Thanks for this very interesting post John where you raise such a plethora of issues. I'm not sure where to start but maybe the best way is to break it down. It is a rather long post so apologies to those who might not be interested in this kind of detail.
The current situation:
NICE:
Last week’s meeting of the NICE Board decided not to adopt what was called value based pricing but is now something rather different called value based assessment, into the formal set of methods NICE uses to appraise new drugs and follows the publication earlier this month of a revised version of the formal processes that NICE deploys to assess new drugs. From a patient and patient organization perspective there have been no substantial changes, at a formal level, to the way the system will operate.
CDF:
The announcement at the end of August of a £80 million increase in support for the £200 million per year Fund this financial year with the same next will assist in maintaining its financial viability until the expiry of the current extension of the Fund’s lifetime at the end of March 2016.
The Fund was overspent in the previous 2013/14 financial year and this has been written off. The overspend for this, 2014/15, year was predicted to be of a different order of magnitude hence the substantial injection of extra money.
However three other actions, two near immediate and one longer term, were also included in the announcement that are of importance which await a statement on any progress made.
The first of two is an 'ask' being made of the pharmaceutical industry on the cost of the drugs in the Fund which would be ‘added’ to the extra money being committed by the NHS to meet the projected overspend.
There are various possibilities for how this would be achieved and negotiations will be taking place with the industry’s trade association, the ABPI, to attempt to arrive at a solution.
The second, which is conjoined to the first in my opinion, is that there will be a clinical performance based evaluation of all drugs on the national CDF list with the least effective potentially being ejected from the list. This is widely referred to as 'de-listing'.
Even in situations where there is only a single treatment for a specified condition which is recognized to be effective but its assessment score is lower than those drugs with a multiplicity of treatments for another specified condition, the theoretical outcome would be the ejection of the lowest scoring drug. In practice it is highly unlikely that this would occur given the consequences that would follow.
Given the Fund is an entirely political creation, I think it doubtful that any true de-listing will take place this side of the May general election.
I'm not saying a drug or maybe several drugs that are clearly and unequivocally clinically ineffective would not be ejected, nor am I saying that some kind of face saving nominal de-listing might not take place. This may take the form of de-listing a drug and then immediately re-listing it with changes to the criteria which must be fulfilled before an application can be made to the Fund for it to be reimbursed.
I should stress there are those who disagree with this view, some fundamentally and some just in the detail.
CML TKIs and the CDF:
As many will be aware three (dasatinib, bosutinib and ponatinib) of the five CML TKIs are only available via applications to the CDF. It's also worth noting that the criteria that govern any application made to the Fund are more restrictive than those for the European Medicines Agency license for their use.
Will this new environment reduce the already limited access to these drugs via the Fund? In my opinion I doubt if there will be further restrictions on access to these drugs.
What there may well be is a more coherent and rational approach taken to CML treatment with TKIs, be they those in the CDF or those with a positive NICE recommendation, for their use (ie imatinib and nilotinib) which if adopted would involve changes in the criteria that govern access to each drug in the CDF. Discussions are currently under way on such an approach but no firm conclusion has been reached.
The evaluation spectrum:
This brings me to the third action contained in the August CDF announcement which was a commitment to examine the process used by the NHS when they make decisions on committing funds for the purchase of cancer drugs.
Currently the NHS is legally obliged to make the drugs that NICE recommends for use in the NHS, including those used to treat cancers, available to patients. Applications to the CDF are treated in a similar manner provided the patient meets the criteria but as noted above this is hedged in with clinical restrictions.
The Fund is also both theoretically finite in size (currently at £280 million/year) and lifetime (with an end of March 2016 expiry date) which makes for uncertainty although not for patients who have been successful in applications made by their clinicians to the Fund who would remain ‘protected’, as it is known, were the Fund not be renewed on its expiry date.
As you point out any company wishing to secure a place on the list of drugs in the CDF must have their drug evaluated by a panel of experts operating within a set of procedures drawn up by the NHS.
Apart from the conceptual difficulty that arises from the existence of these two evaluation systems running, partially and occasionally, in parallel with each other the entire evaluation system is currently pressured by two other factors.
One is driven by scientific advances in genomics which permits patient populations to be subject to increasing differentiation, commonly referred to as ‘stratification’, with as you note in the case of CML many mutations based sub groups emerging.
When you add other pertinent clinical features a patient may exhibit (eg diabetes, a cardiac or lung condition) to the presence of a particular mutation or mutations you can see how the number of clinical configurations possible is so numerous that treatment becomes truly personalised to a particular patient. Hence the term ‘personalised medicine‘ and the slogans of this type that grossly describe the term ‘the right drug, at the right dose, at the right time administered to the right patient’.
The second is the availability of digitalization and the promise it offers in collecting instantly retrievable, real time data from a defined patient population that is subjected to a particular therapeutic regime. This of course theoretically enables what’s called ‘real world‘, as opposed to clinical trial, data to be collected on a vast, exhaustive scale in an entirely manageable way.
The NHS is currently developing a system designed to realise this ambition. It’s called the Systemic Anti Cancer Therapy Dataset (universally referred to as ‘the SACT’). It would be an understatement to say this is in its infancy or that there are not many who believe it will never reach the level of sophistication necessary to deliver that ambition.
However the telling point from an evaluation perspective is the shift of evaluation into the NHS environment rather than that of NICE.
Indeed the SACT is part of a wider NHS programme called Commissioning through Evaluation (CeT) which adds amongst other functions, an economic dimension to the, for cancer, that of the clinical (partially generated by the SACT).
The future: What’s it going to look like?
Very difficult to say is the short answer. There are many competing policy and institutional interests in play some of which I have not mentioned, the most important being industrial policy given the UK’s traditional advantage in this economic sector.
It's evident that everyone recognises that evaluation systems must adapt and change to ensure the system remains viable. That is we must have a system that is transparent, rational and consistent which is fit for purpose for the products it is evaluating.
We clearly do not have that at present.
What role can patient groups like CML Support play in all of this?
Not much on our own given the size of the CML patient population and the unusually, compared to many other cancers, beneficent therapeutic environment most patients exist within.
What we can do is to join coalitions of patient groups with similar interests and in doing so those coalitions can speak for tens, if not hundreds, of thousands of patients and thus obtain a hearing.
In practice this of course is much more difficult to achieve. There are various reasons for this but I’ll leave that for another time.
Best wishes,
David
