David Tuller: Trial By Error: “Talk is Cheap,” Patients Tell NIH

Good suggestions, @Jonathan Edwards . Some of the issues that you address are discussed in detail in the letter attached to the petition. One thing that I do want to mention is that, because RFAs are peer reviewed, they are only granted to the best in the field. The RFAs for the Cooperative Research Centers resulted in grants to Dr Hanson, Dr Lipkin and Dr Unutmaz - all excellent scientists.

A few of your suggestions don’t exactly fit the way that NIH does things. The letter was written by advocates with much better knowledge of the way that NIH works than I do.

Here is the detailed letter, if anyone has the energy to read through it!

https://www.meaction.net/wp-content/uploads/2019/10/NANDS-Report-Response_10-22-19.pdf

 

I would like to repeat my question here. Its not some kind of gotcha. It's a very genuine and important question.

I know that throwing funding at a problem doesn't automatically make it solved. But I have to think that if the NIH or CDC thought this was a public health emergency the way, say, an ebola outbreak in the United states was , that thwy would throw a ton of funding at the problem , but not just as a one time thing... And they would not stop until it's solved.

This is a noble thought but while there is basic science that can be done without much funding there seems to be still a connection between financial resources and ability to work quickly on a problem. Expensive equipment , more lab assistants, all these things that require more pay.

We will probably not see eye to eye on this, although I think we probably see eye to eye on one thing: that the existing literature for this illness is low quality and does not tell us that much about the illness. Which is why I think it's so urgent that we accelerate the pace of research.

You have your experience as a scientist that informs your viewpoint. I have the unfortunate experience to have severe ME. I can say honestly that I doubt I will make it another year with this disease if we do not see breakthroughs. I don't want false hope and i know at this rate nothing is coming. What I do hold onto is the possibility that , even if patients are not experts on science, they can somehow pressure government bodies to fund research into this illness at levels commensurate with the disease burden.

I do have to ask, if you had severe ME I wonder if your opinion on this would be different. Before ME, I had experienced many kinds of ordinary suffering, broken legs, fevers, broken heart, depression and anxiety--and this beats all of them by a mile. It's hard to even describe how hellish it is to have
to watch your life disappear and not have anyone around you do anything about it. I really thought of doctors as superhuman before this.

I guess I don't think that there are zero competent scientists in the field. While i share your opinions that research up to this point has been low quality I do think part of that is due to low funding. Low funding creates low quantity , low speed of replication , etc. I do think there are at least a few competent scientists in the field and I also think that generous grant grant opportunities could bring in the kind of scientists you're talking about --competent people from a different field without a particularly narrow focus on ME.

 

In my experience not. Unless you know exactly what you are looking for, which we don't.

 

I have been around long enough to know what you mean. For a year, my wife, who from my point of view was my life, became insane, because of a drug reaction. I had to nurse her because the health service could not provide care. I looked after a body from which the person I knew had departed. Fortunately, an able young psychiatrist found the solution and she is now completely well ten years on. But I assure you I have seen the bottom, with apparently no way out. My sister in law just said hang in. She was right. That is all I can pass on to anyone.

 

I don't disagree with that up to a point. But money isn't the key. Michael Neuberger, who worked out how B cells mutate DNA to produce different antibodies, said something to me that made sense. He was indicating that a clinical colleague we both knew was not going to achieve great things. He said that only a few people know how to keep on gnawing at the bone until it cracks open. Money distracts from that.

 

I could see how lavish spending could distract from that kind of intense problem solving outlook, but there is probably a happy medium that is probably not even close to being reached imo. I'm sure scientists need to eat and pay rent like anyone else and having decent pay and equipment to work on a problem that is otherwise somewhat unattractive (because there are few leads and so far little glory), makes it slightly more attractive. Even people who are very principled may be swayed by something like that

 

The question in cases like severe ME is always "how long is it rational to hang on". By your own estimation we are not very close to even having an etiology figured out, let alone any possible clinical applications which we could imagine will be several years out even if an etiology is figured out.

 

Rationality does not figure here.
I have had to hang in, in apparently impossible circumstances, three times over fifty years, once for a decade. It has paid off. That is all I can say.

 

There are many terrible illnesses and when I say ME is one of the worst i dont mean to minimize that in these other illnesses one can suffer in clinical limbo. Even in illnesses that have hundreds of millions spent on drug trials and that have many approved drugs sometimes someone is treated awfully and sometimes tries ten drugs without finding one that works.

But ME is one of the worst extremes in terms of not even having a single approved medication to treat it. And when i hear that people are working on this problem and there is hope it seems almost indistinguishable from what people were saying in the 1980s.

 

I agree but you could have said that about rheumatoid arthritis in 1990. By 1999 there were six highly potent new ways to treat the illness. Nobody knows when things will change.

 

I sort of agree. Reason is not an antidote to despair. It's sort of a problem beyond the realm of reason.

But on the other hand I like to frame this problem (of whether or not to hang on) in terms of rationality because there's a viable argument there, and because it is necessary in a defensive way, to dispel ideas that ME patients are offing themselves because they are simply maladaptive and insane (not that I have a negative view of mental illness , but the framing matters when you have a system that can commit people involuntarily because they are seen as not mentally fit). I instead think that, as taboo as it may be to say it, many of the people who take that route are seeing things fairly clearly. And there is a rational argument for it. There's also a rational argument for legalizing euthanasia or doctor assisted suicide in non terminal illnesses that are nevertheless incurable and lead to low quality of life.

Many patients with ME have cognitive PEM and some sort of cognitive impairment, but on the other hand the impairments are in very specific areas and don't necessarily completely block the ability to see things clearly, even if they often make normal life pace and tasks very difficult. If anything Id say the cognitive bias goes the other way--toward irrational hope. I mean, this is a very basic cognitive bias or reflex and i guess it's not always bad. Life isnt all about reason and this reflexive tendency toward hope keeps us alive. But at what point is that bias blinding us too much to the reality?

 

Clinicaltrials site shows 40 trials on Nalterxone are registered (all diseases), with a subset of those with LDN.
https://clinicaltrials.gov/ct2/resu...prcd_e=&sfpd_s=&sfpd_e=&lupd_s=&lupd_e=&sort=

Youngers one on ME/CFS at Alabama was suspended. (he did a previous one for fibromyalgia at Stanford)
https://clinicaltrials.gov/ct2/show/NCT02965768?term=low+dose+naltrexone&draw=2&rank=8

Kind of hard to do a blind trial as many people get disturbed sleep on it.

 

We all recognise that the problem is lack of research capacity and realise that there are unique factors leading to that, requiring a unique response from the NIH. The solution is to fund centres of excellence directly with RFAs. That is where pilot studies and the "happen upon" findings you mention are going to happen.

In the past, those "happen upon" studies were funded by "creative grant accounting", eg. using resources from other grants. That kind of corruption is no longer sanctioned in science, yet funding for such preliminary investigations still needs to come from somewhere.