Leveraging a Compliant Data Repository to Significantly Improve Biostatistics Workflow

Apr 01, 2021

Certara Integral is a scalable cloud-based software as a service (SaaS), validated
data and analysis repository with an intuitive user interface for collecting,
managing, and storing multiple types of data sets for analysis, sharing, and
reporting of all types of clinical data. This regulatory compliant repository
significantly improves the biostatistics workflow, providing analyses that are
traceable, reproducible, and secure.
Certara Integral is designed to be a 21 CFR Part 11 compliance bolt-on solution
to an existing statistical computing environment within biopharmaceutical
organizations. It is compatible with both cloud-based and on premise computing
environments, with all modern operating systems, and is agnostic to the analytical
software being used (SAS, R, Python, etc.). Integral is built on Amazon Web
Services (AWS), uses OKTA for authentication, and has an Oracle database.

Roles and Permission groups govern access in Integral and are assigned by
Customer Administrators. Permission Groups are configurable and are designed
to facilitate easily assigning permissions broadly across studies or projects based
on a user’s function. By attaching simple to build Permission Rules and associating
them with these Permission Groups, an Administrator could instantly assign its
users en-masse to hundreds of projects whilst tightly restricting content according
to business rationale.
In the same way that access can be granted quickly, a user’s access can likewise
be promptly and completely removed. Additionally, project level and folder based
permission assignment or removal is also available to enable granular access
control. Integral Security Group permissions include the ability to Blind and
Unblind repository content.

The folder structure hierarchy and naming conventions in Integral are completely
configurable according to internal programming best practices or standard
operating procedures. Generation of complete folder structure hierarchy for
projects can be automated to enable standardization across users.
Integral provides configurable metadata that can be associated with folder types
so that complex folder hierarchies are not required to organize content. These
metadata can be used to filter the content of the database to facilitate searching.
Integral also leverages elastic search to enable keyword searching of all readable
file content within the repository.
Integral enables the viewing of the most common file types directly through the
application interface. It additionally allows for a side-by-side comparison of script
files to highlight changes between versions.

Integral is a GxP compliant archive. Archiving is accomplished in the same
environment in which active studies are worked on, simply by locking a project,
folder, or file. Once content is locked, it cannot be changed in any way yet still
remains accessible for viewing or copying. Only a user with the Archivist Role has
the ability to unlock content in Integral. Locking and unlocking of content becomes
a permanent part of the audit trail, indicating the user, the date and time, as well
as the reason.

Integral is validated by Certara prior to deployment of each release. Integral
validation is governed by Certara’s SOP driven software development lifecycle. The
Integral validation summary report is published to the Integral help website.

A statistical analysis includes input datasets from various sources, mature reusable
code, bespoke programming, intermediate results, and final output. It is the
collection of these various assets that represent an analysis that is attributable,
traceable, and reproducible. For this reason, Integral is designed to version
entire statistical analyses and not just versions of files. Analyses are intentionally
committed by the user to the repository as Save Points at a point in time of the
user’s choosing. Each Save Point can be viewed independently, detailing all files
associated with the analysis and all dependencies. It is possible to roll-back to a
previous version of a Save Point to make it the most recent version again.

For companies that utilize parallel programming as part of their quality system,
Integral’s access control can be leverage to ensure independence. Code review
can be accomplished directly in the interface via the viewing panes, including the
file comparison view pictured above.
Integral can be used as a global code repository to help manage mature reusable
code. Users can be sure they are using the most recent version of a program, can
be automatically notified if the source program has changed since they started
using it, and can easily see the provenance of the code (who updated it, when it
was updated, what was updated, and why it was updated).

Audit Trails within Integral are created on-demand for files saved within the
repository. Audit trails can be generated for a single file or at the folder level for
the creation of all files within a folder structure. Audit trails show the who, when,
why, and what for content history. Deltas are performed for all text file types
(including .csv, .xpt, etc.) using various mechanisms to highlight differences, with
custom selection of versions to compare. All previous versions of files are retained
within the database and are retrievable. The same technology (OKTA) used for
authentication is used to apply electronic signatures to create, modify, and delete
actions performed by the user.

A critical component of regulated drug development is ensuring reported analyses
are based on accurate study observations. Data are frequently updated, which can
result in statistical analyses becoming out of date. Integral uses a database to track
relationships between input datasets and statistical analyses to ensure analyses
are current. Dependencies are easily set at the time analyses are committed to
the repository. When the dataset upon which an analysis depends is updated the
user will receive a notification and the analysis will become visibly out of date (by
color code).
Statisticians will often need to use materials outside of the project being worked
on in order to complete an analysis, including datasets, programs, etc. Making
copies of files is a common way to introduce untraceable errors into an analysis.
Integral allows the user to make “linked copies” of files that can be auto updated
when the original file is changed.

Integral ensures analysis reproducibility by saving a complete analysis as a Save
Point in the repository. This methodology is analogous to the way source code
control systems work in software development. An analysis inputs, programs,
and outputs are linked together in a single version, irrespective of the various file
versions. Save Points cannot be corrupted by updating single files within the Save
Point without updating the entire Save Point. Integral makes it possible to revert
to previous Save Points at specific points in time to reproduce each set of results
provided that the analytical software used is still available.

Integral enables multiple file uploads into a single folder or the upload of entire
folder structures via the Integral Client Application. Integral is a web application
and may be used as a secure data transfer mechanism between departments
or companies, eliminating the need for sFTP sites and email data exchanges.
Exchanging data directly in the repository results in a closed chain of custody and
enhances traceability as well as audit readiness. Robust access controls ensure
users see only relevant information for their function.
Because Integral is agnostic to operating system and analytical software and
requires no VPN access, collaborating with external partners and resources is easy
to set up and take down through the normal administration of the system. 

Certara is a leading provider of decision support technology and consulting services for
optimizing drug development and improving health outcomes. Certara’s solutions, which
span the drug development and patient care lifecycle, help increase the probability of
regulatory and commercial success by using the most scientifically advanced modeling and
simulation technologies and regulatory strategies. Its clients include hundreds of global
biopharmaceutical companies, leading academic institutions and key regulatory agencies.
For more information visit www.certara.com or email sales@certara.com.

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