Research in pandemic times

[Cheshire]

Against pandemic research exceptionalism
Alex John London, Jonathan Kimmelman

The global outbreak of coronavirus disease 2019 (COVID-19) has seen a deluge of clinical studies, with hundreds registered on clinicaltrials.gov. But a palpable sense of urgency and a lingering concern that “in critical situations, large randomized controlled trials are not always feasible or ethical” (1) perpetuate the perception that, when it comes to the rigors of science, crisis situations demand exceptions to high standards for quality.

The perception that core methodological components of high-quality research are dispensable is underpinned by three problematic assumptions. The first is that some evidence now, even if flawed, seems preferable to expending greater resources on more-demanding studies whose benefits only materialize later. Because the window for learning in pandemics is often short, the need to “balance scientific rigor against speed” seems inevitable (3).

The problem with this view is that challenges that rigorous methods address do not disappear in the face of urgent need. Small studies that build on basic science and preclinical research in early phases of drug development routinely generate signals of promise that are not confirmed in subsequent trials. Even when new drugs are established to be safe and effective, rarely are their benefits so massive that they can be detected in small, open-label, nonrandomized trials.

https://science.sciencemag.org/content/early/2020/04/22/science.abc1731

 

[rvallee]

More peripheral to the topic but also kind of very relevant:



Ultimately I think this is what will make all the difference, how many medical professionals go on to develop PVFS and how many of those develop ME. It's easy to cast off "those patients" to the loopy bin of psychosomatics. Much harder to do with colleagues one respects. Then again, maybe it will, but for institutions it's a lot harder as loopy bin or not, if they aren't going back to work it's a huge direct loss, especially for public health systems. At >$1M a pop, physicians are expensive to train. All that becomes a direct operational loss when they can't work anymore. Usually medicine does not see those direct costs, of how expensive it is to raise an educated adult taxpayer, only to have them barely work for their entire adult life.

I'm still reading the COVID19Positive forum. Mostly a trickle of dozens of posts per day but the trends mostly remain. What I'm seeing most lately is PEM, though in different words. People saying they were getting better, tried to exercise and relapsed for days. Separate from shortness of breath and lung problems, though there are plenty of those. So much dizziness and neuralgia, too.

My impression so far is that PEM is a core symptom of COVID-19. Like, big time. The way some patients describe it it's almost spooky how they use the same terms and language. It definitely confirms that at the very least, COVID-19 should be a serious target of research for how much the overall symptom presentation resembles ME, how it persists so much longer than it should, how it causes overall increases in ALL symptoms following exertion, not just post-exertional fatigue. There are clear differences in the symptoms themselves, it looks especially hard on lungs, but the fluctuations, unpredictability and PEM are very similar.

One thing I do notice is how some see PVFS as a better alternative than remaining sick with COVID, mislead to think it only means fatigue and not pretty much the same as continuing to be sick with COVID. Poor them. There are going to be many suicides if things aren't cleared up, even more so if the BPS framing succeeds at poisoning the well. People need to know things can get better, seeing the dire state of confusion and under-funding of ME research will be devastating to many.

 

[lunarainbows]

More peripheral to the topic but also kind of very relevant:



Ultimately I think this is what will make all the difference, how many medical professionals go on to develop PVFS and how many of those develop ME. It's easy to cast off "those patients" to the loopy bin of psychosomatics. Much harder to do with colleagues one respects. Then again, maybe it will, but for institutions it's a lot harder as loopy bin or not, if they aren't going back to work it's a huge direct loss, especially for public health systems. At >$1M a pop, physicians are expensive to train. All that becomes a direct operational loss when they can't work anymore. Usually medicine does not see those direct costs, of how expensive it is to raise an educated adult taxpayer, only to have them barely work for their entire adult life.

I'm still reading the COVID19Positive forum. Mostly a trickle of dozens of posts per day but the trends mostly remain. What I'm seeing most lately is PEM, though in different words. People saying they were getting better, tried to exercise and relapsed for days. Separate from shortness of breath and lung problems, though there are plenty of those. So much dizziness and neuralgia, too.

My impression so far is that PEM is a core symptom of COVID-19. Like, big time. The way some patients describe it it's almost spooky how they use the same terms and language. It definitely confirms that at the very least, COVID-19 should be a serious target of research for how much the overall symptom presentation resembles ME, how it persists so much longer than it should, how it causes overall increases in ALL symptoms following exertion, not just post-exertional fatigue. There are clear differences in the symptoms themselves, it looks especially hard on lungs, but the fluctuations, unpredictability and PEM are very similar.

One thing I do notice is how some see PVFS as a better alternative than remaining sick with COVID, mislead to think it only means fatigue and not pretty much the same as continuing to be sick with COVID. Poor them. There are going to be many suicides if things aren't cleared up, even more so if the BPS framing succeeds at poisoning the well. People need to know things can get better, seeing the dire state of confusion and under-funding of ME research will be devastating to many.

I have noticed this too, but from anecdotal reports. Doctors on twitter. Talking about how it’s been over a month since they’ve had COVID-19 and still so exhausted. The shortness of breath which comes upon the smallest exertion, as well as exhaustion. And I’ve seen posts like “do you get this too?” And people commenting underneath saying yes. I have no idea what percentage of sufferers this happens to, but it seems to be happening to subset. What I don’t know is if it’s “just” going to be a post viral fatigue that goes away after a few months, as some people get that for glandular fever, but then only a smaller subset go on to develop ME. We will only know months down the line.

Separately, during infection with COVID-19 itself, some do describe PEM as well (smallest exertion, relapse); which is interesting.

 

[Mithriel]

The smallest exertion leading to relapse is not PEM as unique to ME. It is post exertional fatigue, as seen in post viral syndromes. If it is like normal post flu they will have the same thing happen with much the same amount of exertion whereas in ME you can be fine one day then another not manage anything.

Not wanting to minimize the experience and it may be a flaw in how we talk about PEM that it sounds the same. They will have moved from PVFS to ME when they go shopping, enjoy the outing then collapse and be unable to get out of bed three days later.

I think we need to work at distinguishing exactly what happens to us. I read descriptions and it does not match what happens to me. I try to put my experience into words but they do not come out the way I mean so when I listen to what I am saying it does not match my experience either.

Not saying people with ME never get that sort of fatigue but there are other elements involved.

 

[lunarainbows]

The smallest exertion leading to relapse is not PEM as unique to ME. It is post exertional fatigue, as seen in post viral syndromes. If it is like normal post flu they will have the same thing happen with much the same amount of exertion whereas in ME you can be fine one day then another not manage anything.

Not wanting to minimize the experience and it may be a flaw in how we talk about PEM that it sounds the same. They will have moved from PVFS to ME when they go shopping, enjoy the outing then collapse and be unable to get out of bed three days later.

I think we need to work at distinguishing exactly what happens to us. I read descriptions and it does not match what happens to me. I try to put my experience into words but they do not come out the way I mean so when I listen to what I am saying it does not match my experience either.

Not saying people with ME never get that sort of fatigue but there are other elements involved.

I don’t really feel I match the description you’ve given. Whether that means I don’t have ME or not, I don’t know.

But I don’t feel ok one day and then another not manage anything. The amount I manage is pretty much consistent as long as the exertion level or some other factor (eg sleep) doesn’t change. There is some small day to day variability but nothing huge. If I over exert physically, I get severe pain. If I over exert sitting up, I get severe migraines and nausea and feel like I’m about to completely collapse from the strange feeling in my head, and severe fatigue and wooziness. If I over exert cognitively, the migraines and exhaustion and weakness and eye pain as I’ve mentioned before.

For me usually I deteriorate immediately - over time I get better. I do sometimes feel worse the next day. But I won’t be ok for 2 days and then on the third day feel awful.

Edit: having said that though, I can continue to deteriorate over a number of days.. or weeks.

 

[Mithriel]

If your health is really bad all the time then you will not be able to see a delay before you get ill though it might be possible to detect if we had better tools. So not having the delay before feeling any ill effects does not rule out ME but having the delay is the only thing which can positively rule it in.

For patients, their illness must be taken as a whole, but I am talking about all the papers that have come out recently which are claiming that such and such leads to ME when they are only seeing PEM as the prolonged fatigue. They cannot claim that post covid19 is ME unless this is shown in at least some patients for instance.

For the same reason they will not be able to claim that a treatment cures or treats ME unless it has a positive effect in someone who has that symptom. Once a diagnostic test is found in people who experience the delayed PEM then it can be used for patients who don't have it and then we will be able to get to the bottom of everything and be able to define the disease properly.

 

[Mithriel]

I have been thinking about the post covid 19 problems. Dr Paul Cheney spoke about his heart transplant though I can't remember the ME context. He said that as soon as they gave him a new heart he was cured but it took him almost a year to feel back to normal because his body had to recover from the toll his bad heart had taken.

Even with a fairly mild viral infection the virus causes damage in the body. If the corona virus has gone from the body and you are recovered your lungs still have damage from where they were, the alveoli will not be functioning, your blood vessels will be inflamed even, dare I say, there will deconditioning from not exercising and lying in bed.

It would be stranger if people were back to normal quickly.

Some of the people may well develop ME, may already have it as I think it could be something that goes wrong while the virus is present, but any bad reaction to exercise the way we experience it in ME will be masked by the struggle to cope with a body devastated by the virus. Think of an invading army being driven out but the churned fields and bombed buildings still remain.