Dear All,
please can you make sure you visit the NICE website on Monday (probably after midday) when they will make public their appraisal on NHS funding for nilotinib/dasatinib
The ACD and evaluation report will be posted on the Institute’s website on 16th November 2009. People who are not formal consultees or commentators for this appraisal can comment on the ACD through an email link on the website.
Sandy
Hi All,
To save you hunting around the site, here's the link to the report:
I haven't had a chance to read it yet (it's over 500 pages in total!)
If anybody else has the time or inclination to do so, could you post up a quick summary of the key points from the report as I'm not sure I'll understand it without some help.
Bhiru
Hello all,
Both myself & my wife have had a look at this document, but I have to admit that we have not read all 500+ pages, & I doubt very much that I would understand much of it anyway.
From what I can make sense of the results do not look to favourable as to the cost effective use of the drugs in the future. I did ask one of the doctors at the seminar in nottingham about what would happen to those of use allready on Dasatinib if the report went against us. I was told that it would probably depend on how your particular Pct had issued the instrucrions for its prescription to patients in the first place, as to wether the drug could be withdrawn once a final descision has been made.
I am back at hospital on friday & will be asking question about the future. All I can see at the minute is transplant if the drug is removed.
Bob
As far as I am aware NICE have issued a negative appraisal for both drugs (inc. high dose (800mg?)imatinib)
I have to read the document and check the summary (I have been ill) today and will try to summarise as soon as I can. I suspect it is a complete disaster for CML patients!!! I think they have refused on cost grounds.
Sandy
Having worked through the bulk of this, I have to say I'm finding their conclusions very strange indeed. Having rejected the manufacturers' own cost effectiveness analysis they appear to have gone out on a limb with their own analysis and ignored some very unlikely predictions it makes.
They seem to have:
1. predicted their overall survival curve based on MCyR response rates
2. calculated expected times on treatment from the study data
3. taken standard assumptions on length of AP and BP
4. assumed the balancing number is time in chronic phase without treatment after the treatment in question failed.
The results of the exercise are showing time to progression from chronic phase WITHOUT TREATMENT for the HD Imatinib and Nilotinib arms of 7 to 8 years on average. I can't see how this can possibly make sense given that TOTAL life expectency pre TKIs was only 3 to 5 years from diagnosis.
The conclusion that Dasatinib is not cost effective arises ONLY because of the effect of this 'calculated' length of treatment-free chronic phase being so much longer in their HD Imatinib / Nilotinib models, but the fact the the figure produced makes no sense at all in comparison with empirical data (and thus their model clearly doesn't accurately model reality) hasn't been mentioned.
Am I missing something?
Phil
Oh goodness Sandy Here I was lulled into a false sense of security. Talk about been there done that !!!!!! (for newbies this has echos of the fight we had to get Gleevec in the first place)
Well CMLers fought before and I guess we can do it again. If the decision is based on incorrect data how do we/the drug companies/ specialists etc start the appeal ball rolling?
Hope you are getting better, and that this blow does not push you too far down again. Let me know what we need to be doing.
ATB
Pennie
Hi Phil..... no you are not missing anything. You have got it entirely right.
I have waded through the ACD today and made a copy of the conclusions. What they say is that the trials they have studied are seriously flawed according to all their criteria as expert statisticians (do they every get cancer I wonder?)
Their final comment is that open label studies unduly influece the doctors/researchers running the trials. They also comment that some of the trials are industry sponsored (!) and therfore the coordinators might be influenced by the drug co. involved and prescribe their preferred drug. Never mind the patients response.
They would prefer (note 1.6.3) that 3 way double blind randomised controlled trials with separated cohorts of patient populations (one for resistant and one for intolerant) would be the ONLY way to ensure truly robust data.
So, patients would not know what drug or dose they were assigned to, neither would the doctor. The patients would be then be monitored and if they showed progression they would not be allowed to cross over. the 3 arms would be high dose IM; dasatinib; nilotinib without dose escalation/reduction.
Patients should be prepared to die in the interests of a collection of data that would inform their model of cost efficacy/utility per QUALY gained.
If this was done then they believe they would be 'very likely' to produce a very different cost utility picture. In other words they could satisfy themselves that the drugs really did work rather than having to rely on such flawed observational data as produced by clinicians.
I need to produce a response by December 4th to give to NICE to include in the FAD (final appraisal doc.) in January.
Members of the public can only submit objections through the NICE website.... I hope many will do that.
I will produce template letter to send to local MP's/Doctor's/PCT's etc.
I will post the NICE ACD executive summary conclusion in a following post.
Should this ACD turn into the FAD it will be a disaster for all CML patients should they fail 400-600mg imatinib as PCT's can use the FAD to refuse funding of either 2nd gen TKI. Those already on dasatinib or nilotinib will be able to continue until clinically judged not to be responding.
Then they might need to move to Scotland or Wales... unless the FAD effects the SMC decision. I am not sure how this will affect the recent decision by DEVON pct to fund both drugs. see under newswire Oct. 22nd
Sandy
Dasatinib and Nilotinib for CML
Executive Summary
1.6. Conclusions
1.6.1. Chronic phase CML
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. (IMR- resistant to imatinib)
All three models (Novartis, PenTAG and BMS) are seriously flawed in one way or another, again as a consequence of the paucity of data appropriate to construct robust decision analytic models with currently available data.
The economic picture is similar for people who are intolerant of imatinib, for whom even less data exist, and this comparison is made more difficult in structural terms by lack of clarity about what constitutes the appropriate comparator in current practice.
The findings of effectiveness studies suggest, perhaps unsurprisingly, that better responses are shown in people for whom second line therapy is indicated as a consequence of imatinib intolerance than in those who are resistant to first line imatinib.
However, reflecting the uncertainty about duration of therapy in particular, this ranking seems reversed in our economic analyses.
1.6.2. Accelerated and Blast Phase CML
The economic evaluations carried out by the manufacturers of nilotinib and dasatinib are seriously undermined by the absence of evidence on high dose imatinib in these
populations.
In response to this, both models assume that the effectiveness of imatinib therapy can be adduced from evidence obtained in an imatinib-naïve population using normal dose imatinib.
In addition to this factor, problems exist in all evaluations with Dasatinib and Nilotinib for CML
Executive Summary
With respect to cost estimates and only in the blast phase analysis of dasatinib (in which the new TKI dominates) do findings appear robust to changes in parameter assumptions.
1.6.3.
Suggested future research questions and priorities.
There are several randomised clinical trials of the interventions underway. It is perhaps surprising given the oral nature of the interventions and thus the relative ease of blinding of a study, that these are all open studies.
We feel that a three-way, double blind, randomized clinical trial of dasatinib, nilotinib and high dose imatinib would be the most useful addition to the scant existing evidence base
critical shortcomings: (somewhat paraphrased) in that the model used is parametised on the the basis of observation of MCyr and PFS defined and measured in different ways. Double blind 3 way RCT's would very likely produce a different cost utiilty picture.
If you make an objection please do so through their website link. The Appraisal Committees preliminary recommendations in section 1 may change after consultation.
It is very important to object any way you can.
Sandy
Hi everyone. I haven't posted on here for a while but I have continued to read your stories.
This scares me! I have today (!!) taken my first dose of dasatinib because glivec hasn't worked for me - I'm a glivec failure. I was diagnosed with CML in June this year and have failed to reach a haemotological response. For a while I was on an increased glivec dose (600mg) plus hydroxycarbamide to try to get a satisfactory response but to no avail. I was then referred to Hammersmith Hospital who recommended the switch.
I'm really worried that the drugs will be withdrawn - for what I've read as mainly economical reasons - which I'm still struggling to comprehend. Okay, I don't know how I'm going to react to the drug, but at least it's given me one more chance before we have to go down the transplant route.
I'm really, genuinely concerned as to what will happen to me and any others out there like me - or who develop resistance to glivec in the future?!
If there's anything at all I can do, I will. For those who lived through this with glivec, please let us know what we need to do to help.
Rachael x
Hi Sandy
Is it possible to put a link to the NICE website up on here. Also is there a template people can use for their comments- or is it best to do it in our own words (leaving out the defamatory ones!!!) Sorry to be thick but what do the terms FAD ACD SMC mean - do we need to be clear about these when we post on NICE site?
What questions should people be asking of their specialists over the next week?
Thanks for taking this on for us all, and please let us/me know if there is anything constructive to be done in other ways.
ATB
Pennie
Hi Sandy, I'm sure you've already thought of these, but a few points you may want to include in your response:
1. A true double blind trial would be almost impossible - a large proportion of CML patients are very active in finding out about their disease / treatment and many of them would immediately be able to identify which drug they were on eg by the instructions given on when to take the dose regarding mealtimes.
2. Whilst recognising the issues of open label trials, these are far less significant than in many trials as all measures of response are based on objective scientific testing rather than having any element of subjectivity
3. The paper makes no reference to mutation testing. Where resistance is caused by a mutation and it is known that the mutation is responsive to one drug but not another then to keep the patient on a drug known not to work would be grossly negligent. Similarly doctors will not waste money throwing the drugs at mutations such as T315I which they know will not respond.
4. Mutation testing also allows much better targeting of these expensive drugs to the patients on whom they are most likely to work thus improving cost effectiveness
The most fundamental issue of all though remains their grossly simplistic analysis giving a conclusion completely unsupported in the real world that taking Dasatinib will markedly decrease post failure survival times
Best regards
Phil
I'm quite new to this (Dx May 09) but was shocked to read the summary in the NICE report. Every consultant I've seen (and I've seen about half a dozen) has said that if imatinib doesn't work there are alternatives which are effective. That safety net (before considering a transplant) was comforting and that comfort has been taken away. It is clearly far worse for those already in a position where imatinib has stopped working or never worked or can't be tolerated.
I will now have to have a different sort of conversation with my consultant at the Hammersmith later this month as this clearly may affect all our futures in some way.
As a newbie to this, it would be very helpful to know what I should say in my objection. I would also be more than happy to write to my MP or anywhere else effective.
Dear Phil and Sandy
I have just sent of letters of protest to the Secretary and Ministers for Health, the Chief Medical Officer, my PCT and our GP on behalf of my 17 year old son with CML. I have drawn from your thoughtful arguments on the unethical nature of their proposed trial model, the fact that not all CML's are older but younger people contributing still to the Tax and NI system and the fact that these are proven therapies, given for clearly defined clinical needs. The fact that the older population with CML have already contributed over a working lifetime seems to have been ignored.
A letter to my MP (John Bercow; I expect very busy today!) and register of objection on NICE's website went on Monday. I'm trying to think laterally in exploring other media avenues in order to get our voice heard. I contacted the BBC in Oxford and have been successful in getting interviewed along with Sandy on the BBC Oxford radio station. I suggest other like minded people contact the BBC in their area with a view to making this a national voice of protest.
I also object to the fact that these drugs are available in Wales and Scotland when much of the money used to fund these assemblies comes from England. I predict a mass exodus over the Severn Bridge if the final answer is 'No'.
Sarah R
Dear Phil,
I am absolutely in accord with your points. I hope that others will be able to make the same or similar arguments about the inappropriate model that NICE is using and the points about the open label trials.
Your point about the lack of reference to mutation testing was also apparent to me but I think they have purposely and knowingly ignored this as they need to get the model to 'fit' the preferred outcome.
Thanks for your helpful comments. They will certainly assist me in my comment to NICE... and I hope others will be able to use them too.
Best to you,
Sandy
Dear Richard,
firtsly I want to reassure you that you are more than likely to continue to have a good response to imatinib. The majority of CML patients respond very well and hold that response over time.
Resistance or intolerance can be for a wide variety of reasons. Remember we are not machines or objects, but human beings with all the complicated and individual characteristics that that in itself implies.
So to reduce us all to the status of repeatable objects that all respond in exactly the same way to everything is a nonsense.
I know this must be really difficult for newly diagnosed patients as we all hoped that imatinib was/is such a 'good news' story it was bound to lead to even better therapy, and those hopes were right.
However, given the economic climate, health cuts for some are inevitable and it follows that those who will be asked to 'fall on their swords' will be the small rarer cancer populations amongst other groups that are not vocal or well organised.
I think you have voiced your objections very well already and so I suggest that you just use your first point about the safety net being taken away from you, and then move on to the immorality of people being told to go away and die when they know that there are drugs available that will save their lives is truly unacceptable. As I said in a previous post... if this was a childhood disease there would be no question of funding being withheld... I have never heard of a case concerning a child with a rare cancer being refused access to life saving therapy by any PCT exceptional treatment panel. It doesn't happen.
Read my own, and Sarah's comments, about the national insurance contributions that UK working citizens pay all their lives in order to have a humane and equal health system for all.
The economic model NICE's appraisal committee have used is scientific bunkum and should be challenged. NICE are now trying to export this model to other EU countries and I know from CML advocates in those countries are horrified at the prospect, they do not want it and are in fact very worried that their own governments might adopt it as a cost cutting measure.
How about some of those bankers paying back the public for bailing them out of a crisis their own mismanagement and greed brought upon us all?
Why are cancer patients being asked to pay? City bonus's? MP's expenses? Tax evasion? I could go on.
You just need to register your dismay and let your heart say the rest.
Use your own experience and story. Talk about your loss of confidence and loss of peace of mind that these wonderful drugs have brought you and your family. Do put pressure on your MP to ask a question in the House. Contact your local paper, radio etc.
Sarah managed to get her story on BBC radio this morning and it was very effective.
Sandy
