When is a seamless study desirable? Case studies from different pharmaceutical sponsors

Area of Science:

• Clinical trial design
• Drug development

Background:

• Inferentially seamless studies are adaptive trial designs with well-studied statistical inference.
• Regulatory guidance highlights less understood statistical issues in study conduct.
• Early pre-specification of Phase III design and lack of sponsor access to unblinded data are key challenges.

Purpose of the Study:

• To explore the varying success of four inferentially seamless study designs.
• To identify characteristics of drug development programs suitable for seamless trials.
• To pinpoint factors that may indicate difficulties with seamless trial implementation.

Main Methods:

• Analysis of four case studies with different seamless trial designs.
• Evaluation of design success and reasons for variation.
• Identification of program characteristics influencing seamless trial outcomes.

Main Results:

• Seamless studies necessitate significant upfront investment and planning for Phase III design.
• Pivotal seamless studies offer limited sponsor access to unblinded data, restricting adaptation.
• This limitation curtails the sponsor's ability to incorporate new information into the Phase III component.

Conclusions:

• Phase II data often resolve key questions when limited clinical data exist.
• Committing to Phase III plans before Phase II introduces developmental risks.
• Seamless pivotal studies can be advantageous in specific contexts, such as dose selection, if the program allows.