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

[Jonathan Edwards]

NICE evaluates cost against standard life-year benchmarks when evaluating new drugs.

Yes, but that is in terms of extra life and extra quality. of life, not economic impact. Surely the two are completely different. NICE judges whether a treatment relieves suffering. I think SequenceME should be judged on its chance of relieving suffering.

The fact that lots of organisations make spurious economic assessments is to me just a symptom of the general misunderstanding of what people actually value in life.

 

[Utsikt]

Oh, sure, but I find it hard to get engaged with such tasks and I wonder how much one can really judge what the capitalists will respond to.

Money, and the sooner the better.

And of course the other thing is that the economic argument was what gave us PACE and the BACME rehab industry.

Based on calculations that are based on very flawed assumptions.

 

[rvallee]

But government has limited cash to spend and a lot of deserving causes to fund. That which is spent on SequenceME cannot be spent on new hospitals, the benefits system, national defence or a slew of other options. Public funding is a zero sum game - what one cause wins, another loses - so economic impact assessments are a reasonable part of that.

It's also important to point out that most medical research is charity-funded. Governments mostly do basic research, and generally provide little disease-specific funding outside of top killers (heart disease, cancer, etc). This is mostly missing from the equation here, because the illness has no legitimacy and no support from the industry.

It doesn't have to be a zero-sum game because most of that funding doesn't normally come from government coffers. All of this is a consequence of decades of denial, and governments can easily make up for it with very little actual spending, by supporting, encouraging and leveraging the charity sector to contribute, by removing the illness from the shit list. Charity funding could easily be 10x larger without governments spending a single cent.

Had the medical profession taken this position all along, "we don't know what to do here, we are out of our depths, don't even know where to begin, but we encourage and will work to support all efforts at solving this, but we are unwilling to put our own money into it because we rarely do that, and until then everyone loses", we would already have meaningful solutions.

Governments are already spending billions on this issue, they just never see the bill. Having others do the work for them can work just as well, but this requires forcing the issue, using the power of government to stop the denial and blockage that medicine forces. It's not just about money. Money follows legitimacy. Governments can provide that legitimacy with very little money, but it will require swallowing the biggest damn ego pill in history.

I'd even say that ego is a much bigger problem than money, especially since it was always far cheaper to just do the damn work from the start. However liable governments and medical institutions are for this disaster, they are immune from actual consequences, so they should not worry about it. If they ever have to face consequences, all the gains from returning millions of people back to a normal life will more than make up for it anyway.

 

[rvallee]

And of course the other thing is that the economic argument was what gave us PACE and the BACME rehab industry.

It's actually a good example of the economic argument not being followed at all. The economics of the PACE model are absolutely atrocious. In fact, they literally chose the worst of all possible options on the economic front.

Making the right choice perfectly backwards is not following the argument just because it happens to align when its direction is entirely ignored. On normal issues people understand that using a lot of energy to produce less energy than is put in is not a good investment. This is the choice governments have made here, because all rational judgment goes out the window when it comes to chronic illnesses.

So actually following the economic argument would compel a complete reversal.

 

[rvallee]

Actually it's even worth pointing out that the entire psychobehavioral rehab model is the worst possible of all choices in every economic parameter as a general case. Mostly from the fact that it does not do what it aims, so it's a 100% waste from all direct expenses. But even if it worked, it has negative productivity gains from scaling, because the entire model is a fully 1:1 approach. For every hour of therapy spent with a patient, you need one clinical staff present the whole time.

A rehab service that serves 10x more patients is only 10x as "productive" (theoretically, since the real productivity is 0, but still the theoretical gains are strictly linear), but becomes more than 10x as expensive, an inherent problem with a purely staff-based model. Having 10x more therapists requires bigger facilities, more support staff, more complex needs in all areas, from IT and accounting to even just scheduling. And that number grows even larger scaling to 100x.

Every single industry that manages to scale has to grow its productivity per employee. The rehab model fundamentally cannot do that, it will always be stuck at the same level of productivity (which happens to be 0) per clinical staff, while also requiring more support staff. The model they are currently on has zero economies of scale. That's important because the current idea is that it might not work now, but it might be made to work later. And that still fails, because it fails the economics argument on scaling up.

This is why drugs work so well. Economics cannot be ignored, however annoying it might be. When a drug works, producing 100x more of it will leverage multiple industrial benefits that lower the cost per unit, to the point where some drugs can almost be produced for free per dose, and those gains are even larger still as it scales up. None of this is possible with the rehab model, and it's what makes it the worst possible way of even trying to solve any issue, where even if it did work, it wouldn't have a good economic case for it.

 

[Axel]

In research, it does not make much sense to carry out financial studies with immediate and localised benefits. The sequencing study is eagerly awaited by various researchers, funded by other countries. The UK cannot fund the entirety of research into a disease on its own, and any investment in a part that is essential to the continuity and coherence of the overall research will inevitably benefit the investing country.

 

[josepdelafuente]

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'm not sure if it's entirely relevant to your point, but -

I've spent the day putting together a big overview of my "diagnostic odyssey" which started in 2018.
Some if it was with private medicine, but a lot of it was NHS, and in the time period from 2018 - 2026 I've managed to amass a total of 211 test results. A significant number of these are the same tests done years apart.
90% of these are blood tests, with a few urine / stool / other kinds in there as well.
Of these 211 tests, absolutely zero have come back with any result that has warranted any further investigation - so not pointless, but not fruitful.
As well as that - there are all the NHS appointments I've had over that time.
If we assume that is happening for hundreds of thousands of people with ME - could that add up to a significant amount of (in a sense) wasted spending for the NHS?
Not because it's a waste to investigate us, but rather if we understood the illness better, hopefully we wouldn't be having years of pointless and costly investigations..

 

[Jonathan Edwards]

Not because it's a waste to investigate us, but rather if we understood the illness better, hopefully we wouldn't be having years of pointless and costly investigations..

Yes, I think that is a valid argument. A huge amount of money is wasted on not solving ME/CFS. If we had a quick way to deal with it that would actually save money. Interestingly, that may go against the general rule because failing to solve ME/CFS probably does not make people die sooner very often (a few obvious exceptions).

The immediate political problem I see is that any solution to ME/CFS is likely to be hi-tech in comparison to a few nice physio sessions and the current political push is to move everything over to the few nice physio sessions.

Maybe what we really want to push is prevention of ME/CFS. But that might involve protecting people from pandemics and the racegoers at Epsom weren't keen on that.

I am an old cynic.

 

[Hutan]

On the use of consultants versus academics to do the work:

As I mentioned, I have seen consultants' reports have big impacts on the health system infrastructure including research priorities in my country. Perhaps it something for Forward-ME to think about.

It's a matter of knowing who you are trying to influence and what is likely to work for them. Some academics write rubbish papers, some consultants write rubbish reports (although the useless consultants don't tend to last long because, as mentioned upthread, someone is typically paying a lot for the report). But, what the consultants tend to be particularly good at is knowing who needs to be influenced and how to do it.

(I note that the consortium who were successful in getting the EU Horizon EUR7 million plus funding recently used consultants to help put the proposal together.)

Which is why I think contacting people at a consulting firm that you know has been doing work with the decision-makers and finding a way to pick their brains is worth thinking about.

 

[Hutan]

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;

I don't think that is right. I think you have to put a value on the effect of a treatment, because it has the potential to be so large. Sure, discount it for uncertainty, but even a 10% chance of a treatment being found in the next ten years that makes people able to function is likely to produce substantial value. That's because of the number of people involved, including the number of people who will continue to become ill, and the many years of net benefits . If you fix someone in their 20s, then you have decades of them contributing to society, and that benefit is discounted back into a net present value.

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.

It just depends on how you make the model. There is no reason why you can't put in a value on healthy years lived and include that in the model.

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.

yes

But more than anything else I think that discussing research decisions in economic terms is simply demeaning. I went in to medicine to try to relieve suffering. That is what medical research is for. Period.

As others have said, there isn't an endless pot of money for all possible research. Neither should research priorities be determined wholly by the interests of researchers who are good at securing funds.

An analysis of how much net benefit research is likely to produce, using some consistent assumptions including the number of people likely to benefit, and the extent of the individual benefit is a good way to work out what should be prioritised.

There are lots of ways to take into account the aim of limiting suffering and extending life. Put a value on the likely extra healthy years lived and put that into the model. Maybe you see that as demeaning, but the alternative is that research funding is decided only on the whims and fancies of the people in the research funding organisations. An approach of good economic analysis gives you consistency and transparency.

Yes, but that is in terms of extra life and extra quality. of life, not economic impact. Surely the two are completely different. NICE judges whether a treatment relieves suffering. I think SequenceME should be judged on its chance of relieving suffering.

A good cost benefit model will do exactly that. It quantifies the likely individual net benefit, the number of people who will benefit and the timing of the benefit, taking into account the certainty. And that allows you to make informed decisions about what action to take with limited funds.

On NICE deciding whether a treatment relieves suffering - yes, but efficacy can't be the whole question when it comes to government priorities. It is entirely right that expenditure on Treatment A that allows 100,000 children to live long and healthy lives when they otherwise wouldn't should be prioritised over the same amount of expenditure on Treatment B that gives 2,000 people a few more years of compromised life. Of course it's terribly difficult, but those sorts of decisions are being made all the time for government funding allocations, often without much analysis at all.

Doctors have to act in the interest of the patient they see in front of them, but the government decision-makers should be weighing up what is the best way to ensure that benefits to the whole of society are maximised and distributed fairly.

 

[wigglethemouse]

Can I play devil's advocate?

As I understand it, approximately 5MM of funding has been allocated for mostly studying rare variants in a largish (for WGS) study that could highlight relevant pathways in ME/CFS.

What will be the benefit of spending an additional 2x over the 1x already allocated. We are most likely not dealing with common variants so even 2x additional sampling is unlikely to provide much more statistical power unlike the GWAS. Do we even know the number of WGS samples required to provide good statistical data? How reliable is that number?

Secondly, we need to learn from the Stanford WGS ME/CFS study. It used a smaller number of samples yet results seem to broadly align with DecodeME - but I've yet to see what impact that paper has had on the field other than stengthening the DecodeME findings in the brain.

 

[Jonathan Edwards]

What will be the benefit of spending an additional 2x over the 1x already allocated. We are most likely not dealing with common variants so even 2x additional sampling is unlikely to provide much more statistical power unlike the GWAS.

My understanding is that the additional funds are not so much for doing more samples. They are needed for the analysis?

I am not sure that you can get a useful power calculation for rare gene hits in the way that you probably can for GWAS. If a GWAS of 20,000 produced nothing I think there is a reasonable argument that there isn't that much to find at least in terms of independent risk gene variants. But for rare genes you are looking for clues that might be very rare but very specific - specific enough to nail part of the story.

My understandind is also that the Astra Zeneca work on the BTN gene region has been very useful and more of the same is likely to be even more useful.

 

[Utsikt]

What will be the benefit of spending an additional 2x over the 1x already allocated. We are most likely not dealing with common variants so even 2x additional sampling is unlikely to provide much more statistical power unlike the GWAS. Do we even know the number of WGS samples required to provide good statistical data? How reliable is that number?

What do you mean by this?
The £5M is for running 6000 ME/CFS samples through the machines.
The next significant chunk is to do the analyses of those samples.

Then there are even more ME/CFS samples, and the same for LC.

So we’re nowhere near the 1x. They split it up into chucks because getting funding takes time and it’s easier to get 5M than 20M. And this means they can start the bottleneck activity now.