Credit: Matt Herring/Alamy

Model-based Phase II dose-finding studies offer benefits over traditional approaches, say European regulators.

The lowdown: Most dose-finding Phase II studies are currently designed around selecting one out of two or three doses of a drug, based on a head-to-head comparison of each dose with placebo. But sponsors could benefit from shifting the emphasis of these trials to instead focus on understanding the dose–response relationship, says the European Medicines Agency (EMA) in a new draft qualification opinion.

With the Multiple Comparison Procedure-Modelling (MCP-MOD) approach, sponsors first select plausible possible dose–response relationships for their drugs (based, for example, on data from similar compounds or an agent's mechanism of action) and then design the Phase II study and select their dosing levels to test these models. The resulting studies can test more doses of a drug (perhaps four to seven active doses across over a tenfold dose range), in a similar number of patients as traditional trials.

“While a traditional approach might test 20, 40 and 60 mg per kg against placebo, here we can think about the whole dose–response relationship from 0 to 200 mg per kg,” says the EMA's Robert Hemmings. With the traditional approach sponsors usually end up advancing one of the doses they have already tested, but with MCP-MOD they get enough data to be able to choose a more optimal dose that may not have been tested explicitly in patients before.

“We are rather excited about this qualification opinion,” says Hemmings. “It is extremely rare to see something as comprehensive and sophisticated as the MCP-MOD approach. We hope that publishing this qualification opinion will vastly increase the interest in modelling-based approaches, whether it is this one or another one.”