Data storage centralization, centralized management, and consolidation are challenges that all companies face in order to store

and
share data. Data storage centralization provides safety and gives users the ability to stream and download files provided by network
users. The concept of centralized data management opens a variety of possibilities which are essential for any company in today's
competitive and demanding market. What does this mean for the storage industry and for the evolution of storage software? Primarily,
an expanded range of possibilities is changing the standard from an ordinary file server to a complex and multifunctional device.

Why storage centralization is a need

Business users are looking for safe and easy storage solutions to house exponentially increasing amounts of data. There are a few basic
reasons for the growing interest in storage solutions.

Because information is the pillar of any competitive

advantage, storage is of vital necessity in the modern
business world. It is crucial to keep data safe using both
information security and the backup process.

Centralized storage protects data, increases speed,

convenience and efficiency. File sharing allows for quick
and easy access to important data from almost anywhere
in the world. Relative mobility and control of data can
move a company workflow to a higher level of
effectiveness. These advantages cannot be underestimated.

Cost is another all-important advantage of centralized data.

It is possible to store and backup data on multiple
machines, but it is much more logical to use central
storage. Decentralized data is more cumbersome, requires
time-consuming maintenance, and generates higher costs
than centralized storage.

The idea of cost-effectiveness can also relate to power

supplies and peripheral equipment. It is more efficient to supply a central server than to power several individual machines. The same
thing applies to any peripheral equipment. It is much easier to equip a cluster than every individual machine.

Reliability is another commonly overlooked cost-cutting measure. Both modern data centers and individual centralized storage solutions
are more reliable than dispersed individual machines. This single investment will ultimately prove to be more cost-effective and reliable
than seemingly less expensive solutions, based on multiple distributed machines.

Hard drives are undeniably the most burdened and hard-working parts of any computer or server, and therefore no hard drive will work
forever. Storage solutions help users overcome the consequences of damaged hard disks by saving data on several HDDs placed in a
RAID and consolidating data on a single server.

While centralizing data in one location may seem like a security risk, data scattered on several machines increases the number of portals
through which intruders can compromise your company's information. Therefore, protecting a central server is not only easier, but a
more cost effective way of doing business.

These advantages provide one conclusion - storage centralization is a must. The only question remaining is how to find the best possible
solution for your data management requirements.

Solutions for storage centralization

The size of your company and its individual circumstances will determine the best centralization solution for your situation. The choice
is between iSCSI, NAS (Network Attached Storage), or Fibre Channel solutions.
iSCSI is the best option if there is a need to share a drive physically (and locally) for one person. Such a solution is fast and gives a
guarantee of stability working within a network. It is possible to connect iSCSI to a main company Ethernet network or create a dedicated
Storage Area Network (SAN), connected only to a storage array and servers.
The benefits of iSCSI include low cost, ease of use, and recent developments in the iSCSI standard. Creating and maintaining an iSCSI
infrastructure is more economical and less complex to set up than Fibre Channel. New iSCSI storage arrays provide advanced data
management features, including a copy of the point-in-time and synchronous mirroring. For these reasons, iSCSI is chosen mainly by
small and medium enterprises.
NAS provides both storage and a file system, which is the main difference between Network Attached Storage and Storage Area Network
(including i.e. iSCSI). SAN provides mostly block-based storage and leaves file system concerns on the "client" side.
The next difference between NAS and SAN is that NAS appears to the client OS (operating system) as a file server, whereas an allocated
space available through SAN still appears to the client OS as a disk.

Despite their differences, SAN and NAS are not mutually exclusive, and may be combined as a SAN-NAS hybrid, offering both file-
level protocols (NAS) and block-level protocols (SAN) from the same system. It gives a wide range of possibilities, from an ordinary
file sharing platform to an expanded area, created for work and archiving data.
Fibre Channel is a network technology used for storage networking (in Storage Area Network). FC is dedicated for large enterprises
and advanced projects. It offers speed and the ability for implementation of complex solutions.
The biggest advantage of FC is its high performance and the ability to perform distant connections. Fibre Channel is also used with the
most efficient HDDs. The difference between FC (2Gb/s or even 8 Gb/s) and iSCSI (1Gb/s - 10Gb/s in the most expensive option) is
minimal when dealing with point-to-point connections with a bottleneck, for example a server or mass storage device. The main
difference is the ability to create a fast network with a large number of switches.

Fibre Channel-based solutions are quite expensive and complex compared to iSCSI. FC also requires the installation of a second HBA
controller, as well as additional drivers and managing software. These expenses make Fibre Channel unattainable for smaller companies.

What is the best choice for your company?

There is no best choice for everyone. Companies must determine their needs, possibilities, and potential budget. Users must remember
that functionality within a company's individual circumstances is much more important than speed. Businesses should also consider the
skill sets of existing staff members. While FC is more demanding than iSCSI, it can be very effective with proper training.

Technical issues are also important. The efficiency of an Ethernet network may determine whether an additional iSCSI package is an
option.

Storage centralization requires custom solutions and Open-E DSS V7 is flexible enough to execute on your centralization needs with
minimum complexity.

The Benefits of a Central Data Repository

By Mandy Lachney
0
A central repository is a collection of stored data from existing databases merged into one so that it may be shared, analyzed or
updated throughout an organization. A central repository of data or a data warehouse is essentially created by integrating the
data from all available sources. Having all information in a central location allows for the data to be easily organized, analyzed
and secured.
The amount of data organizations collect and store has been rapidly increasing, creating a need for more
efficient ways to manage this data. The increasing complexity of data poses a threat to quality and accuracy,
making integration a necessity. Erroneous data is virtually useless and even possibly harmful to an organization
because if management teams are making critical decisions based on inaccurate data, the results could be costly.
 Benefits
Enhances business decisions
Decisions determine the performance of the entire organization and having access to accurate and organized
data analysis allows management the ability to make effective decisions and execute quickly on a consistent
basis. By making data from various sources available in one location, managers no longer need to make blind
decisions.
Centralizes the storage and maintenance of data
Data integration through a central repository or central database of information allows for users to make
changes to the information and changes are reflected throughout the organization. This avoids having more than
one set of data that requires constant synchronization. This also allows each department within the company to
operate within a centralized workflow by allowing many users access to the same real time data.
Increases Data quality and accuracy
According to the data warehousing institute, poor data quality essentially costs businesses billions of dollars
annually. Data analysis is used to examine trends and establish strategies for the business to be successful. A
central repository offers trustworthy data in order to produce accurate trend analysis. This increased quality is
due to the data being consistently updated as well as standardized across departmental databases.
Reduces time consuming updates and redundancies
Data integration and collaboration also reduces and in most cases eliminates redundancies. The elimination of
redundant information reduces the time it takes to review and make decisions leading to an increase in
productivity. This enhanced collaboration throughout departments ultimately saves decision makers time,
giving the company a competitive advantage.
Maintains data history
Analyzing trends in order to make informed decision is made simple because a central repository stores large
amounts of past data, providing a historical intelligence aspect to decision making.
Generates a higher ROI
The upfront investment costs of implementing a data management strategy can seem high although when poised
against the costs associated with poor data quality, erroneous information, and uniformed decision making, the
benefits are apparent. The data shows that companies that have implemented central data repositories have
generated more revenue and saved more money than companies who have not made the investment.
Because data is such a huge asset for a company, effective data quality management is critical to the success
and even survival of a business. The many benefits of having a central data repository lead to better decisions,
higher productivity, greater efficiency and better informed employees within an organization. Implementing a
central data repository is essentially allowing an organizations business processes to operate at optimal
conditions.

Abstract
Go to:

1. Background and Objectives

The NIH Data Sharing Policy, initially released in 2003, requires all investigator-initiated applications with
direct costs greater than $500,000 in any single year to incorporate data sharing features in the application. This
approach recognizes that the research may have impact beyond the original intent when data can be used by
other researchers without undergoing the expense of data collection. In response to this policy, individual
institutes of the NIH developed data and biological archives (repositories) to house materials generated from
funded studies as a stable, reliable, and cost-effective means for distributing data and materials. Data
repositories ensure safe, secure archiving of data and meta-data, enabling continued use in academic and other
research environments. The National Library of Medicine now lists 45 NIH Data Sharing Repositories [1]. In
addition to clinical research study data, there are resources that aggregate information about mechanistic and
genetic data and information sharing systems.
In 2003 when the data sharing policy was initiated, the National Institute of Diabetes and Digestive and Kidney
Diseases (NIDDK) decided to establish a repository to house data and samples from studies they funded. Three
separate repositories, collectively known as the ‘NIDDK Central Repository’ (CR), now enable scientists not
involved in an initial study to test new hypotheses without conducting data or bio-specimen collections. The CR
stores samples and data from > 70 major multi-site clinical research efforts (125 protocols) in diabetes,
digestive, kidney, liver and urologic diseases. In addition, 11 GWAS datasets from these studies are available
for request (in collaboration with dbGaP) and DNA samples are available from 24 studies. Table 1 shows a
breakdown of studies by disease type.

Table 1

Primary Diseases Represented in CR

The CR also provides the opportunity to pool data across several studies to increase the power of statistical
analyses. In addition, most NIDDK-funded studies generate genetic material for testing and some carry out
high-throughput genotyping, making it possible for other scientists to use repository resources to perform
informative genetic analyses using well-curated phenotypic data.
Go to:

2. Development and Implementation

2.1. System design versus reality

Development began in 2003 with an analysis that considered the requirements of both NIDDK and the scientific
community. A complex system composed of primary databases in a private domain and a support database in a
public domain was envisaged. Creating databases in both domains was deemed necessary for security and
accessibility for authorized users. The primary databases in the private domain would include 1) a project
management database with tables and views (stored queries) to help manage project functions, track and
manage study databases, and provide information for reports; and 2) a studies database with tables that
contained study data, code books, stored samples and information to track researcher requests and provide data
in response to researcher queries. The support database in the public domain was intended as the foundation for
the public website, storing information about available studies and supporting access to private pages, a hosted
user forum, and researcher requests for data based on available fields.
Ultimately, due to time and cost constraints, our system design was modified so that study data were not stored
in databases but rather data files were stored in a secure archive/warehouse that was not searchable by external
researchers. Instead, researchers had to develop a proposal describing how they would utilize the data and upon
approval of their request, the data and supporting documentation were provided to the researcher. This design
involved less IT development and offered greater security for the data but required a greater degree of personal
assistance from repository staff to help the researcher determine if required data and samples were in fact
available. Although this may be viewed as a limitation, it is widely accepted that a high level of personal
assistance from a repository is preferential and beneficial [2], not only to the researcher, but also for the long
term sustainability of the repository. Repositories providing personalized assistance are sought by investigators,
particularly less experienced researchers, and become well known as reliable partners. This level of support is
appreciated by the researcher and is a potential source of revenue since additional support can be incrementally
billed as part of the data/sample request.
The support database implemented on the public side resembled the original design -- presenting materials that
clearly described each NIDDK study included in the archive [or identified for future inclusion]. Materials
presented to a public user included (1) a general description of the study, (2) manuals of operations and
protocols, (3) data forms used to collect clinical data, (4) descriptions of available data, and (5) listings of study
publications.
A web portal served as the interface for electronic information exchange for the NIDDK CR. All of portal’s
data sharing features were accessible to the public, but only registered users accessed and provided information
to the private section of the portal which was governed by role based restrictions. As mentioned above, the
clinical study data were archived on a private network accessible only to CR project staff.
The NIDDK CR portal ran on RTI’s Oracle Application Server 10g (v. 10.1.2.0.2) server farm and used Oracle
technology to manage the information within the repository. The software tools that supported the CR are
summarized in Table 2 and the hardware supporting the web portal including the sample database is presented
in Table 3.

Table 2

Software platforms supporting the design of the CR

Table 3

Hardware Description Required to Support the CR

Study data from the Data Coordinating Centers (DCC) were submitted in SAS and retained in SAS format when
archived stored. Requestors seeking alternative formats were provided with alternative formats using the
dbCOPY tool [3]. All study documentation except some electronic data capture forms was stored in PDF. Some
older data capture forms were delivered as image files. In all cases these were readable via Adobe Acrobat.
Study data were not shared until a request was authorized. At that time the entire contents of the archive of the
requested study was sent by a secure FTP process to the requestor site. This meant that the data could be
uploaded to the requesters system regardless of the target operating system.
Over time, we enhanced the public system to provide some of the functionality of the original design that was
lost during initial implementation. To help users explore the vast amount of data and samples stored in the
repository, we developed a set of Public Query Tools (PQT) that allowed public users to explore data elements
in both structured and unstructured ways [Figure 1]. The structured searches used parameters to identify studies
with resources that could support a new research hypothesis (e.g., types of stored samples, intervention method,
and primary outcomes). PQT opened a window to the data for users and was an important enhancement of
public data sharing for the repository. Researchers and the lay public were able to learn specific results about
the research funded by NIDDK, and in this way PQT served as a valuable public education tool. However, this
value came at a high labor cost since study data was stored only in archived data sets [4]. To fuel PQT, select
data elements were curated by repository staff and uploaded to a database that supported the PQT functionality.
This level of curation required clinical expertise available only through senior repository staff. Thus,
maintaining PQT was a costly effort that required significant investment which ultimately has to be weighed
against the benefit. There were cost advantages. With researchers able to personally explore the availability of
stored samples and link them to specific data elements, the amount of expert labor required for sample request
processing was reduced.

Figure 1

Public Query Tools allowed public users to explore data elements in various ways.

Offering mechanisms that make data more available for public inquiry is surely an important function of a data
repository. In fact, with the increase in genomic research, sharing of actual study results with participants is
increasingly critical [5]. The question becomes one of cost and technological innovation and associated
development costs so that data sharing can take place without a high level of content review by CR curation
staff. Use of data standards and common data elements during collection should allow for a more automated
presentation of results. Such consistency must begin at the design stage and requires that the data repository be
a partner right from the start to streamline processes and reduce the cost of post study data sharing.

2.2. Model growth and adaptation to changing research landscape

Over the course of the development and implementation of the CR, planning and conduct of clinical trials
changed with respect to the application of information technology. Clinical trial management systems (CTMS)
have become common tools used by data coordinating centers to manage the operational features of clinical
trials including designing and annotating the Case Report Form (CRF) and supporting database, data-entry
which is frequently web-based, data validation, and medical coding. The use of laboratory measures to track
patient outcomes and drug reactions is standard operating procedure and with expanded use of genetic analyses,
there is an ever greater reliance on biological samples which means tracking processes and annotations at a
level of greater detail. Recently the FDA approved a Phase 1 trial that used remote patient monitoring to collect
biometric data in patients’ homes and transmit it electronically to the trial database. This technology will
provide more data points and reduce the occurrence of missing data [6]. While these changes are on-going and
will have impacts on the nature of the data entering the repository in the future, they had minimal impact to the
CR to date. In part, this is due to the inherent lag in submission of data to a repository which routinely does not
take place until analysis for publication of results. Submission can occur years after actual collection, a fact that
challenges resolutions if data discrepancies are found during the submission process.
One of the most significant changes in the conduct of clinical trial studies is in its infancy, incorporation of
“omics” data into the fabric of clinical research. Omics aims at the characterization and quantification of pools
of biological molecules that translate into the structure, function, and dynamics of an organism or organisms
[7]. Fields include genomics, proteomics or metabolomics. As the knowledge related to personalized medicine
(tailoring medical decisions, practices, and/or products to the individual patient) increases, treatments based on
a patient’s biological assays will become a routine feature of clinical studies. Omics signatures that predict
disease progression will become a standard part of clinical studies and treatment assignments will be wedded to
both the genetic makeup of patients and disease progression. These changes have had an impact on CR
functions and will continue to do so in coming years. A number of NIDDK studies became part of the database
of genotypes and phenotypes (dbGaP), a platform that was developed to archive and distribute the results of
studies that have investigated the interactions of genotype and phenotypes. A number of the CR studies were
represented in the dbGaP and notification procedures between the CR and dbGaP were developed to direct
requestors from the CR to dbGaP if genotype information was sought and from dbGaP to the CR if the most
recent phenotype information was sought. This interaction required development of additional standardized
procedures and expanded communication for staff at the CR, NIDDK and sometimes, the DCC.
In other examples, omics data appeared as part of ancillary studies that extended investigation of the disease
studied by the parent study investigators. Such studies incorporated immunology, virology, biochemical and
genetic biomarkers. As mentioned earlier, reliance on samples has grown in the past decade due to the wider
availability of testing. Use of omics data in clinical trials requires carefully annotated sample/tissue archives
that reflect sample storage practices and can be linked to outcome information (phenotypes). Annotation of
processing and storage methods is of interest because methods that are adequate for DNA preservation may be
inadequate for metabolite preservation. Thus sample data is as important to the data archive as clinical data
collected during the study. Storage and presentation of omics data presents challenges in staffing, quality
control and storage that we were only beginning to address as these data began to appear for inclusion.

2.3. Working with researchers

A central activity of a data repository is effective interaction with researchers, a function that is served by an
understanding of the research process and an appreciation of the challenges faced by investigators conducting
high quality research. Our operation required working with a variety of researchers: 1) those conducting
NIDDK projects that would submit to the CR; 2) those seeking samples and data from the CR, and 3) those at
NIDDK involved in specific specialty areas. Researchers reflected experience levels from expert to novice and
brought with them differing attitudes towards sending their data to a central repository (discussed below). To
address this degree of complexity, we used an array of staff that brought different strengths to the processes. A
dedicated communications group maintained ongoing relationships with the DCC responsible for preparation
and submission of data, primarily interacting with study managers to keep informed about progress and answer
questions about the submission process. Experienced clinical researchers were among repository staff able to
communicate with sites about details of study protocols, outcomes and issues relating to shipped samples. Often
our statistical experts that performed data assessments communicated with investigators on interpretation of
analytic results. Repository biologists worked with requestors to identify appropriate biospecimens to conduct
their planned research. Genetic analysts worked with the genetic data repository dbGaP to insure that requestors
of NIDDK data from that site were provided with the best phenotype data available for a study, since often, the
CR had richer clinical data sets than those available through dbGaP. We found that repository staffing, in many
ways, mirrors that of a data coordinating center, providing a central counterpart that can effectively
communicate on topic areas (“speak the same language”). A combination of proactive and reactive
communication styles are essential to insure that data are submitted to the CR according to timetables provided
by NIDDK funded researchers. The large group of researchers involved in the operation of the repository can
often overburden the resources of the most responsive and flexible staff.

2.4. Promoting continued use

The essential goal of a repository is to enable additional research using resources already available. This re-use
increases the value of the initial investment and acknowledges the importance of the research subject’s
willingness to contribute to disease prevention or cure. If we establish a smooth functioning comprehensive
archive of research data and samples but no one ever uses them again, what’s the point? What is the role of the
repository in promoting the resource and how is the aim best realized? This important aim can only be
effectively undertaken when the enterprise is strongly established and thus, during our tenure as the CR,
promotion gained priority only in the later years. The repository required time to develop archives and
processes to facilitate requests and approvals. NIDDK, as sponsor, played the dominant role in connecting
interested researchers with the available resources. CR staff raised the visibility of the CR within the scientific
community by attending conferences, although this required support that was not always a budget priority in
comparison to other development needs. The primary means of gaining recognition was through the public
website that contained a portal to which researchers could subscribe to explore CR contents with the assistance
of repository staff. Search tags ensured that the site was a top listing for those searching on an array of key
words related to NIDDK research. In the last year of operation, increased effort was devoted to developing links
with other bio-banks and organizations in the forefront of health information. In 2013, the CR became one of
the Genetic Alliance “Neighborhood”, a position that affords the CR an opportunity to be periodically
highlighted in GA electronic mailings. We feel this type of relationship building across the research community
is vital to increasing repository use. Clear and detailed information about the archive contents must be
accessible for researchers to determine the usefulness for their investigations.
It is also important to connect with the patient and caregiver community, making them aware of the work being
done that may lead to disease control or cure. In addition to providing financial support, disease advocacy
organizations participate directly in multiple aspects of research, ranging from study design and patient
recruitment to data collection and analysis. These organizations believe that scientists and research sponsors
should engage them as partners in the conduct of clinical research [8]. Information sharing of this type can lead
to greater awareness of the important work supported by government funding and may serve to generate new
approaches to health problems. The data repository as an entity in possession of resources, technology and an
extensive network of researcher connections is in a prime position to take the lead in promotion, if there are
funds available to support this aspect of the operation.
Go to:

3. Challenges and Solutions

Our years serving as the CR for NIDDK have yielded a number of observations about the difficulties of running
a repository, an operation that is by definition dependent on many outside parties whose degree of expertise and
efficiency have a direct impact on repository functioning. In this section, we detail five major areas that can be
primary obstacles to effective data and sample sharing.
3.1. Repository challenge: lack of provenance
The NIDDK CR houses individual clinical trials as well as networks with dozens of protocols, some research
carried out as early as 1982. Study data and biospecimens were collected in various forms, formats and
methods. Requirements were developed to standardize the study datasets archived in the Central Repository.
For active research, we were able to work with DCCs to conform to these requirements, but data from early
studies was problematic. Often the research infrastructure had been disbanded so there were few, if any, persons
who could answer questions about the data. Likewise in more current studies, problems arise with data and
biospecimens that are submitted without complete documentation. Usual problems that arise include receipt of
data from unconsented individuals; clinical data files that lack a subject ID; incomplete submission of data (not
all subjects or not all data points included).
Annotation of biospecimens is a recurring and more widespread problem. Often a standard data structure is not
determined at the start of the study so that information about biologic samples is missing, limited or collected in
an ad hoc manner. This is particularly problematic since biospecimens are shipped in advance of study results
and thus, annotations are not scrutinized until the study data is submitted sometimes many years later. Details
about sample processing and preservation that are critical to downstream testing are often overlooked in the
collection/storage stage since it may not be relevant to the protocol being conducted. Consent information that
guides how biospecimens are allowed to be used is usually not incorporated into the annotation. To comply with
confidentiality, biospecimen data is often submitted with no way of linking the sample to the clinical data
(discussed below). All of these omissions constitute a lack of provenance for a sample which can create
uncertainty about its quality and appropriateness for the planned research effort.

3.2. Repository challenge: lack of linkage

Clinical studies typically use one set of subject IDs for internal study purposes, and -- as a privacy precaution --
create “masked” IDs when depositing data with the Repository. Use of a masked ID helps insure that someone
who discovers a participant’s subject ID during the study could not easily identify that individual’s shared data.
While DCCs maintain “linkage files” identifying which study biospecimen IDs belong to which study subject
IDs, the shared data needs an additional linkage file that allows these biospecimen IDs to be linked to the
“masked” IDs employed when the data are deposited with the Repository.
Early in the operation of the repository we discovered that some DCCs did not include such linkage files with
the study documentation when they submitted biospecimens and data to the archive. Requestors would be
unable to link their biospecimens with the phenotype (clinical) data from the study. The Repository PI and staff
undertook a campaign to remind extant and new biospecimen depositors of the crucial need for accurate and
well maintained linkage files to be deposited along with their biospecimens. This problem highlights the
importance of involving repository staff early in the process so that they can work toward linking biospecimens
deposited in the repository to subject data. Often this was a matter of allaying concerns about a breach of
subject confidentiality.

3.3. Repository challenge: data ownership

NIH rules on data sharing are well defined and publically documented. Although timelines by institute may
vary slightly, data is generally expected to be ready for sharing within two years of study completion or no later
than the acceptance for publication of the main findings from the final dataset. If data from large epidemiologic
or longitudinal studies are collected over several discrete time periods or waves, data should be released in
waves as data become available or main findings from waves of the data are published [9]. Data sharing plans
are now a standard required component of proposal submissions. However, since the time period is often after
the conclusion of the funding period, it becomes challenging to insure that an investigator complies with the
proposed plan. For this reason, acquiring study data for sharing sometimes requires a proactive approach by the
data repository. To obtain the data in a timely manner in the proper format requires a collaborative relationship
of mutual respect between the repository, the DCC and principal investigators. The primary concern of any
investigator is data ownership and maintaining control of the intellectual property of research findings. Working
through this sensitive ground requires an understanding of this perspective and recognition that, although data
sharing is required, provision of data to a repository is voluntary. The NIDDK CR sometimes encountered
protracted delays in receiving data or obtaining the linkages needed to share the data with requestors.
Particularly with large longitudinal studies that conduct enrollment over many years, data are typically stored at
the DCC on an open-ended basis since analysis and publication is ongoing. In fact, some long standing research
enterprises prefer to act as their own repository, spending added effort to coordinate requests from outside
researchers. This compliance with data sharing is perfectly responsive to the NIH mandate but tends to dilute
the power of a central repository.

3.4. Repository challenge: consent

Study consent documents are typically generated by methods that make them awkward to automate. They may
vary by study, clinical site, study subpopulation, and time interval, and different restrictions may apply to
different uses of the data or biospecimens (e.g., only for use in diabetes research). These consent parameters are
nonetheless crucial to Repository operations since they govern the conditions under which data and
biospecimens from a study may be released. The critical nature of consent information raises the question of
why a standard approach has not been promoted more forcefully across the research community, as has been
done for other data elements that are common across all research. Perhaps privacy concerns that have
influenced research over the past decade have curtailed efforts at standardization. Consent is usually looked
upon as a very individualized process, one of the only domains where the subject retains ultimate control. This
perspective should not negate an effort to compile consent data in a standardized format for more efficient
sample and data sharing. In fact, standardized consent data would better ensure handling of resources in
compliance with individual subject preferences. However, until recently, consent forms have been isolated from
other data collection instrumentation used in research where efforts towards standardization have gained
increased momentum. The Clinical Data Interchange Standards Consortium (CDISC) was formed to establish
standards to support the acquisition, exchange, submission and archive of clinical research data and metadata.
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 [10] of healthcare; however,
to date there lacks effort to catalogue consent parameters that represent all aspects of subject preferences with
regard to sharing data and biologic samples for continued research.

3.5. Repository challenge: sustainability

Does the importance of data sharing necessitate a centralized data archive and if so, must this archive be
maintained by the institute that initially provides funding for the research? We will discuss the evolving nature
of repositories in the next section but for now will look at the challenge of sustainability for a central repository
such as the CR, rather than a biorepository designed to operate commercially. There are few ways to generate
revenue to maintain repository operations. If the repository is directly aligned with an agency, the expectation is
that the agency bears a major responsibility for maintenance through direct support grants. These costs can be
supplemented by charging requestors for services performed by the repository, costs that may in turn be built
into grant requests submitted by the researcher to fund the planned project. The most straightforward way of
raising revenue is through charges for biologic samples and corresponding data. In fact, high quality clinical
data adds substantial value and having a detailed picture of how samples were handled since collection is
equally important, as discussed in earlier sections. The emphasis on strict quality control is a key characteristic
of an effective repository operation. Usually there are differences in the rates charged for commercial and non-
profit requestors. These fixed rates encompass the labor required to prepare the requested materials and, to a
small degree, maintain the repository infrastructure. However, the financial gains from these charges in no way
offset the cost of running a repository and thus, other services such as statistical expertise would need to be
required. As the contractor for the CR, we did not attempt to achieve sustainability but we were able to raise
revenue on a modest scale.
Go to:
4. The Path Ahead
The bio-banking industry will likely continue to become more globally centralized for studying specific genetic
diseases and monitoring the health of our environment. This effort will gain strength from the more recent push
by patients to form networks that support research into specific diseases. A prominent example of this trend is
the Rare Disease Clinical Research Network. The RDCRN Contact Registry operates in Australia and seeks to
enroll subjects with rare diseases (they can register themselves) in order to be contacted in the future about
clinical research opportunities and updates on the progress of the research projects. The contact registry is
anonymous and free of charge. The RDCRN is designed to enable multiple-level access by a range of user
groups within a region or across regional/country borders in a secure and private manner. This system was
developed for patients with clinical and genetic data in geographical disparate locations. The system addresses
issues of multiple-level access by key stakeholders, security and privacy. Networks such as the RDCRN cut
across borders and funders to join governments and private industry in the research effort.
The role of the biobank (defined as sample or data repositories) may expand in coming years as the issue of
return of research results to individual subjects gains greater traction in the advent of omics testing. Results
based on downstream use of samples may produce results of consequence to the health of the subject. A two
year project funded by NIH resulted in a recommendation that biobanks assume significant responsibility for
considering the return of research results whose samples and data were used in primary or secondary genomic
research if the findings have potential health, reproductive or personal importance to the contributor [11].
The trend toward personalized medicine will continue to impact. To date, these impacts include higher
standards for bio-repositories and the wider development of molecular data repositories (‘atlas’). Translational
research, the ‘bench-to-bedside’ approach to life-science research where what is discovered in the laboratory is
translated into practical applications, will increase the occurrence of personalized medicine and, to a certain
degree, personalized research. In a clinical trial, omics data could be used to guide assignment to the most
appropriate treatment group. Genomic technologies are a key force involved in translational research and have a
vital role in determining how patients are treated. Individuals will be prescribed drugs based on their genetic
profile in combination with traditional clinical signs and symptoms. Oncology has already made strides in this
area by using samples from an individual’s tumor to be tested for biomarkers (indicators of a biological state)
associated with a particular cancer treatment option which in many cases depends on the type of cancerous cell.
The Cancer Genome Atlas (TCGA) program with its supporting repository had a goal to create an atlas of
genetic changes that manifested as a cell became affected by cancer. TGCA characterized tumor types which
required a massive collection of cancer samples. Dozens of bio-repositories in the US assured the effort that at
least 500 samples of each required cancer type could be easily provided. Early in the project, it became clear
that many specimens were unfit for analysis due to the lack of sample storage standards. To achieve their
mission of mapping the genetic changes in cancer, the investigators had to develop standards for storing, and
annotating samples which led to the Office of Biorepositories and Biospecimen Research (OBBR) publishing its
first guidelines for the industry in 2006. Biobanking facilities will need to meet these newer standards and this
may result in fewer facilities that are larger in size with greater resources which should reduce sample storage
failure rates. Such facilities employ modern sample processing technologies that use robotic liquid handling
systems and utilize LIMSs that track samples and maintain chain of custody from collection to storage to
extraction [12]. That said, we do acknowledge that genetic testing methods are becoming more sophisticated
and are able to make better use of degraded samples that have heretofore been of little value (e.g., Molecular
Inversion Probe). There is a dynamic relationship between emerging technologies and the infrastructure needed
to support future research that requires the ability of organizations providing support to remain flexible even
while following established standards.
Another continuing research trend involves national and multinational efforts to launch population-based
biobanks and longitudinal cohort studies for use in large-scale genetic research. These biobanks provide the
materials to support genetic and epidemiological studies that examine health determinants. Including clinical
data about the subject’s health status (phenotypes), an understanding of the complex interactions between genes
and environment is possible [13]. However, conduct of health research can be influenced greatly by the
structure of the health care delivery system in which the research is conducted. A health care system can either
facilitate or hinder the research. Countries with government run health care and a national database of members
can provide a ready source of potential research subjects for large-scale genetic research. The UK Biobank is a
research effort whose strategy relies on centralized conduct of most aspects of a trial but handles recruiting
through multiple temporary assessment centers. Between 2007 and 2010, the UK Biobank completed
recruitment and examination of 503,000 participants. Embedding recruitment in a structure that facilitates
outcome determination, utilizes comprehensive information technology, automated biospecimen processing,
ensuring broad consent and establishing essentially autonomous leadership with appropriate oversight were all
critical to its success [14]. In the US, major health care providers are beginning to establish similar models (e.g.,
Kaiser Research Program on Genes, Environment and Health, Vanderbilt University BioVU, etc.) that enable
recruitment of eligible subjects from an established patient registry and extraction of relevant clinical measures
from the electronic medical record (EMR). This model, which reduces costs, could radically change the method
for conducting medical research and will likely become an important model in the future. Similarly, the
National Institutes of Health, supported by the Common Fund, is investigating the feasibility of conducting
“simplified” clinical trials within a similar model where research takes place in the context of health care
delivery. The Health Care Systems Research Collaboratory (HCSRC) is intended to improve the way clinical
trials are conducted by creating a new infrastructure for collaborative research. The ultimate goal is to ensure
that healthcare providers and patients can make decisions based on the best available clinical evidence [15].
It is uncertain where the role of a repository fits into these newer research models. Will there be a greater
profusion of repositories or an effort to create a national database that would become a resource containing
research data across all types of funders?
In closing, we wish to note that RTI’s tenure as the NIDDK Central Repository ended in August 2013 after an
unsuccessful re-competition bid. However, the CR lives on and NIDDK will continue to offer high quality data
and biologic samples to the wider research community [16]. RTI is pleased to have been a founding partner of
the repository with the rich experience of managing its growth for many years. Over time, data and
biorepositories have evolved from a simple location-management focus to one that supports a much wider and
often institution-wide imperative, such as translational research. For now, the repository remains an essential
component in medical research [17].

Highlights

 Effective operation and maintenance of the NIDDK Central Data Repository required the system to be flexible
and dynamic while at the same time compliant with established data standards.
 We describe some difficulties of managing a large repository, an operation that is by definition dependent on
many outside parties whose degree of expertise and efficiency have a direct impact on repository functioning.
 The bio-banking industry will likely continue to become more globally centralized for studying specific genetic
diseases and monitoring the health of our environment.
 The dynamic relationship between emerging technologies and the existing infrastructure will be needed to
support future research that requires supporting organizations to remain flexible even while following
established standards.

Go to:

Acknowledgments
This work was supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK),
Bethesda, MD 29892, USA, contract number HHSN267200800016C
Go to:
Footnotes
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our
customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final citable form. Please note that during the production process errors
may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Go to:

References
1. National Institutes of Health, Trans-NIH BioMedical Informatics Coordinating Committee (BMIC) [Accessed September
18, 2013.];NIH Data Sharing Repositories. http://www.nlm.nih.gov/NIHbmic/nih_data_sharing_repositories.html.

2. Horn L, Bledsoe M, Sexton K. Marketing Your Biobank Collection Effectively. 2012 Oct 23; Retrieved
from http://www.youtube.com/watch?v=5Et4IIUqBlY.

3. Heinemann Florian, Sven Kolber GbR. [Accessed November 13, 2013.];dbCOPY Database
Tool. http://www.dbcopy.com.

4. Pan H, Ardini MA, et al. “What’s in the NIDDK CDR?”-- public query tools for the NIDDK central data repository.
[Accessed September 18, 2013];Database (Oxford) 2013 Feb; doi: 10.1093/database/bas058.2013:bas058 Print
2013. http://www.ncbi.nlm.nih.gov/pubmed/23396299. [PMC free article] [PubMed][Cross Ref]