Entirely devoted to health news, STAT is much more than a medical update site like, say, Medical News Today. Not content to simply report the latest breakthroughs, STAT thrives on investigative reporting that gets behind the scenes and holds institutions accountable. Where else are you going to hear about herpes patients demanding more federal funding?
For its part, MuckRock, a non-profit – which collaborated with STAT on the long COVID article – has made it its mission to make government more transparent and accountable. Besides doing its own investigative work, MuckRock also provides a unique service by giving citizen advocates access to hard-to-find government documents.
A Year Ago
Over the past year and a half, STATs kept a close eye on the RECOVER Initiative. A year ago in March, it wrote that the NIH was “fumbling its first efforts to study long Covid.” It noted critics’ charges that RECOVER was “acting without urgency”, that it was not quickly testing treatments, and was “not being fully transparent with patient advocates and researchers”. Lauren Stiles of Dysautonomia International bemoaned the fact that “With a half-billion dollars, they could have run multiple clinical trials.”
Two dozen COVID-19 experts released a report noting that, of the 200 long-COVID studies registered on a federal database as of February 2022, only eight were NIH-funded. They concluded: “There is no urgency to get rapid answers to basic questions to guide public health and patient care decisions”. The opaqueness of the project – it was impossible to tell what was actually being done – lead one researcher to call the Initiative a “black box”.
In May of last year, Betsy Ladyzhets in “The U.S. has had the most covid cases in the world. Why isn’t it doing more to study long covid?” reported on how poor the U.S. was at doing large clinical trials and pointed to a 40,000 person effort that was rapidly produced in the U.K. in response to the coronavirus pandemic. She noted that over 50 patient organizations had joined the Patient Lead Research Collaborative in an open letter to RECOVER that cited its opaqueness, lack of patient engagement, and the Initiative’s dearth of ME/CFS and dysautonomia experts.
RECOVER subsequently met with the group but RECOVER is still short of experts in post-viral research. Dysautonomia, for instance, clearly plays a major role in long COVID and ME/CFS yet Ladyzhet reported in “Five Reasons Why Long COVID Research is so Difficult” – posted on her COVID-19 Data Dispatch blog – that while RECOVER was piling on cardiologists, it was neglecting to bring in dysautonomia experts. Dysautonomia International’s founder, Lauren Stiles, stated that “Right now, there are three people with [dysautonomia] expertise on these committees,”.
A Year Later
Citing the slow pace of RECOVER trial, MuckRock gave long COVID patients a place to voice their concerns in November, 2022. STAT was back in December, 2022 with, “After nine months, an update on NIH’s long Covid research“, and some good news. Enrollment – a big problem earlier in the year – was dramatically up. But when STAT – in collaboration with MuckRock – returned to RECOVER a year after its first article, though, with a fuller update by Rachel Cohrs and
The NIH has poured $1 billion into long Covid research — with little to show for it“, had some familiar themes – the glacial pace, no patients in treatment trials, the opaqueness – was still there and now a new concern had popped up – was the money running out before RECOVER could fully assess treatments?“
Not Just About Long COVID
It should be noted that the RECOVER Initiative is not just about long COVID. Yes, people with long COVID are eagerly awaiting its results, but so are people with chronic fatigue syndrome (ME/CFS), post-Lyme Disease Treatment Syndrome (PLDTS), postural orthostatic tachycardia syndrome (POTS), and anyone with a post-infectious illness – and that includes many autoimmune diseases. That list is actually growing: studies are showing that COVID-19 is upping the risk of coming down with many illnesses. The RECOVER Initiative is our best chance to learn what happens during an infection that can cause so many things to go screwy.
I don’t think anyone expects RECOVER to quickly solve long COVID and wrap everything up with a nice bow, but real progress and providing some decent treatments – yes. With a big price tag ($1.15 billion) – which dwarfs any other long-COVID project initiatives by at least ten times – comes big expectations.
Two and half years later, with the RECOVER Initiative failing to provide anything even remotely significant, it’s no surprise to see investigative reporters asking – what the heck is going on? I’m surprised more haven’t, actually.
$1 Billion Dollars…
Note the title of the investigative piece: “The NIH has poured $1 billion into long Covid research — with little to show for it“. It doesn’t say the NIH will pour a billion dollars into long-COVID research – it says it has already poured a billion dollars into RECOVER. (Actually, it’s probably about $811 million.) It makes sense. Congress gave the NIH $1.15 billion over four years and we’re almost 2 1/2 years into the program. (Working at what was truly lightning speed for them, it took the NIH a year to get the program together; after that, they started enrolling patients).
So, almost a billion dollars later, we have a handful of papers and one clinical trial that’s been announced – and postponed repeatedly. The STAT/MuckRock piece reported that RECOVER – in response to upsets regarding the slow pace of the initiative a year ago – told Congress that it expected to launch trials by fall. Then it was by the end of the year. Then it was the first quarter of 2023 – now it’s summer.
Despite the largesse Congress unfolded on the NIH, some signs suggest RECOVER may even be having some money problems. A patient registry – a key infrastructure part of any large-scale disease effort – still isn’t in existence and is currently being reassessed. A RECOVER advisory committee responsible for ranking and evaluating potential treatment options was put on hiatus “due to a lack of funds”. Despite allocating $172 million to clinical trials, RECOVER told Congress in June that it didn’t have enough money to test the full range of treatments for long COVID.
An NIH Lifeline? Not a Chance
Of course, there is the NIH. Could it and its 51.1 billion dollar budget help out with long COVID? Not a chance. Prior to the Congressional allocation, as other federal funders were feeding money into long-COVID research, the NIH simply ignored long COVID. There’s something seriously wrong when the biggest medical research funder in the world sits out the first year or so of post-pandemic illness affecting tens of millions. Could the NIH atone for past sins and throw long COVID some cash?
Not likely. In a response to a question from STAT, the acting NIH director noted that: a) it was hoping that Congress would allocate more funds to long COVID; and b) in any case, in order to do that, it would have to redirect funds from other diseases – which it clearly is not going to do. (The NIH apparently does not have a rainy-day fund…) For now, RECOVER is on its own. (If it can’t make do with over 1 billion dollars, one wonders how eager Congress will be to give it more money.)
That’s how the NIH rolls, though. It depends on Congress almost entirely for new initiatives. Absent that it’s hands off, and if neglected diseases that can’t get researchers interested in them, or they can’t muster enough Congressional support to force the NIH to spend money on them – well, too bad. That approach – which the NIH has apparently never tried to change – probably leaves at least 50 million people (fibromyalgia, ME/CFS, POTS, IBS, migraine) without anything close to adequate medical research funding.
On the ME/CFS end, the NIH could, for instance, give the RECOVER Initiative some money to include people with ME/CFS in it. Getting ME/CFS patients into RECOVER is a golden, once-in-a-generation opportunity to cheaply jumpstart the ME/CFS field – get data the NIH can trust (it doesn’t trust work done outside the NIH) and build on – yet for some reason, it can’t muster up the ability to do this completely sensible, cost-effective thing. Former NIH Director Francis Collins said – “Watch Us. We’re serious about ME/CFS”. Well, we are watching you and you’re clearly not.
For its part, the Biden Administration’s promise to create an Office of Long Covid Research and Practice to oversee federal long-COVID efforts is nothing more than a promise at this point. They say they will try next year.
The truth is we just don’t know what’s going on in RECOVER. RECOVER could be doing all sorts of amazing research, could be on the brink of important findings – and we’d never know. We know lots of smart people are involved. We know considerable thought was put into RECOVER, that it’s been “built for the long term” and is designed to produce lasting results, but the Initiative is pretty much a black hole. We don’t know what decisions are being made or who is making them. All we can do is wait and hope that the Initiative is making real progress.
Lauren Stiles, the founder of Dysautonomia International who actually serves on several RECOVER committees, stated that even within the confines of RECOVER, she can’t tell what’s going on. She told the authors, “There’s a complete lack of transparency. When we ask who made this decision … they won’t tell us”.
We have general estimates of funding for clinical trials, research, and administrative costs (which, thankfully, seem pretty low) but that’s it. This is partly due to the RECOVER outsourcing large parts of the Initiative to outside universities, but even within the NIH, the situation is opaque. RECOVER, for instance, funded $37 million dollars of outside research grants but has yet to post the details of those grants – their size, their scope, their duration. As an example of how foggy things are over there in RECOVER land, the NIH hasn’t gotten around to tracking long-COVID spending in its Estimates of Funding for Diseases and Conditions for publication.
Let’s just hope that the current information on clinical trials is not reflective of the RECOVER Initiative’s approach. It was bad enough that RECOVER is planning to pump considerable amounts of money into a graded exercise trial. What was even worse, though, was how uninformed the clinical trials group was. In other words, they hadn’t done their homework and were about to push out a trial that could have caused real harm and done damage to the Initiative itself.
The authors reported that NIH program officer Antonello Punturieri “pushed back on the concerns” regarding exercise by citing clinical guidelines from the World Health Organization and a U.K. agency – both of which, get this, recommended against exercise for people with ME/CFS. Keystone Kops, anyone? Punturieri, by the way, is a chronic obstructive pulmonary disease (COPD) expert who apparently knows little about the history of the biggest cohort in his clinical trials group. (Exercise is good for COPD.)
An email from inside RECOVER suggested that the clinical trials group simply wasn’t up to snuff on the signature symptom (post-exertional malaise (PEM)) in its largest cohort. After learning that, whoops, exercise might actually be harmful in the huge ME/CFS-like cohort of patients, RECOVER apparently went back to the drawing board and is revising the trial. It’s clear that since few experts in post-infectious diseases exist outside of the ME/CFS, and ME/CFS experts aren’t exactly in leadership positions, RECOVER is prey to experts in other fields who don’t do their homework.
Unfortunately, the clinical trials picture got even less exciting when the STAT/MuckRock paper reported that another one of the five clinical trials RECOVER is going to run (that’s right – 5 clinical trials total) is going to feature “cognitive retraining”. Instead of trying to fix the problem, RECOVER is apparently going to spend money nibbling around the edges of it with exercise and “cognitive retraining” trials.
These kinds of yawn-inducing, move-the-needle-forward inch-at-a-time efforts will only serve to bolster the critiques of the NIH that led to the formation of the new Advanced Research Projects Agency for Health (ARPA-H) (or anti-NIH) agency. RECOVER was the opportunity for the NIH to show that it could be nimble and innovative. Thus far, it’s not working.
Longtime NIH reward recipient Eric Topol, who presumably knows the NIH quite well is certainly not happy. He authored a paper on possible long COVID treatments and told the authors he’d expected the NIH would have launched many large-scale trials by now. He stated, “I don’t know that they’ve contributed anything except more confusion”. Ouch…
Update! RECOVER Announces 1st Slate of Treatment Trials
What We Do Know
We know that RECOVER has enrolled about 12,000 out of the 15,000 adults it wanted to enroll and has published around ten papers. One was a review of possible mechanisms that thankfully fully incorporated ME/CFS into it. Many of the others are electronic health records (EHRs) analyses that appear to be useless for identifying the ME/CFS-like cohort, perhaps because EHRs don’t capture post-exertional malaise, often don’t include fatigue, and don’t assess ME/CFS, POTS or other neglected diseases that make up the ME/CFS long-COVID cohort.
We know about the protocols – we know it’s a three-step process that ends with a limited number of people getting an intense examination. How many, we don’t know. We know that people in the first two tiers are being assessed for ME/CFS, fibromyalgia, and POTS as well as post-exertional malaise, Epstein-Barr virus, getting autoimmune tests, simple tests of coagulation, etc.
We know that people who get to the 3rd tier are getting a real workout. Among many other things, they’re doing:
- a tilt-table test,
- sleep study,
- lumbar puncture,
- full cardiopulmonary exercise test,
- complete neurocognitive testing,
- MRI (of some sort),
- tests of blood vessel health (Endopat),
- proteomics (Serum protein immunofixation eletropheresis+),
- evidence of muscle damage (CPK, aldolase, myositis panel+),
- nerve damage (neurofilament light chain+),
- intestinal inflammation (fecal calprotectin+),
- gut motility,
- nerve conduction,
- muscle and skin biopsy,
- STAT News is a health industry website that reports on everything from the latest medical advances to industry practices. With its focus on investigative reporting, last year it reported on the glacially slow pace, the lack of treatment trials, and the opaqueness of the $1.15 billion dollar RECOVER Initiative.
- A year later, it’s back with the same themes. Remarkably, no patients are in treatment trials, RECOVER is still as opaque as could be, and almost 2 1/2 years later, it has yet to produce anything significant.
- Plus, there’s a new worry. With almost a billion dollars spent, some signs suggest that RECOVER may be having money problems. The patient registry was never built, an oversight office was closed down due to lack of funding, and RECOVER has told Congress the $172 million it’s allocated for clinical trials isn’t enough to fully assess the treatment options for long COVID.
- On the treatment front, the Paxlovid trial has been repeatedly postponed and two other trials in formulation, exercise, and cognitive retraining suggest that RECOVER has not done its homework and is plowing its scarce funds into very, very low-hanging fruit.
- Despite the fact that the ME/CFS cohort makes up about 50% of long COVID, the clinical trials group apparently didn’t know about the disease’s signature symptom – post-exertional malaise – and has been forced to go back to the drawing board for the exercise trial.
- The slow pace and weird choices for the clinical trials have outraged critics who complained a year ago that RECOVER was way behind on the clinical trials front.
- RECOVER has also been likened to a black box. We don’t know exactly where the money is going or what RECOVER, except in the broadest terms, is doing with it. That makes RECOVER difficult to assess, but STAT News believes RECOVER has spent the bulk of its money on observational studies and may not have much left for studies trying to find the mechanisms behind long COVID.
- On the bright side, enrollment in the RECOVER Initiative is up. We know that the Initiative was built for the long term and was designed to produce lasting results. We know a lot of smart people are involved. We know enrollment began about a year and a half ago, and studies take time to produce and write up.
- It’s possible that RECOVER is uncovering amazing things that we just haven’t heard about yet. We won’t really know how RECOVER is doing for the next year or two. Let’s hope the news is better then.
That’s a lot of stuff, but it also leaves a lot out: metabolomics, gene expression, magnetic resonance spectroscopy, SPECT scans, assessing Sjogren’s syndrome (tear production, saliva production or antibodies), extensive coagulation testing, and testing for blood flows to the brain. Since things like gene expression and metabolomics are mainstays of medical research, I think we can assume they will be done, but when is another question.
This, of course, is just the first cut. The big question is what about the second cut? It’s in the second cut – where researchers test hypotheses and try to understand the mechanisms behind the illness, that the big progress is going to be made, and that’s where it gets a little scary.
The authors reported that the RECOVER Initiative has “spent the majority of its money on broader, observational research.” Observational research – collecting just as much data as you can – is, of course, the first step in understanding a new disease like long COVID.
The second and crucial step, though, is designing hypotheses and testing them in an attempt to get at the mechanisms of the illness. I asked Betsy Ladyzhets, one of the authors of the STAT/MuckRock piece, if that statement meant that RECOVER had used a big chunk of its wad on observational data. Her understanding was, yes:
“For the observational study: my understanding is that yes, the main RECOVER cohort is primarily focused on collecting symptom data and following patients over time rather than digging into mechanisms.”
That would be unfortunate, indeed. The long-COVID cohort RECOVER is following – 15,000 people, so far, with a goal of over 25,000 people – is immense. Are the observational studies sucking up much of the money Congress gave to RECOVER? Or has RECOVER laid by a big chunk of change for getting at the mechanisms of the illness? One has to assume that it has. The problem is that we just don’t know. RECOVER is so opaque that it’s impossible to know where it’s putting its money.
Still Early in the Game
It should be noted that in many ways RECOVER is still just beginning. It didn’t start enrolling patients until Sept 2021 and quickly fell behind schedule. It may still not have enough patients and healthy controls to do the studies it wants. (The authors noted that symptom assessments are being dogged by a lack of healthy controls.) It may be waiting for enrollment to get to a certain level before it starts analyzing its data.
Plus, studies take time to get produced, written up, and published. We’ll know a lot more regarding RECOVER over the next year or two. For its part, Betsy Ladyzhets reported that RECOVER is “clearly aware of the many criticisms from scientists, patient advocates, etc.” that it’s received.
In a year, we may think the RECOVER Initiative is the best thing since sliced bread. Let’s hope so. A lot of people are counting on it.
- Please encourage STAT News and MuckRock to continue keeping an eye on the RECOVER Initiative by clicking on the article – The NIH has poured $1 billion into long Covid research — with little to show for it“. Their work is continuing. MuckRock is in the midst of a long Freedom of Information Act (FOIA) process regarding the RECOVER project and we can expect an upcoming story with Science News. It’s great to have journalists keeping an eye on long COVID.
- If you have long COVID and feel the state or federal response to long COVID has not been adequate fill out an engagement form here and tell MuckRock why
- Sign up for Betsy Ladyzhets COVID-19 Dispatch blog here to stay on top of RECOVER news.
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