Different ways to support breathing were the main focus of the second clinical session on day two of the Symposium. Researchers from two MND Association funded studies presented their work looking at diaphragm pacing and also the withdrawal of ventilation support.
The NeuRx diaphragm pacing system (DPS) is a device developed to aid breathing by stimulating the large muscle that helps you to breathe – the diaphragm.
In 2011, the Food and Drug Agency (FDA) in the USA approved NeurRx DPS as a treatment for respiratory failure in motor neurone disease (MND). The treatment was not required to go through the series of clinical trials that is needed for a new drug. The FDA approved it on the basis of one small study because at the time the probable benefit to health outweighed the risk of using it.
Due to this lack of clinical evidence, this prompted further research in the USA and Europe to test its effectiveness on symptom management and survival.
Further studies in the UK and USA
In July we told you about the results from the UK’s first clinical trial of diaphragm pacing. In the UK study of diaphragm pacing in amyotrophic lateral sclerosis (ALS), called DiPALS, the results were significantly different to previous pre-approval studies of the treatment. The trial showed that people who were on diaphragm pacing (together with non-invasive ventilation – NIV) lived on average 11 months less than those on NIV alone.
At the time the results were published, Dr Chris McDermott from the Sheffield Institute for Translational Neuroscience (SITraN), who lead the DiPALS study commented:
“The results from the DiPALS study are incredibly disappointing, because as a researcher and an MND doctor you start out with some hope that this is a treatment that can be truly beneficial for people living with MND.
“Unfortunately, DiPALS did not show any benefits for diaphragm pacing in MND and, in fact, our study showed that it may actually be harmful. Although the results are disappointing, it was an important study to carry out as this evidence shows us that for most people there is no benefit in having diaphragm pacing and that the major surgery needed is something people living with MND should not go through.
Further comments from Dr McDermott on the DiPALS study are available on the Lancet Neurology website.
At the Symposium, Dr Rob Miller (Medical Director of the Forbes Norris ALS/MDA Research Center at CPMC in San Francisco), a representative from the USA research team performing a post-approval study to test out the safety and effectiveness of diaphragm pacing, presented their results. They found that diaphragm pacing did work at helping with breathing, and was beneficial. People using NeuRx DPS lived on average 20.9 months, compared to 19.7 months in the initial FDA study. This was a clear contrast to results from the UK-based DiPALS trial.
Why the difference in results?
This is the key question that prompted a lot of discussion in the room between researchers from both groups. Dr Chris McDermott explained that the results from the UK trial could not be explained by surgical complications, respiratory failure or those using both diaphragm pacing and NIV stopping their use of the latter. He also commented it could be down to differences in the people selected to take part in the various studies, but the lack of published data from the first pre-approval data makes it difficult to know if this is the case.
The bottom line is that we do not yet know for sure why the outcomes of these trials were different.
Which results should I believe?
Even though the studies had different outcomes, neither set of results are ‘wrong’ as such, and the stark contrast in results should prompt much closer scrutiny on future trials of this treatment in order to determine if it is beneficial and should be used as a treatment.
These studies are both good examples of why treatments need several different trials to test them, even when agency such as the FDA has already approved its use.
They show that testing generally is important, and why treatments need to undergo these tests to determine their safety and if they show a survival benefit to people with MND.
What does this mean for the future of diaphragm pacing?
Dr McDermott revealed after his presentation that discussions between representatives from both studies had taken place, and that they agreed a pooling of data from all trials in diaphragm pacing needed to occur – the original study, the ongoing US studies, DiPALS, and a study happening in France which has also stopped due to safety concerns. These will then need to be independently reviewed.
It shows that more attention needs to focus on which stage of the disease to put a person on diaphragm pacing, and in helping select people expected to benefit from the treatment.
Dr McDermott said: ‘In my opinion no further implantations of diaphragm pacers should take place outside of clinical trials for the time being, until a more thorough review of data from all studies has occurred.”
Raymond P. Onders MD, Interim Chair Department of Surgery Professor of Surgery at the University Hospitals/Case Medical Center in Cleveland, Ohio said: ‘I agree with Dr McDermott in that diaphragm pacing should not be done routinely in ALS/MND patients. It should be done with the correct preoperative testing. When done correctly it can significantly help patients.’ Dr Onders is involved in the USA trials of the diaphragm pacing system.
Withdrawal of ventilation support at the request of the patient
We featured this topic on the blog when the results from Professor Christina Faull and colleague’s study were published in September.
This study looked at the practical and emotional aspects of withdrawing ventilation support at the request of a person with MND. A few families of people with MND who had requested to come off ventilation spoke of gaps in the support given to them and their loved one. Professionals also felt that national guidance was needed on the topic of ventilation withdrawal.
At the Symposium, study group member Dr Chris McDermott told us about the new guidance of this topic that have been developed for professionals.
What does the guidance say?
The guidance identify the sorts of discussions and plans to make in advance, and ways to support families after their loved one has passed away.
A full copy of the guidance can be downloaded from the Association for Palliative Medicine’s website.
Why is all this important for you?
You will know that your wishes are being listened to, that it will be seen as a serious request and that you will have piece of mind that after you die family will also receive support from the healthcare professionals involved.
More information on respiratory support
There is much more information available in our care information sheets 8A, 8B, 8C and 8D.