Rituximan - Norweigan Funding Disappointment

[Firestormm]

I picked up on a thread posted by the Invest in ME Charity here in the UK this morning, reporting that whilst it was expected an application for funding would have been reviewed today in Norway, it did not even make it on the agenda at the Norwegian Medicine's Agency conference:

IiME Facebook announcement - 4 December 2012: https://www.facebook.com/groups/5804522506/10151166038877507/?ref=notif&notif_t=group_activity

Tomorrow Norways equivalent of the Medical Research Council will announce whether Professor Mella and Dr Fluge will receive the funding for the next phase of their research.

Update IiME Facebook page - 5 December 2012:

"It seems not to be looking good - no mention of ME on the list"

"It seems that the Norwegian Medical Research Council have not given this funding"

"Unfortunately, nothing ever seems to be easy when it comes to biomedical research into ME. IiME will now take this up with the Norwegian ME Association. We have previously discussed ideas with NMEA and will now begin again. Let's be clear - this will happen."

Back to the drawing board it would seem to search for alternate funding sources. This event apparently was in relation to an update posted by the Norwegian ME Association back in March 2012 (bolded):

What is Happening with the Research ​

into ME and Rituximab?​

By Anette Gilje
Secretary General, Norwegian ME Association

The cancer doctors Øystein Fluge and Olav Mella, Haukeland University Hospital, published their study on ME and rituximab last autumn. Following their sensational and promising findings that some people with ME had benefitted from the immune modulator rituximab, the Government allocated two million Norwegian Kroners (approx. 220 000 £) to the Western Norway Regional Health Authority to help funding a larger follow-up study.

– This is far from enough to fund a larger, double-blinded multi-center study which is necessary to determine the scientific research question: Does rituximab have an effect on this patient group, or not, says Professor Mella.
– We do believe it has, but this has to be confirmed in a larger study to gain scientific credibility internationally. To be reasonably certain to answer the question, the study probably has to include between 120 and 140 carefully selected patients that meet the Canadian Consensus criteria. The patient-sample will be divided into two groups, one of which will receive active treatment with rituximab, the other placebo (i.e. inactive substance). Both groups will be closely observed for potential effects and adverse reactions.

Providing the study can confirm a significant effect in the group that was given rituximab and the adverse reactions are acceptable, the placebo group will be offered treatment with rituximab at a later point of time.

A scientific study of this scale cannot be initiated before the whole project is fully funded. So far Drs Fluge and Mella are working on a draft protocol for a larger study in corporation with the ME/CFS-Centre, Oslo University Hospital (Aker). When the preliminary protocol is completed, it is time to establish collaborations with other research communities that want to take part in the study. After that the research protocol will be submitted to the Committee for Medical and Health Research Ethics and the Norwegian Medicines Agency.

Professor Mella says it is extremely important that the research centers included in the study are dedicated to the task. They need people who are very good at diagnostics and that can administer the rituximab treatment in a safe manner for the patients. - If you can’t accommodate this, it’s probably better for the study to be carried out in fewer institutions.

Adverse reactions
Rituximab is known to have some serious, but very rare adverse reactions.
– Our experiences in working with cancer patients show that this is a drug that do not trigger a lot of adverse reactions, Mella says.
– What you do, is to deplete the B-cell lymphocytes which are normally responsible for production of antibodies. Because this is done only for a limited period of time, many of the mature B-cells are still circulating in the blood stream. The increase in infections in most patients receiving this treatment is small. There is, however, a theoretical risk for serious infections. That is why it is necessary to be alert when looking for emerging signs of infection.

Dr Mella explains that rituximab is a protein substance that is partly produced from human material and partly from mouse material. The tendency for allergic reactions is increased compared with some other drugs. That is why it is important that the patients receive the drug under observation, preferably at a rheumatological-, neurological- or a cancer ward.
– If you are used to administer rituximab and know what to do if allergic reactions occur, we see this as an easy treatment, Dr Mella reassures.
– The patients must be under observation for some hours when they receive the treatment in the ward, and they are admitted for 24 hours to make it possible to deal with potential adverse reactions.
–It is important to stress that we do not know if ME patients may have more or other side effects compared to patients with cancer or rheumatological diseases.

Biomarkers
Drs Fluge and Mella have worked for almost three years in their search for biomarkers for ME, thanks to the funding from Western Norway Regional Health Authority. In their search, biological samples from the study participants are investigated in the laboratory. The patients’ clinical picture is the researchers’ starting point in their search for biomarkers. From there they can reflect where the problem might be located and search for abnormalities. Dr Mella admits that there is always a need for money for research, more can be done and things can move forward a little quicker.

Translated by
Ellen V. Piro and Eva Stormorken
Norwegian ME Association
16th March 2012

The translation has been approved by Professor Olav Mella and is published with his permission.

http://www.investinme.org/InfoCentre-Library-NMEA-Newsletter-1203.htm

Am trying to get more details and will post when I get any.

 

[user9876]

I just saw this blog post suggesting it was rejected. I think it is from one of their original patients

http://translate.google.co.uk/trans...lv-funding-rejected-patientdriven-foundation/

 

[Firestormm]

I just saw this blog post suggesting it was rejected. I think it is from one of their original patients

http://translate.google.co.uk/translate?hl=en&sl=auto&tl=en&u=http://mariasmetode.no/2012/12/forskningsradet-har-avslatt-soknaden-vi-samler-inn-selv-funding-rejected-patientdriven-foundation/

Thanks User. I had that one sent to me too. Just hadn't gotten round to reading it since starting this thread! So it seems they might have turned it down because the agency don't have the money? So it did at least get looked at?

 

[user9876]

I don't really understand why they need such a big trial. I know that this is a fashion from the evidence based medicine crowd but I think that is due to a lot of treatments not really working. If the treatment works in an obvious way why do you need more than 15 in each group.

What I would have thought was more important is to see if other groups can replicate results. This not only helps deal with issues of a trial being a fluke but also ensures that the protocol is workable and reproducable.

 

[user9876]

Another news article via google translate

http://translate.google.com/transla...en-penger-til-videre-meforskning-3940193.html

Despite the lack of assignment is Mella still positive with a view to launch a larger study.

- We will continue to work to start the study. There have been allocated in the state budget this year and next year. It would surprise me if no trial gets underway in the foreseeable future, says Mella.

Should there be long Mella think that other countries will follow.

 

[Sasha]

I don't really understand why they need such a big trial. I know that this is a fashion from the evidence based medicine crowd but I think that is due to a lot of treatments not really working. If the treatment works in an obvious way why do you need more than 15 in each group.

What I would have thought was more important is to see if other groups can replicate results. This not only helps deal with issues of a trial being a fluke but also ensures that the protocol is workable and reproducable.

These two issues are related. Other researchers often won't try to replicate a very small trial: they want to see substantive results before they invest their time and effort. The number of patients to be included in the Fluge & Mella study will have been worked out to a standard formula that uses their estimate of the true effect size of Rituximab to ensure that they've got a good chance of succeeding.

 

[Firestormm]

Another news article via google translate

http://translate.google.com/translate?hl=en&sl=no&tl=en&u=http://mobil.tv2.no/nyheter/innenriks/helse/ingen-penger-til-videre-meforskning-3940193.html

Bloody hard trying to understand these translations, isn't it?

So state funding, in part, for next year then? I think I shall wait for a summary or somesuch to appear. I'm confused - but then that's nothing new

 

[Firestormm]

Picked this up from Norwegian contributor on Facebook:

Actually there were 3 other studies on CFS or ME [also refused funding]:

"Cytokines in relation to CFS/ME, FM and other complex disorders, including depressive symptoms" at the University Hospital in Trondheim. As far as I know they use unexplained chronic fatigue as criterias.

"Disease mechanisms in chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME): an integrated, translational approach" at the University hospital in Oslo. They do use chronic fatigue!

"Lightning Process and Chronic Fatigue Syndrome/Myalgic Encephalomyelitis" at The Norwegian Institute of Public Health

I dare say that last one wouldn't have caused many tears to be shed...

The Norwegian MP Laila Dåvøy, who has fought the battle in Norwegian parliament for ME-sufferers for many years, is furious.
To TV2 she says: "It is sad that we don’t have appropriate treatment for some of the sickest people in our country."

She is disappointed by the MRC but is furious at the government.

I'm tempted to say: "So much for the public apology" but I'm sure there's more to this than what has been commented upon. Lack of money generally is one likely culprit behind these decisions.

 

[user9876]

These two issues are related. Other researchers often won't try to replicate a very small trial: they want to see substantive results before they invest their time and effort. The number of patients to be included in the Fluge & Mella study will have been worked out to a standard formula that uses their estimate of the true effect size of Rituximab to ensure that they've got a good chance of succeeding.

If the effect is sufficiently big then is it necessary to estimate the true effect size. I think evidence based medicine has gone down a route where effect sizes of different drugs are often so small that they need to do big studies and cherry pick results to show anything.

I thought what was more interesting is that Fluge and Mella seem to want to do a lot of blood monitoring to see and understand what is happening. To me this will advance the theory which should provide a much more convincing argument (and hopefully help in predicting who will react).

 

[Aileen]

Picked this up from Norwegian contributor on Facebook:
I'm tempted to say: "So much for the public apology" but I'm sure there's more to this than what has been commented upon. Lack of money generally is one likely culprit behind these decisions.

This keeps happening ... money or help is promised but usually falls through. The only way is to raise it ourselves. With this huge disappointment from Norway, the new Canadian centre in Vancouver is even more important. We are trying to raise $150,000 for a biobank, and all patients need to do is vote. But few will do it.

If you want research, vote. We need to stop complaining and start acting! Please start today. Detailed info is here: http://forums.phoenixrising.me/inde...biobank-for-the-vancouver-clinic.20712/page-2
For detailed voting instructions (brainfogged individuals):
http://forums.phoenixrising.me/index.php?threads/aviva-contest-semi-finals-for-150-000.20742/page-2
(see pdf file in post #30)

 

[Anne]

I agree, Aileen, this just goes to show that we can’t rely on public funding, we need to use all the alternative ways we can, such as the Aviva contest. Please everyone, vote daily and engage friends and family! You can find detailed voting instructions at the link in Aileen's post above or in a public post on my Facebook account (Anne Örtegren/Anne Ortegren).

Perhaps I can clear some of the Google translage confusion up (I'm in Sweden, and Norwegian and Swedish are similar)...

Here's what I wrote on Facebook (public, see Anne Örtegren/Anne Ortegren on Facebook)

"Funding for large Norwegian ME/CFS treatment trial rejected – Patients will start fundraising

The Norwegian Medical Research Council have rejected funding for a larg Rituxan trial for ME/CFS in Norway. The planned multicenter trial (placebo-controlled with 140 patients) is put on hold after the Norwegian MRC has decided to decline funding of the study. This is surprising, given that Rituxan in the previous study has shown promising effect, that 2/3 of ME/CFS patients seem to be responders and that some of the patients even report near complete recovery. Once again ME/CFS patients are left without research funding that could lead to effective treatments.

Norwegian patients are starting two fundraising campaigns to fund the study. Though I think this really should be federally funded, I’m glad we are given a chance to raise money ourselves. The Rituxan research has to continue!

These two fundraising campaigns will soon begin:

Norges ME-forening: Kronerullingsaksjonen
http://me-foreningen.com/meforeningen/?p=4701

Patient driven foundation, started by Maria Gjerpe: MEandYouFoundation.no
http://mariasmetode.no/2012/12/fors...lv-funding-rejected-patientdriven-foundation/ "

On future state funding, Firestormm and others:
<<So state funding, in part, for next year then?>>

Three applications need to be approved for the Norwegian multicenter trial to take place:
1) The large part consists of medicine costs, and this is what Fluge and Mella applied to the Norwegian MRC for (the application that was rejected today)
2) Regional public health council in Bergen (Haukeland Hospital) - for the staff/running costs
3) Regional public health council in Oslo (Aker Hospital) - for the staff/running costs

For the large part (1), they will now need to re-apply to MRC for funding, or find funding elsewhere. They can re-apply to MRC, using different categories, and the Norwegian Minister of Health today said that he would instruct the MRC to give ME/CFS high priority for 2013 (one thinks that statement could have come a little earlier...) So there's still chance for state funding, but it is of course uncertain, and there will be a substantial delay.

The smaller costs, (2) and (3), I'm not so worried about, it's the medicine cost (1) that's the tricky one, I believe.

To try to secure this trial, and not be dependent on future decisions of the MRC, the Norwegian patients are starting these two fundraising campaigns. Should the Rituxan trial receive public funding, the money raised will go to Fluge's and Mella's other projects on biomarkers, disease mechanisms, etc. They are doing some impressive work and have a lot of sharp ideas (wishing we could clone them and give them all the funding they could wish for...)

 

[Kati]

I would like to know if the LP study has received an answer today too, or are they still waiting for an answer?

I am so so so sorry, Norway. We will fight for you.

 

[Anne]

Kati, the LP study didn't get money either. There were 4 proposals for ME/CFS projects: the Rituxan study, a cytokine study, the LP trial and a study by the Pediatric ME/CFS (rather CF...) clinic at Oslo University Hospital. None of them got funded. Those of us who view ME/CFS as a physiological disease whichs needs biomedical research are heaving a sigh of relief that the last two didn't get approved. Lightning Process is of course not the answer for ME/CFS and money should not be wasted on such a study, and the Pediatric ME/CFS clinic at Oslo University Hospital is headed by Dr Vegard Wyller and he and his team are well-known for looking at ME/CFS from a psychosocial angle, and not being too concerned about distinguishing between chronic fatigue and ME/CFS (as defined by CCC or ICC).

As this great Norwegian blogger says (in Norwegian...), perhaps the Norwegian MRC just didn't want to get into the whole debate and instead funded none of the ME/CFS projects.
http://www.serendipitycat.no/?p=9974

 

[Kati]

We will just have to fund our own studies then. It's so terrible there is such a black cloud over our disease.

 

[ukxmrv]

Aileen and Kati,

In what ways will the Biobank allow us to study treatments for ME and CFS more quickly?

I'm just asking as the same question came up on the proposed UK one and I never say an answer here.

 

[Aileen]

From what I understand, and I don't have first-hand knowlege, is that there is already a research project of some sort in at least the planning stages. The clinic is set to open sometime in 2013, I believe they are aiming for spring. They are hiring doctors now.

However, when it opens, if they do not have a place to store the samples or equipment to process them, they will not be able to begin research even if the study is ready to go and funding in place. We want to be able to get this stuff so the clinic can start collecting the samples from the very first patients. And, by having Aviva Insurance company fund this equipment, that means an extra $150,000 for research rather than for a very expensive, special fridge etc.!

 

[Kati]

What Aileen said!

Essentially, when patients come for their visits,they get blood drawn, and if the agree, get it stored for research. the questionnaires will be in place, so it will be easier to fnd the right cohort for the different diseases, all they will need is use the blood.

 

[taniaaust1]

This keeps happening ... money or help is promised but usually falls through. The only way is to raise it ourselves. With this huge disappointment from Norway, the new Canadian centre in Vancouver is even more important. We are trying to raise $150,000 for a biobank, and all patients need to do is vote. But few will do it.

If you want research, vote. We need to stop complaining and start acting! Please start today. Detailed info is here: http://forums.phoenixrising.me/inde...biobank-for-the-vancouver-clinic.20712/page-2
For detailed voting instructions (brainfogged individuals):
http://forums.phoenixrising.me/index.php?threads/aviva-contest-semi-finals-for-150-000.20742/page-2
(see pdf file in post #30)

I think raising money for any one ME/CFS is very hard at the moment as there is currently three VERY MAJOR THINGS which are currently needing more funding to go ahead (the further immune studies that Dr Peterson along with the Australian researchers is also currently trying hard to raise money for a piece of equipement so the study can be done).

Its sad that so much of our major research is being held up due to lack of funding.

We really need like a big public foundation in which some other illness societies have eg like the heart foundation so we can be attracting funding more from the general public to help fund our studies etc. In Australia the MS society also has big public funding campaigns in which a big mail drop asking for donations gets done. This is what where we are lacking which we need and could help us. We need to form this or get our existing ME/CFS foundations doing more active fundraising to general public by helping them in some way to do this.

Can any of our ME/CFS societies get media coverage over that we cant get a much needed study done due to lack of funding and then ask for public donations? We need what is going on in the mainstream media along with request for money to go towards study. (I think in media coverage.. that is where our ME/CFS orgs are generally lacking thou it should be part of their aim things like this). This lack of funding for a very important study, is an ideal advocacy opportunity to which shouldnt be being wasted!!! We need our ME/CFS societies to get smarter and start filling in these gaps if they wont.. we need to find orgs which will which need our help to do so. (there are some small ME orgs around which are currently trying to do a lot).

Maybe we need to form like some kind of committee (if there isnt one already) with goals and aims with the big aim of getting the ME/CFS groups out there working better for us including having better fund raising ways set up (putting pressure on them to actually have goals they are working towards and helping them to see what is lacking and what needs working on for the betterment of ME/CFS worldwide. I generally dont hear about action plans of our societies other then they all have a general goal to support us etc. and we need some kind of action plan in place to work to fix the gaps we have including getting more publicity, getting more money from the general public rather then just thou memberships etc What are those societies we support doing about these important things which we need happening?

Im not bashing our societies with this post but rather wanting to know why our societies are not being very successful compared to some other groups and thinking this needs looking into and should be being worked towards to impovement with set goals and plans to improve this. Yes our societies often dont have much manpower but is it hard for a society to do a media interview on something to help us bring in money? or be arranging better ways to fundraise eg good letter drops like the more successful groups do or whatever. Some of the big groups raise money eg Society of the Blind by selling their products which is sometimes is done via phone (most of us are stuck at home and money of us can use phones so could pitch in to be salespeople at times if a society had good stuff for sale for a fundraising thing). We are missing doing ALL the other things the other successful societies do.

I have an image of my head of one thing which could be sold by our ME/CFS societies which the general public would love (esp since what they think of our illness anyway). A pillow case which says "I have chronic fatigue syndrome" with a picture of a cute dog or cat sprawled out on his back asleep. (yeah I hate the term CFS but if something is bringing in money by being popular with the general public.. I dont care less what it says if it was bringing in money to fund "good" studies for us... the society when the pillow case is sent out could include a good info sheet on the real facts of ME/CFS).

All I know is much more needs to be being done if we are to get and to keep getting the money we need and we need to take a good look at what the other successful medical disorders societies are doing . If we dont make some changes for the better and start fundrasing more for ME/CFS.. we could even end up loosing the researchers who are currently interested in doing good research for us due to lack of funding in ME/CFS. That would be disasterous for us
...........................

I suggest a good first step in regards to this latest news is emailing your local ME/CFS society and asking them to put something on thier website about this latest news and how this study needs more funding to go ahead and ask if they will collect donations for this study (unless there is a certain place they could get people to donate to for this study?)