Some upcoming issues

Hi John

Some points in an even longer response to your long and detailed post. Some of my comments you will be aware of but I thought would write this for a much wider audience who may not know as much as you do.

The post reorganization NHS:

Its an understatement to say that what is called the ‘new world’ of the NHS after 1st April is in a state of unreadiness. As a consequence, quite a lot of the pre April 1st old world will be tolerated for some time within it. In addition what some of the new world will look like in detail is still a work in progress.

Clinical Commissioning Groups: How many? I thought the answer was 221 but on the DH website they mention 229. Who knows but I have never heard anyone mention a figure below 220. There are 152 Primary Care Trusts so we are looking at a 50% or so increase.

CML medication: As most of you will also know there is in the NHS (England) an internal market composed of buyers (referred to as commissioners) and sellers (referred to as providers) of services.

Let us also restrict ourselves to imatinib (glivec), nilotinib (tasigna) and dasatinib (sprycel) when we discuss available CML medication.In terms of commissioning these drugs fall within the chemotherapy category.

From 1st April all chemotherapy drugs will be directly commissioned by the NHS Commissioning Board. Targeted therapies, like the three mentioned for CML, fall within this category because the term is used in its technical rather than everyday sense. Specialist diagnostics for targeted therapies (presumably including PCR) will also be directly commissioned by the Board.

Commissioning includes both a commitment to pay as well as a precise definition of what will be provided to whom by whom from where for what.

NICE: This is where NICE recommendations are relevant.

Currently on diagnosis, and assuming a chronic phase adult CML patient is not recruited onto a clinical trial, NICE says imatinib and nilotinib are the two CML targeted therapy drugs recommended for treatment. If a patient starts on imatinib and proves to be imatinib intolerant or resistant then, as a second line of treatment, NICE says nilotinib would be the recommended treatment.

There is something called a Ministerial Funding Direction that provides patients with a legal right to access NICE recommended drugs and, in theory, patients should not experience any problems accessing these NICE recommended drugs.

For some 15 months no cancer drug has emerged out of the NICE appraisal process with a positive recommendation for its use in the NHS without what is called a Patient Access Scheme (PAS). For all these cases this has involved a confidential discounted price being agreed with the Department of Health and sometimes some other conditions being attached to the recommendation. So yes you are correct about nilotinib.

As you know bosutinib has begun its journey through the NICE process and we expect that if it emerges with a positive recommendation it will only do so if a PAS is offered.

Would I take a bet on the PAS offer? A small one only since there will eventually be an exception.

High Cost Drugs: People, including your former or current GP, can complain about the cost of drugs like imatinib but, if it carries a NICE recommendation, you have a legal entitlement to be prescribed it and have it paid for (reimbursed) provided your specialist consultant thinks its suited to your medical profile.

My feeling is that GPs should keep their personal opinions private otherwise you could always, in the same spirit, breach her/his privacy and ask him how much she/he earns for what etc and comment on whether you think value for money is delivered.

Specialist Hospitals/Units: Lets take your point about clinical commissioning groups and specialist hospitals. These groups commission (buy) services from providers like hospitals.

However there are some services, amongst which are Specialised Services, which the NHS Commissioning Board commissions itself (the process is generally described as being ‘direct commissioning’) including as noted above chemotherapy and specialist diagnostics for targeted therapies.

Many rare cancers, and CML is definitely that, have all or almost all their treatment directly commissioned with the providers generally being the specialist tertiary care provider hospitals or units.

We have a three tier system of service provision consisting of primary (GP care within a Clinical Commissioning Group), secondary (local hospital care, often District General Hospitals) and tertiary (specialist hospital care).

The ‘services‘: in Specialised Services is the important thing to note since we all tend to think in terms of diseases or conditions rather than the services provided to treat them.

There are service specifications and what are called commissioning policies for specialised services that define who gets what, where, when and from whom which together with NICE recommendations should result in CML patients being treated with the three drugs I mentioned continuing to be treated as they are now. The same would apply for the yet to be diagnosed population.

Exceptional funding: let’s restrict ourselves to what are called Individual Funding Requests (IFRs) which patients, or rather their specialist clinicians, currently apply to a patients PCT for payment for (reimbursement).

This system is going to change significantly for services that are directly commissioned by the Commissioning Board. At present it is unclear exactly how the system will operate but the ambition is to eradicate the post code lottery effect you mention to ensure that, no matter where you live in England, there will be uniformity of commissioning.

Dasatinib: as most will know this emerged out the NICE appraisal system with a negative recommendation. Currently patients throughout England are able to obtain dasatinib through applications made to the Cancer Drugs Fund. This is currently administered regionally but from April 1st the Commissioning Board will assume responsibility for the management and oversight of the Fund.

As many will also be aware the Fund reaches the end of its lifetime on April 1st 2014. Although there has been no formal announcement health Ministers have made it clear in replying to Parliamentary Questions from MPs that all patients currently having their drugs reimbursed by the Fund, including those who make successful applications in the future will, continue to receive reimbursement for their drugs after the Fund’s expiry.

How this mechanism will operate is not yet known.

It’s also worth mentioning that the manufacturer(BMS) of dasatinib is involved in attempting to secure a Patient Access Scheme that would make dasatinib available as a NICE recommended drug. We expect an announcement at some point this year.

Ponatinib: has obtained a marketing authorization in the USA (that is, it has obtained approval that it is a safe and effective drug for the treatment of CML) and has a similar application lodged with the European Medicines Agency (EMA). We expect an announcement sometime soon.

We therefore expect it to enter the NICE appraisal system sometime late this year which would result in NICE delivering a decision to recommend (or not) next year.

Given the wholesale price you mention and NICE’s remit (unlike the EMA) to assess both the clinical and cost effectiveness of a drug compared to standard treatments available in the NHS in England we expect ‘difficulties’.

Although as you say ponatinib, unlike any other targeted therapy, exhibits activity against the mutation T315i it also appears to be very effective in the treatment of all manifestations of CML at least in chronic phase.

Value Based Pricing (VBP): this is the new drug pricing scheme you refer to which will begin to operate on January 1st next year. This will only apply to new drugs not to drugs already reimbursed in the NHS like imatinib and nilotinib.

Dasatinib is reimbursed under the Cancer Drugs Fund and last August the Depart of Health indicated that they might enter some drugs reimbursed under the Fund into the VBP assessment system.

VBP is different from NICE because VBP is about ‘setting’ prices whereas NICE ‘takes’ prices drug companies agree internally before they enter a drug into the NICE system.

We know that VBP will consider issues NICE currently excludes from its assessment and appraisal process (HTA). Broadly these cover two areas.

One called 'Wider Societal Benefit’ would involve some sort of calculation of health resources used (referred to as, consumed or, more technically, utilized) by the patient set against those contributed (referred to as production). The balance is described as the negative/positive ‘net resource contribution’ made by a patient.

Consumed resources include NHS healthcare, and any Local Authority provided or contracted social care services, but in addition includes ‘informal’ care provision most typically by carers who are family and/or friends.

Production resources include employment remuneration together with ‘informal’ work performed in the family or community

Targeted therapies often allow people, if of working age, to work, are home based therapies and their use can allow patients not to need the active help of carers because life can often return to much the same as it was before CML manifested itself.

The other area is generally referred to as ‘weightings‘ and concerns patients who face a disadvantage because they have a high ‘burden of illness‘ and a lack of effective treatments available for them to use.

A high or heavy ‘burden of illness’ in essence means the condition or disease is so debilitating, everyday life is severely degraded or disrupted. When you add a lack of treatments that can make an impact that reduces the burden of illness, the condition becomes one for which there is an ‘unmet need’ for effective therapies.

If a drug is developed that dramatically answers that ‘unmet need’ (an example would be imatinib) it would attract a significant weighting advantage that would include it being viewed as innovative (referred to a Therapeutic Innovation and Improvement) in addition to any advantage it would gain by lowering the level of burden of illness.

I think about weightings in the same way as I think about the application of ‘handicaps’ or ‘positive discrimination’ in as much as its about leveling up and/or fairness.

One of the problems with the NICE system is that it is entirely neutral on this issue.

For example it’s theoretically possible (although this would never occur in practice) for a treatment that dramatically improves the success of treating severe fungal infection of toenails to generate the same ‘health gain’ as one that does the same for cystic fibrosis.

VBP weightings attempt to address this issue whilst also attempting to stimulate drug companies to think about developing drugs for conditions they would not normally consider examining for development.

Confidential VBP negotiations are currently taking place between the pharmaceutical industry trade association (ABPI) and the DH.

Given the complexity involved that would join an already complex system like that NICE already uses, my feeling is that simplicity will triumph over comprehensiveness in whatever scheme emerges.

2010 Equalities Act: as of October last year the public sector provisions of the Equalities Act became effective making it a requirement that public services, including healthcare provision, should strive to ensure equality of provision for all especially those known to be disadvantaged in the services they receive or are offered by the adoption of discriminatory practices by service providers. Populations that carry a signature called a ‘protected characteristic’ can seek redress under the Act.

One characteristic relevant to VBP is of course ‘age’ and there is currently much discussion on how a VBP scheme could operate effectively whilst avoiding any Equalities Act challenge.

Drugs for ultra-rare conditions: defined as having a total patient population of less than 500 in any one year. NICE will take over the assessment of drugs for these conditions on April 1st but this will obviously not affect CML patients. The assessment procedure will be different from that usually employed by NICE.

VBP and the Cancer Drugs Fund: you are correct in saying that the government line is that there is no theoretical need for a Fund once the VBP system gets under way.

However the political reality is rather different and there are many, including myself, that believe the government will retain some sort of Fund beyond April 1st next year.

I, unlike many, believe this will not be restricted to cancer drugs and that, although it may be labeled as a ‘transition’ Fund, the reality will be that it will remain in place for a considerable time span.

Imatinib patent expiry: NICE have promised a review of first line CML treatments in 2014.

Although NICE would deny it I assume this would be an attempt to clear up the current confused situation the Committee have navigated themselves into.

My guess is that they would include in their economic assessment a likely discounted post patent expiry imatinib price. The NICE assessment group argued for this in the nilotinib 1st line appraisal but the Committee rejected it.
I doubt they would in reject the same argument in 2014.

There is no disagreement that Novartis would have an ambition for nilotinib to replace imatinib as a first line treatment and could convincingly argue the case, with supporting evidence from NICE, that nilotinib exhibits greater clinical efficacy than imatinib, as it should given its 2nd generation status.

However I am not sure I follow the rest of your argument since other companies will want to enter the market with imatinib based generics on patent expiry.

The only way they will gain market share is by undercutting the imatinib price, whatever that would be, on patent expiry. The pressure on that imatinib price would therefore be firmly downwards.

There is a company called Teva that has a generic imatinib which obtained a marketing authorization late last year from the EMA for limited use which would not include chronic phase adult CML patients in England. I would be amazed if they were not to seek an extension of their authorization to include the vast bulk of the patient population on patent expiry.

So where does that leave patients like yourself? Those who are happy on imatinib and not wanting to change to nilotinib, or another targeted therapy.

I would say very happy because no matter what the outcome of the NICE review I’m almost certain any recommendation will carry a condition that existing patients on imatinib should be allowed to continue (with the usual clinical provisos). As such you will have legal right to access it as you do now.

For newly diagnosed patients I have no idea and I’m no expert on generics and/or their use for treatment of indications for which there are drugs which NICE has approved.

*I would say however that Novartis are one of the largest, manufacturer of generics and so it is not inconceivable that they would produce their own imatinib generic- albeit with a different name/package- which of course would be the same drug. It would make sense to keep the majority market share.

My guess is that commissioners will strive to ensure generics become the norm since a cost advantage gain will be present.

VAT on drugs:
I think you are correct in your description of the anomaly. I also think that what are called homecare medicines are also favoured not just for the VAT exemption but also because of other cost savings they incur. It is certainly a rapidly expanding market and I’m aware that the Commissioning Board have ambitions to extend the use of chemotherapy drugs into homecare provision. This includes drugs you and I normally think of as chemotherapy.

Regarding the emergence of hospital trusts as market traders in high cost drugs seeking commercial returns by predicting and taking advantage of currency fluctuations; I don’t personally see this as anything more than an occasional opportunistic activity, given the risks involved and the damage to the reputations of trusts should it become public knowledge. No doubt I’ll be proved wrong.

On the counterfeit drugs issue I agree this is a big problem for the companies and I know the UK regulator, the MHRA, is active in monitoring and prosecuting offenders.

This extends to those importing drugs that are not counterfeit but which nevertheless violate regulations. For example they recently issued a warning involving drugs imported from Eastern Europe which did not have patient information leaflets in English.

Best wishes,
David