About 1 in 10 people in the USA  and 1 in 12 people in Canada  are estimated to have a rare disease. For many of these diseases, the drug development process is particularly challenging. Incomplete understanding of the natural history, the logistics of clinical trials in small populations, and the lack of national/global registries all limit the evidence that is typically needed to bring new therapies to market. Further, the inherent methodological limitations of clinical trials in rare populations are challenging for HTA deliberations, which historically rely on robust RCTs.
A multi-pronged approach to overcoming these challenges is underway. First, protocols and designs for clinical trials are evolving . A few examples are phase 1 expansion cohorts replacing phase 2 testing; clinical trial approaches like platform studies with adaptive designs; innovative endpoints; and collaborative frameworks to examine the effectiveness of medications.
Second, decision-makers such as FDA, NICE, CADTH, and INESSS are recognizing the challenges of evidence generation for rare diseases, and recently provided more transparency and better guidance on the use and acceptance of real-world evidence (RWE) [4-7].
Third, there have been advances in the standardization of data collection, analytic approaches, and reporting transparency to improve the utility of real-world data (RWD) for generating decision-grade evidence. Quantitative bias analysis as a novel method  and the creation of an RWE registry  are examples of this positive trend.
Medlior’s multidisciplinary team of highly skilled epidemiologists, biostatisticians, and health outcomes researchers has experience studying rare diseases through literature reviews, real-world database analyses, patient surveys, and modeling. Our team has led the collection of RWD and execution of advanced analytics to generate decision-grade evidence to support reimbursement submissions for new therapies for a variety of rare diseases.