set
Subject level dataset has the same number of subjects (records ) as in the SDTM ( DM) domains . It
contains all the required ADaM variables for demographics (AGE), treatment groups, and population
flags. Additional variables are:
SEXN – Numeric equivalent of SEX
RACEN - Numeric equivalent of RACE
EDUQUAL - Education Qualification
GROUP – Group
GROUPN - Numeric equivalent of GROUP
Treatment variables for different periods are relevant to conduct the study.
TRT01P – Planned Treatment for Period 01
TRT01PN- Planned Treatment for Period 01 (N)
TRT01A- Actual Treatment for Period 01
TRT02P- Planned Treatment for Period 02
TRT02PN- Planned Treatment for Period 02 (N)
TRT02A- Actual Treatment for Period 02
TRT02AN- Actual Treatment for Period 02 (N)
TRT03P- Planned Treatment for Period 03
TRT03PN- Planned Treatment for Period 03 (N)
TRT03A- Actual Treatment for Period 03
TRT03AN- Actual Treatment for Period 03 (N)
TRTSEQP- Planned Sequence of Treatments
TRTSEQA- Actual Sequence of Treatments
TRT01AN- Actual Treatment for Period 01 (N)
Flags
SCRNFFL- Screen Failure Flag
ENRLFL- Enrolled Population Flag
COMPFL- Compilation Flags
Mastery Flags
TMSPRFL1- Total Mastery in using Spiromax at step1
TMTURFL1- Total Mastery in using Turbuhaler at step1
TMESYFL1- Total Mastery in using Easyhaler at step1
MSPRFL1- Mastery in using Spiromax at step1
MTURFL1- Mastery in using Turbuhaler at step1
MESYFL1- Mastery in using Easyhaler at step1
MSPRFL2- Mastery in using Spiromax at step2
MTURFL2- Mastery in using Turbuhaler at step2
MESYFL2- Mastery in using Easyhaler at step2
Time Variables
ATMESY2- Time taken in using Easyhaler at step2
ATMSPR1- Time taken in using Spiromax at step1
ATMSPR2- Time taken in using Spiromax at step2
ATMTUR1- Time taken in using Turbuhaler at step1
ATMTUR2- Time taken in using Turbuhaler at step2
ATMESY1- Time taken in using Easyhaler at step1
5.2.1 ADQS- Questionnaire analysis Data set