MCP-Mod, a powerful statistical tool for reliably predicting optimal dose ranges of new drugs for future confirmatory trials, has been deemed “fit for purpose” by the U.S. FDA. The tool could reduce costly Phase III failures and post-approval dose adjustments.

Suboptimal dose finding remains a major drain on pipeline productivity. In fact, it was the most frequent reason for the FDA to reject first-time marketing applications for new molecular entities (NMEs), according to an analysis of rejections between 2000 and 2012. Rejection may require additional trials, which can erode the remaining time on patent. Of the NMEs that were subsequently resubmitted after a rejection for any reason, the median approval delay was 14.5 months, ranging up to 6.5 years.

Regulators including the FDA and EMA are accordingly encouraging industry to develop better dose-finding methods for early clinical trials.

In that drive, significant attention has been directed to the MCP-Mod approach, which is short for Multiple Comparison Procedure – Modelling. In 2014, the EMA issued a qualification opinion that found the method was more “efficient” with available data and will “promote better trial designs incorporating a wider dose range and increased number of dose levels.”

The FDA recently gave MCP-Mod its “fit-for-purpose” designation for guiding dose selection for Phase III testing. Only one other tool had previously received this designation.

Significantly, the FDA convened a multidisciplinary team, from both the Office of Biostatistics and Office of Clinical Pharmacology at CDER, to review the MCP-Mod methodology based on a submission from Janssen and Novartis. The FDA noted in its determination letter that “the methodology is scientifically sound” and “advantageous in that it considers model uncertainty and is efficient in the use of the available data compared to traditional pairwise comparisons.”

With this in mind, MCP-Mod has been incorporated into ICON’s ADDPLAN® DF, which supports the decision process in the design and analysis of dose finding trials using innovative methodologies. The addition of MCP-Mod was tested with the benefit of the input and expertise of the ADDPLAN DF Consortium, made up of statisticians from nine major pharmaceutical companies.