FLEX ADVANTAGE for Adaptive Trials

FLEX ADVANTAGE is ICON's proprietary Interactive Response Technology (IRT) platform for managing patient randomisation, investigator sites and clinical supplies specifically for adaptive trials. It is part of the ICONIK Informatics Hub.

ICON’s understanding of agency requirements, vast experience in adaptive trials, and ADDPLAN technoloogy, uniquely positions us in the industry as a top innovator in this field. Unlike conventional trials, many adaptive randomisation schemes require recalculation of the treatment assignments probabilities during the trial's conduct.

Key concerns for regulatory agencies in adaptive trials include the protection, security, and safeguards against operational bias. Regulatory agencies need assurance that the sponsor, project team, patients, and principal investigators were appropriately firewalled from access to interim results.

By implementing FLEX ADVANTAGE, ICON can satisfy those requirements and concerns. Additionally, we have well‑established workflow practices with SOPs reflecting the requirements of adaptive trials, as shown below.

There are a range of adaptive designs and statistical software design packages available to bring benefits in all the phases of clinical drug development.

However, as noted in the FDA guidance document, maintaining the integrity of the trial by not introducing any operational bias and inadvertently breaking the blind are the key elements of the execution. This emphasises the need to ensure that the validity and integrity of the trial are maintained when using adaptive design:

• Validity: To ensure validity, companies need to ensure that correct statistical inferences are maintained, assuring consistency between different stages of the study and minimising operational bias.
• Integrity: To ensure that integrity of the trial is maintained, companies need to focus on pre-planning and maintaining the blind (who sees what, when, and to what effect).
• Rules: Adaptive design requires the trial to be conducted in multiple stages with access to accumulating data, one or more rules applied at the interim. This definition rule includes any group sequential designs, response adaptive, sample size re-estimation and flexible designs.

Randomisation and drug supply are encrypted in the system so access to this data is limited and role-based. Therefore, FLEX ADVANTAGE is able to provide unblinded information to the appropriate people:

• Audit tracking capabilities capture information on who saw the data, and when.
• The operational team can update the database in real time.
• The clinical supplies team can see drug supply inventory.
• CRAs can review enrollment, and specific information to ensure the database is always inspection ready.
• DMC and independent statistical centre are unblinded and have access to the DMC repository that is web-based and holds DMC reports and information.
• ICON's team of medical experts review the data in real time and raise medical queries.
• In parallel statisticians and data managers review the data and raise appropriate related queries.

ICON's leading edge technologies FLEX ADVANTAGE and ADDPLAN combined with our expertise in adaptive trials make adaptive trials a reality for our clients.