Early Phase Design

Early phase design applies to the ‘Learn’ phase of development from Phase I to Phase IIb. During the phase a number of aspects of the study can be modified. This could include the number of subjects, study duration, endpoint selection, treatment duration, dose range, patient population, number of treatments, number of interim analyses, hypotheses etc.

The exact design will depend on the objectives of the trial and the available data, on the product under development. Regulatory agencies fully support the use of adaptive design in the exploratory phase of development provided appropriate justification supported up by trial simulations data is provided.

The main objective of early phase design is to learn as much about the product under development so that the design selected for pivotal studies increases the probability of trial success.

Adaptive dose finding

Regulatory agencies and the pharmaceutical industry agree that inappropriate dose selection remains the major cause of late phase product attrition, and recognize that they need to improve critical decision‐making in exploratory phase clinical development so that appropriate doses are progressed to pivotal studies.

Adaptive dose finding studies permit more accurate determination of the effective dose to take forward to phase III studies, leading to increased success in pivotal trials at the same time as improving the efficiency of the product development process.

The strategy is to initially include few patients on many doses to determine the dose-response, then to allocate more patients to the dose-range of interest, reducing the allocation of patients to ‘non-informative’ doses.

Design and simulation software

ICON offers fully validated software and technology solutions for the design, simulation of adaptive clinical trials.

ADDPLAN® DF for Early Phase Dose Finding Studies - ADDPLAN DF is the first fully validated design and analysis software based on MCPmod methodology, a preferred tool for dose-finding studies.

ADDPLAN DF covers model-based dose-finding designs for proof-of-concept testing and estimation of target doses in phase II clinical trials. Researchers are able to establish a dose response signal based on a set of candidate models while strongly controlling the type I error, an important step in maintaining trial validity.