Chapter 3: The Challenges of Conducting Clinical Trials in Diseases with Small Target Populations Check Access

Scientific advances are creating enhanced opportunities for development of new therapeutics to treat rare diseases. Regulatory incentives provide added impetus for allocation of sponsor research and development resources to development of treatments for rare diseases. Despite incentives and enablers, development of therapeutics for rare diseases remains a significant undertaking. Drugs for rare diseases are subjected to the same rigour in the assessment of safety and efficacy as drugs developed for more common diseases, usually with the same requirement for clinical data from randomised and well controlled clinical studies. To meet requirements for market authorisation, investigations must overcome challenges that include incomplete understanding of the disease course, lack of validated measures of disease progression or end points to support regulatory approval, incomplete understanding of the standard of care and difficulty accessing sufficient sample size to support hypothesis testing. Tools available to meet these challenges include natural history data, patient registries, clinical trial data repositories, clinical study enrichment strategies, innovative statistical models, use of external control groups and advocacy groups or established clinical networks as partners to facilitate enrolment. Examples of how these tools may be used are provided in this chapter and in the detailed case studies presented in subsequent chapters.