Therapeutic agents for the treatment of rare disease are called “orphan drugs” and have become the object of attention of researchers and pharmaceutical companies in recent years. In 2012, the MHLW announced the 5-year Clinical Trial Activation Plan for the purpose of stimulating clinical research and trials in Japan. As part of that plan, relevant aims were creating a system to operate the clinical trials and establishing a patient registry of rare diseases [9]. To achieve these objectives effectively and to promote clinical trials and clinical research, collaboration was established between the patient registry and MDCTN. A close collaboration with the patients’ registry and standardization of treatment and clinical evaluations among many local sites is very important. It helps increase the availability and accessibility to the latest treatment information and increases the participation of patients with rare diseases and their families in clinical research, regardless of their area of residence. The Rare Diseases Clinical Research Network, supported by the National Institutes of Health (NIH), stated that the success of recruitment depends on many approaches, such as contact registries, referrals from patient advocacy groups, and enrollment of existing patients at consortium sites [10]. The MDCTN is the first national network aimed at facilitating regular and successful operations of clinical trials and research of neuromuscular diseases that comprises medical sites with a long-standing history of treatment for neuromuscular diseases in Asia.
When comparing our registered data to that in TREAT-NMD CTSR, the data for the proportion of patients with dystrophinopathy was similar. The ratio of LGMD is about two-thirds of that registered in TREAT-NMD. The proportions of DM1 and congenital muscular dystrophy (CMD) are 23 % and 7 % (Fukuyama type congenital muscular dystrophy: FCMD 5 %, other CMD 2 %) respectively, which is higher than the ratio in TREAT-NMD (17 % and 9 %, respectively) [11]. There is a remarkably higher proportion of patients with FCMD registered in MDCTN in than in TREAT-NMD CTSR. FCMD is a characteristic neuromuscular disease in the Japanese and Asian populations [12].
Regarding the cooperative sites, over 70 % of the sites can provide general and muscular evaluations. These data suggest that they have enough potential to conduct clinical trials. However, the MDCTN has two limitations regarding the proportion of patients with each disease: the accuracy of the numbers reported and quality of diagnoses. First, the proportion of each patient affected by each neuromuscular disease might be overestimated, especially in large urban areas. Because of the proximity of several sites, the registration of some patients might be duplicated in different sites and reports. Second, not all of the patients were genetically diagnosed because genetically diagnostic techniques were not available at the time of their diagnosis. However, registry data of MDCTN sites are still valuable for the conduction of clinical trials because there are no previous data on the infrastructural situation of clinical sites in Japan, such as that of TREAT-NMD.
There are both differences and similarities between MDCTN and other disease-specific networks, such as CINRG and TREAT-NMD. The main differences between MDCTN and the international networks are that MDCTN is a domestic network, and not all its sites have vast clinical research experience. Its main similarity with CINRG is that the coordinating office works as an ARO. The main similarities with TREAT-NMD are that both apply corroboration with patient registries, standardization of treatment, and establish outcome measures. The MDCTN is equipped with these functions, which are modified depending on the situation in Japan and are going to be improved.
In Japan, the MDCTN has conducted two patient recruitments for clinical trials, as mentioned above. Additionally, we have conducted one feasibility enquiry. Basically, consent for research is based on the relationship between the physicians, the patients, and their family [13]. Before the potential participants join the clinical trial through the recruitment process via the patient registry, we have arranged for patients to be introduced to the site by their treating physicians, with whom trust has been already established. We believe that it is very difficult to recruit the potential candidates through the system.
MDCTN has three advantages. The first one refers to quick inquiries and patient recruitment. To achieve quick inquiries and patient recruitment, a close communication with the patient registry and having updated registry data from all the sites are remarkably important. These data will indicate the location of the patients, which is useful for clinical research because it allows them to easily recognize potential research partners. This can also translate into less time and costs of recruitment for pharmaceutical companies. Additionally, showing the proportions of patient with rare diseases and sites may create opportunities for the Japanese sites to participate in international clinical research.
The second advantage is to be able to share the information of the latest research and clinical trials through the meetings. The MDCTN covers most of the hospitals in Japan with extensive experience in treating neuromuscular diseases. This makes it possible to provide equal opportunities in terms of the latest research information for the benefit of the patients.
There is no doubt that the support of a national network in collaboration with a national patient registry is a powerful source of support for an international network, such as TREAT-NMD and CINRG, by which clinical research for neuromuscular diseases is being promoted energetically. The conduction of global clinical trials is also very important for the development of cutting-edge drugs and treatments, especially for rare diseases. However, cooperative sites are not equally participative all over the world. It may be the case that only a few sites attend the activities from some countries in Asia. This may result in those sites gaining updated international, high-quality evaluation method, research information and/or treatment, and the rest of the sites may be left behind. MDCTN provides resources such as meetings and educational opportunities for health care providers, including PT and CRC. Furthermore, this is a good opportunity to share the latest information, treatment or evaluation for specific rare diseases. We believe that this will contribute to standardization among cooperating sites.
Ando et al. are reported that 15 % of multinational clinical trials were operated in Asia or East Asia in 2012 [14]. In this area, the Asia Oceania Myology Center (AOMC) provides opportunities for standardization of treatment and basic research. The AOMC also provides a forum for the discussion of issues related to their own countries, as well as support to find solutions. Therefore, it is clear that networks operating at a nation level, like MDCTN, are necessary. Each country has different issues that affect the conduction of clinical trials, such as medical environment, drug approval processes and regulations, and social systems, and thus, each country needs to develop different plans and strategies to tackle these issues. The MDCTN can serves as a model of a national network. Additionally, we assure that the activity of improving the national standards will contribute to improve and facilitate international clinical research activities.