Introduction
DISEASE, RECRUITMENT, DISEASES, RARE DISEASES
Because the market for drugs for rare diseases (orphan drugs) is fragmented, there is less competition among new drugs. Generic drugs are less likely to invade the market, even after the patent expires. Thus, it is possible to monopolize the market for a long time while maintaining a higher price [In the United States (US), rare diseases are defined as “diseases with fewer than 200,000 patients in the US” [Despite these efforts, the high cost of clinical trials, difficulty in patient recruitment, and strict regulatory requirements for new drug reviews have been highlighted as hurdles to developing orphan drugs. In many cases, patients are scattered across the country or region, specialized medical institutions are not always located nearby, and accurate diagnosis takes time, which makes conducting clinical trials difficult. Although consideration is given to such circumstances, guidance by regulatory authorities recommends generating as much high-quality evidence as possible [Pharmaceutical companies and regulatory authorities are constructing an optimal orphan drug development strategy that considers the required quality and quantity of evidence. The feasibility of clinical trials for rare diseases is also discussed on a case-by-case basis. Incorporating information outside clinical trials, such as natural history study data, research reports, and the use of real world data, to generate comprehensive evidence is also drawing attention due to the various biases considered [A randomized clinical trial (RCT) is still one of the most important elements in discussing high-quality evidence [In a previous study, we investigated the presence or absence of RCTs in the clinical data package for new drug applications in Japan and reported that the prevalence of the disease and type of primary endpoint was associated with the necessity of an RCT [