The EU FP7 call HEALTH.2013.4.2-3 identifies a need for new or improved statistical methodology for clinical trials for the efficient assessment of safety and/or efficacy of treatment for small population groups. Funded under this call, the InSPiRe project brings together international experts in innovative clinical trial design methodology in these specific areas along with key stakeholders including regulatory authorities, industry, clinicians and patient groups to address this need. Our aim is the development novel methodology for the design and analysis of clinical trials in small populations. We will focus on four specific areas where we believe there are particular challenges: (i) early phase dose-finding studies in small populations, (ii) decision-theoretic methods for clinical trials in small populations, (iii) confirmatory trials in small populations and personalised medicines, (iv) use of evidence synthesis in the planning and interpretation of clinical trials in small populations and rare diseases.Building on recent research advances, we focus on Bayesian and decision-theoretic methods that formally enable comparison of the gain in information with the cost, both in economic and opportunity terms, of clinical experimentation, and assess how information from outside the trial can formally be incorporated in the design and decision-making processes. In the personalised medicine setting, we are developing methods that allow evaluation of efficacy in a number of sub-populations simultaneously in a confirmatory clinical trial without any reduction in scientific or statistical rigour.