UK Genome Wide Association Study (GWAS) project - draft website goes live, feedback sought on recruitment plan, and updates

[Barry]

I think there may be another hurdle to anticipate when seeking DNA samples, as a significant minority may simply be scared to do so in regards to big brother concerns. Might be worth putting some effort into reassuring prospective participants that their data will never find it's way to health insurance companies, potential employers, etc. Remember that for most people clinical studies are far outside their awareness or understanding. But collection of DNA samples may raise groundless fears for some.

 

[dave30th]

The estimates for how many people have ME also seem to indicate that the huge majority of those don't know they have ME and/or haven't been properly diagnosed. That means the audience is not really the quarter million in UK who are estimated to be ill but the 10 or 20% or whatever of that group who have been diagnosed. That would suggest that the vast majority of those who have been diagnosed will have to participate, more or less. What is the time frame to collect this number of samples? Also, I assume this is just within UK? No samples from other countries?

 

[Sasha]

I am rather hoping that patients can be recruited by a grapevine spreading out from S4ME in fact. If there are 2,000 people on here each one only has to reach out to 10 people to get the numbers. Being realistic 200 members might reach out to 10 who, on average, could reach out to 10 themselves. All that is need is goodwill and being prepared to answer a few questions and spit!

I'm a big fan of the idea of patients reaching out via their social networks but I think this is an optimistic calculation. Outside of this forum, I don't know a single other ME patient and am not aware that I have any friends or relatives who know one. Even if I blast out an email to everyone I know (which I fully intend to once we've got a site properly up and running), I don't expect to reach many PwME. And those that I do reach might be less enthused about the study than me and so less likely to pass the message on. Plus, some of us will inevitably reach some of the same people.

I hope that 20k is doable but if it is, I think it's going to take everything we've got, and will need all hands on deck, and will need some serious PR work being done by the researchers.

 

[Andy]

What is the time frame to collect this number of samples?

I'm a bit hazy on this but I know it is planned to be multiple years, either two or three years. Obviously getting it all done in 6 months would be wonderful, but it's likely to take a while.

Also, I assume this is just within UK? No samples from other countries?

Just in the UK would be the easier option for a number of reasons, so that is the plan at the moment. However, we are aware that we might need to look further afield if recruitment is an issue.

 

[lunarainbows]

I agree with some of the other replies here in that I don't think word-of-mouth and social media will be enough. I think a coordinated effort to reach every GP and hospital, Ie doing it through healthcare settings, may help to get that number of people to participate. Especially as GPS will know who has the condition in the surgery. I got advised to do the prince trial bye consultant, obviously it's not the best example as it's quite different and it was a horrible trial, but he had a flyer and I'm pretty sure they told many consultants across hospitals to send patients with fatigue there.

I don't actually know many people with ME. I don't speak to many people and don't socialize online much as it can be tiring, except for the people I already know. For most of my friends, I am the only one they know with this illness. There are lots of Facebook forums for example but they are international and even then there aren't a huge amount of members And you'll be getting overlap in members.

 

[lunarainbows]

Also maybe interviews or features In TV and newspapers! Both broad sheets and tabloids. They are powerful things.

 

[Hoopoe]

I agree with some of the other replies here in that I don't think word-of-mouth and social media will be enough.

I fear that they are underestimating how socially isolated we patients are. And we are certainly not representative of the average patient in terms of motivation and knowledge.

 

[MerryB]

I think there may be another hurdle to anticipate when seeking DNA samples, as a significant minority may simply be scared to do so in regards to big brother concerns. Might be worth putting some effort into reassuring prospective participants that their data will never find it's way to health insurance companies, potential employers, etc. Remember that for most people clinical studies are far outside their awareness or understanding. But collection of DNA samples may raise groundless fears for some.

I agree, I think educating people about what the study is, what it isn't, and what will and won't be done (in lay language) with the genetic data is important.

There is a lot of public fear about modern genetic technologies, and lots of people won't know what the difference is between a GWAS study and other types of research.

I came across another person with ME who thought this GWAS project was a genetic treatment trial and they were planning to refuse to participate because they thought that the imagined 'treatment' would only be given for the duration of the trial, and that providing their genetic data without receiving long-term treatment from the researchers would be unfair.

Obviously lots of misunderstandings there. Hopefully I was successful in clarifying things for them, but I don't think we can assume that people will have any idea about research, so it will be important to explain really clearly exactly what the study is and isn't, and what it will and won't involve.

 

[MerryB]

It may not hit the right note but I wonder whether there is something to be said for putting out a call for everyone in the UK with ME to volunteer for the proposed GWAS project not just out of goodwill and desire to help science (and of course patients) but as a statement of solidarity: in the recognition that PWME are real and matter - that there should come a time when PWME should not need to think maybe they should keep quiet about it.

I quite like this idea. I think there is big opportunity with this study, if the outreach and marketing strategies are planned and pitched right, to really raise awareness and legitimacy for ME.

Perhaps rhetoric along the lines of 'it's time the whole country takes this disease seriously', 'actions rather than words', 'we all have to come together to bring about a sea change', 'the stigma ends here', etc. etc. ?

Would this motivate friends, family, medical professionals, and patients to act, if they felt like participating and promoting the study was part of a national mass action to finally support and legitimise the disease?

Edited to add additional thought (brain fog, sorry): How about using a slogan that people can take on almost as a person commitment? E.g. 'the stigma stops with me' or similar (some kind of firm, motivating statement) that could be used in marketing to encourage people to firmly commit to supporting a lasting change for ME patients, either by donating DNA or by promoting and supporting the study. ?

 

[Andy]

I fear that they are underestimating how socially isolated we patients are. And we are certainly not representative of the average patient in terms of motivation and knowledge.

Those people who are suggesting that it won't be difficult might be underestimating the challenge, we aren't (or at least we are trying our best not too).

 

[Jonathan Edwards]

The estimates for how many people have ME also seem to indicate that the huge majority of those don't know they have ME and/or haven't been properly diagnosed. That means the audience is not really the quarter million in UK who are estimated to be ill but the 10 or 20% or whatever of that group who have been diagnosed.

I think the preferred estimate is 0.2%, which would be 120,000 and that figure comes from diagnosed cases, not from trawling around finding undiagnosed people. So that means that 120,000 should already have a diagnosis.

 

[Sasha]

I'm a bit hazy on this but I know it is planned to be multiple years, either two or three years. Obviously getting it all done in 6 months would be wonderful, but it's likely to take a while.


Just in the UK would be the easier option for a number of reasons, so that is the plan at the moment. However, we are aware that we might need to look further afield if recruitment is an issue.

I'm stating the obvious perhaps but we've been waiting decades without treatment and we're very sick. Speed is of the essence. For patients, there's a huge difference in blasting this thing out in under a year and having it stretch on to three years. The whole community really needs to give it everything it's got.

 

[Andy]

I'm stating the obvious perhaps but we've been waiting decades without treatment and we're very sick. Speed is of the essence. For patients, there's a huge difference in blasting this thing out in under a year and having it stretch on to three years. The whole community really needs to give it everything it's got.

Couldn't agree more - the sooner the community gives us the 20k samples, the sooner it's done.

 

[Jonathan Edwards]

This may have been covered but when asking people to show interest is there a box for saying how they came to know about the project. It is always an irritating question but it might be telling.

 

[Ravn]

Just in the UK would be the easier option for a number of reasons, so that is the plan at the moment. However, we are aware that we might need to look further afield if recruitment is an issue.

Would it be possible to develop an international plan B in parallel with planning UK recruitment efforts? Maybe work with US and Australian* patient organisations (to save your own resources) to find out in advance about all the relevant rules and regulations and local considerations that could get in the way or would need to be addressed. That way, if UK recruitment falters, it would be much quicker to get international recruitment under way. On the other hand, if international recruitment turns out to be unnecessary, it would be work wasted and there'd be a lot of disappointed people who would have liked to have participated.


* Just picked on those two countries as examples because they seem to have strong patient organisations able to reach large numbers of patients. For other countries it may not be worthwhile to work through all the red tape to recruit only a handful of participants (reluctantly I include NZ in that category).

 

[Jonathan Edwards]

Would it be possible to develop an international plan B in parallel with planning UK recruitment efforts?

From my perspective this would be an extremely bad idea. If I were reviewing the grant proposal I would not be happy with bringing in an unknown number of subjects from other countries.

The problem is that genetic studies are only any use if control groups are extremely well matched for all sorts of confounding genetic heterogeneities across populations. The patient and control groups need to have the same racial mix, or you will find your disease associated with not being Chinese or something.

Recruiting subjects through media is fraught with problems because the people who reply may have traits that have spurious genetic markers. A population based study as in the ME Biobank is much better but cannot be done on many thousands. If you are going to go to those numbers then I think you want to try to get every case in a catchment area as near as you can. So for instance it would be better to restrict to England rather than UK if there was a realistic chance of getting numbers.

I feel strongly that the best course is to push as hard as possible for restriction to the UK, even if numbers fall a bit short. A result on a more mixed population I would personally be pretty sceptical of scientifically.

 

[Milo]

To get back to the % of people who were still undiagnosed, consideration must be given to physicians who choose not to diagnose their patients with ME due to the stigma and the fact that the diagnosis is based on reported symptoms. I have encountered comments from patients in Facebook POTS groups, pertaining to just this. And it’s not just family doctors, it is also POTS specialists.

 

[Ravn]

The problem is that genetic studies are only any use if control groups are extremely well matched for all sorts of confounding genetic heterogeneities across populations. The patient and control groups need to have the same racial mix, or you will find your disease associated with not being Chinese or something.

Could that be solved by patients recruiting their own healthy controls, as similar to themselves as possible - apart from having ME obviously - with regards to sex, age, weight, ethnicity and whatever else you want to specify?

So for instance it would be better to restrict to England rather than UK if there was a realistic chance of getting numbers.

I feel strongly that the best course is to push as hard as possible for restriction to the UK, even if numbers fall a bit short. A result on a more mixed population I would personally be pretty sceptical of scientifically.

Wouldn't a more mixed cohort be better - provided controls are well matched - to avoid getting a signal linked to being English?

 

[Jonathan Edwards]

To get back to the % of people who were still undiagnosed, consideration must be given to physicians who choose not to diagnose their patients with ME due to the stigma and the fact that the diagnosis is based on reported symptoms. I have encountered comments from patients in Facebook POTS groups, pertaining to just this. And it’s not just family doctors, it is also POTS specialists.

If I remember rightly the US study that looked at ME/CFS diagnosis by physician indicated that physicians over diagnose ME/CFS by about five fold. Patients' responses to questionnaires were more reliable and produced a smaller cohort.

I assume that recruitment will be done on the basis of either ME or CFS diagnosis, taken together according to CCC and IOM criteria.

There will be people with ME/CFS who have not been diagnosed but we would expect them to be in addition to the 0.2% who had diagnoses confirmed in the epidemiological studies.

 

[Jonathan Edwards]

Could that be solved by patients recruiting their own healthy controls, as similar to themselves as possible - apart from having ME obviously - with regards to sex, age, weight, ethnicity and whatever else you want to specify?

No, that would be a disaster because it would bring in all sorts of genetic association from friends and relations. Studies like this have to be as free as possible from any connection between subjects that might lead to bias.

The key point is that any bias, however small, due to non-random selection, is quite likely to turn up as statistically significant and statistical significance is the only thing that a GWAS study can use to identify candidate genes. Finding genes is very powerful as a way to study cause but it is also very fragile because if bias creeps in you can spend decades studying something that has nothing to do with the illness.

The problem is not too different from the problem of patients 'helping' the researchers in PACE by saying they were better. 'Helping' researchers, however well intentioned, can so easily lead to useless studies.