THE CENTRE OF EXCELLENCE FOR CLINICAL TRIAL DATA

How to Standardize Clinical Data While Controlling Your Costs

By Valeria Vison, Head of Statistical Programming, CROS NT
Many biotech and pharmaceutical companies use 1.
CDISC standards when creating databases for new
clinical studies. Regulatory authorities have found the
use of CDISC has made it more efficient for them to
review and examine information. This, along with the
need to cross analyze data, has led to much stand- 2.
ardization throughout the life science industry.
However, there are many legacy studies with
valuable data that have not been conducted to this 3.
standard. This can create issues when trying to
integrate data from different studies. To correct the
4.
problem it often requires considerable mapping work
which can be expensive.
This article makes some suggestions on how to
apply standardization in current clinical development 5.
programmes and how to minimize the cost and
6.
streamline the process of converting legacy data to
the same standard.

Standardized Data
using SDTM
format,
including the source of the original data
(specify version of SAS to be used).
Mapping documents between the source and
target data, to provide traceability information.
Data Status Table containing the different
source
data
characteristics
including
quantitative and qualitative measurements.
Metadata File (define.xml)
Mapping Program files and execution logs
(.log) which document the mapping process.

7.

Reviewers Guide which contains a detailed

description of the mapping rules and source
data types for each study.

Adopting and implementing CDISC standards can 8.

increase drug development analysis costs. However,
identifying the right process for implementation and
choosing the appropriate technology can reduce the
costs of adopting these standards, making it a very
worthwhile investment in the medium to long term.

Validation Certificate containing signed reports

of quality control checks including resumes of
the personnel involved.

Adopting & Implementing CDISC Standards

Conversion to CDISC standards generally includes

SDTM (Study Data Tabulation Model), ADaM
(Analysis Data Model) and CDASH (Clinical Data
Acquisition Standards Harmonization). It is important
to start implementing CDISC standards during data
collection by having Data Managers design the CRF
using CDASH standards. This makes the process of
mapping data into SDTM and ADaM datasets much
more straight forward.

Preparing a Data Mapping Project

When requesting a CRO or an internal team to map a
set of legacy studies to CDISC standards, requesting
the following deliverables will ensure a structured and
validated approach.

Project Plan and Project Charter to establish

contacts, timelines, frequency of status
reports, project risks and issue resolution
procedure.

Image:Business&LifeDecision


Automation Tools and Managing CDISC Standards to means minimal programming is required and no
Ensure Consistency
derivations should be done during programming of
the statistical analysis but all variables and
Establishing the correct work flow and SOPs to
observations should be included in the dataset.
manage the process is the first step. Then you need
to look at automation tools to create standard To ensure traceability, statistical programmers must
datasets to ensure speed and consistency. Cleverly prepare clear metadata and describe the contents of
designed macros will achieve this objective.
all datasets and statistical analysis using the naming,
labeling and variable conventions.
There
are
commercially
available
software
applications but they can be expensive. SAS can be While the ADaM model can present many challenges
used to convert Excel datasets and apply metadata in terms of adhering to traceability, Senior Statistical
Programmer for CROS NT, Marta Zanus, points out
attributes to the CDISC domains.
ways to ensure traceability:
Becoming a CDISC member organisation and
designating at least one person as a champion is a
The standards, macros and the process
good way of staying up to date and informed on new
currently used by the team should be archived.
developments.

New procedures and standards should be

established.
Ensuring
Traceability
Submission

for

Regulatory

Authority

Using CDISC standards can ensure much better

traceability of data, especially in cases where there is

one global data warehouse.
According to SAS, traceability in context of ADaM
datasets means providing the method followed to
derive an analysis endpoint from source SDTM data.
In order to ensure traceability, it is necessary to
understand the relationship between analysis results,
analysis datasets and SDTM datasets. There are two
types of traceability: data-point traceability and
metadata traceability. These two traceability methods
will facilitate the following for regulatory authority
submissions:

Original/Observed information (SDTM)

Derived/imputed information

Methods and algorithms for all derivations

Supportive or required
statistical analysis

information

for

Resources and time should be allocated to

implement the new process.
Appropriate internal
should be performed.

and

external

training

Data Repositories for Information Management and

Cost Reduction
Implementing CDISC standards means adopting
technologies that can manage the flow of data and
information. Keeping clinical data in multiple
repositories can create a complex management
process and is often prone to error. Managing
multiple respositories can mean spending more time
on vendor management.

the

ADaM datasets allow for the creation of variables or

observations that are not directly used for the
Setting up a central database for all data - whether
from a laboratory, a CRF or an ePRO device - to be
statistical analysis but support traceability. For stored in one place, allows for an easier mapping
example, re-allocation of data may happen for early process.
termination visits in accordance with the Statistical
Analysis
Plan.
Metadata
traceability
includes
documentation
required
to
clearly
describe With a centralized hosting system, the process is
information that already exists in the SDTM datasets linear and traceability is under control. A centralized
together with algorithms and methods used to derive system also provides easy data transfer to the
Sponsor, Regulatory Authority or Purchaser.
an analysis result.
The statistical programming team prepares ADaM
datasets for both traceability and analysis-ready
requirements. Analysis-ready datasets, according to
CDISC ADaM Implementation Guide Version 1.0,

Stefano Piccoli, Chief Operating Officer of ARITHMOS,

CROS NTs technology affiliate, points out the
following benefits in using hosted and centralized
storage:

Cost: Avoid paying multiple CROs to set up a In a recent vaccine study, CROS NT applied CDISC
global library, program macros and perform standards for an integrated summaries submission to
the FDA. This involved creating an annotated CRF,
validation checks.
implementation of data structures within SAS, and
Efficiency and Time: When the team is already creating a global database structure.
familiar with Sponsor requirements the review
cycle reduces. Training and HelpDesk costs Following initial consultancy to discover a Sponsors
needs, CROS NT can offer:
also reduce.
Quality: Measurement scales, design features,
outputs
and
summaries
all
become
standardized.

Access to Data: Reporting and access to data

becomes much more straight forward. Central
web access can be used by Sponsors to obtain
important safety information, efficacy data and

study progress reports.

Mapping of raw data to SDTM and ADaM

standards
CDASH libraries to provide competitive EDC
usage fees
Macros/tools
mapping

to

ensure

fast

and

accurate

Data respositories with flexible data access and

reporting capabilities

CDISC Mapping for Integrated Summaries

Using CDISC standards and automated mapping is
very beneficial when it comes to producing integrated
summaries of efficacy and safety (ISE/ISS). (See
recent CROS NT article on How to Get Full Value
From Integrated Summaries). ISS and ISE are
requirements for New Drug Applications with both the
FDA and EMA (European Medicines Agency).
According to the ICH guidelines for electronic CTD
submission, ADaM is preferred for statistical analysis
in integrated summaries.

CROS NT has helped many companies incorporate

CDASH, SDTM and ADaM standards into their
organizations and mapped legacy studies to create
the
necessary
consistency
in
formats.
The
programming team has developed some excellent
macros to reduce time, costs and ensure
consistency. For further information please contact
info@crosnt.com
or
visit
our
website
www.crosnt.com.

To
perform
CDISC
mapping
for
integrated
summaries, SDTM mapping specifications are defined
and CRFs are annotated. After SDTM conversion,
data pooling based on SDTM
can be used to support the
integrated summaries.

CROS NT & CDISC Mapping

CROS NT is a CDISC Gold Member, meaning it has
constant access to new data standards and new
documentation regarding CDISC standards.
In the field of Clinical Data Management, CROS NT
prides itself on a thorough understanding of
regulatory standards. In order to manage vast
amounts of data in an efficient and cost effective
manner, CROS NT makes full use of CDISC data
standards.
CROS NT Head of Clinical Data Management, Monica
Pimazzoni, points out the importance of implementing
these standards, CROS has developed the
knowledge and expertise to meet the CDISC
requirements and at the same time satisfy Sponsor
requirements by harmonizing reporting standards
across studies and increasing efficiency and quality in
the deliverables to Sponsors.

Celebrating its 20th anniversary this year, CROS

NT has created a centre of excellence for clinical
trial data. With an international presence and a
large set of resources, CROS NT is specialized in
clinical and safety data - collection, analysis and
reporting.
CROS NTs technology affiliate, ARITHMOS, has
expertise in building central data respositories and
collecting and integrating data from ePRO devices
and EDC systems.
For more information, visit the CROS NT website
at www.crosnt.com, and for further details on our
technology competencies, visit the ARITHMOS
website at www.arithmostech.com.

THE CENTRE OF EXCELLENCE FOR CLINICAL TRIAL DATA

VIA GERMANIA 2 - 37136 VERONA ITALY

TEL: +39 045 820 26 66 | FAX +39 045 820 58 75
info@crosnt.com | www.crosnt.com