Download A Unique Application Generator for the Management and Control of Clinical Trials Data

A Unlque Appllcatlon Generator for the
Management & Control
of Cllnlcal Trlal Data
Chaim Singal: Teva Pharmaceutical Ind. Ltd.
Eyal Hasson: M.I.A. Computers Ltd.
Abstract
Innovative drug development requires not only high investment, but an intensive
effort in the management of the various clinical studies data, its collection
quality assurence and statistical analysis.
The SAS system, as an integrative tool capable of coping with all aspects of the
clinical development of new drugs, has thus been selected for this purpose.
The developed application generates screens for double entry on a single fill!,
coupled with on-line quality assurance, reporting and trial aUditing.
The advantage of this unique application is that it is self-generating, flexible and
eBsyto operate by non-experienced SAS programers; also, each clinical trial can
be developed in a few days.
Upon defining the clinical trial structure In their respective control files (that
includes CRF pages, forms, formats, links, ranges, etc.), the system dynamically
generates the entry screens which comprises the SCL compiled source for data
entry, on line reporting and the critical data tracking system.
The system further offers reports along with graphs as a smart EIS station.
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A Unique Application Generator'for the
Management & Control
of Clinical Trial's Data
Chaim Singal: Teva Pharmaceutical Ind. Ltd.
Eyal Hasson: M.I.A Computers Ltd.
Introduction
Innovative drug development requires not only high investment, but an intensive effort in the management of
the various clinical study's data, its collection quality assurance and statistical analysis.
The SAS system, as an integrative tool capable of coping with all aspects of the clinical development of new
drugs, has thus been selected for this purpose.
The TRACE Application that was developed under SAS software version 6.09 contains a full-featured data
management system that includes:
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Generation of screens for double entry on a single file.
CRF Tracking.
On-line quality assurance accompanied by DCRF's form of inclusion/exclusion criteria and any missing
data or abnormalities.
On-line reporting (of patient visit dates and patient data).
Case Report Forms print out and browsing.
Adverse Experience and Drug Reporting.
Trial auditing for any changes in data.
Various graphical presentations of data.
SQl Queries of all clinical and demographic data.
The' advantage of this unique application is that it is self-generating, flexible and easy to operate by nonexperienced SAS programmers. Furthermore, each clinical trial can be developed in a few days.
Upon defining the clinical trial structure in their respective control files (that includes CRF pages, forms,
formats, links, ranges, etc.), The system dynamically generates the entry screens that compromise the SCl
compiled source for data entry, on line reporting and the critical data tracking system.
TRACE Hierarchical Model
TRACE
UBRARY
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Format Library
Oictionnaries
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Study
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APPLICATION OPTIONS
The following section summarizes major application options that enables a non experienced SAS programmer
to build a new study, redesign and update the study and work within the study.
1. TEVA TRACE APPLICATION
TEVA TRACE APPLICA TION
Export Study
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New Study: Updating the system with a new study.
In order to build a new study we must first supply the system with the following information:
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Study definition that includes data library, formats library, study name, protocol number and study
title.
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study's variables which is saved in a file and contains:
File definition: data. set and variable names, format, informat, label and length of variables.
SCL definition: requirements, protection, initial, min, max and list of values.
R@port definition: min, max and list of values.
Information on the structure of the CRF is also required: pages and forms link and pages and visits link.
Once all of the above information is entered the default screens with variable labels (defined for
data entry) are created automatically. The created screens include the SCl source that controls
screen variables during first entry. second entry and data browsing.
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Import Study: Imports SAS data sets and screens into the new system generating all system management
files including the new SCL code for each screen.
Export Study: Creates a subdirectory under each study library named export that includes SAS data sets
screens without SCL and relevant formats. This step should be performed in order to have a frozen copy of
data set files and screens for statistical analysis and reporting.
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Edit Studies: Edits the studies definitions.
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2. MAIN MENU
WORKING WITHIN A STUDY:
After clicking on any 'study Title' there are 12 options to choose from the main menu:
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Receive CRF's: Here the Data Management Unit is able to declare the receipt of the CRF's for further
handling. The computer then asks for the following information that will be updated automatically on
management tables:
Receiving NEW CAPs
TEVA Pharmaceutical Ind .
• SllJOYTITLE'
Patient No.:
Visit No.:
Pages:
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~ndIor From: _
To:_ _ or <Choose FornIs)
<Retum>
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The computer checks the validity of data
and notifies the user with records that
were expected and were not received.
<Update>
DCRF's: Data Clarification and Resolution Form's: 6 options (see section 6).
Data Entry: Dynamic data entry, first entry or second entry. During second entry computer performs online comparisons between the two entries and warns us of any discrepancies.
Entry & Qauble 8Itry at Form.
TBIA Al8rnaceulicallnd
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'sn.D!' l1TLE
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PltientND.:
Visit No.:
VIs.DIIts:
PhysicIM (0 for lilt):
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initialS:
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The system prior to entering the CRF checks for patient
initials to patient number link and patient - physician and
hospital link.
During first and second entry, values that are out of the
range min, max, and IN are not allowed. At the end of
second data entry, each form on irregular data is
automatically performed and creates a DCRF for
abnormalities, protocol violations and miSSing data.
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Study tables: Management and maintenance of formats and dictionaries for all studies: 6 options (see
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section 7).
Mngnt Tables: Management information of the specific study: 6 options (see section 5).
Browse/Print: Browse or print the form that has been designed according to the CRF.
All the combinations are possible by selecting the following:
Browsing Forms
revA R'larmaceuticallnd
BIter: Patient No.:
Page No.:
or:
Visit
No.:
Form:
You can ask to browse through:
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Each patient for all forms and all pages.
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A particular page for all patients and all forms.
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Different patients by selecting patient from the
patient list etc.
<Cancel> <Brow se> <A'int>
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Redesign Study: 12 options (see section 3).
Reports: Generates reports such as : visitdate report, demographic data report and some management
reports.
Graphs: Examples of graphs are enrollment and duration.
SQl Queries: This option enables you to create a data set containing the variables you have a query on.
Variables that are added automatically are patient visit number and visit date.
This includes the option of choosing a variable and a group name that enables you to select variables that
occur with different names and different forms by choosing the group variable name (e.g. DRUG can be
defined in different forms or pages). You obtain the path to variables with no research;
Macro's: Macro's of SAS programming for the analysis remain here and they may be submitted.
989
J. REDESIGN STUDIES
MAIN MENU
REDESIGN STUDY:
Pages: Edit page listings of file pages.
Visits: Edit visit listings.
Variables: 5 options (see section 4).
Date Format: This option changes all the dates that appear in Management files and Study files. You may
choose formats for dates.
Recreate Headers: In case of any damages on system files this option creates the structure of the system
files including indexes, keeping the data.
Recreate Files: You choose the forms you need to recreate in case changes need to be performed (e.g.
changes in variables definition).
Recreate Screens: Updates the last screen created with a new SCL source including changes in Min-Max
protection.
Edit Screens: Enables the selection of form design you wish to edit and redesign.
Verify Status: You may choose the patients that you want to mark as verified;
DeUChng Pat: Delete or change a patient number or initial is done for changing patients screening number
to new number after screening was completed. There is a systematic backup file for patients' data that
were deleted.
Erase Data: The option is given to erase or not the data while building an application and running it on
DEMO. This does not erase the structure of the study.
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4. VARIABLES
Definition
Protection
VARIABLES:
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Definition: Edits the variables.
Min-max: For each variable a minimum and maximum value range for entry and reporting can be defined
as valid.
Protection: The variable is protected under the condition that you specify.
Grouping: If the end user might have later to query about a few variables, he can group these variables
into a group-name and index. By grouping variables with the same information under the same group
name and index makes it easier for selection (e.g. Drug1, Drug2, Drug3 ~n be grouped under drug). Later.
the user can use this group name to find information about all the variables that are part of the groupname.
5. MANAGEMENT TABLES
Trace
Studies
MNGNT TABLES:
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Trace: Trace is a file where information about all records is kept. This file also contains the option of
Barcodes for future use.
Visit date: File Visit Date contains all information on all the visits.
DCRF's: Log of all transactions of the DCRF's.
Studies: File named Trace.Studies that gives all information about the computer location of the study.
Patients: File that gives all demographic information about patients.
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6. DCRF MENU
Create DCRPs
Resolve DCRPs
DCRF's: Data Clarification and Resolution Form's.
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Create DCRF's: Once the computer was notified with the received CRF's and prior to data entry the CRF's
must be checked and reviewed by the Quality Assurance or medical reviewer that may need to create a
DCRF.
DCRF can be created after double entry ( on-line irregularity checked by the computer) and during any
. analysis stage of the data.
Edit DCRF's: Edit the actual DCRF and makes changes before printing.
Print DCRF's: Print the DCRF. Each DCRF has a unique number.
Resolve DCRF's: Make amendments to a DCRF form and the data sets are updated automatically with
the new values.
Reprint DCRF's: Reprint a DCRF by choosing its number.
7. STUDY TABLES
Fhys-Hosp
New Formats
STUDY TABLES:
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New Formats: Create a new format.
Old Formats: Catalogue directory for old formats.
Recreate Formats: Possibility to reshape the formatted data sets formats and tables in case of any
damage.
Phys-Hosp: List of physicians and hospitals' correspondence in the studies.
Drug Groups: Dictionary for drug groups.
ADR Groups: Dictionary for ADR groups.
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