Petition update provided by the ME/CFS Epidemiology and Genomics Alliance (MEGA).
5 OCT 2016 — Many of you have asked us questions about MEGA. We have not yet applied for funding and the patient advisory groups have not yet met to provide advice. So these are our preliminary thoughts at the moment. Some of this will change as we work on the first application (see below) and during consultations prior to future applications. We want to engage with as many people as possible especially in the current planning phase.
Has the study been funded yet?
No. We are planning to apply for funding in 2017 for the first stage of the study, setting up the world’s largest Bioresource of data and samples from CFS/ME patients. Our aim is to create a resource that all researchers all over the world can use. We will then apply for further funding for the subsequent omics-based stages of our study – searching for the biological basis to ME/CFS – once the Bioresource is set up.
Will the data be open access?
Yes. Subject to individuals’ consent, the data and the samples will be available for researchers to use. We want to rapidly increase effective research (by us, by anyone) to understand the biology, causes and different types of CFS/ME.
What case definition will you use?
To do the genetic studies that we want to do, we think we need to recruit at least 10 thousand adults and 2 thousand children. The only way to do this is to recruit patients through NHS clinics throughout England. England is the only place in the world that can collect this large number of patients in a short time frame.
Patients with CFS/ME will be identified by clinicians in the NHS clinics. The clinicians will be asked to identify patients they judge from NICE criteria to have CFS/ME. This means patients with other causes of fatigue will not be recruited including (for example): those with thyroid disease, diabetes or depression that is sufficiently severe to explain their fatigue. Patients will have been examined, a full history taken and they will have had screening blood tests (to ensure other causes of fatigue have been excluded).
We will collect sufficient information on each patient to be able to say whether they have CFS/ME using other research diagnoses (for example, the CDC [Fukuda 1994] diagnostic criteria, the IACFS criteria, Canadian criteria and so on). This is in addition to the diagnoses of CFS/ME that patients will get following NICE guidance. We will listen to our patient advisory group in terms of how much data we can collect on different diagnostic criteria. Our patients advisory groups may recommend collecting less data as patients are so ill.
Why use broad criteria?
As the symptoms and genetics of CFS/ME are highly heterogeneous we think it makes sense to build a Biobank of samples from all people diagnosed with CFS/ME (diagnosed with NICE criteria, without other causes of fatigue, as above). This is because our experience from other diseases is that the genetics found for one set of people with CFS/ME will be relevant to the genetics found for another, and even to the genetics of the population at large. But afterwards, in the computer, we will separate out various subsets of people with CFS/ME according to different diagnostic criteria. This will tell us which diagnostic criteria are more effective for which people.
Why are psychiatrists involved?
The MEGA consortium has brought together many experts from a wide range of different disciplines from across genetics, genomics, metabolomics, pain research, proteomics, psychiatry, sleep research and transcriptomics. Psychiatry needs to be there to complete the big picture yet it is just one minor aspect. MEGA will always be a Big Data ‘omics study, and will never be a psychiatric study.
What data will you collect?
We will collect symptom data on all patients to allow us to identify which patients will be identified as having CFS/ME using different diagnoses. We will also include data on fatigue, disability, anxiety and depression. We would like to collect detailed data on pain. How much data we collect will depend on what our patient advisory group says will be acceptable to consenting patients and how much funding we get.
Will you be doing additional tests?
We would like to do additional, more time-consuming and expensive tests on a sample of patients that will help us more finely phenotype (describe CFS/ME more carefully) those recruited into the study. We don’t think we will have the money to do this for everybody or for everything. We would like to do additional studies to collect more data on pain, exercise-induced stress and sleep studies and possibly some imaging. We also want to be as sure as we can that we have carefully excluded other diagnoses such as depression and anxiety as a cause of fatigue. We haven’t worked on the details for this but will be asking our patient advisory group about what they think would be feasible and acceptable given the funding limits.
What samples will you be taking?
We will take blood and urine samples that allow us to look at the genetics, the epigenetics (how genes are modified chemically), transcriptomics (identifying which genes are turned on and which are turned off), proteomics (the proteins in the blood), and the metabolomics (what small molecules are made by our enzymes and other proteins). We will use standard procedures for collection of these samples developed previously for many other studies.
Please explain why different members are part of the MEGA team?
We will upload a list of biographies and what members have to contribute in the next few days.
I want to be enthusiastic about this, but the explanation above seems to imply this is a giant Biobank project. Why do we need another Biobank? I thought this project was about getting these 12,000 multi-samples and doing tests on them, but it appears testing may be done on a ‘sample’ to assist with their symptom classification groups (phenotypes). I fail to see how interviewing 12,000 people indirectly to separate them into different groups helps move things forward. We want serious research into ME, not another giant delaying tactic. I do not believe this huge, costly project will not move our knowledge forward one bit, unless I have missed something.
From what I understand, the study isn’t a biobank (that’s a store of biological samples) but a big data omics study to try and identify the underlying biochemistry (genotype / chemotype). The interviewing of the sample is to more closely identify their phenotype (e.g. which of the various CFS/ME criteria apply?) then map the biological data to the phenotypic data to see which if any of the criteria are valid.
I would like to make 3 constructive (I hope) comments on this MEGA proposal –
1. In my view, no truly accurate data can be gleaned from this study if there is no representation from the severely affected/ bedbound cohort of patients in the UK. In order to remedy this, I suggest at least some effort, over a period of 3 months, to take samples from these patients in their homes as they will likely have been unable to attend NHS clinics in many cases. (Judy Mikovits research team in the US were able to organise home visits from UK based phlebotomy teams in just this way in the not so distant past, so I can see no reason why UK based research groups are unable to do the same). I suggest some liaison with the 25% group & direct contact with GP surgeries to facilitate this process.
2. I am a former Cardiology nurse and have had this illness for at least 15 years – and yet I have not *attended any NHS clinic for CBT or GET.
[*This is partly because of the distance involved in travel, (as I live in a village area outside a main town), partly because attendance is usually required weekly (& there are many days when I’m not well enough to leave the house), and also because, as we know, CBT & GET are not treatments for ME (cfs).]
This means I would also be excluded from this study, (& many others in a similar situation to me), as I not registered with any NHS ‘fatigue’ clinics – even if I felt it would be helpful to participate in MEGA.
3. As derekcull points out – we have a National ME Biobank of ready blood samples pooled from UK ME patients for exactly this kind of research. Will these samples already contributed to the Biobank be used and if not, why not? My understanding is that campaign funds were donated to establish the Biobank exactly so that the UK had a ready resource of samples for testing for national research projects.