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

Chris Ponting

Senior Member (Voting Rights)
Post copied from the Sequence4ME thread

Dear Science for ME hive mind, I need your help.
I believe that the Sequence ME & LC project needs to make the economic case for further funding, beyond the ~£5m already raised: we need ~ £15m more.
In short, I need guidance in how a cost-benefit analysis of this project should be performed, and who with the skills/background might be able to do this?
Please do get in touch if you have ideas via email. Thanks!
 
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Dear Science for ME hive mind, I need your help.
I believe that the Sequence ME & LC project needs to make the economic case for further funding, beyond the ~£5m already raised: we need ~ £15m more.
In short, I need guidance in how a cost-benefit analysis of this project should be performed, and who with the skills/background might be able to do this?
Please do get in touch if you have ideas via email. Thanks!
Could you provide the email address here?

This in the kind of thing I would have been doing at work when healthy but I have no chance at being involved now.

My first two thoughts are to look at the more direct costs for society for someone having ME/CFS: lost income (i.e. taxes), healthcare usage, benefits, and so on, and to look at the cost of running drug trials and comparing the historic success rates with or without genetic data (you’ve spoken about this earlier). I would be surprised if these analyses have not been done before but I have not kept track of it.

Tjenesten og MEg and the Norwegian MEA has data on e.g. wage trajectories and impact on carers/family in Norway:


Grethe Reinhardtsen
grethe@me-foreningen.no
Trude Schei
trude@me-foreningen.no

I would also consider framing SequenceME as a catalyst, accelerator and enhancer of other research, telling funders that if they fund this first they are going to get a lot more bang for their buck with future research because it’s going to be more targeted. Genetic data might also be what finally draws in big pharma (and their deep pockets), and you can probably find examples of research fields growing massively in the wake of new and exiting data. That could conceivably happen with ME/CFS as well and we’re already seeing some examples with e.g. James Cox and his team looking into leads from DecodeME.
 
Could you provide the email address here?

This in the kind of thing I would have been doing at work when healthy but I have no chance at being involved now.

My first two thoughts are to look at the more direct costs for society for someone having ME/CFS: lost income (i.e. taxes), healthcare usage, benefits, and so on, and to look at the cost of running drug trials and comparing the historic success rates with or without genetic data (you’ve spoken about this earlier). I would be surprised if these analyses have not been done before but I have not kept track of it.

Tjenesten og MEg and the Norwegian MEA has data on e.g. wage trajectories and impact on carers/family in Norway:


Grethe Reinhardtsen
grethe@me-foreningen.no
Trude Schei
trude@me-foreningen.no

I would also consider framing SequenceME as a catalyst, accelerator and enhancer of other research, telling funders that if they fund this first they are going to get a lot more bang for their buck with future research because it’s going to be more targeted. Genetic data might also be what finally draws in big pharma (and their deep pockets), and you can probably find examples of research fields growing massively in the wake of new and exiting data. That could conceivably happen with ME/CFS as well and we’re already seeing some examples with e.g. James Cox and his team looking into leads from DecodeME.
Thank you. Email: chris.ponting@ed.ac.uk, website: https://edwebprofiles.ed.ac.uk/profile/chris-ponting.
 
@Chris Ponting Perhaps you could approach Dr. John Cullinan (Professor of Economics at the University of Galway) for advice or to engage him. He has experience working on ME/CFS. His email is john.cullinan@universityofgalway.ie.


 
and to look at the cost of running drug trials and comparing the historic success rates with or without genetic data (you’ve spoken about this earlier).
The Recover trials are a great example of how little or nonexistent successes there are when you throw money and drugs at a disease that you barely know the pathophysiology of. I don’t know how feasible it would be to blast a huge project in your cost-benefit analysis (I imagine it could be seen as rude), but here’s Hutan’s summary of their trials so far:
So, updating the list of RECOVER trials:
RECOVER-TLC
  • Baricitinib - enrolling
  • GLP-1 receptor agonist - planning stage
  • Low dose naltrexone - planning stage
  • Stellate ganglion nerve block - planning stage

RECOVER-CT
  • RECOVER- VITAL: Paxlovid as a treatment - DIDN'T WORK

  • RECOVER-NEURO: Brain HQ - online cognitive training -DIDN'T WORK
  • RECOVER-NEURO: PASC CoRE - online goal training -DIDN'T WORK
  • RECOVER-NEURO: Transcranial Direct Current Stimulation - DIDN'T WORK

  • RECOVER-AUTONOMIC: IVIG for severe POTS
  • RECOVER-AUTONOMIC: Ivabradine for moderate POTS - DIDN'T WORK

  • RECOVER-SLEEP: Modafinal and solriamfetol for insomnia
  • RECOVER-SLEEP: Melatonin and light therapy for complex sleep disturbances

  • RECOVER-ENERGISE: Exercise for exercise intolerance
  • RECOVER0-ENERGISE: 'Structured Pacing' for post-exertional malaise
 
We have this thread that lists some of the analyses of the impact of ME/CFS

They might be handy as references.
Also clicking on the 'economic impact' tag (top left of the thread) brings up three pages of threads of various relevance.
 
Making cost-benefit analyses at national levels was something I used to do as part of my work - not for health issues though. I know about things like the selection of discount rates, words like internal rates of return, sensitivity analyses on assumptions.

My biggest tip would be that none of this is science, at best, it is persuasion based on facts. It's just a matter of building a defendable case, one that looks plausible, and in this case, probably conservative. There will be many other answers that are also defendable, so it's not worth worrying about the details too much.

I think it should be easy enough to make a strong case for a very large value, so don't try to make it a comprehensive sum of every possible benefit. Probably no one that matters in terms of making the decision will read the detail. If you try to quantify too many things that are a little bit of a stretch, it's too easy for someone to jump on what they see as an error and write off the whole analysis. Just go with what is easy to defend and explain and is compelling, and make it clear that there are many other benefits that you haven't quantified.
i.e. make your spreadsheet model with the key quantitatively compelling factors, but list other factors that are harder to quantify as well, ie. 'look -there's all this other stuff too'.

I imagine you will want to get an academic with some sort of reputation in this field? Actually though, someone from a big consulting firm could probably do a great job too and actually might even be more persuasive when it comes to governments.

Think about who you are needing to convince. Do they often use a particular consulting firm e.g. developing strategies for organisation reform or something? It could be worth the investment to get that company to make the case for you. As we all know, it's often not so much the quality of the message as who delivers it.

Always happy to try to help if you think there might be something I can do, a proofread or something.
 
My biggest tip would be that none of this is science, at best, it is persuasion based on facts. It's just a matter of building a defendable case, one that looks plausible, and in this case, probably conservative. There will be many other answers that are also defendable, so it's not worth worrying about the details too much.
I agree with this. Precision isn't required. The idea is to give an indication of the likely magnitude of the problem.

In my former life, I was an economist and I had to assess cost-benefit analyses as part of my job. Unfortunately I am so cognitively challenged these days, I can barely string a coherent sentence together let alone comment on economic matters.

I never worked on health policy so have little expertise in that area. These two Australian studies attempting to measure the burden of ME/CFS looked plausible enough from memory:


 
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See this report produced by consulting firm Price Waterhouse Coopers as a lobbying document for a pharmaceutical company.

tldr: This is an example of a report produced by a consulting company to sway government towards a set of policies. Most of the policies align extremely well with funding SequenceME.

So, liaising with a consulting company that has already written the sort of words you need might be a way to get an effective report written. The example report was funded by a pharmaceutical company - they have a foundation that might sponsor the writing of a repot about the benefits of SequenceME.

***

I think the PWC report is interesting in relation to this query because it shows how interest groups use the consulting firms to make arguments that can be used to lobby government and influence decision-makers - and they are. I've seen PWC Australia reports influencing health care strategy in New Zealand.

I think the report has also got a lot of arguments that are useful to support investment in SequenceME +LC. It's not just medical costs and welfare benefits saved and taxes paid by people who are back at work. Completing SequenceME +LC also gives pharmaceutical companies something to work with, to start to work on therapies. That can build industries.

Genomics is enormously trendy, so is AI which I imagine is part of the analysis process somewhere along the way. SequenceME+LC is leading edge technology enabling precision medicine, positioning the UK and its pharmaceutical companies to tackle a health condition of enormous global consequence. Yes, I know, most of that is buzz words. It doesn't matter, it's also mostly true.

I reckon it could be worth reaching out to Bristol Myers Squibb UK and the team at PWC who put this report together. They might have some connections and advice. They might even be willing to fund a report (Bristol Myers Squibb has a Foundation).

You aren't begging for funding - you are offering the government an opportunity to get involved in something exciting, something that could be a cornerstone of the UK's life science ambitions.

One of the identified priorities
"The UK should look to integrate both traditional and non-traditional health care datasets including genomics, phenomics, patient reported data, lifestyle data and wearables....

And SequenceME+LC has that impressive pedigree in patient engagement, it's a massive asset for a project dealing with people's most personal and revealing data
The report says "There is also room for greater citizen engagement with data and AI programmes to reduce misperceptions and improve trust'.
"Not only do patients need to be engaged in their own heath care so that they have the best chance of living longer and healthier lives, but also the public needs to be involved in policy development and system design. From identifying unmet needs to prompting academic research to improve access to medicines, more needs to be done to engage patients and improve their health care experiences as well as they health outcomes."

'Additionally, a skills gap is emerging caused by the difficulties attracting and retaining healthcare-related data scientists and there is a lack of diversity in both the data analysed and the data scientists that conduct the analyses'
Not in Chris' team there isn't.

You've got a terrific story, totally aligned with everything that governments get excited about these days. I reckon it would be worth talking to companies like Pricewaterhouse Coopers - find the staff who have already written the sorts of words you need. I think if you find the right staff member, they will love DecodeME and SequenceME - it has the makings of a fabulous case study on a PwC report.

I think it could even be worth contacting Bristol Myers Squibbs and pharmaceutical companies like them to see if they would sponsor the report, or perhaps even make a donation to the project itself.

If you can get a few organisations like that on your side, I think the millions needed might suddenly become quite achievable.
 
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It might be worth making the point that the PACE trial showed that existing psychobehavioural interventions and management strategies do not have a significant effect on ability to work - Wilshire, C.E., Kindlon, T., Courtney, R. et al. Rethinking the treatment of chronic fatigue syndrome—a reanalysis and evaluation of findings from a recent major trial of graded exercise and CBT. BMC Psychol 6, 6 (2018). https://doi.org/10.1186/s40359-018-0218-3 .

This key point is often lost in the mud around the PACE trial.

Current interventions essentially make no dent on the economic burden of this illness.
 
As far as I'm aware there have been two analyses of the economic cost of ME/CFS in the UK; the first was this one:
Bibby J and Kershaw A. (2003) How much is ME costing the country? Report prepared by the Survey and Statistical Research Centre, Sheffield Hallam University for Action for ME, 2003, and Action for ME and The ME Association, 1996.
While the headline result (£3.5 billion) & some other details were published the entire paper never appears to have been; nonetheless, presumably the charities will have copies.

The second was the "Counting the Cost" report that was subsequently promoted by MEA. Unfortunately I do not think it can be relied upon as it seems to have been a project sponsored & funded by a pseudoscience-peddling entity called the "Optimum Health Clinic", employees of which were involved in its production; it contains a number of dubious statements.

There have also been reasonable-looking studies done in other English-speaking countries. Obviously our healthcare & benefits systems and care costs differ and aren't comparable, but in terms of the economic effects in a similar economy there may be something of use. I did have a quick look at the 2023 Australian study ("The economic burden of myalgic encephalomyelitis/chronic fatigue syndrome in Australia"); that one used patient cost diaries & data from administrative datasets, considering direct medical & indirect societal costs, accounting for severity, age, gender, educational level & marital status using a regression model. We have a thread intended to aggregate studies of economic costs & impacts, although I don't think it has them all. IOM also reviewed what was known about the economic effects in the U.S. in their report, as I recall.

The Kielland & Liu analysis from Norwegian population register data suggests that rehabilitation-based interventions do not produce improvement in wage earning capacity.

Given evidence from such analyses, it should be feasible to make a case that, as ME/CFS usually begins in young to middle-aged adults, and is sufficiently disabling as to often limit very severely our participation in education & employment, that the broader economic effects are severe and that the costs of research that could help offset that are trivial by comparison.

I suspect that analyses of this sort are more about making a convincing political case than a scientific matter, unfortunately.
 
There's this one by Collin, Crawley et al. 2011 (apologies if someone has already posted this and I missed it):
The impact of CFS/ME on employment and productivity in the UK: a cross-sectional study based on the CFS/ME national outcomes database

Note this is for people attending specialist services early in the illness, so true economic burden would be a lot higher:
Data were available for 2,170 patients, of whom 1,669 (76.9%) were women. Current employment status was recorded for 1,991 patients (91.8%), of whom 811 patients (40.7%) were currently employed and 998 (50.1%) had discontinued their employment "because of fatigue-related symptoms". Older age, male sex, disability, fatigue, pain, and duration of illness were associated with cessation of employment. In a multivariable model, age, male sex, and disability remained as independent predictors. Total productivity costs among the 2,170 patients due to discontinuation of employment in the years preceding assessment by a specialist CFS/ME service (median duration of illness = 36 months) were £49.2 million. Our sample was equivalent to 4,424 UK adults accessing specialist services each year, representing productivity costs to the UK economy of £102.2 million. Sensitivity analyses suggested a range between £75.5-£128.9 million.
 
See this report produced by consulting firm Price Waterhouse Coopers as a lobbying document for a pharmaceutical company.

tldr: This is an example of a report produced by a consulting company to sway government towards a set of policies. Most of the policies align extremely well with funding SequenceME.

So, liaising with a consulting company that has already written the sort of words you need might be a way to get an effective report written. The example report was funded by a pharmaceutical company - they have a foundation that might sponsor the writing of a repot about the benefits of SequenceME.

***

I think the PWC report is interesting in relation to this query because it shows how interest groups use the consulting firms to make arguments that can be used to lobby government and influence decision-makers - and they are. I've seen PWC Australia reports influencing health care strategy in New Zealand.

I think the report has also got a lot of arguments that are useful to support investment in SequenceME +LC. It's not just medical costs and welfare benefits saved and taxes paid by people who are back at work. Completing SequenceME +LC also gives pharmaceutical companies something to work with, to start to work on therapies. That can build industries.

Genomics is enormously trendy, so is AI which I imagine is part of the analysis process somewhere along the way. SequenceME+LC is leading edge technology enabling precision medicine, positioning the UK and its pharmaceutical companies to tackle a health condition of enormous global consequence. Yes, I know, most of that is buzz words. It doesn't matter, it's also mostly true.

I reckon it could be worth reaching out to Bristol Myers Squibb UK and the team at PWC who put this report together. They might have some connections and advice. They might even be willing to fund a report (Bristol Myers Squibb has a Foundation).

You aren't begging for funding - you are offering the government an opportunity to get involved in something exciting, something that could be a cornerstone of the UK's life science ambitions.

One of the identified priorities
"The UK should look to integrate both traditional and non-traditional health care datasets including genomics, phenomics, patient reported data, lifestyle data and wearables....

And SequenceME+LC has that impressive pedigree in patient engagement, it's a massive asset for a project dealing with people's most personal and revealing data
The report says "There is also room for greater citizen engagement with data and AI programmes to reduce misperceptions and improve trust'.
"Not only do patients need to be engaged in their own heath care so that they have the best chance of living longer and healthier lives, but also the public needs to be involved in policy development and system design. From identifying unmet needs to prompting academic research to improve access to medicines, more needs to be done to engage patients and improve their health care experiences as well as they health outcomes."

'Additionally, a skills gap is emerging caused by the difficulties attracting and retaining healthcare-related data scientists and there is a lack of diversity in both the data analysed and the data scientists that conduct the analyses'
Not in Chris' team there isn't.

You've got a terrific story, totally aligned with everything that governments get excited about these days. I reckon it would be worth talking to companies like Pricewaterhouse Coopers - find the staff who have already written the sorts of words you need. I think if you find the right staff member, they will love DecodeME and SequenceME - it has the makings of a fabulous case study on a PwC report.

I think it could even be worth contacting Bristol Myers Squibbs and pharmaceutical companies like them to see if they would sponsor the report, or perhaps even make a donation to the project itself.

If you can get a few organisations like that on your side, I think the millions needed might suddenly become quite achievable.
The day rates for consulting firms in the UK are between £500 and £6000 depending on seniority according to various online resources.

If we estimate 200 hrs to make the report we’re at up to £150k, but probably closer to £50-100k. They know how to sell any project because they write offers all the time.
 
Apart from who has been mentioned David Cutler has written analyses on the economic costs of Long-Covid (see here and discussion here). The analyses weren't rigorous or detailed, however Cutler is an economics professor at Harvard, so if one wants to involve someone whose word might carry some weight, it might be a good person to approach.
 
You aren't begging for funding - you are offering the government an opportunity to get involved in something exciting, something that could be a cornerstone of the UK's life science ambitions.
I think this is the right angle. We've seen over the years how factual arguments have no sway, even with experts, and neither does a moral one. It's about opportunity, about fear of missing (FOMO) out on something big. The chance to unblock a large set of issues that have been completely stalled for generations.

This is why the psychobehavioral case sells. It has zero factual basis, but it's chock full of FOMO: it might work on some people, and it's worth putting everything into it. It's actually a depraved argument, one that ignores all the relevant facts, but it promises grand mansions in the cloud, filled with gold and only accessible by magical bean stalks. Just because it never delivers doesn't change what it promises. It's the promise that drives people, it can even make a giant industry be happy with plodding around in circles.

There is a middle case to be made that respects the facts, and still carries the FOMO. There is a strong case to make about how everything biopsychosocial is a complete dead-end, that in fact even continuing with it is abandoning all ambition. It's probably best to leave it to the imagination, but it doesn't take much to fill in the gaps, to persuade between a choice with betting everything on magical beans, with no possibility of achieving anything (and the destruction of scientific credibility in the process, because experts betting everything on magical beans really is terrible for credibility), of taking on the problem seriously and beating the crap out of it, of taking control of the situation instead of the endless stream of whiny woe-is-me lack of ambition that psychosomatic ideology thrives on as it flops aimlessly.
 
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