what's the followup to the biomarker study that was just published (Spring 2019)?

ebethc

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I didn't see anything in the reporting (yet) referencing timelines... The next step is a larger study to validate, but it doesn't provide a timeline or say if the larger study is funded or initiated.

Does anyone know if the larger study is funded yet? is it underway? what's the timeline for results to be evaluated and released?
 

ebethc

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There's validation on a larger dataset as well as validation of the biomarker against other "fatiguing illnesses," but I don't think there's much information publicly available beyond the general plan and the sense that this is underway to some degree.
are you saying that the larger study has already taken place? sorry, I don't understand
 

used_to_race

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are you saying that the larger study has already taken place? sorry, I don't understand
Sorry, no. I'm just reiterating what everyone else is saying: the larger study needs to happen and there have been general statements from various individuals at OMF and Stanford indicating that they have plans to do it.
 

ljimbo423

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@Cort just interviewed Ron Davis and Rahim Esfandyarpour (the lead author) about the paper here: https://www.healthrising.org/blog/2...e-nanoneedle-scores-big-in-first-me-cfs-test/
Thanks @waiting.

This quote is from Cort's blog-

Probabilities tell the tale in research. The highest probability that is considered significant or meaningful in medical research is a less than one in twenty probability (p<0.05) that a result occurred by chance.

Studies are designed around the need to hit that probability. Miss it even by a small amount, and your results are worthless. Statistical analyses are done to determine how many participants are needed to hit that probability target.

There was no need for that in the nanoneedle study. The statistics indicated that the probability that the study results were due to chance ranged in the billions.

That kind of probability is more commonly seen when trolling for a mega lotto win than in biology. Put another way, the nanoneedle study was actually far, far larger statistically than it needed to be to demonstrate that the ME/CFS samples could be differentiated from the healthy control samples.

Differentiating ME/CFS from other diseases is the next step, but the big takeaway is that Davis appears to have produced a test that irrevocably demonstrates that people with ME/CFS have a biological illness.
 

Cort

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The big need for the nanoneedle as I understand it is for the production of a high throughput machine which will allow the samples to be processed much more slowly. I can't post from my blog - PR won't allow that - but the needle in its current iteration can only assess 2 samples over 2-3 hours. With all the work the needle is involved in - from assess other diseases, to drug testing, to plasma testing - it's no wonder that it's taking a while.

Other than resources, there are no barriers to making that machine. Davis and Esfandyarpour are submitting a grant application to the NIH to continue work on the nanoneedle. Davis has been turned down twice thus far - hopefully the 3rd time is the charm. With the strong PNAS paper I'm hopeful that he will get it.
 
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It's a good basic explanation combined with a powerful call to action. I hope OMF keeps getting more funding to use this device, and also channels more of its own resources toward this and away from more speculative pursuits.
 

joshualevy

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I think the next steps in the research are three fold:
  1. Run trials which are larger and which are blinded (the first study was not blinded).
  2. Run trials aimed at comparing ME/CFS with other fatiguing diseases, and more generally determining if the nanoneedle is measuring a symptom of the diseases or a cause of the disease. (This doesn't matter as far as using the test as a biomarker, but it does matter in terms of creating a cure.)
  3. Run trials aimed a showing that this is a generally applicable test: It can be run at many labs, it works for people all over the world, the results are consistent both person-to-person and lab-to-lab, what procedures are important to collecting blood, etc.
Now the real question is: how long will this take?

I think the answer to this question depends on how the Davis lab moves forward. Here they have several paths forward, and they can follow more than one at the same time if they get enough funding, and if they are willing to:
  • Use the nanoneedle they have to do as much research as they can.
  • Develop a higher through put version of the nanometer, so they can do more research.
  • Use their nanoneedles to test other people's blood samples, so those other people can publish collaborative papers.
  • Sell or otherwise distribute nanoneedles so that other labs can publish their own papers.
Simply put, if they are the only lab who can publish papers (because they are the only lab with nanoneedles), then getting the nanoneedle test accepted by researchers in general will take years. They can only publish so much, and it will take several big published studies to build a foundation of acceptance. And at some point there will need to be confirmation from other labs. Compare this to the two day max-O2 tests. Those have been replicated a couple of times over the last several years, and they still are not widely used. Now I do think that as a blood test, the nanoneedle has a big advantage over the max-O2 test, but even if this results in a much faster acceptance, it is still going to be years (just fewer years).

The other option is to make the nanoneedle available to any lab that can pay for it. That could speed things up considerably. It allows several labs to publish papers all at the same time, which means that all three steps described above could be done at the same time. More importantly, no one will worry that this is a effect of the Davis lab, if the same thing is seen at many labs.

As a comparison, consider the XMRV paper. This was a similar situation in that it was a blood test, but it was different in that many labs could do it with equipment and expertise they already had. In that case, at least four different labs did research and published results within four months! Now they happened to disprove the test, but if things had gone the other way, then there would have been five successful tests in four months. That would be a near instantaneous (by ME/CFS standards) confirmation, and would build a lot of momentum. Conversely, if we had had to wait around for the WPI lab to publish five papers, it would have taken a lot longer. Even if successful, no momentum, and the fact that they all came from the same lab would have been a problem.

I thought I read somewhere that making a nanoneedle (copy of the existing slow version) would cost about $30,000. If that is right, then the thing that OMF could do to speed the research more than anything else, would be to spend $90,000 to make three more of them, and then have four labs publishing papers. In the scientific world, consensus happens much faster if mulitple labs are publishing similar results, than if just one is.

Joshua
 

ebethc

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I thought I read somewhere that making a nanoneedle (copy of the existing slow version) would cost about $30,000. If that is right, then the thing that OMF could do to speed the research more than anything else, would be to spend $90,000 to make three more of them, and then have four labs publishing papers. In the scientific world, consensus happens much faster if mulitple labs are publishing similar results, than if just one is.
they may want control over the process, too... ie, it's a new instrument and a new test, so to ensure consistency, they may want run the tests themselves for awhile..

what is the cost of running a larger test, and how much money do they have towards that goal? hopefully the article that CNN published will generate some buzz that will bring the money to get the next stage funded.
https://www.cnn.com/2019/05/12/health/stanford-geneticist-chronic-fatigue-syndrome-trnd/index.html