EMA wants debate on clinical data extrapolation; new concept paper

The EMA wants a debate on the extrapolation of clinical data to see if a framework is needed to govern this potential approach to reducing unnecessary research and letting industry use resources more efficiently.

The concept of extrapolation - applying data from one clinical trial in one population to another - is not new. The European Medicines Agency (EMA) discusses the approach in ICH E11 in relation to developing drugs for children.

Similarly the US Food and Drug Administration (FDA) has an assumptions-based framework for the extrapolation of efficacy data from adults to the paediatric population, that allows extrapolation if there is sufficient similarity of disease progression and response to intervention between source and target population only requiring PK studies for dosing.

But the EMA wants to push the debate further. A new concept paper published last week sets out to “go beyond these documents and to discuss the possibility to develop an expanded and refined algorithm for extrapolation in all areas of medicine development.”

The agency suggests that: “The primary rationale for extrapolation is to avoid unnecessary studies in the target population for ethical reasons, for efficiency, and to allocate resources to areas where studies are the most needed.”

Framework

The EMA also sets out a proposed framework suggesting that drug developers considering the approach would need to justify its validity for the specific case, with considerations like a desire not to replicate studies, ethical and resource reasons and feasibility restrictions being taken into account.

Researchers would also be required to develop an ‘extrapolation plan’ using PK/PD data from one population to predict efficacy in the target population. This would then be assessed to see if the assumptions made are valid.

“If the data do not confirm the extrapolation concept, the concept needs to be updated by the emerging data regarding the true extent of similarity and, hence, ability to extrapolate.

“Consequently, the need to generate more data in the target population should be assessed and the extrapolation plan adjusted. This may be an iterative process using adaptive designs, particularly when moving into successive population subsets.”

Next steps

The agency concludes the concept paper by calling for feedback and comments from academics and the drug industry, adding that it plans to publish a reflection paper within 12 months.