Advance Information

Management through eTMF

and CTMS Convergence

Troy Deck

Wingspan Technology

Agenda

• Purpose of and Intersections between

eTMF and CTMS

• Benefits of Integration

• Challenges of Integration

• Integration Scenarios

• Success Factors

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

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

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

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

Where is the Authoritative Source?

eTMF

• Master list of TMF documents expected and received for a trial

• TMF document classification, content and metadata

• TMF document status

• Overall progress of documents needed for milestones

CTMS

• Trial data: study, sites,

milestones

• Overall tracking of

milestones including non-

document requirements

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

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

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

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

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

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

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

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

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

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

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

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?

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

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

QUESTIONS?