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

[poetinsf]

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'll have to summon my analogy of getting lost in the wilderness again. If you believe the rescue chopper is coming soon enough, the best thing to do is to stay put. If not, however, you have to try to find your way back home on your own, because it's a certain death from hypothermia or starvation if you don't. The problem is, as you say, no one knows enough about ME to perfectly judge the risk one way or the other. Given that, it seems prudent to me to provide ways for individuals to try different ways, as long as they are known to be safe enough in general.

edit: rephrase

 

[Utsikt]

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

I strongly object to that characterisation of my arguments.

I have never said that the average patients don’t have knowledge about their disease.

I have said that they don’t have adequate knowledge about the medical treatments and all of the assessments that goes into calculating the risks vs benefits, in order to make those assessments on their own.

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.

You’re assuming that X is ‘safe enough’. Who has determined that and on what grounds? What’s the threshold for ‘safe enough’?

And what about the heterogenous nature of the patients - don’t we need to assess the risks on a case by case basis?

Most prescription drugs can be harmfull and many supplements can do damage under the right circumstances.

 

[rapidboson]

I haven't been following this thread closely, but to me it seems like these last few posts are basically just about different philosophies?

Some people are more risk averse and prefer not to take symptomatic ("experimental") treatments due to potential negative effects, while others prefer testing out different things to potentially improve quality of life.

Both are in a sense about keeping agency over their body and life, but are looking at the matter from different points of view. Emphasizing potential upsides or downsides.

I don't think there's anything inherently wrong with this on an individual level. I also don't think there's anything inherently wrong with presenting potential symptomatic treatments on an institutional level.

When it comes down to the patient trying a treatment (or not), a professional educated guess on potential upsides or downsides for the individual (based on their presentation of symptoms) should be a given.

 

[Utsikt]

I haven't been following this thread closely, but to me it seems like these last few posts are basically just about different philosophies?

Some people are more risk averse and prefer not to take symptomatic ("experimental") treatments due to potential negative effects, while others prefer testing out different things to potentially improve quality of life.

My disagreement is not caused by risk aversion. It’s caused by the responsibility we as fellow patients (and the providers) have for not causing harm.

When it comes down to the patient trying a treatment (or not), a professional educated guess on potential upsides or downsides for the individual (based on their presentation of symptoms) should be a given.

I don’t think that’s a given. There are plenty of doctors out there that are willing to prescribe most experimental treatments, and I seriously doubt that all of them do a thorough and impartial risk assessment. Partially due to the financial incentives of being known as someone that can get you access to treatments you want to try. That could be outright predatory behaviour.

 

[rapidboson]

My disagreement is not caused by risk aversion. It’s caused by the responsibility we as fellow patients (and the providers) have for not causing harm.

Sounds like risk aversion to me. Nothing is without potential side effects/harm. It's always about the balance between effects and side effects and what risks are ok to be taken given the patient's circumstances.
Potential pros and cons shall ideally be assessed on an individual case by case basis.

I take for you it might be irresponsible to offer somebody in pain a paracetamol without being 1000% sure they don't have any preexisting conditions, that might result in harm (e.g. liver failure). Fair POV, but not everybody's POV.

In the end it's an individual taking the final decision to either take or deny a treatment. And if they deem the potential benefits outweighing the potential risks or vice versa, it's on them.

I don’t think that’s a given. There are plenty of doctors out there that are willing to prescribe most experimental treatments, and I seriously doubt that all of them do a thorough and impartial risk assessment. Partially due to the financial incentives of being known as someone that can get you access to treatments you want to try. That could be outright predatory behaviour.

I'm saying it should be a given, as in it ought to be. Not that it is a given.

 

[Utsikt]

Sounds like risk aversion to me.

Risk aversion means to want to avoid risk. I’m not saying that we should avoid risk. I’m saying that we need to adequately assess the risks first.

I take for you it might be irresponsible to offer somebody in pain a paracetamol without being 1000% sure they don't have any preexisting conditions, that might result in harm (e.g. liver failure). Fair POV, but not everybody's POV.

Yes, of course we should ensure that they can take paracetamol, but I’m not saying that we have to be 1000 % sure of that. Or even 100 %.

When I started low dose beta blockers, my cardiologist asked me if I had diabetes. I said ‘not to my knowledge’. That, combined with my description of my symptoms made it very unlikely that I have diabetes. But I have not done any tests, so I can’t know with a 100 % certainty. But that’s fine.

In the end it's an individual taking the final decision to either take or deny a treatment. And if they deem the potential benefits outweighing the potential risks or vice versa, it's on them.

We’re not talking about the autonomy of the patients. We’re talking about if they should get access to any (restricted) treatments just because they want to try it.

As an example - do you believe that any patient that is willing to try cyclophosphamide should be allowed to try it? If not, where do you draw the line? And if you do - does there exist a line at all?

I'm saying it should be a given, as in it ought to be. Not that it is a given.

My bad. But that kind of proves my point. If we know that the medical assessments by the provider might be inadequate, we have a heightened responsibility to not push fellow patients towards potentially harmfull treatments.

 

[rapidboson]

Risk aversion means to want to avoid risk. I’m not saying that we should avoid risk. I’m saying that we need to adequately assess the risks first.

In my understanding risk aversion is a tendency to go for certain outcomes over incertain outcomes. It's not about always avoiding risk all together.

Just quoting quick google search: "Risk aversion is a preference for a sure outcome over a gamble with higher or equal expected value." or "(...) risk aversion is the tendency of people to prefer outcomes with low uncertainty to those outcomes with high uncertainty, even if the average outcome of the latter is equal to or higher in monetary value than the more certain outcome."

I think this can be transferred quite literally to the medical field as well.

One can only adequately assess risk so far - if there are uncertainties it will be an educated guess rather than a proper risk assessment. Where we'd loop back to risk aversion. Is a medical educated guess good enough? Depends on the case.

As an example - do you believe that any patient that is willing to try cyclophosphamide should be allowed to try it? If not, where do you draw the line? And if you do - does there exist a line at all?

The line is different on a case by case basis. Way too individual to give a clear answer. Should somebody with a 6-month old mild case of ME take it - probably not. What about somebody suffering severely for 35 years with the desperate wish to try it, even if it could make them worse? Maybe, depends on the case.

My bad. But that kind of proves my point. If we know that the medical assessments by the provider might be inadequate, we have a heightened responsibility to not push fellow patients towards potentially harmfull treatments.

As fellow patients, imho, we shouldn't push anybody towards any treatments. We can share experiences, give insights on our personal case but in the end it should be a professional suggesting a treatment and the patient deciding whether to take it or not.

 

[Trish]

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.

I think the key point here is whether the patient is provided with honestly presented impartial information. If a pwME is told that GET has been shown to have no long term benefit, no benefit to fitness, stamina or return to work, and thousands report long term deterioration, then I can't imagine any pwME wanting it. The problem there is false claims of expertise by clinicians.

The same applies to drugs and supplements. If a doctor sets out for a pwME the evidence or lack of it for harms and benefits, then it is up to the pwME to do their own risk/benefit decision making.

But there is also desperation to take into account. It's hard in the midst of pain and suffering to balance a small and possibly illusory chance of some improvement against the chance of even worse suffering.

I say illusory, because there seem to be far too many clinicians willing to say to patients that they know from their clinical experience that their favoured exercise routine or drug is effective when all they are basing it on is short term anecdotes from those patients who return, with no long term or comprehensive follow up and no clinical trial evidence.

 

[Utsikt]

In my understanding risk aversion is a tendency to go for certain outcomes over incertain outcomes. It's not about always avoiding risk all together.

Just quoting quick google search: "Risk aversion is a preference for a sure outcome over a gamble with higher or equal expected value." or "(...) risk aversion is the tendency of people to prefer outcomes with low uncertainty to those outcomes with high uncertainty, even if the average outcome of the latter is equal to or higher in monetary value than the more certain outcome."

As your quote says, risk aversion is to prefer a more certain option over a less certain option if the expected outcome is equal.

When we do a risk assessment, we essentially try to quantify the probability that any given event occurs and the the consequence of the event. When you sum the products of all of them, you get a value that represents the expected outcome.

If the expected outcome is negative and you don’t want to pursue it, that is not risk aversion. It’s only risk aversion if the expected outcome is zero or positive and you still don’t want to chose the less certain option.

However, the expected outcome is not the full picture, because you also have to consider the distribution of the severity of the consequences. An extreme example would be to play russian roulette for a billion dollars.

The expected monetary value of your life is probably far less than one billion dollar. So even just a 1/2 chance to die would make the expected monetary value of playing positive. But I don’t think anyone can argue that I’m overly risk averse if I don’t want to play, because I simply don’t want to risk my life and I might value non-monetary aspects higher than money.

The line is different on a case by case basis. Way too individual to give a clear answer. Should somebody with a 6-month old mild case of ME take it - probably not. What about somebody suffering severely for 35 years with the desperate wish to try it, even if it could make them worse? Maybe, depends on the case.

But that’s been my point the entire way - we can’t just say that people should (get to) try things, full stop. We have to do individual assessments.

As fellow patients, imho, we shouldn't push anybody towards any treatments. We can share experiences, give insights on our personal case but in the end it should be a professional suggesting a treatment and the patient deciding whether to take it or not.

Agreed, as long as we can trust that the professional is impartial. Which we rarely can, meaning that we have to be even more cautious, imo.

 

[Kitty]

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.

I don't know how the science comes into it, but for the record I've never thought it's coming to rescue me.

Even if I did, it's a struggle not to take offence that anyone would think for a second I'd be so selfish that it would affect my position on the social and medical ethics of this. I understand no offence is meant, and none's taken of course; I just need to point out how morally compromising that suggestion appears.

 

[rapidboson]

As your quote says, risk aversion is to prefer a more certain option over a less certain option if the expected outcome is equal.

When we do a risk assessment, we essentially try to quantify the probability that any given event occurs and the the consequence of the event. When you sum the products of all of them, you get a value that represents the expected outcome.

If the expected outcome is negative and you don’t want to pursue it, that is not risk aversion. It’s only risk aversion if the expected outcome is zero or positive and you still don’t want to chose the less certain option.

However, the expected outcome is not the full picture, because you also have to consider the distribution of the severity of the consequences. An extreme example would be to play russian roulette for a billion dollars.

The expected monetary value of your life is probably far less than one billion dollar. So even just a 1/2 chance to die would make the expected monetary value of playing positive. But I don’t think anyone can argue that I’m overly risk averse if I don’t want to play, because I simply don’t want to risk my life and I might value non-monetary aspects higher than money.

If the expected out come is of equal or higher value. You missed a crucial part of the definition.
It's obvious that anybody rational would take the certain option if the outcome is equal.

The thing is, as in our case there's many unknowns, the risk assessment is inherently imprecise. Hence the "expected outcome" is more of an educated guess and susceptible to individual/personal risk aversion. The risk aversion is baked into the risk assessment (due to de facto unknowns).

For some people taking mestinon or low dose aripiprazole might be too risky as there's the big unknown of short and long term risks/harm. For those opposed to taking these medications, the risk of potential harm (severity of negative consequences) is greater than their perceived potential benefit. For others who are less risk averse (due to whatever reasons, be it their medical history, their current physical state or just their personality), this is different - because the potential improvement in quality of life is worth it in their opinions.

 

[V.R.T.]

If the science does not 'come through' for us, what do we have really? Mild people might have a positive response to mestinon or ldn and go back to work with adjustments. The odd moderate or severe person might get better, mild again even with lda but does it last?

We don't have anything objective to base these decisions on. I have been prescribed mestinon by a private GP but I cannot bring myself to take it after reading accounts of people who took one or two doses and have become very severe.

I don't think this is a common experience but having been at least borderline very severe I will do anything I can not to go back.

We can be endlessly cynical about whether science will come through for us, and take blind risks. Or we can hope that things change and in five years the treatment landscape looks different. Or we can do both.

I don't think there is anything naive in believing that the science may come through for us. In fact I have a lot more hope in what has been said on here about drug targets and accelerated clinical trials than I do that I will get back to mild or even moderate by tinkering around with LDN and such.

 

[Trish]

I don't think this is a common experience but having been at least borderline very severe I will do anything I can not to go back.

It may not be very common to get as far as having a bottle of pills and not taking them, but I think it's very common for many of us to prefer our current state to the risk of a much worse state, even if it means we miss out on the chance of improvement. Especially when that chance of improvement is based solely on a few anecodes.

 

[Utsikt]

If the expected out come is of equal or higher value. You missed a crucial part of the definition.

It was included in the third paragraph even though I missed it in the first.

The thing is, as in our case there's many unknowns, the risk assessment is inherently imprecise. Hence the "expected outcome" is more of an educated guess and susceptible to individual/personal risk aversion. The risk aversion is baked into the risk assessment (due to de facto unknowns).

As far as I can remember, some experiments have shown that risk aversion is not correlated with the degree of realism in the perception of probabilities or outcomes. Risk aversion is about what you put more weight on after you’ve made an assessment if the outcomes and probabilities.

If there is uncertainty in regards to the effect of an outcome or the probability of an outcome, you can incorporate that in the calculations so that you end up with a range for the expected value.

It is only after that range has been calculated that you decide how you want to proceed. If the range (of a possible -1 to 1) goes from -0.05 to 0.25 with an assumed uniform distribution, you could be said to be risk averse if you decide to not go trough with it because the average is 0.1.

Or you decide to not go through with it because one of the potential outcomes are unacceptable to you, like severe worsening or death.

We obviously rarely use numbers in real life, but it makes it easier to explain what I’m talking about.

For some people taking mestinon or low dose aripiprazole might be too risky as there's the big unknown of short and long term risks/harm. For those opposed to taking these medications, the risk of potential harm (severity of negative consequences) is greater than their perceived potential benefit. For others who are less risk averse (due to whatever reasons, be it their medical history, their current physical state or just their personality), this is different - because the potential improvement in quality of life is worth it in their opinions.

Again, the perceptions of the probabilities and consequences are not substantially different. The difference lies in the weighting of the outcomes after an initial assessment and calculation has been made.

Edit: some even argue that risk aversion is more of a dislike of ambiguity than a dislike of negative consequences per se.

 

[Creekside]

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.

Food allergies and intolerances are part of ME. I probably reported that I was intolerant of malic acid (apples). Likewise carrots, while I was intolerant of fermentable fibre. Yet I'm sure "the experts" would insist that "apples and carrots are good for you". For ME, we simply don't have any reliable information about risk/benefits of any substance for an individual with ME. LDN has a risk of making ME worse, but there's probably also a risk (unknown value) of the person getting worse at that point because they didn't get LDN at the time when it could have helped avoid getting worse.

My point is that we really don't have any reliable expert knowledge about risks/benefits for ME treatments. A specific PWME can judge whether an expert is a better judge of which treatments to try or avoid, but even that isn't reliable because it's personal judgement of the quality of experts. We also don't know when proper knowledge of treatments will be available, so it's not a case of "just waiting a few more months or years". I certainly wouldn't want the burden of deciding to deny a potential treatment for someone who was suffering from severe ME just because a 20-year study of that treatment had just been announced--with no guarantee that the conclusion wouldn't be a wishy-washy "It helps as many patients as it harms".

Maybe a severe patient will provide their opinion on this topic. No, even that won't make a difference, because one might have gone from mild to severe due to a treatment, while another went from severe to mild because they tried a treatment.

My personal perspective is that I benefited greatly from trying different things, and never suffered serious consequences from any. However, I did mainly test non-risky substances, and the few risky pharmaceuticals I tried only a few doses of. Cyclosporin was probably the riskiest, and I just wanted to test whether reducing cytokine levels made a difference in symptom severity (it didn't).

 

[Utsikt]

Food allergies and intolerances are part of ME. I probably reported that I was intolerant of malic acid (apples). Likewise carrots, while I was intolerant of fermentable fibre. Yet I'm sure "the experts" would insist that "apples and carrots are good for you". For ME, we simply don't have any reliable information about risk/benefits of any substance for an individual with ME.

If we don’t have any reliable information about the risk of substances for pwME/CFS, you can’t also say that food intolerances are a part of ME/CFS. You can’t have your cake and eat it too.

Do some pwME/CFS experience food intolerances? Yes. But other people do that as well. Unless you have empirically robust evidence of a higher prevalence of food intolerances for pwME, all we can say it that we don’t know.

LDN has a risk of making ME worse, but there's probably also a risk (unknown value) of the person getting worse at that point because they didn't get LDN at the time when it could have helped avoid getting worse.

Do you think it’s reasonable to assume that the latter risk is greater than the former (let’s ignore the size of the effect for the sake of simplicity)?

I certainly wouldn't want the burden of deciding to deny a potential treatment for someone who was suffering from severe ME just because a 20-year study of that treatment had just been announced--with no guarantee that the conclusion wouldn't be a wishy-washy "It helps as many patients as it harms".

And I certainly wouldn’t want the burden of deciding that a patient could try a treatment that caused them long-term or permanent worsening. It goes both ways.

My personal perspective is that I benefited greatly from trying different things, and never suffered serious consequences from any. However, I did mainly test non-risky substances, and the few risky pharmaceuticals I tried only a few doses of. Cyclosporin was probably the riskiest, and I just wanted to test whether reducing cytokine levels made a difference in symptom severity (it didn't).

Do this mean that you only support experimenting with substances that could reasonably be perceived to be of low risk?

If that is the case, it would make this discussion a lot easier.

 

[Creekside]

Do this mean that you only support experimenting with substances that could reasonably be perceived to be of low risk?

Yes. IMO there hasn't been adequate evidence to support risky pharmaceutical treatments for ME. However, if a PWME really, really wants to try a risky drug, I think that's their choice, although they should get proper data on the risks involved, not just "I read about it on a forum!"

Do you think it’s reasonable to assume that the latter risk is greater than the former (let’s ignore the size of the effect for the sake of simplicity)?

No. There's just not enough data to support any judgement about risks for LDN for PWME.

As for your earlier suggestion to wait for Dr. Davis's LDN study result, I expect that after however long people wait for it, the result will likely be "Of 30 patients, 3 had reduced symptoms (different symptoms in each patient) and 3 had worse symptoms (again, different symptoms in each)." So, the end result would be still pure guesswork as to what the effect LDN would have on a given individual. I'm not sure how large of a study would be required to give people a significantly better chance of getting good results rather than bad ones.

If we don’t have any reliable information about the risk of substances for pwME/CFS, you can’t also say that food intolerances are a part of ME/CFS.

The CCC includes "New food sensitivities, medication sensitivities and/or chemical sensitivities". I agree that we don't know for sure that food intolerances are definitely part of ME, but that uncertainty applies to the rest of the CCC as well, since we lack adequate data. For that matter, there's probably not much absolute surety in medicine in general. You might test Ibuprofen on 100k people with no fatalities, then discover someone who had a fatal reaction to it.

Then we can argue about the definition of "low risk". Is a bad reaction from LDN in 1/10000 patients low risk, or is your definition 1/10000000?

 

[Utsikt]

Thank you for clarifying!

However, if a PWME really, really wants to try a risky drug, I think that's their choice, although they should get proper data on the risks involved, not just "I read about it on a forum!"

I don’t think I’d ever support a hail mary unless the patient was on track to die (of other causes than suicide because that’s a different ethical scenario).

Then we can argue about the definition of "low risk". Is a bad reaction from LDN in 1/10000 patients low risk, or is your definition 1/10000000?

Depends on the consequence. If bad = death or permanent worsening, it would have to be pretty rare. How rare would depend on the excess mortality/harm of other ‘normal’ medications, measured in something like lost DALY per person year of usage or something like that.

It would obviously be impossible to get those numbers for pwME/CFS, so we would have to go by estimates from other conditions.

 

[Kitty]

If bad = death or permanent worsening

Which of course can be the consequence of anything. Things that don't normally cause severe reactions. Things that don't normally cause any reaction, until suddenly they do.

That's why responsible medical practitioners are so unwilling to experiment on patients, or to prescribe drugs for self experimentation. They know of cases where very low risk drugs caused death or devastating impairment, and the fact that it was so unlikely it couldn't have been foreseen doesn't help that person in the slightest. It doesn't remove the cost to society of their death or disability.

I'm still reluctant to accept that ME/CFS can be made a special case, one that's allowed to sit outside normal medical ethics.

I'm also still worried about the social ethics of encouraging experimentation on the public internet, where you can never be sure who's reading it.*

Yes, maybe we should be able to have spaces where grown adults can bat these things back and forth. There's a good argument for that, of course there is. But I keep pushing back because I can't help worrying that people may be persuaded that experimentation is reasonable, not because they understand the risks and ethical ramifications, but because they're inexperienced, or easily influenced, or are parents so desperate to help their sick child they'd willingly sacrifice a limb if they thought it would help.

So if I sound a bit arsy (which I do sometimes, I know!) that's why.


* I don't think using a members-only forum makes much practical difference in groups where the presumption is to approve people who ask to join, if it appears they have a genuine reason for being interested and agree to abide by the rules.

ETA: edited slightly to tidy up.

 

[Utsikt]

Well said, @Kitty