Clinical trial network for the promotion of clinical research for rare diseases in Japan: muscular dystrophy clinical trial network

Abstract

Background: Duchenne muscular dystrophy (DMD) is the most commonly inherited neuromuscular disease. Therapeutic agents for the treatment of rare disease, namely "orphan drugs", have recently drawn the attention of researchers and pharmaceutical companies. To ensure the successful conduction of clinical trials to evaluate novel treatments for patients with rare diseases, an appropriate infrastructure is needed. One of the effective solutions for the lack of infrastructure is to establish a network of rare diseases.

Methods: To accomplish the conduction of clinical trials in Japan, the Muscular dystrophy clinical trial network (MDCTN) was established by the clinical research group for muscular dystrophy, including the National Center of Neurology and Psychiatry, as well as national and university hospitals, all which have a long-standing history of research cooperation.

Results: Thirty-one medical institutions (17 national hospital organizations, 10 university hospitals, 1 national center, 2 public hospitals, and 1 private hospital) belong to this network and collaborate to facilitate clinical trials. The Care and Treatment Site Registry (CTSR) calculates and reports the proportion of patients with neuromuscular diseases in the cooperating sites. In total, there are 5,589 patients with neuromuscular diseases in Japan and the proportion of patients with each disease is as follows: DMD, 29 %; myotonic dystrophy type 1, 23 %; limb girdle muscular dystrophy, 11 %; Becker muscular dystrophy, 10 %. We work jointly to share updated health care information and standardized evaluations of clinical outcomes as well. The collaboration with the patient registry (CTSR), allows the MDCTN to recruit DMD participants with specific mutations and conditions, in a remarkably short period of time.

Conclusion: Counting with a network that operates at a national level is important to address the corresponding national issues. Thus, our network will be able to contribute with international research activity, which can lead to an improvement of neuromuscular disease treatment in Japan.

Keywords: Clinical trial network; Muscular dystrophy; Muscular dystrophy clinical trial network (MDCTN); Neuromuscular diseases; Orphan drugs; Rare diseases; Registry of Muscular Dystrophy (Remudy).

Fig. 1

Structure of the Muscular dystrophy clinical trial network (MDCTN). This network consists of the steering committee, coordinating sites, working group and coordinating office. The coordinating office is the hub that communicates between clients, patient registry, and cooperative sites. The TMC supports research activities if necessary, and it provides protocol management. The MDCTN also includes a data manager, protocol development support, biostatistics analyses, and monitoring. Abbreviations: MDCTN, Muscular dystrophy clinical trial network; NCNP, National Center of Neurology and Psychiatry; TMC, Translational medical center

Fig. 2

Patient recruitment pathway. First, the client (researcher or pharmaceutical company) requests the patient recruitment to Muscular dystrophy clinical trial network (MDCTN) coordinating office. The coordinating office communicates with the patient registry and sends recruitment letters to registered patients who might the meet criteria. Through communications with patients and their local doctor, participants are able to enter the clinical trial

Fig. 3

Map of the cooperative sites. Thirty-one sites have joined the Muscular dystrophy clinical trial network and are widespread across Japan. Several urban sites are concentrated in the large cities, such as Tokyo and Osaka. (Source http://www.mdctn.jp/network.html)

Fig. 4

Overall patient cohort of the MDCTN. From 30 out of 31 cooperative sites, 5,589 patients have been reported. This data were calculated based on a rough estimate of the proportion of patients with each disease reported at each site. Abbreviations: MDCTN, Muscular dystrophy clinical trial network; GNE, UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase; DM1 and 2, myotonic dystrophy type 1 and type 2; DMD, Duchenne muscular dystrophy; LGMD, Limb-girdle muscular dystrophy; BMD, Becker muscular dystrophy; FCMD, Fukuyama type neuromuscular dystrophy; FSHMD, Facioscapulohumeral muscular dystrophy; CM, Congenital myopathy; CMD, Congenital muscular dystrophy; mito, Mitochondrial myopathy

Fig. 5

Available evaluations. This figure shows the number of sites, which provide the listed evaluations. This data were obtained from 30 out of 31 site reports