Leukaemia patients Rudolf Wenk, Hugo Geluk and Helen Pickering say the Government should fund cancer drug Glivec to keep them out of hospital.

See also... Tunnel vision approach to funding Glivec

Wednesday, 26 June 2002

PHARMAC
PO Box 10 254
Wellington

Attention Cristine Della Barca

Dear Cristine,

Submission on the Proposed Funding of Glivec for Chronic Myloid Leukaemia.

Introduction:

The Leukaemia and Blood Foundation of New Zealand is a Charitable Trust formed some 25 years ago. It was originally a research based- trust. However, in 2000 it’s objectives were extended to include Patient Support, Advocacy and Education.

Our Vision:

A world free from Leukaemia and other Blood Disorders.

Our Mission:

Making a Difference…by helping to find a cure for Leukaemia, lymphoma, myeloma and other blood disorders and improving care for patients, and their families, living with these diseases, by providing…
 Support
 Research
 Education
 Advocacy
 Medical equipment and facilitie

Our Objectives:

 Support and operate programmes for patients, and their families, with Leukaemia and other Blood disorders
 Fund research into Leukaemia, other blood disorders and services and the practical application of such research
 Provide educational opportunities for patients, families, health professionals and the community
 Fund medical equipment, services and facilities for use in the areas of Leukaemia and other Blood disorders

Submission.

Key points:

 Government and its agency Pharmac are under legal obligation to provide the highest obtainable standard of health to New Zealanders
 Pharmac’s proposed criteria for use of Glivec are discriminatory
 The proposed entry and exit critera offer little benefit to most patients with CML
 They also place severe limitations on therapy for the small patient group they purport to address i.e. patients with advanced disease
 The proposed criteria withhold therapy from the patients in whom Glivec produces the best results i.e. those in chronic phase
 The cost of Glivec is relative to its innovation and effectiveness
 Most patients on interferon incur downstream costs to Government through inability to work; disability benefits; and consumption of healthcare services
 Most patients on Glivec lead a normal life.

Our submission is in three parts.

Firstly: Legal Obligations

1. This submission from the Leukaemia and Blood Foundation of New Zealand (the LBF) addresses the question of the proposed restricted or partial funding of Glivec for patients suffering from CML. and the implications of such rationing; and access to pharmaceutical treatments.
2. Pharmac’s published comments in it’s operating Policies and Procedures about it’s obligations at law (1.2.3) are relevant to this submission, and some of our comments are directed to those issues. Of particular relevance is the expiry of the exemption under the Human Rights Act for Government and Government agencies. We believe this has a major impact on Pharmac’s decision- making protocols.
3. The proposal to restrict the entry and exit criteria for treatment by Glivec is no longer justified (if it ever was) under law as it now stands with the Government exemption specifically removed. Should such restricts be put in place, we believe they would be in breach of this country’s obligations under the International Covenant on Economic, Social and Cultural Rights to provide the ‘highest obtainable standard of…health’ and against other international protocols to which this country is a signatory.
4. We believe the proposed restriction to be in breach of the Human Rights Act because it will discriminate on the grounds of disability, a specific illness and the presence in the body of specific organisms causing that condition.
5. We believe that any approach to rationing of expenditure, when seen in context with the removal of the previously mentioned exemption and open ended availability of other drugs, would to be in conflict with Pharmac’s primary legal responsibility to ‘secure for eligible people in need of pharmaceuticals, the best health outcomes that are reasonably achievable from pharmaceutical treatment from within the amount of funding provided’. We interpret ‘eligible people’ as those suffering from CML and who are in need of this drug.
6. We believe that any discrimination will breach the Bill of Rights standard of a ‘reasonable limit justified in a free and democratic society’ and as recently outlined to District Health Boards by the Ministry of Health.(Changes to the Human Fights Act 1993 and implications for the Health and Disability Sector- Letter from MOH-21st November 2001). The Ministry made particular note of case law that refers to ‘whether the distinction which exists is based on the personal characteristics of the individual or group and has the effect of imposing burdens, obligations or disadvantages on that individual or group that are not imposed on others’ and of the criteria for deciding if this distinction is justified.
7. We believe the role of Pharmac managing the total national drug budget must be exercised with due regard to equity and equality. Such criteria are implied in international obligations, the Bill of Rights standards and Pharmac’s own references to equity, law and fair process.
8. It seems obvious that Pharmac’s proposed limitations to access have been based on financial considerations. Pharmac’s attitude in this regard has been well documented and publicly stated. It is both unacceptable ethically and in conflict with most of the above when there are no such limits on a wide range of other pharmaceuticals for other groups of patients. The difference is especially marked when one considers that Glivec cannot only save lives but additionally offer a quality of life during treatment that no other pharmaceutical can match. It is further noted that the benefit to sufferers from CML , for example, by objective measure, are much greater than for many unrestricted subsidised pharmaceuticals.
9. We submit that it is Pharmac’s duty to maintain and manage a pharmaceutical schedule that applies consistently across New Zealand and should include consistency and equity between groups as well as consistency geographically. Limitations, on certain drugs but not others, are not consistent with this principle.
10. Given the trends in Court interpretation of such issues, we believe that the Court might be inclined to our view on these matters.

Secondly: Proposed Terms of Supply

In specifying the ‘terms of supply’ the following phrase is conspicuous by it’s absence - “Clinical / Medical best practice”. The following points are made:

1. The entry/exit criteria are too restrictive. In our view such criteria will result in Glivec not being available to the majority of those suffering from CML and who would otherwise benefit from this therapy. (A cynic would say it is Claytons’s Funding). Terms of entry/exit need to be liberalised considerably.
 For example, there are only 1 to 2 blast crisis patients with a donor per year in New Zealand. There would be a 50% response rate to Glivec and patients would then go on and have a bone marrow transplant. They would be treated with Glivec for 2 to 4 months in most cases. If the cost per patient were $90,000 per year, with only 2 to 3 months of treatment maximum, the actual cost of Glivec therapy would be $14,000 to $21,000 per patient
 There are 5 to 6 accelerated phase patients per year in New Zealand. On Glivec, 25 to 30% would have a major cytogenetic response rate. This could occur up to 12 months, with a median response achieved at 3 months. However, 50% of patients would achieve a response after 3 months. Therefore after 6 months there would only be 1, perhaps 2 patients, still on Glivec under the criteria proposed. Yet most of the other 5 patients would be responding and may achieve a major cytogenetic response.
 The proposed extry/exit criteria offer little benefit to the majority of patients with CML i.e. chronic phase patients. The real cost will be the unnecessary deaths.
 For chronic phase patients who have failed interferon, the complete haematological response rate on Glivec was 95%, the major cytogenetic response rate was 60% and the complete cytogenetic response rate was 41%. There was no comparator in the international clinical study that produced this data as these patients had already failed the best available therapy (interferon). The prognosis for this group of patients is otherwise poor with 20% progression to accelerated or blast crisis per year.
 It is worth noting also that in newly diagnosed chronic phase patients (who are not yet an indication for Glivec in New Zealand) the results are phenomenal. Clinical results released in May 2002 showed the complete haematological response rate in this group of patients was 96% versus 67% on interferon; the major cytogenetic response rate was 84% versus 30% ; and the complete cytogenetic response rate was 69% versus 11.5% on interferon with less than 3% progressing to a more advanced stage of their leukaemia after 1 year on Glivec versus 20% on interferon. These were results are from a randomised study of 1106 patients with median follow up of 14 months.
2. Even the period of proposed availability for those in either accelerated phase or in blast crisis may be (if automatic renewal is not granted) insufficient to arrest a decline and return a patient to the point where a bone marrow transplant might be prudent (if available). Again, we submit that this is not ‘best practice’.
3. We submit that ‘monotherapy’ may not always be best practice. For example, where a person is in blast crisis, multiple therapies may well be necessary in order to quickly bring their condition under control. Stipulating monotherapy also blocks out the possibility/probability that, as more is learned about this drug, even more effective use of it can be made.
4. Against the advice of your own committee of experts (Catsop), it is proposed to withhold Glivec from those who could obtain the greatest benefit (those in chronic phase where trial results indicate that Glivec is three times more effective than when used at a later stage) and for whom the dosage would be likely to be lower with a consequent saving in costs. Again, we submit this is not ‘best practice’.
5. We understand that the annual cost of a full year’s treatment with a-interferon is about $35,000. In the chronic phase, if Glivec is likely to be three times more effective, then any figure below $105,000 per annum is, on the face of it, good value. To argue to the contrary, is unconscionable. However, Pharmac has gone further than that. It has stated that it wants to pay 30 % of the price of a treatment that has failed for a drug that is about three times more effective. Refer appendix i
6. It has been publicly stated by Pharmac that the originally proposed terms of supply were in line with both Australia and England. In Australia there are statutory constraints, which do not apply in New Zealand and in England there is great pressure being brought to bear to liberalise the supply proposals. Scotland, alongwith other countries in the EU, proposes to fund Glivec for all stages of CML. In any case, we are talking about New Zealanders and what is appropriate for users of tax-funded health services in this country.
7. Many of the patients who would benefit from Glivec are on a-interferon. Those who are intolerant to or fail under a-interferon, and for whom Glivec is not available, struggle on on a-interferon because there is no reasonable alternative. Hydroxyurea is cheap, well tolerated and controls symptoms but has no impact on the disease progression ie. the progression to accelerated phase/blast crisis and ultimately, to death.
8. In addition, it is unreasonable to contend that a new and more effective drug should cost the same as (or less than) the drug it is intended to replace and which offers less effectiveness. Refer Appendix ii.
9. Although the author of these submissions is not a medical practitioner, we can bring expert evidence (if required) to support all the above contentions.

Thirdly: The Human Factor

In taking the human factor into account, it is necessary to not only look at the usual factors, but to think outside the square. In other words, we must consider those factors which have not been brought into the equation earlier.

Glivec is the first of a new generation of drugs. For the first time we have a drug which targets only the leukaemiac cells as opposed to previous drugs (a-interferon) which were a scatter gun approach attacking both infected and healthy cells.

This means that for the first time we have a bullet (not a shot gun shell).

In your considerations you are obliged to consider what we would describe as the human aspects of successful Glivec therapy.

 Glivac is administered simply by taking a PILL. This can be done at home
 There is no need to attend the hospital oncology ward to be infused (a significant cost saving)
 Glivec patients are not so sick (ill, but not sick in the usual sense).
 Glivec has, at worst, only minor side effects. As a consequence, patients live a relatively normal life.
 Family life is not disrupted to the degree previously experienced.
 Glivec patients go to work.
 Glivec patients pay taxes.
 Glivec patients and their families do not need to be supported by WINZ.
 Glivec patients do not suffer depression. In certain US states, patients on a-interferon receive mandatory psychological counselling .
 A relative normality exists for these patients.
 While delays and unrealistically onerous terms of treatment exist or continue, patients will die unnecessarily for lack of effective treatment.
 We do not believe that the cost/benefit analysis done by Pharmac takes into account the downstream and off budget (the Pharmac budget) benefits that would be gained elsewhere (WINZ & DHB Budgets in particular) by providing wider access to Glivec. Refer Appendix iii
 By contrast, patients being treated with a-interferon suffer severe side effects. Usually they can’t work. There are downstream costs born by the District Health Boards and by WINZ .eg. a-interferon costs:
$30,000-$35,000 per year
40-50% unable to continue to work
30% hospitalised at some time with side effects
Unwritten costs-loss of income, loss of tax, welfare benefits paid, effect on and costs of caregiver

 Before assessing the benefit of a drug such as Glivec, it is necessary to have some sort of yardstick against which to assess the value of human life ie. a statistical value of human . In the USA and Britain, this figure can range up to nearly $235,000. refer Appendix iv

In New Zealand this has been established. In a report prepared by Porter Wigglesworth and Grayburn Limited for the costing of establishing a Cord Blood Bank in October 1998, it was quoted,
“ … If this benefit is to be weighed against the costs in dollar terms, it is necessary to assign a $ value per life saved. As it happens such a value has already been determined for the purposes of public sector investment and has been accepted and used before in the health sector (Lennon & Ashton report to Ministry of Health on HIB vaccination – 1992-3; & Easton 1997). The Minister of Transport originally set the ‘value of statistical life’ at $2 million at 1 April 1990 prices. (Miller and Guria, 1991.) In the words of the Minister, ‘projects providing transport safety will now be able to be appropriately prioritized within the transport sector.’ The comment applies with equal force to life-saving interventions in the health sector. Subsequently the amount was increased with inflation (measured by an ordinary time wage rate index) to a value of $2.l5 million in 1996. Adding a further 2.5% for inflation to 1997 gives a ‘Value of Statistical Life’ in 1997 prices of $2.2 million … ”

Summary:

Bearing in mind the above contentions, we ask that:
1. Glivec be funded for all those who qualify (within the terms of it’s registration) and who would benefit from such treatment. We interpret ‘qualify’ as being diagnosed with CML and, in the opinion of the treating haematologist, would be likely to achieve a cytogenetic and/or a haematological improvement in their condition.
2. Early registration of Glivec in respect of Chronic Phase is a priority.
3. That, bearing in mind that Gilvec is such a new drug, the responses to treatment with Glivec are monitored on a national basis. To treat such use as a national trial cannot but render précis data on it’s long-term effectiveness as time progresses. (Pharmac complains that this data is not available and this is a means to satisfy that demand)
4. If funding is the constraint, then Pharmac must ask and Government must grant, sufficient extra funds in order that the best drugs and treatment can be provided for New Zealanders (as is Pharmac’s responsibility) thus enabling the Government to honour those obligations that it has entered into.

Yours faithfully,

J.D.S.Strong
Chairman, Board of Trustees

Appendix i
Sent: Wednesday, April 10, 2002 11:10 AM
Subject: Pharmac on Glivec

Extract from Media Release

"PHARMAC does have money available to make some new investments, but PHARMAC has to be sure it is getting value for taxpayers and that is why we are asking Novartis to justify its high price. If Novartis was to drop its price to around $10,000 per patient per year, PHARMAC would ask its Board to approve funding, even though it would still be comparably, an expensive drug."

[Ends]
Appendix ii.
In a recent article in the New England Journal of Medicine “When Increased Therapeutic Benefit Comes at Increased Cost”, (June 6 2002) Alastair Wood MD, Vanderbilt University School of Medicine, Nashville, Tennessee, debates the cost effectiveness of new drugs against established drugs. He writes:
“… New drugs are inevitably more expensive; drug development is risky and demands the expenditure of huge amounts of money. The costs of drug development are the subject of heated debate, with estimates running up to US$802 million; thus, the price of new drugs is determined more by the cost of drug development than by the incremental cost of producing an additional tablet. The quest for new cures demands not just the identification of treatments for diseases that are unresponsive to current therapy but, in most cases, are not optimally treated. To abandon the search for improved therapies by describing them unattractive on the basis of cost would represent an enormous disservice to patients and would distinguish attempts to improve patient care from the quest for better (safer) automobiles, audio systems, or computers, or from any other area of human endeavor.” … “ It is reasonable to expect new therapies to have an advantage over previous therapies, either in increased efficacy or reduced toxicity, which justifies their implementation at a higher cost. However, to demand also that the costs of a new therapy compare favorably with that of a standard therapy, seems an insurmountable hurdle for any novel drug to leap …”

Appendix iii
Work and Income Support Costs for a patient on interferon who is unable to work.
Weekly Weekly
Husband & Wife $278.70 $278.70
Children six $192.00 none 0.00
Mortgage/Accommodation allowance $75.00 $75.00
Special $181.62 $181.62
Disability Allowance $46.18 $46.18
$773.50 $581.50
Annual benefits (net of tax) $40222.00 $30238.00
Add
Cost of interferon, up to $35000.00 $35000.00
$75222.00 $65238.00
(WINZ costs above do not include possible further benefits to which CML patients may be entitled to e.g. Special Needs Grant, Special Benefit, Residential Care subsidy, which would increase the total cost of annual benefits).

Appendix iv

Extract from an article in the Sydney Morning Herald of March 8, 2002.

LOWER VALUE OF LIFE PUTS DRUGS OUT OF REACH.

“ … Australia puts a lower value on life than the United States and Britain when it comes to how much the nation will pay for life-saving drugs, Canberra research shows. Drug approval authorities had in recent years set an informal ceiling of $A40,000 to $A50,000 a year per patient on cost-effectiveness ratios used to calculate overall cost and benefits of drugs before listing on the Pharmaceutical Benefits Scheme. According to the Canberra University researchers, that limit compares unfavourably with other countries such as Britain, and the US, where similar cost-effectiveness ratios range up to nearly $A200,000”.

© Scoop Media