<img alt="" src="https://secure.lote1otto.com/219869.png" style="display:none;">
Skip to content
  • Frnch flag

"Empowering Statisticians to Create Complex Bayesian Designs."

MUCE is a Bayesian solution for cohort expansion trials where multiple dose(s) and multiple indication(s) are tested in parallel. Such methods are particularly important for areas like oncology  where several doses and several indications must be tested for successful completion of early phase trials, and optimal choice of dose and population to move on from early phase to a reasonable dosage for Phase 3.

Note that for these situations the number of comparator arms for a trial can increase rather rapidly. Testing three doses with three indications essentially requires 9 different trials. An efficient way to test a higher number of trials is therefore necessary for accelerated clinical development.

Built on Bayesian hierarchical models with multiplicity control, MUCE adaptively borrows information across patient groups from different indications treated with different doses.

The hierarchical model reflects the fact that treatment-arms with similar doses or for similar indications might be more similar than others, giving appropriate weight to such borrowing. This enables MUCE to Control Type 1 Error while increasing power and reducing sample size.

These efficient designs can be applied in any clinical trials with two or more arms. For an expansion cohort trial in the US, the MUCE design showed saving in sample size of up to 16.67% compared to Simon’s 2-stage design.

A particular application of MUCE is in Phase 1b expansion cohort trials. In these trials, one or more candidate dose levels with reasonable safety profiles are selected for further evaluation of efficacy following a dose escalation part (Phase 1a) in which different dose levels of the drug are investigated for safety. This leads to the determination of the maximum tolerated dose (MTD). Following that, up to three doses typically, none higher than the MTD, are considered for expansion in the phase 1b study, and a number of different indications, say I,-indications based on histology are considered. This leads to a maximum of 3*I arms, each with a unique dose-indication combination.


contact iconSubscribe back to top