Preventing the use of an unsafe new treatment in patients with motor neurone disease
Amyotrophic lateral sclerosis (ALS), named motor neurone disease (MND) in the UK, is a devastating illness that leads to muscle weakness and death, usually within 2-3 years of symptom onset.
Non-Invasive Ventilation (NIV)
Breathing issues (known as respiratory insufficiency) are a common cause of death for MND patients. Non-Invasive Ventilation (NIV), where the patient wears a facemask that helps them to breathe, is the current standard therapy to manage respiratory insufficiency. However, some patients do not tolerate NIV due to a number of issues, including discomfort.
The NeuRx RA/4 Diaphragm Pacing System (DPS) is a device that is implanted into the diaphragm and, when used in conjunction with NIV, helps the patient to breathe. Although there was limited evidence to suggest the device was safe and effective, in 2011 it was approved by the United States Food and Drug Administration (FDA) for use in ALS/MND and was being used across the US.
The DiPALS study
In 2011, we undertook the Diaphragm Pacing in Patients with Amyotrophic Lateral Sclerosis (DiPALS) study.
Led by Professor Chris McDermott, Professor of Translational Neurology, and implemented by Sheffield researchers and the Sheffield Clinical Trials Research Unit, it was the first randomised controlled trial (RCT) designed to determine if the DPS was safe and effective. In the trial, we recruited 74 participants diagnosed with MND, half of which received the current treatment (NIV) and the other half received DPS (plus NIV).
Results
In June 2014 the trial was stopped due to concerns around the safety of the DPS. The addition of DPS to standard care with NIV was associated with decreased survival in patients with MND, demonstrating that DPS should not be used as a routine treatment for patients with ALS/MND in respiratory failure.
Impact
The results from this trial prevented DPS from becoming standard care for patients with ALS/MND and therefore prevented countless patients from coming to harm. The trial has been included in National Institute for Health and Care Excellence (NICE), Canadian and European guidance documents, stipulating that the provision of care for patients with MND should not include DPS.
In 2019, we surveyed clinicians across Europe from 12 countries with the majority stating that the results of the trial had affected their use of DPS, or they no longer use DPS at their centre.
Professor Chris McDermott said: "The results of DiPALS demonstrate the importance of evaluating new therapies appropriately before their adoption into routine practice. There is increasing pressure to make experimental interventions available to patients early before full evaluation. The lesson from DiPALS is that significant harm can be done to patients with that approach."