You are here

Some ideas

Some of you have contacted me privately to ask for clarification of some of the NICE ADC point so that you can make comments on the NICE website.

I have sent this to one person just now and tried to answer some of his particular points and add a little more.

although I am still working on CML Supports submission (deadline 7th December) I think you should really use your personal viewpoints when commenting to NICE.

Your own views need to be expressed and I cannot help you with that.. nor should I. You all know the evidence in real every day clinical practice is there. You are patients, you are the ones who are expert on how these drugs affect you as patients... this is powerful information and NICE need to hear it expressed by the people that benefit and have most to lose should these 2nd Generation drugs of high dose imatinib become unavailable and people are instead offered... Interferon Alpha or best supportive care.

However as a guide you might find the following helpful, please use your own words when drafting your comments both to NICE and to your MP's.

1.
the evidence for both 2nd generation drugs efficacy in dealing with some of the imatinib resistant mutations that are apparent in some patients is well documented both in clinical trials of both drugs and in clinical practice.

NICE' appraisal committee seem to be saying that they do not accept the way the trials have been designed stating that because the data is from open label trials (drug is clearly identified) then it follows that the data are flawed because there is a possibility that the clinician would be biased in favour of one drug over the other !...

That is why they view the data as unreliable and would prefer to see double blinded trials... drug is not identified to the clinician or the patient.
Of course as both patients and clinicians know... all the drugs in question have differing side effects and also nilotinib has a completely different regime of administration based on fasting 2 hours before and 1 hour after taking the dose.. this is 2 x daily.. so double blind trials are/would be unworkable on that point alone.

NICE seem to have ignored the existence of mutational analysis and the clinical consequence imatinib resistant mutations...

2.
Why do they make the comparison with Interferon, when Interferon is of little use to CML patients?

Although they note that in clinical practice Interferon alpha is very rarely used now, as very few patients had/have a cytogenetic response over time, but the side effects were/are very severe for most and were/are disabling for many.
This is not a life saving option for the majority of CML patients but it is cheaper.
However the extra costs of interferon come in when you consider the side effects... lack of quality of life... lack of ability to continue to work and all those wider social costs to society... and lack of cytogenetic response for majority and therefore lack of overall progression free survival.

You might also remember that the Scottish Medicines Consortium have approved these drugs for use in chronic stage CML.
the All Wales Medicines Strategy Group approved them for CP and AC patients (or maybe all phases/), also the London Cancer New Drugs Group have given a positive appraisal.
You could try a google search on all the above for more details

Most recently the Peninsula Health Technology Commissioning Groups (PHTCG) produced a positive appraisal of both drugs for use in IM Resistant and IM intolerant CML patients who live within the Devon PCT areas.... 4 pct's covering Devon and Cornwall ... see the newswire section of CML Support Group website for details dates etc.

Devon PCT have told me that they will persist with their guidance and wait for (and then follow) the TAG produced by NICE in April 2010 (TAG= Technology Appraisal Guidance and represents final policy)

The numbers of CML patients who show resistance to imatinib is small...but this does vary, depending on sources used, from between 23% - 49% ...

Both drugs and HD IM are recommended by the European Leukaemia Network (ELNet) for use in IM resistant/intolerant CP CML if stem cell transplant is not appropriate.

They are also both useful in AC although the percentages decline depending on disease load. Dasatinib is effective to some extent in Blast Crisis and has been approved for use in BC. Nilotinib is not approved for BC.

Hope this gives some background and is helpful.

HI Sandy
Sorry, have been out of the country for a couple of weeks and am trying to catch up with all of these changes, but does this mean that for those of us who are resistance to Glivec and their local PCT have agreed funding for Dasatanib that this could be withdrawn due to this guidance?
K

Hi Sandy,

Thank you for all the work you are doing on this. I am currently wading through the NICE report trying to understand it and marvel at you are able to grasp the essentials so quickly. I am finding a lot that makes me angry when I think of the consequences of their finding for some people.

One statement I do not understand is:

"In our base-case deterministic analysis, our model predicts that dasatinib will typically be
taken for far longer than the other technologies under review, so incurring much higher drug
acquisition costs." Page 20

If dasatinib is only taken after failure of imatinib, how can it be taken for longer than someone who successfully uses Imatinib for the rest of their lives. Perhaps I am missing the point here. This becomes very important when you look at their cost analyses and comments like:

"The paucity of comparative clinical evidence in which treatment with dasatinib and
treatment with nilotinib has been compared with any other treatment in individuals with
imatinib-resistant or imatinib-intolerant CML impacts on the assessment of both the cost
and clinical effectiveness of the interventions".

In fact, their conclusion should have led them to agree the use of Imatinib and Nilotanib pending further work.

i.e they should be treated as innocent until proven guilty

"Effectiveness data are limited, but dasatinib and nilotinib appear efficacious in terms of
obtaining cytogenetic and hematological responses in both IMR and IMI populations. The
extent to which greater frequency and/or degrees of response which may impact on long
term outcomes is more difficult to conclude given the limited nature of the evidence base.
In particular, only one trial has compared either agent (dasatinib) with high dose imatinib.
The findings of this open label study, that higher proportions of patients experience positive
responses to dasatinib than high dose imatinib are importantly confounded by substantial
cross over at an early point in follow up.
In terms of cost effectiveness, it is extremely difficult to reach any conclusions regarding
either agent in the IMR population."

I think that this paragraph could be used to MP's and the media.

Basically, they are saying that, although they obviously work for a significant number of patients, because we do not have proper, independent scientific data, we are rejecting them.

Another one in the Daily Mail today to add to this and the liver drug a week or so ago. This is topical.

For those of you who'd like a quick link to the article Richard has highlighted above, here it is.

http://www.dailymail.co.uk/news/article-1230349/Bowel-cancer-victims-UK-...

The paragraph I found of particular interest (struggling to translate some of the article) was the one which mentions that NICE's maximum limit of £30,000 has been the same for 10 years which takes no account of inflation. For those of you yet to write your letters, I feel this is a good hard-hitting fact to raise.

Thank you Richard

Vickie

Hi Karena,

NICE ACD says that for those already treated with either nilotinib or dasatinb, they will have the 'option' of staying on treatment until the treatment is no longer of any clinical benefit.
However should those CML patients who are being treated with 400/600mg imatinib develop resistance/intolerance they would be offered (if transplant is not an option) Interferon Alpha and/or chemotherapy/Hydroxyurea or best supportive care. Neither second generation TKI's not high dose imatinib (800mg) will be available.

Vicky mentioned the threshhold NICE use for health interventions is at £30,000. This has not been changed nor has it been adjusted for inflation over the years since NICE started. We and other rare cancer groups have used this argument with NICE before.... they are fairly contemptuous of it. But it is a good one to include with the fact that these drugs are of high value and in the real world are saving many peoples lives..... plus the wider societal costs of cancer are much reduced. CML patients can remain in work and continue to pay tax, nat.insurance etc. They can continue education and go on to university or training etc. and so remain part of UK's investment in our economic future, and because the majority of us no longer die, the collateral psychological damage previously inflicted on our close family members- particularly spouses and children- is avoided and the costs of that are also saved.

I think ultimately this will be a political decision and it will really depend on how much media attention we can get in order to put pressure on the DH. I know they say that NICE is independent (ha) but our votes matter and politicians care about that!
Register your disapproval through the NICE website link and contact your MP. Try to get them to ask a question in the house.
WE know that it is not easy for those that do not understand how CML works and how these drugs have and are saving lives, so the need to get the message across in a clear and coherent way will be crucial.

Sandy

Thanks for that Sandy, my reading had come to that conclusion but it is a truly worrying option for others.
I have some sympathy (and I know this will get me into hot water) with NICE as I think the Government have put them into an impossible situation with regard to finances and they have been made the scapegoats for not enough money being invested into the NHS - clearly when finances are limited some unpleasant decisions have to be made but when you have politicians saying they must have diagnosis within 2 weeks for cancer it then seems a mockery that treatment won't then be available - its a case of we will tell you what you have wrong with you and then watch you die because we can't afford to treat you. All those sufferers in the lesser known cancers need to raise their voices as one to attempt to get things changed - will people in individual areas contacting their local press help?
K

Hi all,

Would it be at all possible for someone to come up with our main points of argument with the NICE report, in a more user friendly way, ie, a way in which we can get across these points in a short direct form. As we al know, MP's need quite a lot of time to fill their expenses forms in !.
Also, I would agree with other postings that any and all press coverage is valuable. The only time anything gets changed in this wonderful country is if there is bad publicity or civil unrest.
I also read in one of the Sunday papers that some PCT's are actually spending NHS funding on setting up groups to enable them to lobby NICE, actively encouraging them to decline expensive treatments !!, this is utterly farcical and in any sane persons mind, a national disgrace. Perhaps we also need to get these PCT's to be held accountable for this.

Craig A

There are a couple of very useful responses to the document on the NICE website from the Royal College of Physicians
http://www.nice.org.uk/nicemedia/pdf/RCPhysiciansComments.pdf
and the Roysl College of Pathologists
http://www.nice.org.uk/nicemedia/pdf/RCPathologistsAssessmentReportComme...

Both reports highlight the real difficulties faced in modelling the cost of these treatments versus the gain in life expectancy. Both reports flag up how uncertain are the assumptions in the appraisal report and indicate that changes in these assumptions will drastically change the outcome of the model, with a resultant differing outcome. May be helpful in any response to the consultation document..

Many thanks to Sandy for all her work in forming the CML.org response!
Regards

Andy

Andy,

Thanks for those links. The first one answers my question above, about the longer duration of treatment for dasatanib. This will only be true when dasatanib is the initial treatment. I had ignorantly assumed that most patients were started on imatinib.

John

Dear Andy..... thanks very much for the links to the RCP response to NICE on their website. I am sure these arguments will help a lot of people (including me) to formulate responses to NICE.

I noted in the a free London paper that the Health Secretary, Andy Burnham, said that Cancer research spending will not be cut. He said that 'scientific research' was 'ring-fenced' from cuts.
That's great but I wonder what is the use of scientific research if we, as citizens, cannot benefit by it?

Sandy

Simple question for anyone:-

How can anyone appeal the way NICE have reached a decision? I know we can appeal the decision itself, but how do we appeal the methods used by NICE?