LEARNING PHASE, CONFIRMATORY PHASE
The typical clinical process of pre-marketing development consists of two successive periods that complete each other. The first one or learning phase that “investigates”, and the second one or confirmatory phase that “validates”. The learning phase corresponds to the phases traditionally labelled I and II and the confirmatory phase covers the traditional late phase II and phase III.
ICTA'S LEADERSHIP IN CLINICAL R&D
The route followed by clinical R&D until submission for international marketing authorization is a long one and a rough one.
The role played by ICTA’s full-service is to foresee the obstacles, to elaborate study protocols to elude them, and more generally speaking to set up the infrastructure to pave the way for a successful Marketing Authorization.
To reach this target, whether it is a traditional or an adaptive clinical development, ICTA provides its clients with the efficiency of a twofold design process: managerial and medico-scientific.
Adaptive phase i studies
Prior to this phase, a so-called translational phase can be conducted with the aim to select markers that will follow the drug throughout its development.
Phase I, first-in-man administration, requires conducting studies on doses administered progressively so as to define the therapeutic window best suited to an efficacy/safety ratio.
Thus, the CRM studies (Continuous Reassessment Method) in adaptive Bayesian mode for which ICTA has first-hand experience, in particular in oncology, can be proposed.
With such a protocol design, the dose escalation evolution recommended by calculation has to be validated by a quality control clinical management board (DSMB)* able to discuss about methodology. ICTA manages such committees in phase I within the scope of its full-service as well as all along the development whether it is adaptive or with interim analyses.
WHICH OPTION FOR PHASE II STUDIES: TRADITIONAL OR ADAPTIVE?
Once the judgment criterion or criteria is (are) selected, the most relevant methodology should be chosen for each study: conventional frequentist or Bayesian frequentist methodology and the numerous possible modalities have to be determined.
Choosing between the traditional and adaptive methodology partly depends on the development stage of the new molecule.
Today, adaptive studies are mostly reserved for the exploratory development phase whereas so called traditional or classical studies are reserved for confirmatory phases following a frequentist logical approach (late phase II and phase III).
Adaptive Phase II studies
When achieved with quality, they secure the wholeness of the development thanks to more precise definition of the therapeutic window and assess the relevance of the selection of judgement criteria that will be kept in phase III, namely when phases I and II are conducted in the Bayesian mode.
ICTA’s experience in clinical R&D of phase II covers both confirmatory traditional studies and Bayesian learning studies applied to key therapeutic fields including oncology, cell therapy and products stemming from biotechnology, and all indications where it is necessary to find the best efficacy/safety ratio.
PHASE II AND III CLASSICAL STUDIES
Classical confirmatory studies which are inherently frequentist have been used for decades and have often been used successfully in the clinical development in phases II and III.
For numerous studies, even in phases I and II, it may happen that the frequentist method is more adapted to the development of products of interest since adaptive design is always more complex to implement, therefore often more costly and sometimes not necessary.
On the other hand, except for some, phase III studies have to be managed in a traditional mode since they are confirmatory.
ICTA's EXPERIENCE IN PRE-AUTHORISATION CLINICAL R&D
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