Azithromycin in Chronic Fatigue Syndrome (CFS), an analysis of clinical data

[Jenny]

Has anyone on the forum used azithromycin? and if so, did it help?

Yes, for a few months in combination with other abx. It did nothing.

 

[Eeyore]

@Valentijn

Has anyone on the forum used azithromycin? and if so, did it help?

I've found azithromycin to be quite helpful. No benefit from abx in general (amoxicillin, doxycycline, others). I do not believe it has anything to do with the antibacterial action of the drug.

There are a number of drugs that mediate antigen presentation and azithromycin is one of them. If you pretreat people with azithromycin, they do not create antibodies to pneumococcal vaccine (which is not alive). It concentrates in the lysosomes and increases lysosomal pH preventing breakdown of the contents of the lysosomes. Antigens presented on MHC I molecules (i.e. by non professional APC's) derive from the ubiquitin proteosome system. Antigens presented on MHC II molecules (i.e. by professional APC's - macrophages/dendritic cells/B-cells) come from lysosomal degradation. Hence, if you alter lysosomal pH (increase it - i.e. make it less acidic) - fewer antigens get presented.

The actions of azithromycin look remarkably like hydroxychloroquine (there's at least one paper on this on pubmed), which is a drug frequently used in the treatment of autoimmune diseases, especially lupus, but also RA sometimes and others. Like zithro, it concentrates in the lysosomes.

I have a strong suspicion that azithromycin works much like hydroxychloroquine in autoimmunity (and in general in antigen presentation). For me, it works better than anti-inflammatories (like naproxen etc.)

Another drug that may work something like this is immunovir / isprinosine. It contains 3 chemicals, one is inosine, one is PABA (probably irrelevant - just to make a salt), and the last is an aminoalcohol (specifically, dimethylisopropanolamine, or dimethylaminoisopropanol). Structurally, it would be expected to behave much like hydroxychloroquine or azithromycin. Additionally, a closely related amino alcohol, dimethylaminoethanol (DMAE) is mentioned in the patent for imunovir as being more or less interchangeable with it. This chemical has been used in some skin creams, and when tissue is examined, sure enough, we find that the DMAE has caused the formation of large vacuoles. Imunovir may do this too (but likely not inosine).

If ME is in fact autoimmune, this could be a mechanism that would explain the efficacy of azithromycin, and would also suggest efficacy of hydroxychloroquine. Any rheum would be familiar with the latter.

Another interesting point is that some nephrologists have used azithromycin in renal transplantation, as it seems to reduce the rate of allograft rejection. this probably is related to its property of reducing antigen presentation, so that the new/foreign kidney is not presented as a foreign antigen as much.

The other interesting action of azithromycin from an immunomodulatory perspective is that it inhibits mTOR, or mammalian target of rapamycin. Doing so should activate autophagy pathways and it functions as an immune suppressant just like rapamycin (rapamycin, or sirolimus, is a potent immune suppressant which is used to extend allograft survival in many kinds of transplantation). There is a recent paper in Nature about this - I think 2014 or 2015. Zithro, depending on dose, was just as potent as sirolimus in activating mTOR.

A lot of this is speculative, so I wouldn't bank on it or start treating based on it, but I do think that more exploration into the efficacy of azithromycin is warranted. Personally, I do gain benefit from zithro.

 

[Artemisia]

This seems like a promising study.

I wonder why more research hasn't gone into antibiotics for ME.

Does anyone know why they only took the Zithro 3 times a week?

One of the treatment protocols that were offered in our Center from April 2000 till August 2005 was azithromycin 500 mg on 3 consecutive days of the week during 6 weeks [29].

 

[joshualevy]

This seems like a promising study.

Unfortunately, this is not a promising study. I think it is important to understand why it is not promising, because it is a mistake made over and over in the ME/CFS world, that studies like this one are considered promising, when they are unsuccessful and will not lead anywhere. To understand that this study is a complete failure, you only need to look at one fact:

The study was completed in 2015 (10 years ago) and no follow up study as been done by anyone.

What does this mean? It means, no matter how successful the results looked at the time, no one has successfully completed a follow on study.

First, this means that not a single researcher, anywhere in the world, looked at these results and thought they were really promising and worthy of follow on work (or if they did, the follow on work did not result in anything publishable). Even if you, a spectator, thinks this looks promising, you should ask yourself why all these researchers all over the world who saw this research published, do not agree with you, and realize that they are likely right. The mass of them, anyway.

Second, it means that the researchers who published this work themselves did not think it was promising enough to follow up on. We know they thought it was promising at the start of their first study: they invested years of their lives and lots of research money into the study. However, now that the study is done any published, they themselves (who know more about the research than anyone) have elected not to do the follow up. Again, that should tell you that people who want the research to succeed and have a lot more knowledge about it than you do, think it is not promising.

Third, it means that no medical company, anywhere in the world, thought this research was promising enough to put their own money into it. Companies can hire researchers. They want to make money, which means they need to develop successful treatments or cures. Especially for a disease like ME/CFS (no treatments, no cures, many people with the disease), there is a huge amount of money to be made. Even in just a good test. Yet, all these companies could read the research, and none of them thought it was promising enough to put money into.

Bottom line: any research worth doing, which has not been followed up in N years, is not promising. Different people have different beliefs about the N in the sentence above. I think it is about 2 years for most research. Maybe 4 years if the disease being studied is particularly small and niche. You might be more patient, and willing to wait longer, maybe 5 years. But in the modern world, with rapid communication and lots of research infrastructure, any research which makes no progress in 10 years, is not promising at all.

I think that you, and many other people here, have fallen victim to a flaw in the way we teach science. The people teaching science want their students to actually become scientists, rather than become people who understand scientific news. Therefore, they teach students how to do good research studies and evaluate the details of their scientific design, and give them bad grades for every flaw in the design. These students grow up to "grade" individual studies and think that a study without design flaws is good "promising" research.

But that is not how real research works; it is how school projects work. Real research is a larger research project involving many studies, some of these studies confirm previous ones, many more extend previous studies forward, yet others expand previous studies into related areas. A program is successful because of these follow on studies. Over the years, you can see it (the whole program) grow and see it successfully used in different areas. That is the true measure of success. The downside of this method (watching follow on studies over time) is time: it takes a while to learn if the research is correct. But the upside is certainty. If you wait a few years, and you see good results from the studies, you know it is successful. Similarly, if you wait a few years and no one is doing those studies, then you know it is unsuccessful. This is true no matter the wishful thinking of spectators.

 

[cfs since 1998]

Unfortunately, this is not a promising study. I think it is important to understand why it is not promising, because it is a mistake made over and over in the ME/CFS world, that studies like this one are considered promising, when they are unsuccessful and will not lead anywhere. To understand that this study is a complete failure, you only need to look at one fact:

The study was completed in 2015 (10 years ago) and no follow up study as been done by anyone.

What does this mean? It means, no matter how successful the results looked at the time, no one has successfully completed a follow on study.

First, this means that not a single researcher, anywhere in the world, looked at these results and thought they were really promising and worthy of follow on work (or if they did, the follow on work did not result in anything publishable). Even if you, a spectator, thinks this looks promising, you should ask yourself why all these researchers all over the world who saw this research published, do not agree with you, and realize that they are likely right. The mass of them, anyway.

Second, it means that the researchers who published this work themselves did not think it was promising enough to follow up on. We know they thought it was promising at the start of their first study: they invested years of their lives and lots of research money into the study. However, now that the study is done any published, they themselves (who know more about the research than anyone) have elected not to do the follow up. Again, that should tell you that people who want the research to succeed and have a lot more knowledge about it than you do, think it is not promising.

Third, it means that no medical company, anywhere in the world, thought this research was promising enough to put their own money into it. Companies can hire researchers. They want to make money, which means they need to develop successful treatments or cures. Especially for a disease like ME/CFS (no treatments, no cures, many people with the disease), there is a huge amount of money to be made. Even in just a good test. Yet, all these companies could read the research, and none of them thought it was promising enough to put money into.

Bottom line: any research worth doing, which has not been followed up in N years, is not promising. Different people have different beliefs about the N in the sentence above. I think it is about 2 years for most research. Maybe 4 years if the disease being studied is particularly small and niche. You might be more patient, and willing to wait longer, maybe 5 years. But in the modern world, with rapid communication and lots of research infrastructure, any research which makes no progress in 10 years, is not promising at all.

I think that you, and many other people here, have fallen victim to a flaw in the way we teach science. The people teaching science want their students to actually become scientists, rather than become people who understand scientific news. Therefore, they teach students how to do good research studies and evaluate the details of their scientific design, and give them bad grades for every flaw in the design. These students grow up to "grade" individual studies and think that a study without design flaws is good "promising" research.

But that is not how real research works; it is how school projects work. Real research is a larger research project involving many studies, some of these studies confirm previous ones, many more extend previous studies forward, yet others expand previous studies into related areas. A program is successful because of these follow on studies. Over the years, you can see it (the whole program) grow and see it successfully used in different areas. That is the true measure of success. The downside of this method (watching follow on studies over time) is time: it takes a while to learn if the research is correct. But the upside is certainty. If you wait a few years, and you see good results from the studies, you know it is successful. Similarly, if you wait a few years and no one is doing those studies, then you know it is unsuccessful. This is true no matter the wishful thinking of spectators.

The flaw in your thinking is the idea that researchers have the money to do anything they want. Science is expensive and funding is nearly always the limiting factor. This is especially true for ME/CFS research which is one of the lowest funded diseases. Azithromycin is a cheap generic drug and no drug company is going to fund a study of it especially not for CFS. Absence of evidence is not evidence of absence. Ignoring less than perfect research is exactly why CFS is stuck in a black hole.

And you are incorrect that there has been no additional research. Azithromycin use was associated with reduce risk of CFS in a 2023 study: https://pubmed.ncbi.nlm.nih.gov/37951920/

 

[joshualevy]

The flaw in your thinking is the idea that researchers have the money to do anything they want. Science is expensive and funding is nearly always the limiting factor. This is especially true for ME/CFS research which is one of the lowest funded diseases.

I don't assume that. I do make two assumptions, both of which are true: (1) success attracts funding. If someone runs a truly successful study, they will have no problems raising money for the follow on. After all, they have the best possible evidence, one successful study, that shows they are on the right track. Our whole economic medical system is based on the idea that people make money by putting money into successful research.

(2) There are tens of thousands of researchers in this world, and they all got funding to do research (or they would not be researchers. None of them are working on this. There are thousand of companies spending millions (in a few cases, billions) of dollars on medical research. None of them thought this research was worthwhile.

Look at it this way: the original researchers got enough money to do the original research and publish the results. If those results had been successful, of course they would be in the best possible position to get funding for the follow up research. They would already be in contract with a funding source, everyone would know they could do the research, and have "successful" results to show them. But in your world, the funding dries up after the "successful" research. Does that make sense to you? The truth is obvious: they put a good face on their results for publication (and fooled a lot of spectators), but the research was not really successful, and they know it, their funders know it, and the people active in the field know it.

Azithromycin is a cheap generic drug and no drug company is going to fund a study of it especially not for CFS. Absence of evidence is not evidence of absence. Ignoring less than perfect research is exactly why CFS is stuck in a black hole.

This is a complete red herring. Companies (more than one) are producing Azithromycin right now. Every one of those companies will make more money if they sell more of it. How big is the ME/CFS market? Of course they would fund it. There are huge pharma companies that specialize is producing old, cheap drugs and would be overjoyed to increase their market. The problem isn't money, it is success, or lack of it. The economics are different, of course, but many companies make a lot of money producing old, unpatented drugs. It is just a different business model.

You are suggesting we live in a world where producing Azithromycin is profitable and companies do it, but doing research (which already has signs of "success") which will increase the volume you sell, would not be profitable. Those facts are in conflict. A drug to treat or cure ME/CFS has no competition. The disease effects something like 0.5% of the population, and the drug is profitably produced right now. How could it not be more profitable to up your sales volume?

And you are incorrect that there has been no additional research. Azithromycin use was associated with reduce risk of CFS in a 2023 study: https://pubmed.ncbi.nlm.nih.gov/37951920/

Which proves my point: the research in 2015 was aimed at treating ME/CFS and was a total failure. This new research is aimed a preventing ME/CFS: a different question. (I hope you understand that two studies both using Azithromycin in ME/CFS do not necessarily support each other.) In this case, one was treatment one was prevention. They are separate. The new study was published in 2023 (2 years ago). My guess is that it failed as well (see my comment about years above). But with only 2 years of age, I do not begrudge you some hope. Come back in a year or three and see if anything has happened on the prevention front.

 

[cfs since 1998]

This is a complete red herring. Companies (more than one) are producing Azithromycin right now. Every one of those companies will make more money if they sell more of it. How big is the ME/CFS market? Of course they would fund it. There are huge pharma companies that specialize is producing old, cheap drugs and would be overjoyed to increase their market. The problem isn't money, it is success, or lack of it. The economics are different, of course, but many companies make a lot of money producing old, unpatented drugs. It is just a different business model.

This shows me you have a lot to say while knowing very little. It doesn't work that way at all. Generic drugs are a commodity item. The profit margin is small and there is a ton of competition from companies all over the world. Generic drug manufacturers don't do scientific research. That is not part of their business model at all. You don't have any understanding of how the pharmaceutical industry works. Your entire post is a red herring.

You are suggesting we live in a world where producing Azithromycin is profitable and companies do it, but doing research (which already has signs of "success") which will increase the volume you sell, would not be profitable. Those facts are in conflict. A drug to treat or cure ME/CFS has no competition. The disease effects something like 0.5% of the population, and the drug is profitably produced right now. How could it not be more profitable to up your sales volume?

They would increase their competition at the same time. There is no profit in finding new indications for generic drugs. None. I am not replying to the rest of your post point by point. It's all one big fallacy.

 

[joshualevy]

If no one will fund generic drug studies, how did the first Azithromycin study come to be funded? How did the second one that you reference? If you were right, those studies would never have been funded! Surely you can see the internal inconsistency of your position. We are discussing studies done on generic drugs, and you are arguing that studies can't be funded on generic drugs!

This shows me you have a lot to say while knowing very little. It doesn't work that way at all. Generic drugs are a commodity item. The profit margin is small and there is a ton of competition from companies all over the world. Generic drug manufacturers don't do scientific research. That is not part of their business model at all. You don't have any understanding of how the pharmaceutical industry works. Your entire post is a red herring.

Then how do you explain the use of aspirin to prevent heart attack? All of that research and the FDA approval, was done on a generic drug (aspirin!) long after it was out of patent protection. Indeed, aspirin has been in use for so long, I don't think it ever had a patent. Yet, someone funded enough research to
get a new dose approved specifically to prevent heart attack! And those were some very large, very long term studies. If what you were saying is true, that could never have happened, yet it did.

On a more quantitative front, years ago I tallied all drugs in clinical trials for one particular disease (not ME/CFS). The disease has been well understood for about 100 years. From memory, when I did the tally, about 20% of the drugs in clinical trails were generic or out of patent. 80% were patented or would become patented, if approved.

If you open your eyes, you will see that research on generic drugs (like aspirin and Azithromycin itself) is funded, and can be funded even to the point of FDA approval.

 

[Artemisia]

First, this means that not a single researcher, anywhere in the world, looked at these results and thought they were really promising and worthy of follow on work (or if they did, the follow on work did not result in anything publishable). Even if you, a spectator, thinks this looks promising, you should ask yourself why all these researchers all over the world who saw this research published, do not agree with you, and realize that they are likely right. The mass of them, anyway.

This would apply if we lived in a perfect world where medical research were completely separate from profit. Only then could we judge whether something is promising based on whether further research has been done on it. In reality, the research that is done has everything to do with making profit for someone or some entity

Have you never heard any researchers or whistleblowers say that scientists are regularly tasked with finding some outcome that favors a profitable drug? Because they do.

you, and many other people here, have fallen victim to a flaw in the way we teach science.

You're not considering the way the governmental agencies have actively tried to suppress activism from mecfs patients and denied funding to us for decades. We don't live in a romanticized version of the world in which corporations and public health directors care deeply about helping vulnerable sick people.

 

[Artemisia]

The truth is obvious: they put a good face on their results for publication (and fooled a lot of spectators), but the research was not really successful, and they know it, their funders know it, and the people active in the field know it.

But that is not how real research works; it is how school projects work.

Which proves my point: the research in 2015 was aimed at treating ME/CFS and was a total failure

So what about this study is a failure? What made it a failure in 2006?* If we spectators are being fooled by this, and you see that we are being fooled, what did researchers see that told them that further research was not warranted?

The answer cannot simply be that it's 19 years old. That's circular reasoning. It was not always this old.

If I had said in 2006 that the study looks promising, no one could shoot me down based on the "it's old research that hasn't been followed up on" argument. So if it could have looked promising in 2006, the fact that it's 19 years later does not change the outcome of the study.

And what was that outcome? 58% of the participants improved. Yes it was a small study, but that result cannot be ignored.

It seems like a total distraction to focus on the age of the study rather than the outcome.

* the drug lost its patent in 2006 also. coincidence?

 

[Artemisia]

A program is successful because of these follow on studies. Over the years, you can see it (the whole program) grow and see it successfully used in different areas. That is the true measure of success. The downside of this method (watching follow on studies over time) is time: it takes a while to learn if the research is correct. But the upside is certainty. If you wait a few years, and you see good results from the studies, you know it is successful. Similarly, if you wait a few years and no one is doing those studies, then you know it is unsuccessful. This is true no matter the wishful thinking of spectators.

TLDR
Those of us with ME/CFS are desperately ill people who are spending energy we don't have to discuss the scraps of research we are given.

If you want to help, since you are a researcher who does not have ME/CFS, please explain what is flawed with this study without relying on the "old research" argument.

When I read your last comment, it made me think that you don't have ME/CFS, which you confirm on your profile. Your focus here is on the sanctity of scientific research as an institution. Our focus is on getting better.

For those of us who are sick with ME, it DOES matter when something improves 58% of people who took it. I get that you're deeply invested in the idea that "science" is always the driving factor behind what passes for medical research, and that everyone is perfectly altruistic including billion-dollar companies that have repeatedly demonstrated their lack of concern for human collateral, but we patients are not here to toe some line on this matter. We all know medical research is profit-driven.

We represent the most abused and neglected patient group in history, and we desperately need to get better. The outcome of a well-designed study matters whether it's done yesterday or 50 years ago.

 

[cfs since 1998]

If no one will fund generic drug studies, how did the first Azithromycin study come to be funded? How did the second one that you reference? If you were right, those studies would never have been funded!

You cannot possibly be this obtuse. Did you read them? They clearly weren't funded by the pharmaceutical industry. They were chart review studies.

Surely you can see the internal inconsistency of your position. We are discussing studies done on generic drugs, and you are arguing that studies can't be funded on generic drugs!

There is no internal inconsistency. They were not "azithromycin" studies. They were ME/CFS studies, which happened to find data concerning a particular drug worthy of publishing.

Then how do you explain the use of aspirin to prevent heart attack?

Believe it or not, institutions interested in public health occasionally fund studies of cheap or generic treatments. This is generally done in conditions of widespread health concern that affect large quantities of people, such as heart attacks. Heart disease is the #1 cause of death. So there is a lot of interest in studying anything and everything that might help. These institutions are generally not interested in ME/CFS research.

If you open your eyes, you will see that research on generic drugs (like aspirin and Azithromycin itself) is funded, and can be funded even to the point of FDA approval.

This is the exception, not the rule. Your argument is nonsense. "It must not work because the pharmaceutical industry hasn't funded new studies" is a circular argument. Whether something works or not is not dependent upon whether a company is interested in funding it. You talk about not understanding science. I have never seen a more unscientific argument than yours.

Furthermore you have a very poor understanding of the economic realities of medical and pharmaceutical research. Your idea that manufacturers of off-patent generics would be chomping at the bit to fund new research on generic drugs like azithromycin for ME/CFS is laugh worthy, and your black-and-white, binary interpretation of the situation shows a lack of critical thinking ability.

Not sure what your agenda is here, but we are perfectly capable of understanding science without your condescending rebukes.

 

[joshualevy]

If you want to help, since you are a researcher who does not have ME/CFS, please explain what is flawed with this study without relying on the "old research" argument.

That is what I was trying to do the first time, but obviously I did not succeed. Let me try a different approach. Consider the following statements, all of which are true. (If you doubt these, please Google the data, or talk to a chatbot, or cull through the data yourself.)
1. Most research studies which report successful results in animals never result in successful results when tested in people.
2. Most initial clinical trials (research done on people for the first time) which report successful results, do not result in a successful result in their second clinical trial.
3. Researchers are highly optimistic people. This is for two reasons: first research is inherently optimistic, you are doing work in the hope that it will help people, make money, and so on. Someone who is not optimistic will go into a different field. Second, they need to be optimistic in order to convince other people to put money or effort into their research. (I think we agree that money causes researchers to be overly optimistic about whatever is funding them, as you point out.)

So what does this mean in real life? (Not academic grading of research experiments.)

First, it means that all researchers will be overly optimistic about their own results. This is not a problem for other researchers or corporate America. They know this and "discount" the research findings. They evaluate the research in depth, and so on. They look at statements by the researchers like "improves 58% of people who took it" and look at the details of what really happened, not what the research summarize happened. Unfortunately, spectators, who are just reading what the researchers wrote and evaluating things in a very superficial way, are left out. They are mislead by the overly optimistic hopes of the researchers.

Second, you seem to think that most research studies are correct in their results and lead to successful medicines. That is just not true. Points 1 and 2 above mean that the failure of follow on experiments which are reported as successful is normal. It is not caused by flaws, it is inherent to the system. It is what happens most of the time. I don't have to explain the flaws in the research, because flawed research is normal.

Think how many drugs are "successful" in mice but then fail human trials or are never tested in humans because the follow on animal tests fail. As an example, one year I kept track of all animal studies aimed a curing one specific disease (not ME/CFS). Working from memory there were 13 successful animal tests. Twelve of these were never even tried in people, not even by the researchers who claimed success in animals. One was, and it failed in its first clinical trial. That is all normal. You need to explain why you think the study might be successful, and just saying "well the researchers were very optimistic and reported very optimistic results" is not good enough. It is true for all research everywhere, the vast majority of which does not end up being successful.

This is why the "old research is bad research" is more accurate than the "the researchers reported success" in the real world.

For those of us who are sick with ME, it DOES matter when something improves 58% of people who took it. I get that you're deeply invested in the idea that "science" is always the driving factor behind what passes for medical research, and that everyone is perfectly altruistic including billion-dollar companies that have repeatedly demonstrated their lack of concern for human collateral, but we patients are not here to toe some line on this matter. We all know medical research is profit-driven.

I do not think that research is, in any way altruistic. Companies (and venture capitalists) care about one thing: money. Researchers need money, and are naturally optimistic, so their reports are overly optimistic because they want that money. You and I seem to agree on this. But that is the exact reason that clinical trials which are reported as wildly successful (58%!) usually are not that successful. This is exactly the point I'm trying to make. That is why looking at follow ups is so important. This is why reading the clinical trial report "with a grain of salt" is so important.

But the fact that corporate America, and also research, is not altruistic helps us in the world of ME/CFS, because there is so much money to be made. This is a disease which impacts more than 0.5% of the total population. It has no cure and no treatment. That is a huge market! Even a medicine that only worked 10% of the time would make a ton of money.

If these researchers, or any researchers, could improve 58% of the people who took it, they would be fighting off the venture capitalists with a stick! (To use an American English phrase.) They wouldn't be asking for money, they would be deciding what terms they would accept they money people wanted to give them. Think about how many long term prescriptions would be written in the first year. Millions in America alone. That is a lot of money for any drug, generic or not.

The outcome of a well-designed study matters whether it's done yesterday or 50 years ago.

No. This is exactly the "grading a school project" vs. real world science mistake. A study that appears to be perfect will turn out to be incorrect unless it is built upon by future studies (to confirm it, to expand it, and to see exactly when it applies and when it does not).

The only exception to this rule is research which is unimportant when done in the past, but becomes important later. Unimportant research might be ignored for a time, simply because it is unimportant. However, no ME/CFS research is unimportant, because of the huge amount of people, loss time, and money involved.

But that 58% is not real. As a spectator, who only reads the journal article, you and I can not tell why it is flawed, but it is flawed. I can not tell you exactly why that 58% number is not real, because I did not do the research. But the people who did do the research don't believe it, ether or they would have done the follow on research. The money-people who finance research (never altruistically) don't think it is real, either, or they would have funded the researchers to do follow on work or hired other researchers to do it.

 

[Artemisia]

But the fact that corporate America, and also research, is not altruistic helps us in the world of ME/CFS, because there is so much money to be made. This is a disease which impacts more than 0.5% of the total population. It has no cure and no treatment. That is a huge market! Even a medicine that only worked 10% of the time would make a ton of money.

Yes it would. So why is ME so under-funded for research? It wasn't researched at all for years. Then patients had to fight for some research funding. Now we get pennies on the dollar of what other disabling illnesses get. Any ideas why we are in this situation when big bucks stand to be made on treatment?

 

[joshualevy]

Yes it would. So why is ME so under-funded for research? It wasn't researched at all for years. Then patients had to fight for some research funding. Now we get pennies on the dollar of what other disabling illnesses get. Any ideas why we are in this situation when big bucks stand to be made on treatment?

I don't have a complete answer for that, but here are some parts of an answer:
Part of the answer is that ME/CFS attracts less government and non-profit funding that it "should". For that part, I wrote something years ago:
https://forums.phoenixrising.me/thr...ew-of-the-iom-report.36380/page-7#post-577676
https://forums.phoenixrising.me/thr...ew-of-the-iom-report.36380/page-4#post-576650
These two posts only cover government and non-profit, and they are sort summaries, not completely detailed, but hopefully they give some idea of why ME/CFS is underfunded by government and non-profits.

But the big question is: what about corporate America. Why doesn't pharma fund ME/CFS research better? I think there are two strong possibilities (and some smaller possibilities).

One is that pharma fundamentally doesn't believe ME/CFS prevalence numbers (the 0.5% of the population number). They might think that ME/CFS is far more rare than we think it is. The prevalence numbers I used are from survey data done by Jason and CDC and is widely used by ME/CFS patients and advocates. However, as we all know there is no diagnostic test, there are many definitions in use, the data all comes from surveys. It just is not clear how common ME/CFS is, and the corps might be of the opinion that it is much more rare (much less profitable) than we think it is.

Second, it might be that pharma companies already have psychological drugs (anti-depressants and so on). So the question they have is: do non-psychological drugs work better for ME/CFS patients than the psychological drugs they already sell them. If they have not seen convincing evidence that non-psychological drugs work, they aren't going to fund their development. Of course, this problem happens with all drugs (it is a sort of chicken and egg problem), but in other diseases government and the non-profits help out. But in ME/CFS, because of the reasons I discuss in the links above, those groups don't help out as much.

Here is a little digression on government funding. I read a great dissertation about this, but did not keep the reference. I'm very sorry for that, but the basic summary was this: Up until the 1970s and 80s, the politicians viewed research money as a benefit for researchers and Universities. So if they like a university, they gave it money for research. Starting the 1980s and 90s attitudes changed, and research funding was seen as a benefit to the people with the disease. Another finding was that advocacy funding resulted in about 11x government research funding. So if an advocacy group started spending 1 million, that would result in the government spending 11 million more money on the disease. No idea if any of this stuff is true now, or will be true in the future.

 

[joshualevy]

They clearly weren't funded by the pharmaceutical industry.
...

Believe it or not, institutions interested in public health occasionally fund studies of cheap or generic treatments.

Previously, you argued that there was no funding for generic drugs, but now you seem to understand that was wrong, and now you are arguing that there is no pharmaceutical company funding. That shows improvement in your thinking, but lets try to take the next step.

Fundamentally, research is funded by three different sources: the government, non-profits, and the pharmaceutical industry. But the pharmaceutical industry is not one thing, it is thousand of companies. Some of those companies specialize in selling new drugs, some in old drugs, and some do both.

So in the case of azithromycin, it could be funded by the government, non-profits, pharma that specializes in old drugs (azithromycin is an old drug), or pharma which does both old and new drugs. So that means dozens of governments (even more different agencies), plus non-profits, plus hundreds of pharma companies that make older drugs, they all passed on this research. That should tell you something.

Of course a pharma company that only invests in new drugs will not invest in azithromycin, and that does rule out some companies, but that is always true of all drugs. It does not change the real issue: There are 100s of potential sources of research funding, none of whom thought this drug was worth it.

"It must not work because the pharmaceutical industry hasn't funded new studies" is a circular argument.

That was never my argument. My argument was that no one would fund it. Not the government, not the non-profits, not the pharmaceutical companies that specialize in older medicines.

This is the exception, not the rule.

I understand, when I provide an example that shows you are wrong, you ignore it. That doesn't mean it doesn't exist. But lets try something different: how many drugs that are generic / out of patent control specifically for ME/CFS have been tested in clinical trials? Are they are exceptions too? Pyridostigmine, rituximab, LDN, cyclophosphamide, all of those have been tested in clinical trials. Are they all exceptions? Are you going to ignore them all? How many "exceptions" do you need until you realize that lots of generic drugs are tested in clinical trials all the time.

 

[joshualevy]

Both @Artemisia and @cfs since 1998 think my argument is circular. I think it is reality based, not circular, but lets discuss this issue.

Start out with the most basic question: when is research successful? My answer is simple: when it results in a cure or a better treatment. But research can only lead to a cure or better treatment if it is followed up, if it is continued, if it ends up with something that comes into widespread use. Therefore, any research that is not continued can never be successful because it can never lead to a cure or a better treatment.

You can object to this definition, and claim it is circular, but what other definition could you use? How would your definition be any less circular than my definition?

In the world of Physics, this is the Schrödinger's cat problem. If you don't look at the cat, you don't know if it is alive or not. In this case, if no follow on experiment is ever done, how do you know if the first experiment is a success? And if you don't know, and never know, then is it a success or not? However, in the world of medicine, for me, the answer is clear: no cure or treatment improvement, no success. If you think of that as circular reasoning, you can, but I think it is real world thinking.

I have some sympathy for the idea that, from a logical or rhetorical point of view, if the research really is good, then it is good. But we can never know that, it is just one spectator's opinion. From a practical point of view, from a medical point of view, the experiment has failed. There might be a philosophical argument that the experiment is good, but in reality, no one would ever know for sure, and certainly no one would ever benefit from it. (Because benefit requires follow on, and there is no follow on.) In my opinion, the fact that there is a valid philosophical argument does not impact the fact that in the practical world of medicine, there is no argument. It is unsuccessful.

 

[NameHere]

Joshualevy, point me in the direction of ground-breaking or high-quality medical research being done in CFS/ME.

 

[joshualevy]

Joshualevy, point me in the direction of ground-breaking or high-quality medical research being done in CFS/ME.

Well, for ground-breaking, I don't think it is possible to know that something is ground breaking when it happens. My whole point is that you need to wait 10 years and see. So, if you are asking me, what research done 10 years ago was a big breakthrough, I would say "none". (That is why you and all of us are so frustrated.) For example, Dr. Naviaux's dauer / cell danger response theory is about 10 years old, and I don't think anything has come of it. XMRV is about 15 years old, it is clearly dead.

As for high quality medical research. For me, high quality medical research would look like this: 10 years ago, someone published a small pilot study showing a treatment, cure, or diagnostic test for ME/CFS. Then, a few years later, someone published a bigger, better, follow on study. Then, a few years later, someone published something even bigger, more expansive, or better than either of the preceding studies. That is what I want in research. I've never seen biomedical studies like that in ME/CFS. The closest is probably the 2 day CPET test as a diagnostic, but it is not quite there yet. So again, there are no high quality studies right now, and that is why we are all so frustrated.

 

[cfs since 1998]

Previously, you argued that there was no funding for generic drugs,

You are misquoting me.

but now you seem to understand that was wrong,

I did not admit to being wrong, because I was not wrong. My post was correct.

and now you are arguing that there is no pharmaceutical company funding. That shows improvement in your thinking, but lets try to take the next step.

You asked why *drug companies* didn't fund azithromycin trials in ME/CFS. I answered the question. You twisted my words around, made a straw man out of my post, and proceeded to patronize me with your superiority complex. I will not be replying to any more of your posts. As far as I am concerned, you are a troll. I have reported you to the moderators, but they seem to be asleep at the wheel.