I don't think this is a fully accurate portrayal of LC advocacy logic in that a) almost every major LC advocacy organisation has demanded large-scale funding over a 10-year period (the moonshot has demanded $1 billion a year for 10 years), and b) there has actually been a great deal of emphasis on the quality of research. On the political side of things, you have all these groups calling for a tonne of research funding, but then you also have patient-led research collaborative on the more scientific side of things. PLRC is made up of patients who have advanced degrees in the sciences. They've published various studies, but most importantly, almost every member of PLRC has worked as a patient-representative within the RECOVER initiative. Of course, there's only a certain amount they're able to do - no-one could control the fact that RECOVER decided in 2021 that Long Covid was an entirely novel entity, or that RECOVER decided early on to spend the vast majority of its funding on essentially a very large symptom survey. But the efforts of those patient advocates have had a significant impact - they helped somewhat temper the exercise trial, but most importantly they've created a situation where, if the NIH spent a lot of money on Long Covid today, that money would be better spent than it was 4 years ago.
And on the question of large-scale funding - there is no way lots of good research happens without consistent research funding. There are several reasons for this. In the first place, significant funding significantly increases the odds of good research happening. But more importantly, consistent funding would help actually establish post-viral illnesses as a field - at the moment, it's near-impossible for biomedical researchers to have a career in ME research because there's next to no guarantee that in 5 years their research will be funded. And you need researchers working at a problem not just for 2-3 years, but for much longer stretches. Researchers also need to be in dialogue with each other - which means that lots of different people need to get funding. Certainly, if Long Covid research received a billion a year there would be a lot of wastage and a lot of low-quality research. But you'd also be guaranteeing the fact that some good researchers would receive a fair bit of funding over a longer period, and I'd be very surprised if the quality of research didn't improve over time.
RECOVER is a good example of how research is supposed to improve over time - probably the main reason it has been so poor is that the NIH treated Long Covid as if it was an entirely novel entity, so they were essentially starting from scratch, which you never really want to do as an academic - you want to work off a large and pre-existing literature. Four years on, RECOVER has spent its money very poorly, but the NIH is far more aware of the good research produced outside of RECOVER, and they're also very aware of the various criticisms patient-representatives and the advocacy community has made of RECOVER. Now for me those criticisms center a bit too much on the need for treatment trials as opposed to fundamental research, but this is all a case study in how research improves over time - at first you're feeling around in the dark, which means you'll almost certainly waste a lot of your money, but as the field develops, research becomes much more focused.
The viral persistence literature is another case in point here - we're seeing a steady stream of increasingly focused viral persistence studies because it's the only hypothesis within the Long Covid field that's received a consistent amount of funding, primarily from polybio but also from other funding sources. Within a few years, we'll have much more precise answers about viral persistence - whether it is solely viral remnants rather than live, replicating virus that persists within the body, whether there are indeed viral reservoirs in places like the gut. And the only way to get those kind of answers is to have lots of teams attacking viral persistence from a number of different angles, which requires lots of funding.
Also, it seems to me that dementia and alzheimers are the exception - in general, throwing money at a problem is the way to get results. Why do we have far better treatments for most diseases today than 50 years ago? Because most diseases have, globally, received hundreds of millions of dollars in research funding a year during that period which has all but guaranteed that there have been top researchers continually working at the problem for decades. Why are there no treatments for ME? Partly because of the dominance of the BPS cabal, partly because there's been no research funding so it's been near-impossible for good researchers to consistently delve into the disease on any sort of scale. Until research receives proper funding, that divergence between most diseases and ME will never change.
It seems my post came across far too critical of some of the LC advocacy groups. If that was the case I want to correct that in stating that I think the vast majority of different LC advocacy groups have done and are continuously doing an amazing job and that in particular the PLRC as you have pointed out have truely done a remarkable job, especially on the research side of things and I certainly agree that predominantly due to the efforts of such groups, if the NIH were to spend their money on LC research today it would be better spent then previously. However, whether it would be well spent is an entirely different question and the influence of the PLRC on that can remain rather limited as they have repeatedly pointed out themselves.
We all agree that no one needs to trial melatonin, exercise, light-therapy and what not, but that doesn't mean that trials of IVIG and Ivabradine are the pinnacle of enlightenment. Nor that there is any evidence to suggest that based on the intramural study results certain substances should now be trialled. In that sense I agree with
@Jonathan Edwards.
I was in no way trying to suggest that long-term funding was not needed for LC or ME/CFS or that LC advocacy groups have skipped over that step in their demands, when that has been their entire focus for the past 2 years. As everyone I think is aware, you need sufficient funding over a long-time period of at least 5 years, if not decades. Whether that is 300 million, 1 billion or 2 billion per year is possibly debatable and if there is sufficient research of high quality, it is possibly less relevant.
The quality of research is not supposed to improve over time. What you want to see is a consistent sufficiently high quality of research over a long-time frame. That’s very different to an increase in quality over time. A constant quality of research automatically ensures solutions to problems over long time-frames, if they are even solvable. It is arguable that in a new field of research such as Long-Covid an optimisation process ensuring a quality increase over the first couple of renewal of funding rounds is necessary and could be expected when it comes to beaurocratic gargantuans like the NIH. But I'm not too certain that such an optimisation process will naturally provide you with the answers you are looking. The question is more so why anybody was expecting to get answers with the type of research that was conducted and whether those thought processes are still the same once new funding arrives or whether they have simply shifted to LC research that is now viewed as trendy. From what I’ve seen there certainly has been an increase in the quality of LC research, which however isn’t particularly hard when you start of with absolutely useless research, but mostly that increase is so small that it might not be sufficiently large to change things over say a time-frame of 10 years. The question is whether you get to a sufficiently high quality of research over a relatively short period of time, which 10 years certainly is, with such an approach.
Also, it seems to me that dementia and alzheimers are the exception - in general, throwing money at a problem is the way to get results.
I'm not too sure of that. You have to supply research fields with a somewhat continuous funding stream over several years to ensure that clever minds that are genuinely interested in solving a problem have the means to do so, but that doesn’t mean that throwing money at the problem is the way you are getting your results, because you are judging the problem a posteriori and from the outside. We have better treatments for most diseases because knowledge has improved over decades, sometimes continuously and more often than not in leaps and breakthroughs. In other cases there has been no progress because no one was doing the work that would have been necessary for progress or simply becaus it isn't possibly yet. Knowledge improvement does not automatically follow from an increased amount of funding as several scientific disciples in which methodologies have not only remained abismal but sometimes seem to have even gotten worse over time, have shown. The German mathematician Lejeune Dirichlet once said that there was a time in which he considered himself among the 8 leading mathematicians in the world, with the other seven being Gauss. You have to ensure a research environment which raises your chances of people such as Gauss being able to thrive. That requires funding but it requires more than just that and criticising bad research, so that it can improve, can certainly be part of that process. Many researchers are very robust to receiving criticism if it sharpens their senses, especially those that are well aware that their research has little meaning to begin with, which many are very aware of.
The WAFS3 study, the study by Wüst et al, which of course was partially funded by the PLRC and DecodeME are all studies that can provide us with vital clues, none of those required particularly much funding and perhaps apart from the study by Wüst et al, which wouldn’t exist if it wasn’t for the noise LC has been making, just required someone looking at something from a slightly different angle. Good research is not always a product of an abundance of research happening, which automatically results in some of it being useful.
I’m not so sure whether the problem with RECOVER was that they treated LC as if it was an entirely novel entity. If it had been an entirely novel entity RECOVER would still not have yielded any insightful data and on the other hand had it been an entirely novel entity I could think of many ways in which more meaningful research could have been conducted. The problem is not novelty. Of course that assessment suffers from a strong hindsight bias on my behalf, but I think it remains largely true when I look at the predictions made on this forum several years ago. That is not unique to the NIH and certainly true for me as well. Whilst myself and others were hyping up the microclot research, it had already been very apparent to forum members here that the methodological mistakes are that big that the microclot data is inherently useless. If anything I wouldn’t blame it on LC being an entirely novel entity, it more seems to be the usual progress of doing that work you can do for which you know you’ll obtain funding in the knowledge that you’ll receive further grants once that is done. In that case LC research doesn't seem to have changed much, the few valuable leads are largely not being followed-up on precisely because replicating findings and possibly producing null results is not attractive to most, including funding agencies.
I’m not saying that 1 billion for 10 years won’t deliver answers. I want to see 1 billion for 10 years and have been doing as much advocacy as I can in the hope that this goal is achieved. I’m simply stating that it’s naive to assume that, that is the way answers will automatically be delivered because sufficient improvements seems to be occurring within the NIH. I’m not suggesting that LC advocacy groups are that naive and I’m fully aware that it’s far more productive to go down this road than to drown oneself in self-pity and that they are and have changed the NIH's approach already. I completely agree that targeting the NIH is by far the most important, most vital and most sensible target for LC advocacy groups, given the vast amounts of possible funding. But to come back to the earlier analogy, surprisingly many of Gauss’ colleagues that would follow in his footsteps, were Hungarian jews, so called “Martians”. I cannot claim to fully understand the historical reasons for that, but it was certainly not because Hungarian jews dominated global funding sources and it’s more likely that the answer probably lies somewhere in a traditionally strong school of logical reasoning whose reasoning was sharpened over years and where doing grunt work was favoured above publishing something simply to publish. If a post-viral research field can be established via advocacy work and via lots of long-term funding, one may same day look at this as the beginning of a traditionally strong field of research, however what I've seen so far, with my very limited knowledge, seems more of a word salad of MCAS, microclots and other topics that seem trendy, rather then getting the foundations right.
