BACKGROUND

  Leukaemia CARE is a national charity founded in 1967, which exists to provide vital care and support services to patients, their families and carers during the difficult journey through the diagnosis and treatment of all forms of blood cancer (leukaemia; lymphoma; Hodgkin's lymphoma; non-Hodgkin's Lymphoma; multiple myeloma; myelodysplastic syndrome; myeloproliferative disorders and aplastic anaemia).

EXECUTIVE SUMMARY

  1.  Leukaemia CARE is grateful for the opportunity to have an input into this inquiry to review all aspects of the workings of the National Institute of Health Clinical Excellence (NICE). Leukaemia CARE believes that the current approach by NICE and the NHS over the access to new and innovative treatments for patients affected by leukaemia, lymphoma and the allied blood disorders is disadvantageous to these patients, and is in need of urgent and fundamental review.

  2.  This inquiry is very timely with regard to the future development of new treatments for patients suffering from all blood cancers; and the consequent impact that those cancers, and cancer treatments will have on the quality of life (QOL) of patients undergoing treatment. There is an increasing public awareness of these newer treatments and an increasing public pressure for the provision of equal and equitable treatment of all patient groups by NICE such that no patient groups are seen to be disadvantaged by NICE pronouncements:

—  There are an increasing number of new blood cancer treatments coming through the research pipeline.

—  The development of specific targeted treatments means that a unique but smaller patient group can be selected to benefit from innovative research.

—  More sophisticated differential diagnostic techniques are making it possible for physicians to identify in advance which patients will benefit from these newer treatments thus further fragmenting an already small target patient population.

—  NICE is out-of-step with Europe and the United States when it comes to the definition and treatment of Orphan drugs (and by default orphan diseases).

  3.  NICE has a challenging and important role to play in guaranteeing the economic health and future of the NHS, but equally it has a vital role to play in developing an equitable and homogenous health service that is not just fair to all who have a need to use it, but is seen to be fair to all. There are certain aspect of the NICE process that could benefit from change to move closer to this ideal:

—  The use of appropriate expertise on the appraisal committees, (there are no consultants with a knowledge of haematological cancers sitting on any of the committees who pass judgement on blood cancer products).

—  A more pragmatic approach to the consideration of QOL issues; and a greater degree of involvement of the "patient expert witnesses". The NICE appeals I have attended where "patient experts" were allowed to give evidence in my judgement were there only as a nod protocol, and not because their evidence was being taken seriously.

—  Transparency of cost considerations, ie does the cost of treatment involve just the drug costs, or does it take into account the total cost of treating that patient (all indirect costs should be considered during the appraisal process, even if these considerations ultimately do not impact on the final guidance outcome). Silo budgets are the bane of an efficiently run business, and particularly so the NHS.

—  Successful appeals (eg erythropoietin) should not be sent back to the same Evidence Review Group for further consideration, but go to another independent body.

—  An earlier involvement in drug development in order to enable faster assessment of new drugs.

  4.  Because the NHS does not have an unlimited budget, sound health economic strategies will be vital if we want to ensure that the NHS survives in a recognisable form well into the future, and NICE should have a pivotal part to play in formulating those strategies, but not in isolation, the Government, the Pharmaceutical & Biotechnology Industries and the patient and research focused not for profit organisations should all have an input to make certain that we have an equitable and homogenous health service that will deliver that same standard of care to all, not matter what your post-code or socio-economic status.

NICE'S EVALUATION PROCESS, AND WHETHER ANY PARTICULAR GROUPS ARE DISADVANTAGED BY THE PROCESS

  5.  Leukaemia CARE believes that patients suffering from the rarer diseases (specifically the blood cancers) are being disadvantaged by NICE's evaluation process.

  6.  Given the pipeline of targeted cancer medicines, many of which may only be appropriate for a small number of patients we believe there are several issues that need to be explored in detail.

  7.  The costs involved in Research and Development of treatments for the rarer diseases (including all blood cancers) are the same as those for developing treatments for the very common diseases, over £500 million for pharmaceutical products, and over £800 million for biotechnological advances. It was recognised many years ago by the United States of America (USA) that special incentives were required if pharmaceutical manufacturers were to be encouraged to develop and market treatments in this area.

  8.  In 1983 the USA designated the term "orphan drug" to this group of rare diseases ("orphan diseases"), and granted research based pharmaceutical companies certain specific incentives to develop and market drugs for these diseases including; exclusive marketing rights for a 10 year period; assistance with clinical trial protocols; reduced regulatory fees etc.

  9.  The USA defined an orphan disease as one with a prevalence of less than 200,000 people; (in the USA that equates to >7.5/10,000).

  10.  Legislation by the European Parliament and the Council and Commission Regulation on orphan medicines entered into force January 2000 and their definition or an orphan disease was one with a prevalence or >5/10,000.

  11.  NICE reviewed orphan disease status in 2006 (23 years after the USA, and six years after the rest of the EU), redefined the term, and decided on an incidence of >1/50,000, referring to this group of diseases as "ultra-orphan", but by their own terms of reference it is an "informal subcategory" and has no legal definition, recognised by no other authoritative body in the USA or throughout Europe.[88]

  12.  NICE suggest that orphan drugs can be fairly appraised using the normal assessment process88 para 17(a), however in para 17(b), go on to state "Many however, have had incremental cost effectiveness ratios (ICERs) at the high end of what NICE and its appraisal committee consider to be cost effective".

  13.  Drugs that would normally fall into the generally held view of "orphan status" when considered by NICE have fared particularly badly when reviewed using the standard methodology, eg bortezomib.[89]

  14.  Leukaemia CARE feels that this single act of NICE (redefining orphan to ultra-orphan) will disadvantage all blood cancer patients, because the prevalence of the different blood cancer types will fall outside the NICE definition of "ultra-orphan" but inside the USA and EU definition of "orphan".

  15.  Leukaemia CARE suggests that this "informal sub-category" designated by NICE as "ultra-orphan diseases" should be removed as the facts used to define the need for this sub-category are fundamentally flawed, and are in no way concordant with the rest or Europe, or the USA.

  16.  Leukaemia CARE further suggests that NICE adopt the definition of orphan disease status as defined by EU regulations, and that the rarer diseases should be appraised through a separate process where additional criteria are considered, including clinical efficacy, unmet need, total "global" costs to the NHS and patient quality of life issues.

WHY NICE'S DECISIONS ARE INCREASINGLY BEING CHALLENGED

  17.  Leukaemia CARE believes that NICE's decisions are increasingly being challenged, because:

—  They are being seen as not treating all patient groups equally and equitably. Eg the undue haste with which Herceptin was given clearance to specific patient groups even though the evidence base was clearly not there and the perceived lack of consideration to QOL issues to cancer patients suffering from chemotherapy induced anaemia/fatigue by its decision not to issue guidance on erythropoietin, and it decision to withdraw treatments for Alzheimer's disease.

—  There is a lack of use of appropriate expertise on the appraisal committees. Leukaemia CARE has been involved in several NICE guidance reviews, and no haemato-oncologist has ever played a part in the appraisal process.

—  There is a lack of consistency in the criteria considered when making an appraisal determination. Eg during the erythropoietin appeal, we were told that QOL issues took a second place to survival data when the FAD was made, but during the bortezomib appeal we were informed that QOL issues superseded survival data in determining the outcome of the FAD (both of which were negative!).

  18.  Leukaemia CARE would suggest that both survival and QOL issues should carry equal weight when making a Final Appraisal Determination, because to the patient both are of paramount importance. There is no way of knowing in advance which patients want improved QOL, and which patients want extended survival, some may wish to live to reach a special wedding anniversary, or to see one last Christmas with the family, or see a son, daughter or grandchild born or christened; and some just want their last days on Earth to be pain free and joyous, Leukaemia CARE would like this to be a decision between the patient and the doctor, not decided by dictat from NICE.

WHETHER THE PUBLIC CONFIDENCE IN THE INSTITUTE IS WANING

  19.  If the media is to be believed about recent decisions made by NICE, then the suggestion is that public confidence isn't high. This may be due in part to a lack of understanding of the role of NICE, and the processes undertaken by NICE when producing guidelines. Leukaemia CARE believes however that certain areas of that process do need attention.

  20.  The use by NICE of evidence from patient expert witnesses was/is an excellent idea (and much publicity can be made from this), and should only elicit praise from all of the reviewers involved in this enquiry, unfortunately NICE appears only to pay lip-service to their evidence. Having patients experts attend NICE should inform and give an insight into the "human" aspect of the treatments under consideration, but the feedback from those attending was that their presence merely enabled NICE to tick the appropriate box, and to move onto more weighty matters.

  21.  Leukaemia CARE suggests that if patient experts are to be consulted, (and due notice should be taken of para 19), then NICE must report on the impact that their evidence has had on the final outcome of the appraisal document.

  22.  Despite being a requirement for all NICE appraisals to take into account the recommendation from other Government bodies, this isn't always seen to be the case. Eg concerning the appraisal reviewing the use of erythropoietin for the treatment of chemotherapy induced anaemia, NICE ignored the 2002 Health Services Circular that instructed Trusts to take action to avoid unnecessary use of donor blood and to consider effective alternatives.[90] Also during this particular appraisal (erythropoietin) NICE were seen to be completely out of step with guidelines and recommendations that should have impacted on this appraisal from many other pre-eminent bodies, EORTC (European Organisation for the Research and Treatment of Cancer), WHO, BCSH (British Committee for Standardisation in Haematology, ASH & ASCO (American Society of Haematologist & American Society of Clinical Oncologist).

  23.  Leukaemia CARE applauds NICE's determination to make completely independent decisions, but in order to engender public confidence in those decisions, NICE should at least explain why it has come to such radically different conclusion to other widely respected advisory organizations on those occasions when it does, because not to exhibits a lack of transparency and displays an air of arrogance.

THE APPEAL SYSTEM

  24.  Leukaemia CARE feels that the appeal system in the main is fair, and applauds NICE's intent to give all stakeholders sufficient time and scope to appeal both the ACD's and FAD's. There is however one aspect of the appeal system, that until recently was untried, that Leukaemia CARE feels does need to be addressed. The appeal against the FAD of cancer-treatment induced anaemia: Epoetin (alfa & beta) and darbepoetin alfa was up held by the appeals committee, but then it was sent back to the original Evidence Review Group (ERG) for reappraisal. Leukaemia CARE feels that this is unacceptable, as the ERG may come to the re-appraisal process with preconceived ideas of how the outcome should be. Leukaemia CARE feels that under these circumstances if an FAD appeal is upheld, then a different ERG should be commissioned to re-review the evidence presented.

THE SPEED OF PUBLISHING GUIDANCE

  25.  Leukaemia CARE feels that the time to issue appraisals through NICE has improved but is still not optimal. Leukaemia CARE welcomes the introduction of NICE's Single Technology Appraisal (STA) process, which has been shown to be faster and effective. However it is important that the existence of the STA does not disadvantage drugs being appraised by NICE not selected for this process. Patients with rarer diseases (including blood cancers) are still waiting too long for access to new treatments once they have been shown to be effective in clinical trials/research and/or have received an EMEA marketing authorisation:

—  Clearer guidance should be issued by NICE to commissioners in the interim period before final Health Technology Assessment (HTA) appraisals are issued where treatments are already available in the NHS.

—  Guidance should also be issued where treatments are available for an unlicensed indication of a medicine on the market that has not yet be appraised. (This may occur in cancer treatments where initial licenses are usually gained in late stage diseases and there is a time delay before marketing authorisation of a new indication can be put before NICE again for guidance.

—  For rarer blood cancers guidance is also required for commissioners for treatments that will not be reviewed at all by NICE.

—  One of the main issues with NICE that constantly frustrates Leukaemia CARE, is the speed with which NICE picks up and reviews new and innovative treatments. NICE does not begin to assess new agents until they have been through EMEA/UK approval and gained Marketing Authorisation. Leukaemia CARE believes that this disconnect is out of step with the otherwise professional approach that NICE takes in its role in assessing new agents:

—  Leukaemia CARE would like to see NICE involved at a much earlier stage in drug development in order to enable faster assessment of clinical and cost effectiveness.

—  NICE should be involved with new drugs when they are being submitted for approval to the regulator, and could even have input into the approval process, by for example recommending support for a drug being used in a national phase 3 trial.

SUMMARY

  26.  Leukaemia CARE feels that the role NICE plays in the delivery of a health care system that is fair and equitable to all at the point of delivery is, and will be a fundamental one, but it also needs to be seen to fair and equitable. It has got many things right in the short time it has been in existence, and should reap due praise for that. Now it needs to be made ready to appraise future technology, and make the revolutionary developments, which in the greater part are being made by British scientific research, available to the citizenry of the UK. (This is currently not the case—within Europe the UK is the slowest to adopt innovative new treatments).

  27.  Leukaemia CARE is in agreement with the finding published in the Cooksey report,[91] Cooksey highlighted three main barriers that hinder the pharmaceutical sector's ability to deliver new medicines, diagnostics and devices "at prices that reward innovation and are affordable to health systems (in the UK and abroad)". Firstly the NHS culture is cautious with respect to innovation; secondly, regulation has not kept pace with advances in drug development science and technology. Thirdly, the NHS Health Technology Assessment limits uptake of new drugs.

Anthony M Gavin

Chief Executive Officer, Leukaemia CARE

89   National Institute for Health and Clinical Excellence, FAD Bortezomib, October 2006. Back

90   National Institute for Health and Clinical Excellence, FAD Erythropoietin March 2006. Back

91   The Cooksey Review of Health Research Funding, Sir David Cooksey, December 2006. Back