Clin Eval 40（1）2012

CDISC as the global standards

Extracting the value of standards:
The role of CDISC
in a pharmaceutical research strategy ＊1
Frank W. Rockhold 1）＊ 2

Simon Bishop 2）＊ 3

1）Global Clinical Safety and Pharmacovigilance, GlaxoSmithKline
2）Data Stewardship Operations, GlaxoSmithKline

Abstract
Regardless of your role in drug development (Clinical, Statistics, Data Management, Safety, etc.), theimportance of information that is of high quality and open to immediate and reliable access has never been
more apparent. The ultimate utility of the information is directly related to how it is collected, stored andable to be located. That is to say, it has little value if not retrievable. The need for clear, useable andavailable standards to accomplish this is essential. The true value of standards is only seen when they areabsent and information cannot be used. Not only is information our most expensive and valuable resource,
when patients are asked to sign an informed consent to enroll in one of our clinical trials, they are assured
the information gathered will be used to better the health of future patients. If we cannot store, find andretrieve the information in a reliable way, not only are we wasting valuable time and money, we are notmeeting our commitment to patients or supporting the research goals. CDISC (Clinical Data InterchangeStandards Consortium) is an organization that was created and is tasked with being in the middle of solving
this most critical piece of transforming the data from trials into a true information-based model that willallow subject matter experts to derive practical wisdom on behalf of patients. This paper outlines both at a
strategic and tactical level how standards in general and CDISC in particular help us be more efficient inour handling of research data and sustain valuable contributions to science.
Key words
clinical research, clinical trials, data standards, regulatory submissions, data exchange＊1Japanese translation of this article originally written in English is included in. 40（1）：91-6. English version is published only in the journal web-site (http://homepage3.nifty.com/cont/40̲1/p916eng.pdf).
＊2
Past Chair of the Board, CDISC＊3
Member CDISC advisory Board
−1−

臨床評価

40 巻 1 号

2012

process is

1．Introduction

major asset we build in R&D(research and development). It is the end product ofevery experiment and clinical study that we per-Regardless of your role in drug development,

form. We need it for decision making internally,(Clinical, Statistics, Data Management, Safety, etc)

achievement of regulatory approval and reimburse-

the importance of information that is of high qual-

ment, monitoring and ensuring the safety of ourity and open to immediate and reliable access has

medicines in the market place. Ensuring the appro-

never been more apparent. The ultimate utility ofpriate governance and integrity in our use of data

the information is directly related to how it is col-is part of the commitment we make to the investiga-

lected, stored and able to be retrieved. That is totor and the patient when we undertake a study withsay, it has little value if not retrievable. The true

them. We commit to the use of information to fur-value of standards is only seen when they are absent

ther benefit future patients in a standard informed

and information cannot be used.

consent form.

Many, if not most, pharmaceutical companies-

Our data also offer real opportunity, for exam-including GlaxoSmithKline (GSK)-have engaged in,ple, to build better experiments and studies using

or are engaging in, overhauls of their data collec-

existing data and to plan recruitment strategies.

tion and storage systems. These all aim to reduce

Competence in design, rigour and use of our data is

and standardize the myriad systems that exist in

both an essential for GSK and the source of poten-

clinical development. By simplifying our systems

tial productivity and innovation opportunities. In

landscape, we expect to greatly improve the speed

addition, the ability to do this is a critical part ofat which data are available. Many are turning tosimplification and trust and transparency initia-“off the shelf” systems to reduce development time

tives in place across our industry. It is difficult toand compliance efforts. In fact, most vendors pre-maintain trust without transparency, both inside

fer to work with customers who employ commonly-

and outside of an organization, and in turn it isaccepted standards for the same reasons ofhard to be transparent without reliable access toefficiency and cost. That, in turn, will enhance theinformation (a.k.a. standards). Standards further

quality and consistency of data and documents,

enhance our, ability to in-license and out-license

resulting in delivery of products that reach patientsdevelopment compounds, outsource data collection

sooner, at a lower cost, with less effort involved

and management, share patient level data, or engage

for clinical teams.

in other data transfers.

Systems process improvement and standards

2．Principle strategic focus ofstandards

development have shared goals of enabling companies to reliably find, understand, and use clinical
trial data to deliver differentiated medicines ofvalue and sustain them in the marketplace. This

There are three major areas we need to focus on

article intends to provide support to the impor-

to meet the challenges and take the opportunities:

tance of the concept of applying standards and theacquiring the right data, making sure we can con-need for dedicated staff to develop and maintainsistently store and find them and, finally, under-them.

standing and being innovative (e.g., re-use) with the

The data resource we build in the development

data resources that we have.
−2−

Clin Eval 40（1）2012

First, we have to ensure that we collect the rightalready use our data for in-stream detection ofdata. This sounds obvious, but various analyses

safety signals. There are pockets of people using

over the past few years have demonstrated that 20(or re-using) clinical trials data for many purposes

to 40 percent of data items collected may not haveranging from planning clinical trials, to reviewing

been required and were never used in drawing

information within classes of compound to boost

inferences about our trials. Much of the cost reduc-early development, to validating the designs in newtion in GSKʼs programs was achieved by reducing

toxicology screens to reduce the usage of animals

patient visits by one-third and eliminating a num-in safety studies. New search technologies andber of laboratory visits. Our information planning

improved data resources will offer many moremust follow on from medicines development strat-

opportunities. We have to know as much about ouregy and development plans to build a coherent

medicines as we possibly can to help our patients.
A global non-profit organization called theinformation resource based on the right science.
Second, we must ensure that we can find andClinical Data Interchange Standards Consortium

understand our data. We have many examples in(CDISC) was formed 15 years ago to create anwhich 70 to 80 percent of the cost and effort ofenvironment to enable researchers to deliver on theanswering regulatory or safety queries has beenneed expressed above.

spent finding, retrieving and shaping the data so

3．CDISC

they can be used (or re-used) to address the question. Standards are essential for industry to meet
regulatory and other stakeholder demands and to

The CDISC (www.cdisc.org) mission as described

reduce the cost of data ownership ‒ in acquisition,on the website:

retrieval and use of data. Standards and systems“CDISC is a global, open, multidisciplinary, non-are necessary to achieve the goals above, but per-profit organization that has established standards

sonal accountability and competence are also essen-

to support the acquisition, exchange, submission

tial. All researchers must behave as though they

and archive of clinical research data and metadata.

personally own this valuable resource. The behav-

The CDISC mission is to develop and support

ioural shift needed to make this work is not to be

global, platform-independent data standards

taken lightly. From the most senior manager to thethat enable information system interoperability

front line scientists, the value and access to ourto improve medical research and related areas

information must be held sacrosanct. This takesof healthcare. CDISC standards are vendor-neu-skill in communication-all the way from the seniortral, platform-independent and freely available via

manager who must allocate the time and money to

the CDISC website”.

achieve the goal to the front-line scientist who

This organization is the sole Standards Develop-

must assume that someone, 5 ‒ 10 years from now,

ment Organization devoted to clinical research.

will need a clear path to retrieve and reuse the

The CEO, management team and Board of Directors

information.

represent some of the brightest and most experi-

Finally, we need to make the best use of ourenced minds involved in the standards business.

data. We are using our data in regulatory applica-

They are the standards selected by regulators (e.g.

tions and in support of our medicines reimburse-

FDA), health authorities (e.g. NCI) and profes-

ment efforts, but this is just the beginning. We

sional societies to drive their research and health−3−

臨床評価40 巻 1 号

2012

approach needed generally.

care agendas.
The Strategic Themes of CDISC are:

4．The CDISC approach at GSK

�Achieve significant progress in the use of
CDISC standards to allow scientifically sounddata aggregation and support secondary uses

While this may differ somewhat from what otherof research data for the purposes of scientificcompanies have done, this represents one current

investigation and comparative effectiveness.

approach to delivering on the strategy outlined

�Achieveenabling

above. Since its merger in 2001, GSK has valued

interoperability between clinical care andsignificant

progressinthe importance of the information model and rap-

clinical research, and explore expansion fromidly evolved to driving a standards model which hadbench to bedside (translational research);

begun to evolve in each of its two parent companies.

accelerate the cycle through which healthcare

Each employed the standards based on the CDISC

informs research and research informs clinical

Submission Data Standards (SDS) available at thatdecisions.

time, or developed employing the principles that

�Develop CDISC SHARE, a global, accessible,

underlay the SDS standards. The GSK standards,

Shared Health And Clinical Research Elec-like SDS, focused on data collected across multiple

tronic library for CDISC content/semantics

kinds of studies, primarily safety data. GSK thera-that will enable precise and standardized data

peutic areas developed additional standards or col-element definitions and richer metadata that

lected data in one-off study-specific datasets. Aftercan be reused within applications and acrossthe release of the Study Data Tabulation Model

studies to improve biomedical research and its(SDTM) standards, new GSK standards werelink with healthcare.

developed following the principles that underlay

�Expedite the development and rollout of new

the SDTM standards. The standards comprised

therapeutic-area or specialty standards,

paper and electronic case report (CRF and eCRF)

while continuing to refine, support and edu-

forms, collection datasets and in some cases analy-

cate on existing/foundational standards, tosis datasets and data displays (mainly tables andensure consistency in data capture and analy-

listings). GSK currently has about 60 “core” stan-

sis related to efficacy in addition to patient

dards, standards for over 250 questionnaires andsafety.

around 400 “therapeutic” standards.

�Leverage our global, non-profit, vendor-neu-

FDAʼs increasing desire for the provision oftral, independent status to forge productive

SDTM and Analysis Dataset Model (ADaM) data-collaborations with and provide value to key

sets led GSK to examine how best to incorporate

stakeholder communities.

SDTM datasets into the clinical study process. We

In order to accomplish this “higher” purpose,found, as others had, that there were two approaches

operational skill, experience and focus are essen-available: the incorporation of “SDTM aligned”

tial to create a robust and sustainable product.

datasets into the overall data flow or a back-end

What follows is an example of the time, intellectual

process that mapped existing datasets to SDTM.

investment, and discipline it takes to make thisAs part of tactical delivery of SDTM, we cre-happen. This is taken from the efforts at GSK, butated mapping specifications from our standards towould be a good example of the process and

SDTM. This was time consuming and exposed the−4−Clin Eval 40（1）2012

limitations of both the GSK standards and thebased on the same approach as that of CDISC

SDTM standards.

SHARE, recognising that SHARE would not be
available in time for launch.

A review of GSKʼs 700+ datasets and 25,000+
variables revealed issues of duplication and ambi-

The GSK approach is to separate the definition

guity, and our mapping to SDTM demonstrated thatof clinical data from the creation of operational

different studies had used some of our variables inobjects (e.g., eCRFs, datasets). There are four lay-unintended/inconsistent ways. We also knew thaters:

although GSKʼs dataset-based standards did deliver

1. Definitions of clinical concepts (e.g., a systolicbenefits, they provided only limited opportunities

blood pressure observation; a height result)for automation and aggregation of data across stud-

together with the identification of all compo-

ies and across compounds was often difficult.

nent parts (e.g. date body position). It should
be possible for these to be used across the

The limitations of SDTM as a standard include

whole pharmaceutical industry.

the absence of therapeutic data domains, the need

2. Terminology used for component parts (e.g., a

for a 300-page implementation guide, and its broad

set of valid values for the body position com-unsuitability as an operational standard.
At this point, we realised that we want more thanponent of the systolic blood pressure observa-

just successful implementation of SDTM, ADaMtion). It is desirable that these be industry
standard.

and their metadata (in the CDISC define.xml for-3. Groupings of individual clinical concepts (e.g.,mat). We want�quicker study set-up and reporting

those comprising the set of vital signs). It may�easier aggregation and re-use of all data

be difficult to agree this classification acrossthe industry.

�easier sharing of data with partners (e.g.

4. Standard definition of operational objects

development partners, CROs and FDA)

(e.g., as eCRFs, SDTM datasets, company

�the ability to implement new systems without

specific datasets). Of these, only CDASH

completely redeveloping our standards
�greater capability for automation.

modules and SDTM datasets can be stan-

Individuals from Lilly, Novartis and GSK recog-

dardised across the industry.
Our expectation is that CDISC SHARE will

nised the limitations of SDTM at much the samedefine and hold the industry standard content.

time and triggered the development of CDISC

The value we obtain from the two industry stan-

SHARE. SHARE is based on two industry stan-dards that underpin the approach is significant:dards, the Biomedical Research Integrated Domain
Group (BRIDG) model and the ISO21090 data type

�The standards provide the basis for templates

standards) and in time will underpin SDTM andfrom which the data items for a particular

Clinical Data Acquisition Standards Harmonization

clinical concept can be selected, eliminating
duplication and ambiguity.

(CDASH), and help speed the creation of future
SDTM domains. GSK remains involved in and com-

�The relationships between many data items are

mitted to the development of the CDISC SHARE.

automatic (e.g., the relationship between a

Following GSKʼs decision to replace the wholevalue and its unit or between a heart rateclinical computing toolset with best-of-breed sys-observation and the body position of the sub-tems, we began development of new GSK standards

ject during the observation).
−5−

臨床評価

40 巻 1 号

2012

CDISC SHARE content when that becomes avail-�Other relationships can be documented as partable.

of the definition of a clinical concept (e.g., thata lab test is performed on a specimen, while a

5．Governance and maintenance ofstandards

heart rate observation is performed on a person) and there is the facility to document relationships between clinical concepts at the

In order for standards to retain their value overstudy level (e.g. heart rate measurements weretens of years, the objects that make up those stan-taken during an exercise test).
�Using a mapping between SDTM and BRIDG,

dards must have unambiguous definitions that do

SDTM datasets can be auto-generated, elimi-

not change over time and must not be tied to any

nating inconsistencies in the current processes.

particular technological solution. New objects

Mappings to future versions of SDTM will beshould be added when new indications or new scien-

accomplished through updates to the SDTM-

tific information are to be included in the standards

BRIDG mapping.

and, when scientific knowledge advances, it may be

Our target at GSK is to use the clinical concepts

necessary to “retire” out of date objects. Controls

described above within our new eProtocol tool toneed to be in place to avoid the creation of multiple

start developing the studyʼs time and events. Thisobjects with essentially the same definition. Strong

information will then be extracted and refined, andgovernance is necessary to ensure that the require-terminology added resulting in a detailed study

ments detailed above are met, in order to protect

specification independent of any of the GSK con-the long term value of the information we collectsuming systems but from which such specifications

from the patients who volunteer to be in our tri-

as an eCRF specification, a data management data-als.

set specification (for data cleaning) and an SDTM

The inherent capability of the standards is also

specification will then be generated. ADaM data-

important. Clinical research is complex and thesets will use the SDTM datasets as their starting

standards need to be able to represent that com-point. For re-use purposes, the study data will also

plexity in a usable form. The creation of indepen-be held in a “clinical concept aligned” form auto-

dent clinical data elements is not sufficient. For

generated using the detailed study specification.

example, understanding the relationships between

This process will enable us to optimise study

separate pieces of information is important toexecution whilst providing the ability to deliver

ensure appropriate utilisation of that information.

quality datasets (SDTM and ADaM) to FDA. Long

To gain maximum scientific knowledge from theterm, cross-compound data aggregation and re-use

totality of data collected across the clinicalwill be made quick and simple. Using a largely

research community, we need to eliminate “compet-

metadata-driven approach will ensure that trace-ing” standards. The ultimate vision of total inter-ability is built into our processes rather than being

operability and transparency will only be achieved

an expensive afterthought. Ensuring that the oper-

if people collect and store data in a way that enables

ational objects can always be mapped back to theothers to quickly access and utilise them. We mustclinical concepts will be the key to success of theguard against directing time and rare criticalnew GSK standards. Our expectation is that weresource onto multiple solutions, as this would add

will migrate from GSK SHARE-like content toto the burden of researchers and ultimately impede−6−

Clin Eval 40（1）2012

better the health of future patients. If we cannot

the help we can provide to patients.
The FDAʼs “55 in 5” initiative, i.e., developing

store, find and retrieve the information in a reli-standards for 55 indications in 5 years, which isable way we are not meeting our commitment tobeing done in partnership between CDISC and thepatients or supporting the business of R&D and

Critical Path Institute, has a laudable aim. CDISC

GSK.

SHARE has the potential to deliver higher value

CDISC is an organization that was created andstandards in a faster and less resource intensive

is tasked with being in the middle of solving thismanner than has been the case for other recently

most critical piece of transforming the data fromdeveloped therapeutic standards such as those fortrials into a true information-based model that will

Alzheimerʼs and Parkinsonʼs.

allow subject matter experts to derive practical
wisdom on behalf of patients.

6．SummaryAcknowledgements

Information is our most expensive and valuable

The authors would like to thank Robbin Safron, andresource. When patients are asked to sign anDrs. Suzanne Markel-Fox and Diane Wold for their help

informed consent to enrol in one of our trials, theyin preparing the manuscript. Their editorial suggestions

are assured we will use the information gathered toand direction were invaluable in finishing this work.

＊

＊

−7−

＊