CRED Understanding Clinical Development 2024

08/10/2024

What is an ‘adaptive trial design’?

⚫ A study design is called “adaptive” if statistical methodology allows the modification of a design element (e.g. sample-size, randomisation ratio, number of treatment arms) at an interim analysis with full control of the type I error.

⚫ Important aspects are:

⚫ Adaptive design means making changes following an interim analysis

⚫ Can shorten the development process but could introduce bias ⚫ Involves an interim analysis and allows for adaptations. BUT, they must be prospectively defined in the protocol ⚫ Carried out by an independent data monitoring committee (IDMC – usually mandated by regulators) ⚫ Predefined criteria for changing the study design is required

POTENTIAL BIAS

The Organisation for Professionals in Regulatory Affairs

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Prospectively planned interim analysis (IDMC)

#4

Arm A (n=60)

SCREENING

Q2W dosing Placebo devostatin

24 weeks

Arm B (n=60)

Key eligibility criteria (incl/exclu criteria) • Age (≥18 yrs) • Definition of disease • Stage of disease • Concomitant medication • Risk factor • Prior disease • Biomarker positive

Q2W dosing devostatin – Dose 1

Single PE Arm B vs Arm A

24 weeks

N=240 1:1:1:1

Arm C (n=60)

Q2W dosing devostatin – Dose 2

Single PE Arm C vs Arm A

24 weeks

Arm D (n=60)

Q2W dosing devostatin – Dose 3

Single PE Arm D vs Arm A

24 weeks

Tapering of con-med

Stratification: • Disease severity (moderate/severe) • Biomarker status (+ve/ve)

Key SE: Clinical improvement (PRO); number of AE’s; PK/PD relationship; QOL

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ADAPTIVE DESIGN – SEAMLESS Ph 2 / Ph 3

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