Outcome measures for DMD clinical trials
Duchenne UK has been working with scientists and researchers to look at how to improve the outcomes of clinical trials. One area of concern is whether or not companies are using the right measurements to determine whether or not a drug in a clinical trial is working or not. These are known as “Endpoints or Outcome Measures”.
Currently the most common endpoints in clinical trials are the six-minute walk test (6MWT), the North Star Ambulatory Assessment (NSAA) and/or the four-stair climb.
These measures have limitations, because they rely heavily on how the child is feeling on that specific day of the appointment. They can therefore be an unreliable indicator of how a child may or may not be responding to a treatment overall. Research published in 2014 showed that children can be bribed to perform better in some tests such as the 6MWT – read the paper here.
Duchenne UK has been keen to promote the use of wearable devices which children can wear on their wrists or ankle. Using continuous data collected from wearable devices at home could detect more sensitive and subtle changes and provide more reliable results about the impact or not of a new medicine.
Duchenne UK is supporting this effort in 3 ways:
ActiMyo is a device which has been developed to evaluate the physical condition of patients suffering with movement disorders. It is the result of a close collaboration between the Institute of Myology and Sysnav. ActiMyo records movement of daily life of a patient in their usual environment using a wearable device.
In 2016, Duchenne UK awarded £3,500 to support the EMA qualification procedure of this technology. Recently, the European Medicines Agency (EMA) published a draft qualification opinion on the use of Stride Velocity 95th centile as a secondary endpoint in DMD trials, using the wearable device. The qualification is now open for consultation until the 30th of November. Read the draft qualification here.
This is an important step for the acceptance of new endpoints by European regulators.
Utilising continuous data from a wearable device has the aim to be more sensitive to subtle changes observed in the home environment and to overcome some of the barriers encountered in hospital based appointments.
The European Medicine Agency utilise a process known as a “Qualification of novel methodologies for medicine development” - which involves a detailed evaluation from members of the agency and the Committee for Medicinal Products for Human Use (CHMP) which can lead to an opinion or an advice. This qualification from the regulators is aimed to give pharmaceutical industries and academics the confidence to consider new methodologies in their study designs.
- OUTCOME MEASURES REPORT
In January 2017, Duchenne UK co-funded – with Parent Project Muscular Dystrophy (USA), Duchenne Parent Project (Netherlands) and Duchenne Parent Project Onlus (Italy) – a workshop to review the clinical outcome measures used to date in DMD clinical trials. The workshop brought together clinicians, physiotherapists, imaging experts and patient advocacy groups to discuss current clinical outcome measures and highlight the gaps.
Read the report here, which was published in Neuromuscular Disorders in March 2018.
The discussions throughout this two-day workshop highlighted both the need and commitment to reach a consensus with the community, to involve all stakeholders and to enter into urgent discussions with regulators to create more meaningful outcome measures for DMD and to ensure that appropriate outcome measures are validated and accepted for the use in the ever-increasing number of DMD clinical trials.
Duchenne UK is also funding a study in partnership with Aparito, a wearable device which is worn on the wrists and constantly tracks physical activity data – both levels and intensity. The watch is paired with an app which collects patient reported outcome measures (PROMs) and real time events/ symptoms such as falls, so patients can share their experiences of the treatment they are receiving. By combining real-time continuous wearable data with patient/parent generated data it allows for the combination of objective and subjective data
This project recruited patients via Newcastle upon Tyne NHS Hospital Foundation Trust
and aims to collate and share meaningful, relevant and real-time data between patients and clinicians in a way that actively supports and enhances treatment and drug development.
Other outcome measure projects:
KINEDMD is a study developing an activity monitoring biomarker. Throughout the study patients will wear Apple watches to collect data on everyday movements at home and school. During clinical assessments participants will wear a sensor suit to measure how their body interacts with the world around them.
Using this data the researchers will use artificial intelligence to make sense of the data patterns. From there, doctors will be able to monitor disease progression with more precision. For more information about KINEDMD, watch this video.
NOTES FOR EDITORS
What is Duchenne Muscular Dystrophy Duchenne Muscular Dystrophy is the most common fatal genetic disease diagnosed in childhood. Children born with DMD cannot produce the protein dystrophin which is vital for muscle strength and function. Muscle weakness starts in early childhood. Many use a wheelchair by around the age of 12. As deterioration continues it leads to paralysis and early death, often in their 20s. It almost exclusively affects boys. There is no cure. In the UK there are around 2,500 boys affected and around 300, 000 worldwide. It is classified as a rare disease.
Who are Duchenne UK? Duchenne UK is a lean, ambitious and highly focused charity with a clear vision: to fund and accelerate treatments and a cure for Duchenne muscular dystrophy. The charity has been formed by the coming together of Joining Jack and Duchenne Children's Trust, the two biggest funders of research in the UK in the last three years. Its president is HRH The Duchess of Cornwall. Its patrons include the broadcasters Krishnan Guru-Murthy and Mary Nightingale, and the sports stars Owen Farrell, Kris Radlinski and Andy Farrell.
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