Aim: This thesis explores the challenges relating to the provision of orphan drugs in the UK by the NHS. It aims to provide empirical evidence from a societal perspective to inform the development of orphan drug policy, to determine the cost that society is willing to pay for orphan drugs, to advance the methodology of evaluating these medicines and attempts to address some of the challenges presented. Methods and Results: A person trade off study (Chapter 2) found that the general population is unwilling to divert funding from common disease areas to fund more expensive rare disease treatments. This holds true when the framing of the question is changed to reflect waiting lists and staffing levels. A stated-preference discrete choice experiment (DCE) analysis (Chapter 3) found that the attributes: disease severity, availability of other drug treatments, treatment benefit, improvements to everyday life and cost, have significant effect on societal preferences for funding orphan drugs. The application of the random utility maximisation framework allowed for the estimation of a value-based price for approved orphan drugs, which indicated that they did not meet the societal threshold for reimbursement. Performing systematic reviews in a rare disease can be challenging due to poor quality evidence. Chapter 4 explores the application of novel techniques to synthesise in relation to the treatment of neuromyelitis optica (NMO). Individual patient data (IPD) meta-analysis highlighted the alternative method that can be used to combine data to produce re sults on a whole body of research. Chapter 5 estimated the considerable burden of illness of NMO at both the societal and patient levels. The disease leads to substantial costs, patients' disability and dependency progresses. Conclusions: Incorporating societal preferences may provide a more transparent basis for policy development for orphan drug reimbursement. Including new ways to synthesise and present data relating to orphan drugs can help improve health technology assessments and provide a more robust evidence base for HTA decisions.