As pharmaceutical companies face intense pressures from looming patent expirations, weak drug pipelines, and heightened competition,
they are implementing new technologies to improve operational efficiencies in clinical trials and speed drugs to market. Document
workflows in a clinical trial environment require coordination of tasks and people from multiple organizations including the
study sponsors, CROs, investigator sites, academic institutions, and research ethics boards. During study start-up and throughout
the course of a trial, a number of essential regulatory documents have to be processed in a short period of time. Most recently,
CTMS and investigator portals have automated trial master files (TMF) and regulatory workflows and played a central role in
enabling companies to expedite study start-up while significantly reducing costs, improving collaboration and data management,
and speeding site/study initiation.
A TMF consists of thousands of pages, and includes everything from regulatory documents, correspondence, and data to documentation
that supports compliance with local regulations. With paper-based TMF systems, managing documentation is a time-consuming
and cumbersome task that often involves eliminating duplicates (generated in multi-center clinical trial environments where
documents reside in various organizations and/or across geographical regions), replacing lost documents, scanning, indexing,
and filing. Ensuring that all required documents are included in the final TMF, with required approvals, and managing metadata
also become arduous tasks when using a paper-based system. With an eTMF solution, however, all documentation—including documents
from sponsors, subsidiaries, CROs, and field-based personnel—is located in a centralized place, making it readily available
for viewing and tracking by trial personnel from any geographic location. eTMF solutions also allow assembly of the TMF to
occur gradually during the course of the study. As such, eTMFs accelerate the production, review, approval, and submission
stages in addition to eliminating time-consuming and costly processes that diminish clinical trial efficiency.
EntraLogix, a site management organization that developed an investigator portal solution for its own needs, which is now
commercialized, reports cutting study site initiation time from an average of 102 days to an average of 49 days through the
use of its investigator portal system. By automating the clinical development process and cutting down the days to site initiation,
CROs and sponsors can potentially gain valuable time to market their approved compounds under patent protection.
Evolution of the investigator portal
Second generation investigator portals are web-based collaboration platforms designed to aid in TMF management. The TMF consists
of regulatory documents as well as artifacts related to the clinical trial that permit the evaluation of the trial conduct
and quality of the data produced. The latest portal technologies leverage enterprise-level collaboration, document management,
electronic forms, and digital signature technology to integrate the TMF with investigator site files (ISF), data, and metadata.
These new clinical trial applications handle documents electronically throughout the entire document lifecycle, and cover
all steps from site selection to study close out. Third generation investigator portals are designed and developed specifically
for TMF requirements. Using enterprise level portal/application technology such as Websphere or Weblogic, the clinical trial
web applications offer a full set of features for online collaboration, regulatory document processing, and data integration.
Through document workflow and task management capabilities combined with electronic forms and digital signatures, organizations
are using these investigator portals to streamline operations while significantly shortening timelines, reducing costs, and
With investigator portals, life science companies are also meeting the desire of regulatory authorities to have clinical documents
submitted electronically. One of the key initiatives of investigator portals is referred to by the FDA as "Leaving the Paper-Based
World Behind—Creating an All-Electronic Environment for Managing Data on FDA-Regulated Products."1 The Agency has been developing standards and systems that will enable the electronic receipt, management, and storage of
FDA-regulated product information. The FDA will use the Janus data warehouse to store and manage study data about the products
it regulates, as well as clinical study information. Further, data exchange standards are being developed to provide a consistent
way for information across organizations to be handled and to ensure that sending and receiving systems both understand what
information is being exchanged. This is a significant leap forward as it demonstrates direct exchange of data from the systems
of life science companies to the FDA's system. Whereas transmission of scanned PDF documents provides information that is
static, difficult to query, and non-relational, electronic forms allow end users to enter, retrieve, and display data, while
digital signatures are used to authorize it.