Rare diseases are complex and perplexing to medical science. The low prevalence, diversity and limited knowledge, makes it very challenging to recruit subjects into a clinical trial. Rare diseases adds a significant burden on mankind with 80% of rare diseases being genetic in nature and 50% of these conditions being diagnosed in children.In Japan too, there is a significant prevalence of rare diseases in the general population, for example the condition Amyotrophic Lateral Sclerosis (ALS) is present in 1-2.5 per 100,000 individuals with over 9200 receiving medication throughout Japan.This is mostly seen in the middle age group where individuals suffer from muscle weakness in their limbs, throat and lungs, hindering the breathing process.

Pharmaceutical companies are now increasingly focusing on developing new therapies for rare diseases, and in recent years the PMDA has been active in conferring approvals for innovative and orphan drugs. PMDA has been flexible in approving orphan drugs covering neurological diseases through conditional approval and Sakigake designation where review time by PMDA is faster. This conditional approval is frequent in rare diseases as clinical trial conduct for rare diseases is difficult to do or takes too long for conducting a confirmatory study. 3H remains focused and geared up in the game of clinical development for rare diseases and 3H has supported global biopharma companies to successfully conduct clinical trials on rare diseases in Japan.

Conducting clinical trials in rare diseases is challenging and time testing. There are many reasons behind this.

• Limited Patient Pool: Orphan diseases are classed by this term since it occurs in less than 1 individual among 2000 people making it challenging for subject recruitment in clinical trials. In addition there is a significant geographic dispersion of subjects making the patient to site ratio low and it is important to locate the clinical trial sites adequately for subjects to enrol in clinical trials. The care givers of these patients too face many logistical challenges in transporting such patients, due to the high disease burden and complications. This can affect clinical trial participation and retention. Since there is a limited population of such patients, Pharma Companies need support in enrolling and retaining each and every patient they find and 3H supports with patient recruitment and retention strategies which ultimately helps to keep the trial cost at control for the pharma companies.

The raresnet.com is one such website maintained by 3H, which has a special segment on orphan diseases housing a wealth of information for over 116 orphan diseases. It is free for public use and provides a platform for social interaction of such patients and an opportunity to reach out. Rare diseases have a limited knowledge bank and therefore it is challenging to have a thorough understanding of the disease process. Raresnet.com is a great resource in building awareness of rare diseases among the public. Public awareness helps in identifying such patients easily. 3H always adds value to patients who participate in these clinical trials. Appreciation and thank you cards along with a patient-centric work flow plan, has helped 3H in the past with better retention rates. In addition 3H facilitates in finding the right investigators with experience and infrastructure to ease the conduct of any clinical trial for Pharma Companies.

•  Paediatrics Population: Conducting clinical trials with children is not easy. With rare diseases presenting in nearly 50% in children, it is important to have a flexible and more ethical consideration towards enrolling such patients. Thus, clinical trials should be designed with child friendly protocols which ensure that child safety and protection is taken into consideration as children are a vulnerable population with restrictions in decision making on their own. 3H has completed many paediatrics studies successfully in the past and have the experience to handle the needs.

3H has successfully integrated itself in conducting clinical trials for rare diseases in Japan and across Asia. 3H helps with technological support for patient identification, site selection, subject enrolments and retention. As a service provider for clinical trials, 3H helps in enrolling subjects sooner and at a greater scale to minimise on the costs. Through established patient registries, it has become easy to track patients with rare diseases and the web portal raresnet.com helps in connecting the public and doctors involved in research, shortening diagnosis time.

One of the key studies which was completed by 3H successfully in rare disease space was for the indication amyotrophic lateral sclerosis (ALS). At the moment there is no effective treatment established for the cure of this disease. Currently there is only symptomatic treatment for gastrostomy and muscle weakness. The website https://raresnet.com/ gave a great millage in enrolling patients to this study with disease awareness, events and details of clinical trials running for rare diseases. 3H facilitated a multicentre, long-term safety study for patients with ALS. Both men and women with the condition aged between 18 to 75 years were able to take part in the study. To help in recruitment, there was advertising done in the website raresnet.com, in-hospital posters and spreading the word of the trial in patients’ associations. The ALS study was able to gain the needed patient population through referrals, and there was a great response from the ALS Association which has over 4100 patients. 3H was able to meet the recruitment target through fine-tuned recruitment strategies to suit the ALS population.

Most of the queries regarding the study were made by the patients themselves which accounted for 62.8% followed by family members of a patient accounting for 59% while the rest of queries were made by friends, doctors and caregivers. As the website educates the public on rare diseases, it is significant that 47% of patients with less than a year of on-set of the disease and 32% within 1 to 2 years of onset of the disease made queries.

When listening to the patient’s voice of the ALS disease, it is important to understand that such patients are eagerly waiting for an approved drug in the Japanese market. Some narratives from patients show that they have even attempted suicide and felt isolated without friends. For some, it had become an agony of being unable to work productively with all paid leave being used up for ALS related symptoms and having to make alterations in work locations and industries. Patients with ALS live with a lot of uncertainty and they had been looking forward for an opportunity to be a part of clinical trial for a better future.

Precision medicine targeting patient populations is increasing through innovative novel drugs and technology. 3H builds the right strategies to tap the right patient pools, reducing the cost of conducting clinical trials while better facilitating clinical research conduct through high quality data. 3H has become a great platform for Japanese and Asian clinical trials in the orphan disease space and the network keeps growing.

To know more about 3H approach for Rare disease patient recruitment in Japan, please contact imran@3h-ms.co.jp