2026: International: Request for help with a cost-benefit analysis of Sequence4ME and LC

[Chandelier]

The ME/CFS Research Foundation did this for Germany: https://mecfs-research.org/en/costreport-long-covid-and-mecfs/

Economics Professor Goldschmidt might be another interesting connection.
An article from today:

Post in thread 'News from Germany'

Tuesday at 11:41 AM

Tübinger Wissenschaftler warnt: Folgekosten von Long Covid und ME/CFS dramatisch hoch - Kreis Tübingen - Reutlinger General-Anzeiger - gea.de

Viele Menschen leiden an den Spätfolgen von Corona, andere an ME/CFS. Sie alle sind erschöpft, viele können nicht mehr arbeiten. Der Tübinger ...

www.gea.de

Paywalled.

Tübingen Scholar Warns: The Long-Term Costs of Long COVID and ME/CFS Are Dramatically High

Many people continue to suffer from the long-term effects of COVID-19, while others are living with ME/CFS. All are affected by profound exhaustion, and many are no longer able to work. Professor Nils Goldschmidt of Tübingen warns that the societal costs of these illnesses must not be ignored.

ME/CFS...​

• Chandelier

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[Braganca]

Comparing the £15m cost of Sequence ME to the £billions in health and care costs potentially saved, and the £billions in productivity unlocked could be simple enough, but the same argument can be made about Alzheimers, Parkinsons, and Cancer. Plus those diseases have larger lobbying and comms teams to carry the message to decision-makers.

Productivity statement needs to take priority since that argument cannot be made for Alzheimer’s or Parkinson’s, both of which are diseases of the 65+ age group. Should be important to emphasize that ME cuts people down in youth or prime and is much more common than PD. Productivity and reducing disability in working age people is already a huge concern and priority for the UK govt.

 

[Utsikt]

@Chris Ponting this may be helpful.

OECD: Addressing the Costs and Care for Long COVID
The Long Shadow of the Pandemic

https://www.oecd.org/en/publications/addressing-the-costs-and-care-for-long-covid_87a0c171-en.html

Probably on the radar, as from April. Andy's thread here.

While prevalence of long COVID is projected to remain below 1% from 2025 to 2035 (affecting 0.6‑1.0% of the OECD and EU population), the direct healthcare costs for tackling long COVID – even under conservative assumptions – will remain high: around USD 11 billion a year.

Additionally, the indirect economic costs of long COVID are set to far outweigh the associated healthcare costs from 2025 to 2035. Long COVID will continue to dent workforce participation and productivity at a time of modest economic growth and population ageing. These losses are rooted in illness-related absenteeism, presenteeism and people dropping out of the workforce. Studies suggest that long COVID leads to employment disruption in around one in five affected workers. That is equivalent to a 5‑10% loss of labour input per affected individual during the first year of infection.

In total, projected losses of 0.1‑0.2% of GDP, which assume low or moderate residual transmission of the virus leading to new cases of long COVID, could create a major drag on the economy amounting to USD 135 billion per annum over the next decade, comparable to the entire annual health budget of the Netherlands or Spain.

That model has some major issues, though.

If I remember correctly, it assumes 10 % get LC, that everyone with LC stay sick for exactly two years, and the infection rates are at about 10 % of the population per year.

The infection rates are far higher and the LC rates are far lower.

The values for the costs might be useful, though, you’d just have to plug them into your own ME/CFS model (I’d just do current prevalence and expected yearly new cases).

 

[Chris Ponting]

Thank you for all of these considered responses. I'm so grateful for so many offers of help, and even funds to help pay for a Cost-Benefit Analysis. I've been put in touch with an academic economist and we met yesterday; I'll meet another today. Thus far, advice is that: (a) any cost-benefit analysis should prioritise the economic impact of accurate genetic diagnoses (albeit for an expected minority of pwME, given the rare variant approach of SeqME&LC) as its assumptions would be stronger, (b) the cost-benefit of ultimate effective treatments should be secondary as its assumptions will be weaker; (c) an academic report would be less well received than one from a consultancy firm whose reports have been previously used/accepted by the funder; (d) account for the higher lost economic productivity for those with youngest ME/CFS onset; (e) compare the economic advantage of spending on SeqME&LC over the same spend on other diseases/projects; and, (f) any analysis should deliver its evidence in accordance with the UK Govt’s guidance on appraisal, The Green Book. Informally, we will next ask around among UK Govt contacts whether they believe such a cost-benefit analysis would help our cause.

 

[Axel]

I don’t entirely agree with the standard reasoning behind the argument

any cost-benefit analysis should prioritise the economic impact of accurate genetic diagnoses (albeit for an expected minority of pwME, given the rare variant approach of SeqME&LC)

Which is based on the idea that the pathological mechanism has been identified through other means, genetic research being an added benefit that would help to refine the diagnose for a subgroup of patients.

This is not the case with ME/CFS, where observations have not yet been linked to one another due to the lack of an overall picture. Genetic research can shed light on this broader picture; it is therefore crucial at this stage and potentially beneficial to all patients, whether or not they carry a rare variant.

It would may be possible to compile examples of deseases where the discovery of a rare variant has helped to save time in the search for a universal treatment ?

 

[Braganca]

c) an academic report would be less well received than one from a consultancy firm whose reports have been previously used/accepted by the funder

Do you know what consultancy firms have done this work before? You could approach them and ask for pro-bono work. If you know the name of firms — put here so community could use their network to get names of people to contact.

 

[Jonathan Edwards]

I don’t entirely agree with the standard reasoning behind the argument

To me all the points completely miss the value of the research - which is to gain a deep understanding of ME/CFS and quite likely a range of other puzzling diseases through working out the mechanism. I can see that an economic analysis might have political value (but might well not) but across the board the economic case for medical reseaech is hopeless. If you make people well they will live longer and in the end cost more to society in terms of care. Relief of suffering, which is the real aim, does not even appear on a balance sheet.

I would stick to the scientific arguments but i am not having to raise £15M.

 

[Utsikt]

Thank you for the update!

Thus far, advice is that: (a) any cost-benefit analysis should prioritise the economic impact of accurate genetic diagnoses (albeit for an expected minority of pwME, given the rare variant approach of SeqME&LC) as its assumptions would be stronger,

I’m struggling to think of any immediate impact of accurate genetic diagnoses, other than enabling more targeted research.

(b) the cost-benefit of ultimate effective treatments should be secondary as its assumptions will be weaker;

Does this include the impact of genetic data on the success rate of drug trials?

(c) an academic report would be less well received than one from a consultancy firm whose reports have been previously used/accepted by the funder;

This is depressing, but probably true. Consultancy reports are inherently biased because the mandate is determined by the buyer (i.e. the people trying to get funding), and there’s an obvious conflict of interest in that the people seeking funding are paying the bills of the consulting firm.

(d) account for the higher lost economic productivity for those with youngest ME/CFS onset;

This is a very good point. You could look at the two age peaks and point out how the first is before working age and the second is nowhere near halfway into working age.

(e) compare the economic advantage of spending on SeqME&LC over the same spend on other diseases/projects; and,

This should be easy. High prevalence, affects the young, highly disabling and no treatments whatsoever.

EU might have some reasoning for why ME/CFS was included in the recent EU Horizon call, I’m sure ME/CFS would tick a lot of boxes.

 

[Chris Ponting]

I don’t entirely agree with the standard reasoning behind the argument

Which is based on the idea that the pathological mechanism has been identified through other means, genetic research being an added benefit that would help to refine the diagnose for a subgroup of patients.

This is not the case with ME/CFS, where observations have not yet been linked to one another due to the lack of an overall picture. Genetic research can shed light on this broader picture; it is therefore crucial at this stage and potentially beneficial to all patients, whether or not they carry a rare variant.

It would may be possible to compile examples of deseases where the discovery of a rare variant has helped to save time in the search for a universal treatment ?

The closest relevant example I know is for POTS: a family-specific mutation, A457P, in the norepinephrine (NE; also known as noradrenaline) transporter (NET; encoded by SLC6A2): https://doi.org/10.1242/dmm.012203. But unfortunately this doesn't appear to have hastened drug development. I do 100% agree that genetics can begin to reveal the "overall picture" leading quickly to more targeted follow-up studies. Today, the task is to make a compelling economic case for funding of the remaining £15m for SeqME&LC. As we go forward, we need always consider how to have impact - either on diagnosis or eventually on effective therapies.

 

[jnmaciuch]

The closest relevant example I know is for POTS: a family-specific mutation, A457P, in the norepinephrine (NE; also known as noradrenaline) transporter (NET; encoded by SLC6A2): https://doi.org/10.1242/dmm.012203. But unfortunately this doesn't appear to have hastened drug development.

@Jonathan Edwards can tell you firsthand how much the rare C1q deficiencies pointed a big flashing arrow at lupus being an autoantibody-driven disease (especially coupled with the other evidence of anti-C1q antibodies). There are definitely more examples even just within autoimmune disease--Behcet's is the other one that comes to mind immediately.

Even if you can't immediately jump to drug development, identifying monogenic forms of ME/CFS means being able to do knockout models, which already puts us lightyears ahead of where we are now. People outside of science just need to have it explained why that is such a big deal, because it's not immediately obvious why that would completely change the playing field.

 

[Chris Ponting]

@Jonathan Edwards can tell you firsthand how much the rare C1q deficiencies pointed a big flashing arrow at lupus being an autoantibody-driven disease (especially coupled with the other evidence of anti-C1q antibodies). There are definitely more examples even just within autoimmune disease--Behcet's is the other one that comes to mind immediately.

Even if you can't immediately jump to drug development, identifying monogenic forms of ME/CFS means being able to do knockout models, which already puts us lightyears ahead of where we are now. People outside of science just need to have it explained why that is such a big deal, because it's not immediately obvious why that would completely change the playing field.

I agree. We're writing a review article at the moment, on exactly this.

 

[Jonathan Edwards]

The closest relevant example I know is for POTS: a family-specific mutation, A457P, in the norepinephrine (NE; also known as noradrenaline) transporter (NET; encoded by SLC6A2):

I am not sure that this is a good analogy. I suspect that the family with the A457P mutation have A457P mutation disease and that this has precious little to do with the problems of other people diagnosed as POTS, which is a far more troublesome clinical concept than ME/CFS. Noradrenaline was already a target for POTS and so far looks to have been unhelpful. For ME/CFS we have had no pathways or mediators that looked remotely plausible. DecodeME has pointed us to a bunch of pathways, even if tentatively. A rare gene could very easily pinpoint a key pathway of relevance to the majority of people with an ME/CFS diagnosis.

The key thing about homozygous C1q deficiency in lupus is that it tells us why lupus is lupus and not rheumatoid. It places C1q as a pivot that explains the type of immune complex involved and its effects and also the failure of early B cell triage. Other complement component defects add more detail to the story. The link to TLR-7 gene defects fills in another part of the story.

If Sequence pulls out a CRHR2 variant the whole picture may suddenly fall into place.

 

[jnmaciuch]

Another useful contact might be Chris Donohue at the NIH in the US. I briefly worked with him on a rotation project last year. He was very interested/involved in trying to quantify the total amount of research gains spurred by findings from NIH-funded genomics studies (coming from a concern that the long-term benefits of those studies are continually underestimated). I am not sure how much headway has been made on those projects in the time since, but he might be able to provide (or at least point you towards) some hard numbers for the net "benefit" of funding a WGS. Plus he's a lovely person to chat with

 

[Utsikt]

Today, the task is to make a compelling economic case for funding of the remaining £15m for SeqME&LC. As we go forward, we need always consider how to have impact - either on diagnosis or eventually on effective therapies.

What’s the potential benefit for «diagnosis» if we don’t have any treatments?

Unless the results show that there are two or more fundamentally different diseases in the group that we currently call ME/CFS and we’d be able to finally split them, how are you getting any benefits?

A diagnostic test that is calibrated based on fulfilling criteria X can’t be more accurate that just applying criteria X. It would be nice to have a test that definitively says that this is ME/CFS and not something else, but I can’t imagine how you’d get that without it being based on some kind of pathology that we understand (and possibly is unique to ME/CFS). If we have pathology we understand, surely the benefit of that in terms of guiding searches for treatments would far outweigh the benefit of a test.

It’s probably not like you could skip all of the differential tests either because you might very well have two things at the same time, and not just ME/CFS.

You could argue that having an «ME/CFS test» could alter the public opinion of ME/CFS which would be nice, but that would be challenging to quantify in any meaningful way.

 

[MrMagoo]

I keep seeing questions which Chris can’t really answer - if the team have had relevant advice on what the grant application needs to include, then that’s what it needs to include.
Doesn’t matter (for the purposes of this thread asking for contacts who could work on the application) whether we think that’s good, bad or indifferent, it just is.

 

[PeterW]

I can see that an economic analysis might have political value (but might well not) but across the board the economic case for medical research is hopeless. If you make people well they will live longer and in the end cost more to society in terms of care. Relief of suffering, which is the real aim, does not even appear on a balance sheet.

I don't think that's a fair assessment.

Improving the health and capacity of people with ME could turn people from receivers of benefits into tax contributors (median salary of £40,000 contributes ~£7,500 in NI and Income Tax plus ~£5200 in employer's NI, as well as VAT, and other taxes).

Those people also free-up the time and capacity of carers, save funds for their own pensions, innovate new businesses, and all sorts of wider economic benefits which I can't begin to quantify.

Also people with ME don't necessarily die young. If it's about comparing a rapid death aged 50 to a protracted death aged 90, then I would see your point, but that's not the case with ME.

If anything, ME might be comparable to starting aged care very early in life.