BCG Tuberculosis vaccine - and related testing - EpicGenetics

I actually regard that as evidence that to move forward either we abandon it or use a diagnostic test. Since we have a putative test it can be validated more and more over time ... or it can fail to be useful. This is a pragmatic issue to a large extent, but with enough data there can be further analyses over time. How it pans out in the real clinical world is important.

The same issues over clinician diagnosis with CFS and ME occur. Diagnostic variation ranges from nothing wrong, psychogenic, ME, CFS, fibro (again), MS and so on. What that tells you is there is not enough data to have a great diagnostic protocol yet (at least in common use), so its no wonder clinicians get a range of diagnoses. Diagnostic biomarkers are mandatory to move that situation forward, however each does have to undergo a lot of validation, including in a clinical setting, so its hard to say where this test lies right now on the timeline from putative to near certain, or if there is enough data to disprove the valid use of the test ... we don't know if that data exists yet. It would also be great if they could figure out causal mechanisms, as these help immensely in determining what is and is not a good test.

In developing diagnostic tests it seems to me it starts with an initial test, which is often badly flawed, and then successive tests compare to that test and many iterations later we have much better tests.

 

This is the point. The test is actually a test for low levels of cytokine production on cell stimulation, not a 'test for fibromyalgia'. Why such a test should have any relevance to widespread pain, or suggest that it might be a good idea to give people BCG beats me. Except that I can see exactly what the pseudo-rationale is - the bogus train of thought. It is a bit like a kid who have had a doctors set for Christmas telling his sister to put the bottom end of the stethoscope under her tongue so that he can hear her temperature.

 

Or a bunch of different diseases, but yes, figuring out causal mechanisms is good for figuring out biomarkers, but we also need biomarkers to figure out causal mechanisms. These and consensus definitions feed back into each other, until eventually we should have testing based on validated diagnostic biomarkers, rather than consensus definitions.

 

Which just means it needs much more development to be used as a valid test, not that it is not an hypthetical test. However if its only found in fibro patients, and not other autoimmune diseases, or rheumatological diseases, then its still a candidate biomarker until we can figure out more.

I think the reason the FDA approves such early tests, in cases like these, is there are NO other tests. Clinician feedback and further studies should give us enough data to properly evaluate it in time.

So I agree there are grounds to be sceptical, but I don't think there are grounds to totally dismiss it.

The only reason I would use such a test right now is if I had a need to find evidence of fibro in a legal battle, but if many fibro patients show up negative on the test that could backfire.

Its the same with CPET and ME, I would use that if I had medico-legal reasons to validate my situation, such as in a disability review.

 

Sorry, @alex3619, but you are arguing upside down here. Almost everyone does but having been through the process of working out the pathologic basis of a syndrome I have learnt how upside down it is.

Yes we want a diagnostic test but the whole point of that is to show that some clinical diagnoses were wrong - so you want a test that identifies something objective and which agrees with clinical diagnosis less than 95% of the time. What that means in reality is that if the agreement was 99% it would prove that the clinical criteria were objective in their own right - i.e. reliably agreed upon in 99% of cases by a range of physicians. For a condition like fibromyalgia there is no possibility of 99% sensitivity or specificity because physicians do not agree even to a 10% level.

In other words, the bottom line is that this test claim is completely bogus. We know it must be. The fact that they think 99% is a good number indicates that they have no idea what they are doing so it is not surprising.

 

I would argue this just means such a test with less than 95% clinical agreement is more scientifically interesting, we can learn more from it, maybe much more. It might also mean its only a test for a subgroup, which is something we need to consider in fibro and ME. Coming from a background in neural networks, I can say that its common to find it detecting something that is not important, in other words association not causation, or even secondary consequences. So for example it might pick up a general marker that is found in many other diseases, but they did not use those in comparison groups for specificity analysis. Its a problem with the whole specificity issue.

With biomarker defined groups, rather than consensus guessing groups, you can then do further research. Maybe it will fail .. I expect the majority of such finds will fail. The point is you have a more focused group to do further testing with. So its scientifically valid at the level of a pilot study .. but as we know later, larger, and better designed trials often find these hypotheses are wrong.

Taking the line of reasoning with discordance would mean that a test which is 100% accurate, like one that exists now for ME, or 85% for a recent test, have little clinical or research utility. It might mean we could not have much hope in metabolomics, CPET, cytokine testing, and so on. Now I agree that we should not great hope in any of these, there is a long way to go, but you have to start somewhere. If its wrong and enough researchers are looking for the fatal flaws then they might rule it out. That happened with XMRV.

I would suspect that someone will use that fibro test with other similar diseases ... and there is a high chance they will find it positive, maybe in Lupus or something. That would then invalidate it as diagnostic, but it still might give clues as to pathology, which might require investigation. Indeed it might be an artefact of a too small cohort, and a larger cohort test will invalidate it.

The fact that the biomarker found is not obviously useful in identifying mechanism means that it needs more investigation, not that it is wrong.

Now a test with low clinician agreement, say at 60% or less, we might find something very interesting as to causal mechanisms, or it might just be an invalid test. So again it offers opportunity for investigation. It might also, as I already said, only be valid for a subgroup, which can then be separated from the rest in future studies.

The problems with fibro diagnostic biomarker discovery are a close parallel with ME biomarker diagnostic discovery. So I think this is useful exemplar of the issues we are going to have with future putative ME tests.

Now I would MUCH prefer we had an understanding of underlying causal mechanisms, with identification of subgroups or alternative diagnoses, and testing were based on that. However I see it as a chicken and egg thing ... how do you isolate causal mechanisms in potentially highly heterogeneous cohorts, with poor understanding of causal mechanisms, and multiple consensus definitions? Candidate biomarkers offer one way of doing that, even if flawed biomarkers are used initially. I am sure there are other ways, including those used in some of the current studies in the US and elsewhere, but which is the better path? Why?

There are other candidate markers for fibro I think, including possible SFPN, but they are also a long way from being fully validated or tested. In particular the problem with small fibers is that the testing is likely to have a high false negative rate.

Having said all that its painfully obvious that many tests have been put forward as useful, with one or two limited studies, then failed in the real world or in later studies. XMRV testing for example. Yet I would argue we learned a lot when we finally ruled out XMRV as a candidate cause for ME.

If you want to argue that this test will eventually prove to be wrong I would agree, to a high probability. That is the batting average, especially where causal mechanisms are still not understood. That does not mean it should not be investigated further. Proving it wrong, not just inferring it is wrong, is also valuable to us.

In general though, nearly all these theories and tests for things like ME have proven false over time, with a small selection still pending. This will continue until one (or more) are correct.

 

It may turn out to be like an SED test. There can be any number of things wrong with the patient, and further blood tests and even a whole body scan can be done.

When a patient is diagnosed with the Fibromyalgia criteria (yes, Fibromyalgia has criteria too) and then they are positive with the blood test (whereas a healthy control will not test positive and just about no one but a Fibro patient will get through the diagnostic criteria) then yes you have a blood test that can support the criteria diagnosed disease of Fibromyalgia. Then those patients can be in a study for a vaccine. And if the trial is successful, then people that are diagnosed with the criteria and then are positive with the blood test can get the vaccine.

 

Exactly. The US Medicare system and most health insurance companies, including BCBS, are using the test. I am on BCBS but the HMO won't cover it although all other plans will. And, of course, I have the HMO plan.

 

Hello there,
I’m new to this, so please forgive me if I’m posting in the wrong place. I don’t know if this question has been answered before, but does anyone know if the only place to get the vaccine will be in Massachusetts? Will everyone selected for the trial have to travel there to get it?
I’ve done a little research and it appears that this vaccine will be given once a year for three years to each of those who choose to receive it. So it’s not a one time thing. Also, not everyone who participates will get the actual vaccine, many will only get the placebo, normal saline. Could you imagine going through this for 3 years and getting the placebo? Much less if you have to travel to get it. I don’t know why I didn’t think about this earlier... every trial has placebos.. but the only place I could find out substantial info about this was at clinicaltrials.gov.
Here is just a little info:


“Study Type : Interventional (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Half of the subjects will be placed in the multi-dose BCG group and half will be placed in the placebo group.
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double Blind
Primary Purpose: Treatment
Official Title: Phase II Clinical Trial: Multi-dosing the BCG Vaccine for Fibromyalgia
Estimated Study Start Date : January 1, 2019
Estimated Primary Completion Date : January 1, 2022
Estimated Study Completion Date : January 1, 2022

Arm Intervention/treatment
Experimental: Bacillus Calmette-Guerin (BCG)
3 BCG vaccinations spaced 1 year apart.
Biological: Bacillus Calmette Guerin Vaccine
Experimental
Other Name: BCG

Placebo Comparator: Placebo Comparator: Saline injections
3 saline injections spaced 1 year apart.
Biological: Saline Injection
Placebo”

I’m a little disappointed

 

An update on the use of the BCG vaccination to treat type 1 diabetes:

An 8-year clinical trial on 211 T1D patients published in 2018 showed that this vaccine is helpful in treating diabetes.

Unfortunately the trials of the BCG vaccination to treat interstitial cystitis did not fare so well.

 

Hi @Laurenkay, I understand your disappointment however this is how science and clinical trial work! In order to find out whether a drug or a product works in a patient population, we need to test for response against placebo response. This is a normal and required phase to go through.

While clinical trials may not be everyone’s cup of tea, the results provide much information which guides FDA and other regulatory bodies in determining whether a drug is safe and effective in treating a disease.

Your participating to this study may not personally benefit you, but you will provide data for researchers that is invaluable for the future of this treatments. It is entirely up to you, and there will not be any repercussion should you decide not to go ahead.

Best wishes

 

Staphylococcus toxoid vaccines were also used to treat diabetes, and according to this 1936 paper: "patients showed improvement in their clinical condition, often considerable and sometimes dramatic".

Given that type 1 diabetes is linked to persistent coxsackievirus B infection of the pancreas, it's possible that the mechanism of action of Staphylococcus toxoid vaccines on T1D may relate to its effects on CVB (Staphylococcus alpha toxoid has been shown to correct immunological deficits caused by CVB).

 

Merged thread
Selling Certainty
In a sea of skeptics, this physician was one of fibromyalgia patients’ few true allies. Or was he?

https://www.statnews.com/2021/10/20...romyalgia-patients-few-true-allies-or-was-he/

I have not read the whole article, just skimmed the first part. I stumbled across it and thought I'd share it here because I remember some forum members have mentioned EpicGenetics in the past.

 

Interesting in-depth article. The physician owner of Epicgenetics was not much of a scientist--his "test" was a cytokine signature for FM that has not borne out. He should have gone to the little trouble of disproving his hypothesis instead of building a company around it, but that was his thing, starting companies.

He was also involved briefly with a BCG study (Tuberculosis vaccine) for fibro, an attempt at boosting the immune system.

In essence, medical fraud or ineptitude.

 

merged thread

Consumer watchdog Center for Science sues EpicGenetics over misleading claims about FM-test.

Go to,

https://www.cspinet.org/press-relea...test-fibromyalgia-false-and-misleading-claims

https://www.statnews.com/2023/10/04...ng-misleading-claims-about-fibromyalgia-test/

https://www.statnews.com/2021/10/20...romyalgia-patients-few-true-allies-or-was-he/