Updated NIH reponse to CFSAC recommendations

[searcher]

I agree that Roche should study Obinutuzumab on ME patients but that isn't something NIH can control, unless there is something I don't know? I am sure Roche has been considering it.

 

[*GG*]

Here is an idea to get around the excuse of loss of patent for Rituxumab, that Pharma won't risk funding a costly phase 3 trial.

There are many advantages to doing Rituximab and obinutuzimab testing.

Seems like it would be an "excuse" because Lyrica first came out for Fibromyalgia in 2007. And is now advertised for diabetic nerve pain and I think something else!?

GG

 

[searcher]

Seems like it would be an "excuse" because Lyrica first came out for Fibromyalgia in 2007. And is now advertised for diabetic nerve pain and I think something else!?

GG

"Pfizer Inc., the world’s biggest drugmaker, won a court ruling that will block generic versions of its No. 1 product, Lyrica, in the U.S. until December 2018. "

http://www.bloomberg.com/news/artic...ins-ruling-to-block-generic-lyrica-until-2018

It's frustrating but drug companies really have no incentive to spend tens of millions of dollars on Phase III trials unless they can get a return on their investment. To make it worth their while they need to extend their patents, create slightly modified versions of their drugs, or develop entirely new drugs (with the first two options being much cheaper and easier.)

 

[Kati]

I agree that Roche should study Obinutuzumab on ME patients but that isn't something NIH can control, unless there is something I don't know? I am sure Roche has been considering it.

There are no law out there saying that a pharmaceutical company is obligated to put a ME-designated drug on the market, which implies to fund clinical trials and pay for drug development which is a billion or more venture these days.

This is not how things go, unfortunately. Pharma follows the money. Cancer, HIV, erectile dysfunction, male pattern baldness is where things are at.

Moreover, in order to 'get' clinical trials, there needs to be one of our ME expert, ideally, to work with pharma. Which means, we need a larger base of physicians experienced with ME and co-morbidities. Centers of Excellence would help this process greatly.

Also in order to send a strong message to pharma to invest in ME, we need the Pace trial retracted and the Cochrane reviews demolished as well. Because as of now, the best treatments for ME are CBT and GET.

The best that patients can do is to build a relationship with NIH to ensure the best possible case scenario study, funding opportunities for new researchers to enter the field, and speak with their political representant to vote funding money.

The need for biomarkers is crucial for us to move forward.

Don't blame pharma.

@searcher I am not pointing the finger at you but I am simply commenting on where the conversation has been going

 

[searcher]

There are no law out there saying that a pharmaceutical company is obligated to put a ME-designated drug on the market, which implies to fund clinical trials and pay for drug development.

This is not how things go, unfortunately. Pharma follows the money. Cancer, HIV, erectile dysfunction, male pattern baldness is where things are at.

Moreover, in order to 'get' clinical trials, there needs to be one of our ME expert, ideally, to work with pharma. Which means, we need a larger base of physicians experienced with ME and co-morbidities. Centers of Excellence would help this process greatly.

Also in order to send a strong message to pharma to invest in ME, we need the Pace trial retracted and the Cochrane reviews demolished as well. Because as of now, the best treatments for ME are CBT and GET.

The best that patients can do is to build a relationship with NIH to ensure the best possible case scenario study, funding opportunities for new researchers to enter the field, and speak with their political representant to vote funding money.

The need for biomarkers is crucial for us to move forward.

Don't blame pharma.

@searcher I am not pointing the finger at you but I am simply commenting on where the conversation has been going

No worries-- I think we are saying the same thing. We need new researchers, Centers of Excellence, and biomarkers. NIH seems to understand right now that they need to encourage new researchers to enter the field using mechanisms like RFAs, and it sounds like we will find out many more details in May. I don't think pharma is to blame in any way (although Hemispherx has definitely made their share of missteps), but in the US pharma is who generally funds Phase III studies. It's hard to imagine drug companies stepping in right now when even patient selection is so controversial.

 

[LiveAgain]

The stupidest thing I just cant get over about this NIH study is why is there not a huge component dealing with Dyautonomia, blood volume, tilt tables, biopsyies for SFN....Why have none of the organizations brought this up????? This could explain most of it....just like the overlapp and stats related to POTS.

@Justin30 I think they're doing tilt and sweat tests so they may be thinking along these lines. Would love to see skin biopsies too though.

 

[Justin30]

Get that punch out! Lol

I think it really important as both Oaklander and one of her colleagues pointed out how SFN besides causing pain redirects blood flows by affecting the blood vessels from what I can remember. This is what causes thee autonomic dyfunction and these fibers are connected to your brain/CNS.

It just seems that SFN if systemic and in the brain, spinal cords, muscles, skin and organs could cause and lead to severe dysfunction and damage.....possibly this damage could be what is talked about when they refer to damage to the Basal Root Ganglia?

 

[Snow Leopard]

I'll believe it when I see it. Worthwhile action, not words.

 

[joshualevy]

Unfortunately NIH does not often do Phase III trials (that is usually the responsibility of drug companies)

Is that by federal law or by tradition? If they don't know how to organize one they could probably get a few pointers from Professor Edwards or Dr Fluge or Dr Mella.

It's not law, and it's not really tradition, either. It's more because of practicality. Phase-3 studies must be large (their goal is to get FDA approval). Therefore, they are very expensive, which makes them hard for the NIH to fund. Also, they are supposed to be done after successful Phase-1 and Phase-2 studies. But at that point, the company that is developing the drug or treatment is usually well positioned to fund the study itself or find a partner to help fund it. (Based on the good results from the phase-1 and phase-2 studies.) Therefore, from a practical matter, government agencies rarely fund phase-3 studies.

 

[viggster]

It's not law, and it's not really tradition, either. It's more because of practicality. Phase-3 studies must be large (their goal is to get FDA approval). Therefore, they are very expensive, which makes them hard for the NIH to fund. Also, they are supposed to be done after successful Phase-1 and Phase-2 studies. But at that point, the company that is developing the drug or treatment is usually well positioned to fund the study itself or find a partner to help fund it. (Based on the good results from the phase-1 and phase-2 studies.) Therefore, from a practical matter, government agencies rarely fund phase-3 studies.

This is true. Also, NIH is funding fewer trials (of all phases) than it used to. NIH budget is down 30% in real dollars from peak in 2006, and trials are getting more expensive. Phase 3 studies are the most complex & expensive, and they almost always must be multi-site (sometimes dozens or even hundreds of sites are involved). https://www.washingtonpost.com/news...-is-on-the-rise-why-that-worries-some-people/

 

[Justin30]

Tl

This is true. Also, NIH is funding fewer trials (of all phases) than it used to. NIH budget is down 30% in real dollars from peak in 2006, and trials are getting more expensive. Phase 3 studies are the most complex & expensive, and they almost always must be multi-site (sometimes dozens or even hundreds of sites are involved). https://www.washingtonpost.com/news...-is-on-the-rise-why-that-worries-some-people/

I am bothered by that article in a couple ways.
First HIV Funding = 10% of the whole buget at NIH goes to this. HIV has a minimal burden on patient health compared to other diseases. This is an area of research that should be handed off to the private sector while NIH works on a vaccine. The meds available for this disease virtually eridicate it making virus levels undectable in human serum.

Private Sector/Big Pharma-like the Dr in the article said what do i prescribe my patients. There are too many medications being developed for the same illness so that big phama can capitalize continuosly on disease and symptoms once their drugs go off payent. This shows a lack of regulation and directed focus by the FDA and government. The example is that big pharma will make a new blood pressure med every time one goes off patented instead of having to focus on diseases that have no available treatments.

NIH budget Down 30%- Well maybe Fast Food Chains, Cigarettes, Alcohol and Big Pharma should be taxed higher so that the disease that these 4 major components of american society can be funnelled back into the NIH Budget because. Diabetes, obesity, heart disease, cancer, emphsyma, asthma, liver disease, kidney disease, and the list goes on. Why is the NIH left to clean up their mess while they capitalize on exponential monetary gain.

As far as I concerned they should be taxed more and that tax should be allocated to NIH. For example if Cigarettes are linked to cancer, heart diseaes, hpyertension, stroke, aneurysm, etc. Then they should have an extra tax thata pays for the disease it causes.

The additional funds should then be funneled into diseases with little support or research.

They may already do this in the US but then maybe instead of letting big pharma do as they please maybe they should be madated in direction that leads to better health for all diseases.

 

[medfeb]

It's not law, and it's not really tradition, either. It's more because of practicality. Phase-3 studies must be large (their goal is to get FDA approval). Therefore, they are very expensive, which makes them hard for the NIH to fund. Also, they are supposed to be done after successful Phase-1 and Phase-2 studies. But at that point, the company that is developing the drug or treatment is usually well positioned to fund the study itself or find a partner to help fund it. (Based on the good results from the phase-1 and phase-2 studies.) Therefore, from a practical matter, government agencies rarely fund phase-3 studies.

This made me think about the challenges with identifying the right patients for trials, especially when as many as 90% are not diagnosed - for a 1M prevalence, that would mean only about 100,000 diagnosed patients. Do you think there is anything in the lack of diagnosed patients and the FDA process that could be used to justify a smaller Phase III trial?

 

[joshualevy]

This made me think about the challenges with identifying the right patients for trials, especially when as many as 90% are not diagnosed - for a 1M prevalence, that would mean only about 100,000 diagnosed patients. Do you think there is anything in the lack of diagnosed patients and the FDA process that could be used to justify a smaller Phase III trial?

No. Phase-III trials are the final stage of testing; they are supposed to be rigorous. And a 100,000 patients is not exactly a small number, anyway.

If you really want to know how big a study is required, it is easy to find out. Just choose a disease similar to ME/CFS which is in a patient population similar to ME/CFS patients, and find out how big the studies were to get approval for a drug for that disease. MS comes to mind. Look at the size of the phase-III trials for the drug(s) approved for MS.

Remember that diseases that "come and go" in severity require larger trials to be sure the treatment is causing the recovery, and it is not just chance. Also, diseases in populations which have a lot of co-morbid diseases also require larger studies, because they "naturally" have more bad side effects, so it's harder to judge treatment safety. ME/CFS has both issues.

 

[medfeb]

No. Phase-III trials are the final stage of testing; they are supposed to be rigorous. And a 100,000 patients is not exactly a small number, anyway.

If you really want to know how big a study is required, it is easy to find out. Just choose a disease similar to ME/CFS which is in a patient population similar to ME/CFS patients, and find out how big the studies were to get approval for a drug for that disease. MS comes to mind. Look at the size of the phase-III trials for the drug(s) approved for MS.

Remember that diseases that "come and go" in severity require larger trials to be sure the treatment is causing the recovery, and it is not just chance. Also, diseases in populations which have a lot of co-morbid diseases also require larger studies, because they "naturally" have more bad side effects, so it's harder to judge treatment safety. ME/CFS has both issues.

Thanks for the feedback, Joshualevy

 

[Bob]

NIH ME/CFS funding announcement.
April 7, 2016.
http://grants.nih.gov/grants/guide/...46.html?utm_source=dlvr.it&utm_medium=twitter

Extract:

Multiple Institutes and Centers are interested in accepting investigator-initiated administrative supplement requests for existing awards to expand ME/CFS research within the scope of the parent award. For the purpose of this Notice, “within scope” may include the addition of assays, bioinformatics/modeling approaches, or human cohorts to the parent studies (e.g., adding ME/CFS cohort to a fibromyalgia study in humans). However, supplement requests for studies that are in a substantially different direction than the parent award may be deemed "out of scope." In such situations, applicants are strongly encouraged to discuss the aims of the proposed work and the scope of the parent grant with NIH program staff (see below).

Areas of interest include, but are not limited to, the following:

• Characterization of CNS-related biomarkers between new onset and established ME/CFS patients and appropriate comparison groups
• Identification of biomarkers in cerebrospinal fluid, blood, urine, etc. that can identify physiologically relevant subgroups of ME/CFS
• Studies elucidating autonomic abnormalities seen in the central or peripheral nervous system of patients with ME/CFS
• Studies to provide a better understanding of ME/CFS, prevalence, pathogenesis, and pathophysiology
• Identification of potential triggers or modifiers of immune responses or immune cell metabolism that contribute to ME/CFS
• Application of current methodologies (e.g., immune phenotyping) or computational modeling to better characterize human immune responses triggered by ME/CFS
• Elucidation of etiology of ME/CFS and physiological determinants involved in ME/CFS manifestations including but not limited to microbiome-related studies

 

[Sasha]

NIH ME/CFS funding announcement.
April 7, 2016.
http://grants.nih.gov/grants/guide/...46.html?utm_source=dlvr.it&utm_medium=twitter

Extract:

I think that deserves a new thread, @Bob

Is this an RFA?

 

[jimells]

Multiple Institutes and Centers are interested in accepting investigator-initiated administrative supplement requests for existing awards to expand ME/CFS research within the scope of the parent award.

This is good news for anybody with an existing grant. It looks like real progress.

Although it is for very small amounts of money:

NIAID: The requested award budget cannot exceed $150,000 in direct costs for up to 12 months.

 

[jimells]

Is this an RFA?

No. It tells existing researchers to ask for more money. Kinda like your boss is inviting you to ask for a raise. Who would say no to that?

 

[BurnA]

What is a typical level of funding - it says they shouldn't exceed 100 000 for most of them.

 

[viggster]

I think that deserves a new thread, @Bob

Is this an RFA?

It's not an RFA. It's a different funding mechanism. Researchers with existing NIH grants can apply to extend their studies to ME/cfs. This mechanism is a way of drawing scientists studying other (but possibly related) illnesses/phenomenon to ME/cfs. It's a smart move.

Edit: Some people on twitter are saying $550,000 is the total amount available. This is incorrect. The figures listed are dollar caps *per grant* (between $100,000 and $150,000 each).