With the increasing need for oversight of studies taking place across the globe, effective TMF management through an eTMF is just the tip of the iceberg for enhancing your organizations’ collaboration strategies. By utilizing an eTMF in conjunction with a CTMS, the opportunity to improve management of information is afforded.

1. Advance Information
Management through eTMF
and CTMS Convergence
Troy Deck
Wingspan Technology

2. Agenda
• Purpose of and Intersections between
eTMF and CTMS
• Benefits of Integration
• Challenges of Integration
• Integration Scenarios
• Success Factors

3. Purpose of the Clinical Trial
Management System
• A CTMS manages the large amounts of data
involved with the operation of a clinical trial
– Maintains and manages the planning,
preparation, performance, and reporting of clinical
trials
– Emphasis on keeping up-to-date contact
information for participants and tracking deadlines
and milestones such as those for regulatory
approval or the issue of progress reports

4. Purpose of the electronic Trial
Master File (eTMF)
• Manages the documentation associated
with a clinical trial to ensure that it is
accurate, legible, contemporaneous, original,
attributable, complete, consistent, and
enduring
• Provides functionality to:
– Upload and quality check trial documents
– Monitor the timelines and completeness of the
TMF at any point in the trial
– Based on the receipt of all expected documents
for a specific trial tied to milestones defined for
that trial

5. Where do the CTMS and eTMF
intersect? (1 of 2)
• To plan and monitor the TMF for a specific trial,
information is required about:
– the countries in which the trial will be conducted
– the sites that will participate and the investigators/sub-
investigators and subjects who will participate at each
site
– the milestones defined for the trial and for each site
specifically, the laboratories and other vendors that will
support the study
– … and more
• The “source of truth” for this information is the CTMS
– If it is independently created in the EDMS, errors will
inevitably result

6. Where do the CTMS and eTMF
intersect? (2 of 2)
• To make valid decisions about the study,
such as when to ship the IP to each site or
whether a site can be closed out, study
managers need to understand if documents
required by regulators and sponsor have
been received and verified
– But the CTMS is not designed for document
management
– It lacks the workflow and metadata tracking
capacities needed to receive and verify
documents efficiently and accurately

7. Where is the Authoritative Source?
eTMF CTMS
• Master list of TMF • Trial data: study, sites,
documents expected and milestones
received for a trial
• Overall tracking of
• TMF document milestones including non-
classification, content and
metadata document requirements
• TMF document status
• Overall progress of
documents needed for
milestones

8. Benefits of eTMF/CTMS Integration
• Decreased manual data entry – increased
accuracy
• Timely updates that are not dependent on email
messages or other manual hand-offs
• Guaranteed impact to eTMF when conditions
change (site added, PIs change, milestone dates
change)
– That might otherwise result in missing documentation
being detected at the end of the trial if ever
• Insight into decisions that require specific packets
of documents

9. eTMF – CTMS Integration
Challenges
• Literally dozens of
CTMS vendors and 10 –
20 eTMF vendors in the
marketplace
• And they change
and upgrade all the
time
• Building a specific
integration between any
two has a very limited
audience

10. eTMF – CTMS Integration:
The Optimal Approach
• Integrations based on the architecture,
design or functionality of a specific eTMF and
CTMS are fragile and limiting
• Instead, look for an integration based on
“loose coupling” of the systems
– Focused on exchanging data, not tightly
integrating processes
– Designed to handle a superset of data, allowing
any specific implementation to use a subset
– Runnable on demand or on a schedule

11. Scenario 1: Study Start Up
• CTMS has information about the study,
Investigational Product, and initial
countries, sites, milestones
– Which is pushed into/pulled into the eTMF
• This prepares the eTMF with the basic
information needed to provision the study
and sites
– Without manual data entry or
duplicate work

12. But… the CTMS does not have all
the information in most cases
• The list of essential documentation is
different for each trial. Just a few examples
of conditions affecting TMF contents:
– Is there an Independent Data Monitoring
Committee for the trial?
– Will there be subject recruitment materials such
as posters or radio commercials?
– Will data be collected using paper CRFs,
Electronic Data Capture, or both?
• Therefore, the CTMS cannot define the
required contents of the specific TMF

13. CTMS and eTMF Working Together
• To make best use of both systems and the
training and experience of their users:
– CTMS collects product, study, and site data
and pushes into eTMF
– Study managers in eTMF use the information
as a trigger to specify the specific documents
needed in their TMFs, with those documents
automatically attached to related milestones
– CTMS can then monitor progress against
those milestones

14. Scenario 2: Mid-Trial Updates
• During the course of the trial, sites are added,
investigators change, milestones slip…
– Impact on documents in the TMF is significant
– New sites require whole new sets of documents,
monitored against their own milestones
– New PI requires new 1572, CV, protocol receipt…
– Updated milestones mean that the set of
documents considered overdue changes

15. CTMS and eTMF Working Together
• CTMS pushes updated information into
eTMF
• Placeholders automatically created
wherever possible (e.g., for new PI 1572)
• Notifications sent to study managers so
they can take actions that can’t be
automated, and are aware of new
milestone dates

16. Scenario 3: Milestone Status
• CTMS user needs to know whether IP
green-light has been achieved and drugs
can be released and shipped to a specific
site
• CTMS will track non-document
requirements but eTMF holds the
documents needed for the milestone

17. CTMS and eTMF Working Together
• Study manager has been monitoring
status of the milestone documents in the
eTMF and taking actions so the milestone
can be achieved
• CTMS pulls information from TMF to
understand completeness of document
package
– Information is always up to date so IMP can
be shipped as soon as all documentation is
available

18. Sponsors and CROs
• Sponsors generally deal with a single
CTMS (or a few legacy systems)
– Making a more sophisticated integration
feasible
• CROs may have to accept CTMS data
from their sponsors instead of or in
addition to their own CTMS
– Making a simple, general approach even
more important

19. Success Factors: Risk vs. Reward
• Keep the integration as simple as
reasonable
– Don’t attempt to trigger elaborate processes
or handle fringe conditions in one system
based on events in the other
• Always consider risk and validation impact
– Will changes in one system trigger the need
to re-validate the other, or will a focus on the
data that is exchanged largely de-couple the
systems?

20. Success Factors: Alignment
• Only exchange data that is useful
– Otherwise you introduce complications and
dependencies with no benefit
• Ensure that data is accurately mapped
– That is, has the same meaning in both systems
• Understand and agree upon the mapping of
documents to milestones
– So that tracking data from the eTMF clearly
expresses the completeness requirements of
stakeholders using the CTMS

21. Success Factors: Focus
• Each system should be used for what it does best
• Think carefully before managing documents in the
CTMS, even if it has that capability
– Consistency of QC processes
– Ability to support an audit
– Ability to determine completeness of documentation
for a milestone or the overall TMF
• Avoid attempting to duplicate CTMS features in
TMF as well
– For example, extending milestone tracking past
documentation

22. QUESTIONS?