  Where there are a limited number of patients, such as in a rare disease,
clinical trials in these small populations present several challenges,
including statistical issues. This led to an EU FP7 call for proposals in 2013.
One of the three projects funded was the Innovative Methodology for Small
Populations Research (InSPiRe) project. This paper summarizes the main results
of the project, which was completed in 2017. The InSPiRe project has led to
development of novel statistical methodology for clinical trials in small
populations in four areas. We have explored new decision-making methods for
small population clinical trials using a Bayesian decision-theoretic framework
to compare costs with potential benefits, developed approaches for targeted
treatment trials, enabling simultaneous identification of subgroups and
confirmation of treatment effect for these patients, worked on early phase
clinical trial design and on extrapolation from adult to pediatric studies,
developing methods to enable use of pharmacokinetics and pharmacodynamics data,
and also developed improved robust meta-analysis methods for a small number of
trials to support the planning, analysis and interpretation of a trial as well
as enabling extrapolation between patient groups. In addition to scientific
publications, we have contributed to regulatory guidance and produced free
software in order to facilitate implementation of the novel methods.

Applications;Methodology