R&D for long COVID is collapsing Public and private funding is lacking, scrambling opportunities to develop treatments by Rowan Walrath September 18, 2024 | A version of this story appeared in Volume 102, Issue 30 https://cen.acs.org/pharmaceuticals/drug-development/RD-long-COVID-collapsing/102/i30 Twitter thread Can be read here https://threadreaderapp.com/thread/1836560090209632319.html
At this point, is it more cost-effective to fund basic research (viral mechanisms and effects) or to test blindly for things that might affect the infection or effects? If we don't know the mechanisms of LC, how can we judge whether <expensive drug> is more likely to be effective than dandelion root?
Maybe Big Pharma is worried that someone might accidentally stumble across a cheap non-patentable treatment that works well?
I strongly doubt that there is a reasonable chance that 'pragmatic' trials find anything useful without having a biological target in mind. If there was anything like this, given all the experimentation that has happened early on, it would have been found. But even in general, I would really like to know what is the number of effective treatments have ever been discovered completely blind with a pragmatic trial methodology, with zero lead in terms of a biological target. My guess would be close to 0, and if a bit higher than that, most have probably happened decades ago. Easy pickings have long been exhausted in medicine, the rest needs hard work and the profession just hasn't adjusted to that. At least not everywhere. It's like gold prospecting in the old American West. In the very early days people could randomly walk to a river and find nuggets using only their eyes. Modern methods of gold mining involve giant mines that process thousands of tons of ore per day to separate the various minerals and some of it is gold, in microscopic bits. But it's as if there was still an old style industry selling picks and sifters to people who think they'll still find nuggets lying around. What's needed is a mix of basic and targeted research that also includes looking at existing findings and makes sure that the whole effort is coherent, away from the extreme redundancy model we've had so far. It's been one of the most frustrating aspects of LC research that almost none of the research teams ever seem to look at what's already been found. They have their own projects and they do it in complete isolation from everything else. It's maddening.
Of course I'm just blown away by the fact that it seems the same issue that means real treatments aren't being invested in - too much risk whilst we don't know the mechanism, which I assume is partly due to harm potential? and maybe some due to them not being able to predict whether it will be profitable long-term (if it turns out it helps but the mechanism was totally different so gets eclipsed by something else)? is the exact reason that the rehab stuff keeps pushing harmful treatments and misinformation about our very intimate identities as personality etc. Because 'therapist-based' is somehow loopholed out of having to measure harms, which means whether they actually do harm or not they make the proof impossible to obtain and won't acknowledge it. The 'don't know the mechanism' has led to not being interested to speak to patients to find out what's going on being sponsored but random models based on no insight being said with utter determination as if they were true - which would be fine if that was so that they can be tested definitively with strong null hypotheses, but they aren't. So they aren't even using them to get closer to 'truth' or 'knowledge'. I understand that theoretically the £ss involved are different for researching in one area vs the other. However, in truth the last decade + has actually just been one giant experiment with a HUGE amount of money and training invested in training people up eg for IAPT long term condition stuff, functional initiatives and the latest rehab rebrand. With what has often seemed no intention for it to be measured honestly. So the only difference there is the regulations and measurement system. And then being able to do a flouncys ales pitche claiming 'cheap at any cost' whilst faking figures to claim 'because it could cost a lot if we were hte people who went to the doctor or hospital a lot (but I don't think we are, I think that is a lie and a switch and bait)'. Anyway, it seems one area disbenefits from medical systems that don't record things properly and aren't trying to group patients into sensible homogenous categories to enable some sort of research and making sure that follow-up measurements are actually useful and can't be nonsense. And another area is thriving on it. Because they can fill in the gaps with anything. If we step aside from the condition-specific for a moment, was the 2021 ME/CFS Nice guideline where they actually went through the therapist-based research without prejudice and assessed against basic standards - as happened for the other research (and other stuff on top due to regulations) pretty massively significant for these companies? Because it feels like they are hindered by this groundwork they'd need, which would in the past have been done by a medical system having decent notes and facilities for specific diseases at least starting to build these basic recruitment samples and clues to see if there are any groups that do have findings of one sort or another. HOw many diseases in the past could have been tackled with this basic removed from underneath them?
OK that's interesting because I assume from the UK that the focus was very much on the 'covid' and trying things that 'saved lives' , maybe some useful stuff from the clinics that included people who had heart, lung etc siphoned off for research and treatment in the 'long covid' larger category. What do I need to be reminded of or have missed that has been looked into regarding either the actual virus and body's reaction either in covid or long covid? I remember a big announcement that dexamethasone had been found to help, based on them running different drug trials in those acutely ill and watching outcomes. Maybe I'm cynical but I just felt like sadly the ME/CFS infrastructure that they were wondering what they were going to do with if rehab was no longer going to be able to be pushed at that just got rolled out like a well-oiled machine pretending to be adapted to look specific for LC, but just repeating the same old steps we've seen before. I'd also be intrigued what tests were done that had much likelihood of finding anything in anyone who didn't have one of the few red flag diseases those 'basic tests' cover. And I'd be intrigued if someone knows where that list of tests comes from - whether it is the QOF for GPs (so check for diabetes, blood pressure) + a few red flag things, maybe vit D if that's trendy at that time because those tablets are cheap etc. or if the FBCs or whatnot give any kind of picture or clue of 'general health' and 'where any issue might be'. Is there any health system that anywhere, even just the odd hospital or region etc, has been running some sort of battery you could actually call insightful to give a picture of what's right vs what's wrong in LC bodies? Or things that might be cropping up enough in significant minorities it might be a clue etc.
Random testing of things is the only method we have for ME at present. I've blindly stumbled across several treatments for my ME: cumin, iodine/T2, carnitine, eggs (prevents insomnia cause by exertion) and conjugated linoleic acids (reduces nighttime wakings). There were a few others that helped, but only for a short time. Aside from carnitine, which I theorized might help my intolerance to fatty acids, the others were complete surprises. Most of the treatments found pre-science must have been found the same way, since they didn't have theories to base predictions on. I'm still hoping that some person with ME somewhere will stumble across some weed or mold that effectively treats their ME and works for most PWME. I recently ate a bunch of wintergreen berries (it wasn't for their flavour) just to see whether they might be that magic treatment (sadly, no effect). Neither did the various vegetation leaves I tried (raspberry, wild rose, plantain, a few others), at least for the small amounts I ate. The probability of finding something this was is low enough that I'm not tempted to eat bark beetle larvae,rotting vegetation, or other unpleasant things. With millions of PWME, spread all over the world, trying various things in their locales, there's at least a chance of someone finding something.
I think that testing of more-or-less random chemicals (foods, herbs, etc) does have potential for finding a treatment for ME. Of the treatments that worked for me, most had a dramatic effect within 24 hrs. Diseases that need weeks or months for a treatment to show an effect are not viable for this method, but ME is. ME can abruptly switch off (temporarily at least), and that happened to me from at least three chemicals that seem unrelated, so it's not like a lock with a really complex and specific key. Today's rapid development of medical technology may find the mechanism behind ME in not too long a time. If this was the 1950's instead, I'd definitely consider testing all non-harmful foodstuffs and drugs on PWME (volunteers!) as more likely to succeed than looking for the mechanism behind ME (and then having to develop a safe treatment).
