Adaptive trials

Use of adaptive design has rapidly risen as sponsors capitalise on its ability to increase portfolio valuation by protecting good drugs from failure and improved decision-making at critical junctures in the development process.

ICON offers design, simulation and execution of adaptive clinical trials. We have:

• More than fifteen years of experience in successfully planning and managing adaptive clinical trials
• Experts with direct involvement in regulatory agency adoption of adaptive design trials and subsequent agency guidance
• Operational teams and technologies to apply the power of adaptive techniques to drug and medical device trials

ICON offers design, simulation and execution of adaptive clinical trials. We have:

• More than twenty years of experience in successfully planning and managing adaptive clinical trials
• Operational teams and technologies to apply the power of adaptive techniques to drug and medical device trials

Examples of adaptive design projects include:

 

Pivotal adaptive designs

• Operationally and inferentially seamless adaptive phase 2/3 designs

• 2-stage adaptive designs for dose selection and confirmation

• 2-stage adaptive p-value combination designs
• Group sequential MAMS designs
• Unblinded sample size re-estimation designs including Cui-Hung-Wang, Chen-Lan-DeMets and Promising Zone (Mehta/Pocock) designs
• Mixed dose selection/confirmation and uSSR (unblinded sample size re-estimation) designs, group sequential and hybrid group sequential/conditional power adaptive designs

Pre-pivotal / early phase adaptive designs

• Phase 1 oncology/hematology and immuno-oncology dose escalation designs (including m3+3, BOIN, CRM/nCRM/CCD/mTPI, mTPI-2/i3+3)
• Phase 1 clinical pharmacology escalation designs incorporating safety, PK and PD responses
• Phase 2 adaptive dose selection designs and MCP-Mod (latter not “adaptive” in the sense of interim analyses but certainly an innovative design promoted by regulators globally)
• Seamless phase 1/2 designs

Optimised clinical development plans using adaptive designs

Our consulting teams can help you realise the potential of adaptive trial design by:

• Conducting simulation studies  to demonstrate the value of an adaptive design trial over a conventional study
• Reviewing existing development strategies to identify where adaptive trial designs can speed up drug development
• Providing insight into adaptive trial  design methodologies and statistical approaches
• Providing design, simulation and execution of adaptive trials across all phases of development
• Providing advice and guidance on the logistical and operational requirements for successful adaptive trial execution
• Overseeing ongoing adaptive trials to ensure that trial integrity and validity are maintained at all times

Regulatory agency discussions

For certain types of adaptive design trials it is advisable to meet and discuss the trial design with regulatory agencies. This is particularly true for confirmatory trials.

ICON has experience in helping sponsor companies discuss their adaptive designs with regulatory agencies including pre-IND and end-of-phase II meetings with the FDA and scientific advice and protocol assistance meetings with the European authorities (EMA and national agencies).

Our global regulatory team, in conjunction with our adaptive design experts, provide comprehensive support covering all the requirements for agency meetings including:​

• Preparation and submission of the formal meeting request
• Preparation of the briefing book including finalization of questions
• Management of meeting logistics and meeting rehearsal
• Attendance and representation at the meeting
• Authorship and review of meeting minutes