List of diseases with a known mechanism but no cure/treatment

[Jonathan Edwards]

So, will it still produce 200 unnecessary deaths if we make available drugs that's been proven safe enough in general?

What is safe enough? We used to think that drugs that killed one person in 10,000 or 1 in 100,000 from things like aplastic anaemia were the bad ones. Then it dawned on us that commonly used drugs like indomethacin and naproxen might be killing one person in 50 or maybe even more. Commonly used drugs have fairly common lethal side effects.

What I said was: try plausible ones first and then go down the list. I wouldn't get boxed in by the plausibility in this semi random experiment.

That sounds like sitting on the fence.

In my view you only try a drug if you really believe that there is a rationale that makes the chances of benefit significantly more than the chances of harm. I have made that decision twice in my career and both times it was worth it. Dozens of other times I have been sceptical about the value of trying a drug and in general I have been vindicated. It requires a huge amount of background knowledge, both clinical and scientific. The political pressures on medical science now are such that I see few people well paced to judge. Most cling on to tired old theories that might seem 'plausible' to them but which are full of holes.

We will know where to look for the right drugs fairly soon I think, so everything is telling us to wait a bit until we know what we are doing.

 

[Utsikt]

We will know where to look for the right drugs fairly soon I think, so everything is telling us to wait a bit until we know what we are doing.

Based on DecodeME? Or are there other sources of new info that you anticipate (other than your upcoming paper)?

 

[Jonathan Edwards]

Based on DecodeME? Or are there other sources of new info that you anticipate (other than your upcoming paper)?

Based on an overview of research activity.

 

[Utsikt]

Based on an overview of research activity.

That’s even more encouraging!

 

[Creekside]

I really don’t think the basic science has been done yet.

I wouldn't consider it even barely started. Decades of doing the same blood tests over and over doesn't constitute basic science. We still don't know why many of the symptoms are happening. We don't even have clear definitions of the symptoms. It seems that many researchers get hung up on their theory of ME, and when testing of that theory doesn't support it, they keep digging in deeper rather than moving on to a new hypothesis. That's not basic science.

 

[poetinsf]

Re: if the basic science has been done.

If the researchers on here says that we’re at least a decade behind other diseases, then I would be fairly confident in saying that the basic research has not been done properly and at a sufficient scale yet.

What would they have to do to do it properly? I think there was a thread about something like "what research would you do if money was no object?". I'll have to revisit and see what ideas there are. Frankly, I don't see many alternatives left other than drug trials.

 

[poetinsf]

Of course we know it doesn't work for everybody as this has been shown in multiple trials.

That is what I meant by frequentist science. The objective truth is black and white and p < 0.05 means black. (well, actually I don't know much about stats, so feel free to correct me). That may suit other diseases, but ME/CFS seems to behave unlike any other; each case appears to have personality to some degree. Given that, I think some subjectivity and first-person view is in order. If we strictly stick to the rigueur of science, ME/CFS does not exist, after all.

Whether or not something works is not a question of whether someone believes it works but depends on the evidence.

Evidence updates the belief, but it's still a belief until you get to p=1. Even then, some may say it's still a belief.

I'm really not sure what your argument is. People can do all sorts of esoteric things they want, they already do it and nobody is hindering them.

I'm arguing for a possibility of making that easier and more systematic. A platform for people to explore on their own would be nice, and it would be nicer if compounds are easily accessible on such a platform.

 

[poetinsf]

That sounds like sitting on the fence.

Exactly. To borrow @Creekside, it doesn't have to be one or the other. I'm normally a hardcore proponent of forming hypothesis and then testing, but ME/CFS is not like any other. Kicking it around and see what shakes loose should be one way to deal with something as intractable as ME/CFS.

In my view you only try a drug if you really believe that there is a rationale that makes the chances of benefit significantly more than the chances of harm.

Completely agree. In the absence of other devices however, drugs could serve as a tool to kick it around. As long as that is safe enough. And I haven't got a foggiest idea what that means in reality since I'm not a medical professional. I'm just throwing "safe enough" in there as an abstract concept.

We will know where to look for the right drugs fairly soon I think, so everything is telling us to wait a bit until we know what we are doing.

I'm glad you are optimistic. Too bad I don't share the optimism.

 

[Jonathan Edwards]

I'm just throwing "safe enough" in there as an abstract concept.

Hmm, yes. If we are arguing hard pragmatic realities, which we are, then abstract concepts tend not to cut it!

 

[Trish]

That is what I meant by frequentist science. The objective truth is black and white and p < 0.05 means black. (well, actually I don't know much about stats, so feel free to correct me). That may suit other diseases, but ME/CFS seems to behave unlike any other; each case appears to have personality to some degree. Given that, I think some subjectivity and first-person view is in order. If we strictly stick to the rigueur of science, ME/CFS does not exist, after all.

I'm not sure what you are arguing here. The trials of exercise based therapies for ME/CFS have uniformly failed to show benefit. Large surveys indicate when put into clinical practice these therapies cause harm.

Surely it is unethical for a clinic to offer it on the grounds of a few anecdotes from people who say it helped. If they are acting ethically they would have to warn their patients that nobody knows whether they will be harmed until it's too late, and there is no good quality evidence of any benefit. It's also not cost effective for clinics to offer something that doesn't help people improve, recover, or return to work.

A p value of 0.05 is not a black and white, true or false, it's a one in twenty probability that what is taken to be an effective a treatment may just be random variation in results from an ineffective treatment.

 

[poetinsf]

I'm not sure what you are arguing here. The trials of exercise based therapies for ME/CFS have uniformly failed to show benefit.

All that says is that the therapy doesn't work for enough people and those that improved *could* be by chance alone. It doesn't necessarily mean that it doesn't work for anybody. It only means that the therapy should not be recommended in general, or worse, imposed on.

I'm proposing the possibility that those that benefited by therapy X may not be by chance alone. It may be true that individual patients are free to try whatever they want. But it would be nicer to make it easier for them to experiment, with more tools in a more systematic way.

You could put all eggs in one basket and wait if you have the faith in the trajectory of ME/CFS research. I don't have such faith. I don't think it's a bad idea to facilitate first-person exploration in parallel.

 

[poetinsf]

Hmm, yes. If we are arguing hard pragmatic realities, which we are, then abstract concepts tend not to cut it!

No it doesn't. I meant abstract concept for me, to be concretized by practitioners like you.

 

[Utsikt]

I don't think it's a bad idea to facilitate first-person exploration in parallel.

I think it’s unethical to facilitate the exploration of treatments that are known to cause serious harm just because some patients would be willing to try them due to the level of suffering and disability they currently experience as a result of their illness.

 

[Kitty]

You could put all eggs in one basket and wait if you have the faith in the trajectory of ME/CFS research. I don't have such faith.

It's not about faith.

It's about knowing ME/CFS can always be made worse, and it's easy to fool yourself into thinking something's working when it's not, then choosing not to stake your health on a bet with woefully poor odds.

It's rational decision-making.

 

[Creekside]

I think it’s unethical to facilitate the exploration of treatments that are known to cause serious harm

Ah, but what about treatments that aren't known to reliably cause harm to PWME? After all, water is known to cause harm in certain situations. LDN causes harm to some PWME, but provides great benefits for others. Should trying LDN be discouraged because a few people suffered harm from it? What about an ordinary apple or carrot? I wouldn't be surprised if someone reported their ME getting worse after consuming one, while someone else reported benefits. I think this sort of risk/benefit judgment should be left up to the individual. I agree that there needs to be care to avoid biasing the data available for people's judgement: not just reporting some anecdotal recovery stories while hiding the reports of harm.

 

[Utsikt]

LDN causes harm to some PWME, but provides great benefits for others. Should trying LDN be discouraged because a few people suffered harm from it?

Yes because we’re waiting on results from ongoing trials.

What about an ordinary apple or carrot? I wouldn't be surprised if someone reported their ME getting worse after consuming one, while someone else reported benefits.

That’s a ridiculous example that isn’t worth discussing.

I think this sort of risk/benefit judgment should be left up to the individual.

The average individual doesn’t have the knowledge to make risk assessments like that. I certainly don’t myself even though I’ve work experience with risk assessments in other fields of work.

 

[Creekside]

That’s a ridiculous example that isn’t worth discussing.

Actually, it isn't, because our knowledge of the actual risks and benefits of something like LDN for ME is no better than our knowledge of the effects of apples or carrots. There are diseases understood well enough to make knowledge-based judgements, but for ME, that knowledge is still nearly zero. There are treatments that are known to be harmful to the body regardless of its effect on ME, so you'd need strong evidence of possible benefits to try those. Conversely, there are treatments that are well-known to be harmless ... except in the case of ME, where we have no idea whether it might be harmful for a given individual.

Regarding LDN and ME, I'm absolutely glad that I did give it a try, even though I had little confidence of it helping. I'd hate to have lost that benefit (blocked pain) because some bureaucrat decided everyone had to wait for the 20-year trial to produce results.

The average individual doesn’t have the knowledge to make risk assessments like that.

Sure they do. They can read some studies or discussions. Their knowledge and judgement may not be very good, but nothing is absolute. Even the top experts in those fields don't have adequate knowledge about effects of treatments on ME. I wouldn't want national level decisions (ban LDN for example) to be made based on discussions on PR, but for individuals to judge whether to try something I think it's better than committing suicide because there's no hope at all. There's a risk of harm by not trying treatments too, and no one knows enough about ME to perfectly judge the risk of harm from a treatment vs the risk from not trying it.

 

[Utsikt]

Actually, it isn't, because our knowledge of the actual risks and benefits of something like LDN for ME is no better than our knowledge of the effects of apples or carrots.

I don’t think that’s a true statement. The recent patient survey that Davis co-authored showed that some patients reported negative effects from LDN. I have yet to hear any ME/CFS patient mention harm from eating an apple or carrot, unless it’s in the context of allergies or food intolerances.

Sure they do. They can read some studies or discussions. Their knowledge and judgement may not be very good, but nothing is absolute.

‘Nothing is absolute’ doesn’t mean that most people’s knowledge is good enough to adequately assess the risks.

but for individuals to judge whether to try something I think it's better than committing suicide because there's no hope at all.

I would say that there are plenty of potential sources of hope outside experimenting with drugs for a condition we barely know anything about.

And there will never be a situation in which the only two options for a person is suicide and experimenting with treatments. If a person is suicidal due to their health and a treatment makes their health worse, the risk of suicide has increased.

There's a risk of harm by not trying treatments too, and no one knows enough about ME to perfectly judge the risk of harm from a treatment vs the risk from not trying it.

I believe this highlights our different philosophical perspectives, and maybe the source of our disagreement.

I put more weight on the risks and harm from providing an unevidenced and completely experimental treatment without a plausible scientific explanation, compared to the risks and harm of not providing said treatment.

 

[poetinsf]

It's about knowing ME/CFS can always be made worse, and it's easy to fool yourself into thinking something's working when it's not, then choosing not to stake your health on a bet with woefully poor odds.

It's rational decision-making.

That depends on your belief of the odds of your ME/CFS getting worse by X vs odds of the science coming through for you.

As much as some people think they know, both are no more than beliefs. Given that, the choice should be left to individual patients and either choice should be accommodated.

 

[poetinsf]

The average individual doesn’t have the knowledge to make risk assessments like that. I certainly don’t myself even though I’ve work experience with risk assessments in other fields of work.

This sure sounds like CBT/GET people: average patients don't have knowledge, so we the experts should shove it down their throat.

It is as unethical to deny people with intractable disease from experimenting with X as to impose Y on everybody, when X is known to be safe enough and Y is known to be harmful enough.