Associate Member/patient and researcher session
- Working together for more and better research that benefits people with CFS/ME, a workshop facilitated by Sally Crowe
- Panel discussion for researchers and Associate Members, chaired by Prof Stephen Holgate, CMRC Chair
Unfortunately the Workshop overview has a lot of tables that won't reproduce on the forum, so I suggest you
download the pdf
Panel discussion for researchers and Associate Members
Prof Stephen Holgate, CMRC Chair
The following researchers gave a short overview of their work, picking out their key findings and explaining why they were important:
• Prof Robert Dantzer (see p X)
• Prof Andrew Lloyd (see p X)
• Prof Ian Lipkin (see p X)
• Dr Stuart Watson (see p X)
• Prof Wan-Fai Ng (see p X)
• Prof Carmine Pariante (see p X)
• Dr Sue Wilson (see p X)
• Prof Anne McArdle (see p X)
• Dr Esther Crawley (see p X)
The panel then took questions from the audience.
The first question was to Prof Pariante regarding fatigue in his cohort of Hepatitis C patients. Able to observe onset and duration of fatigue once Interferon-alpha treatment starts, he then monitors recovery once treatment stops.
“Data is still being collected,” he said, “but there does not seem to be a direct relationship between the improvement and viral infection.” Some people remained profoundly fatigued despite completely clearing the virus and their general health improving, he said. For others, the opposite was true: their fatigue abated once treatment stopped, even though the infection was still present.
Prof Pariante concluded, “So unfortunately it [fatigue] is not directly related to the virus. I think it’s more about how the body responds to this massive, massive inflammation and obviously some people will be more sensitive to that.”
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Next, a patient explained that he had had severe fatigue and brain fog when he first got M.E. “I went from being a programmer and holding everything in my head to not knowing what day of the week it was,” he recalled. “I could barely walk anymore.” He felt that unless someone had these symptoms they didn’t have M.E. and continued, “I feel very strongly that we have to tighten up the criteria on what M.E. is and what it isn’t.”
The bigger picture
“I think you make some excellent points but I would caution you against trying to make the overall umbrella too small,” replied Prof Lipkin, stressing the importance of looking at the bigger picture. “It’s very difficult to get funded to do research in this arena. I think if you talk to my colleagues they will tell you this is a huge challenge, and has been now for decades.”
However, there are organisations that are very successful at pulling in big money. “If you use cancer as an analogy, the American Cancer Society is very useful for all the people who have different types of cancer to come together under one banner and get the resources to support a whole range of cancers.”
There was a problem with that, said the patient. If you applied therapy to a mixed bag of people you got skewed results.
“Absolutely, I agree with you completely,” replied Prof Lipkin. “At the level of investigating pathogenesis, which is how you get ill in the first place, or [if you’re looking at] ways in which people respond to different kinds of therapy, there, it’s very important to parse narrowly.”
Using a whole range of symptoms and biomarkers is useful in describing specific groups of people, he said. “From the vantage point of science and doing research, you should find ways in which you can be more discrete in terms of thinking about mechanism and disease.”
Picking up this theme, Prof Dantzer drew on his experience in cancer research and agreed it was really important to cast the net wide at first. “The symptom such as fatigue never happens by itself, it happens in a cluster of other symptoms and we see that very well in cancer patients.”
There will be common mechanisms, he said, such as inflammation or mitochondrial dysfunction but they may present similarly or differently in a given selection of patients. He suggested the need to study all symptoms, only pulling out the differences at a later stage.
Perceptions of the condition
“Does the panel think that a different perception of ME and CFS would actually help improve the availability of funding?’ asked a UK film producer working on a film about CFS/ME, Canary in a Coal Mine.
“From the children’s perspective,” said Dr Crawley, “they would say they really need a different public perception to enable them to go back to school, to enable them to talk to their friends, even just to enable them to talk to their siblings. This is a very stigmatising illness, particularly for children and we should take every opportunity to talk about how devastating the illness is.”
Dr Crawley felt taking a drip, drip, drip approach was necessary to change the public perception of CFS/ME, and that events such as this patient-researcher session and working together were really important to achieve this.
Referring to his work on the 2011 film Contagion, which generated worldwide exposure for issues related to his own field of emerging infectious diseases, Prof
Lipkin suggested that a well -known narrator for the producer’s documentary was critical. “You need to get somebody who is visible and well known who can promote something you are trying to do, otherwise it just gets lost.”
Selecting patients for research
A patient commented to the panel that if the principle selection of patient cohorts is flawed then so are the results. He suggested using the Canadian Consensus Criteria to avoid this problem.
“Your point is that if the wrong people go into the research, then the research becomes pointless,” reflected Dr Watson. “I think you’re both right and wrong all at the same time.”
He explained that in a recent study at Newcastle, they had selected candidates very carefully, excluding anybody who had a current or previous episode of a psychiatric disorder like depression or anxiety. Consequently they had found different results from previous studies regarding childhood adversity.
Agreeing with the rest of the panel, Dr Watson emphasised that looking at a broad range of symptoms was important.
“We wanted to characterise patients very well,” he said, “and so we recorded lots of different things and one of the things that we recorded was pain in the jaw.” It threw up some interesting results.
“We found that those with chronic fatigue and jaw pain were different to people who had chronic fatigue and didn’t have jaw pain.” Primarily, they found a difference in cognitive performance and brain fog.
Though these might be chance findings, Dr Watson said that stratifying within this umbrella allowed them to draw out differences that were potentially markers of separate biological processes. He concluded, “Inclusivity but stratification is the message that is coming through across the panel, I think.
Purpose of criteria
Prof Lloyd, involved in both the Australian criteria and reviewing the Center for Disease Control and Prevention case definition, said there were now a total of 11 different criteria sets for CFS/ME.
“One thing I would advise is to be very clear about the purpose of the criteria,” he added. “From the point of view of making a diagnosis, the criteria broadly matter but actually what really matters is the care that leads from the diagnosis.”
This was a completely different issue for criteria for entry into a clinical trial or a research study, he said, where it was important to understand the similarities and differences within the disorder.
“I have the strong sense that we could generate another thirty criteria and it won’t advance the cause. My sense is we need to get on and do good quality research, characterising our patients by a broad range of characteristics, using various criteria to understand their similarities and differences and then to understand what the biology of the disorder is.”
Prof Holgate summed up this part of the discussion, saying, “The whole idea of stratifying this condition is obviously a major topic, and something we’ll be talking about as we move this whole field forward.”
Referring to his own speciality of bronchial asthma, Prof Holgate explained how classification was by severity because it linked to therapeutic options. But as it was now known that there are at least six different variants of asthma, he feels that, in fact, this hides ignorance about the illness.
What we call CFS/ME
A patient wondered about the meaning of chronic pain syndrome, asking Dr Crawley,
“Isn’t it just another term to confuse things?”
“What you call fibromyalgia in adults presents slightly differently in children, so we tend to call it chronic pain syndrome,” said Dr Crawley. “I completely agree it’s likely to be a fibromyalgia type problem,” she added, but that ultimately she didn’t choose what to call it.
Prof Holgate acknowledged that there is anger around certain terms, and drew attention to the Multiple Sclerosis Society, which has been very successful in raising funds and its profile.
“They’ve got one word, but there is likely to be 30 diseases under that one heading with different pathways and different factors,” he explained. “I think that is part of the problem. We have this acronym, called chronic fatigue syndrome or ME, or fibromyalgia if you want to blur the edges. It really adds to the confusion and it gives a false security that we understand what we’re talking about.”
Once the biological pathways become clear, he said, there will be a way of renaming this disease, or range of diseases, based on the driving mechanisms. “And the sooner we get to the mechanistic pathways the better,” he concluded. Finally, he asked Prof Lloyd if they have the same problem with naming it in Australia.
“I think we’re a bit more laid back, to be honest,” replied Prof Lloyd languidly, and the audience burst into laughter.
Integration of services
A carer asked if adult CFS/ME services were going to be integrated in the same way as children’s services. Her son had fallen ill at 15 and had lots of people investigating in a joined-up way, she said. But as soon as he turned 16, he was considered an adult and was looked after by a variety of departments who failed to communicate with one another.
“I think that is really, really important, that sense of bringing people together with different skills” said Dr Watson, explaining that they are attempting this at Newcastle by, for example, drawing together immunology and autonomic research, and attempting to coordinate at a clinical level and a research level.
“I think in a way this meeting is about that,” said Prof Holgate, “about joining things up, not splitting them apart.” Referring to the fragmentation in services, he said the same problem had existed in adult cystic fibrosis and that, “in the end, they had to redesign adult services.”
Translational research
A complementary practitioner said he would like more diagnostic tests available, including one for measuring cortisol.
“I think the important point you are trying to make is that there is scientific underpinning of the mechanisms that are involved in this disease,” reflected Prof Holgate. “And these need to be linked to some of the therapeutic outcomes that you actually deliver within your different clinical domains.”
Prof Lloyd felt that new approaches should be underpinned by research evidence. “We don’t yet have that,” he said, “science has to drive the outcomes.” But typically with science, moving from discovery into impact is a slow process.
“We need to make sure that the outcomes that are emerging out of the research are captured by the people who then develop that next phase,” said Prof Holgate. “We need to pick them up and run with them.”
Co-morbidities
An audience member said that gut problems such as IBS were common in people with ME and asked if that linked to recovery.
“Co-morbidities are obviously massive subject,” confirmed Prof Holgate, citing fibromyalgia, allergies and joint pain as just some of the illnesses and symptoms that were linked to ME/CFS.
Dr Crawley agreed co-morbidities should be investigated further. “This goes back to what all of us have been saying, which is that you need really well classified patients. We need to follow them and describe them and their co-morbid disorders. We just finished a study looking at eating disorders and symptoms, which are a really big problem in children. I completely agree we need to look at it in more detail.”
Prof Holgate concludes
The session ended with Prof Holgate thanking all those who had attended. He kept the door wide open for further collaboration with patients.
“What would be interesting is if you wanted to send in any questions that you have to us, we can reflect on those,” he said. “So if you have issues you want to raise, put them in an email, put them on paper and let us know. We’ll discuss them and think about them.”
Further patient-researcher sessions could also be arranged, if people had liked the way it had been done. The audience applauded enthusiastically.
“Don’t forget, for the Collaborative,” said Professor Holgate, “this isn’t the end of the meeting: this is the beginning of the journey.”
