Poor dose selection for Phase II and III trials is one area that can lead to the study failing and, given the rate of attrition through these stages, the industry is seeking to improve planning and design.
By holding EOP2A meetings the US Food and Drug Administration (FDA) aims to interact with sponsors and offer guidance on clinical trial design, simulation and use of quantitative modelling of prior knowledge.
It is often impossible to have these in-depth discussions, which the agency believes can be important, at the other meetings between sponsors and the FDA. Consequently the agency launched an EOP2A pilot programme in 2004 and has now issued final guidance.
The guidance sets out how the meeting is requested, arranged, what information should be provided and the objectives. Regarding the objectives the FDA states the primary purpose of an EOP2A meeting is to select the dosing regime and design “informative dose-response trials”.
It is preferable that prior to the meeting the sponsor and FDA agree on modelling and simulation approaches, allowing the EOP2A to be focused on interpreting results and discussing dosage and trial design issues.
The guidance cites the use of available preclinical and clinical exposure-response data and alternative trial designs and analyses among the possible areas of discussion at the meeting.
Setting up the meeting
The FDA recommends that the request for an EOP2A meeting includes a list of objectives, specific issues for discussion and expected outcomes. Furthermore, the sponsor should provide a list of completed trials and their key design features.
With this knowledge, and other information requested in the guidance, the FDA evaluates the meeting based on factors such as agency resources, the product’s therapeutic need and the benefits of modelling and simulation.
The guidance states that most proposals for EOP2A have been granted, with the exceptions being a result of the request not fitting the intended purpose of the meeting or there being insufficient resources.
A copy of the complete guidance can be found here.