1.  EXECUTIVE SUMMARY

—  NICE are increasingly giving negative decisions to new treatments. There is also growing recognition of the fact that their recommendations are not lining up with current clinical practice or translating into fair and sensible treatment availability for patients.

—  Public confidence in NICE is waning after several high-profile negative decisions. Only 11% of 131 people surveyed by Myeloma UK were confident that NICE generally makes the right decisions when assessing treatments for use on the NHS, compared with 70% who disagreed or strongly disagreed with this statement. There is a strong perception of government interference in NICE decisions that are deemed more `worthy' than others.

—  It is the opinion of Myeloma UK that patients with rare cancers, who could be treated with highly effective orphan medicines, are disadvantaged by the NICE process. We supply evidence to this effect.

—  There must be faster and timely decisions made on new and novel treatments because for patients, time is of the essence. It is nonsensical that different bodies exist across the UK duplicating efforts in appraising drugs.

—  There is no independent appeal process to NICE's appraisal system, the appeals process is lengthy and the timelines for appellants are unrealistic.

—  There continues to be both widespread inequity in access to cancer treatments and confusion out in the Service as to the protocol when awaiting final NICE guidance.

RECOMMENDATIONS FOR ACTION

—  NICE should place greater emphasis on: transparency and willingness to share methods of working, greater public and patient involvement, improving public perception of political and financial motives behind their decisions.

—  A complete review of the NICE appraisal methodology and in particular the arbitrary cost per QALY is required so that NICE can assess orphan, higher-cost treatments within relevant and appropriate parameters that can then translate into fair and sensible treatment availability on the NHS.

—  One body should be created that produces the guidance for the whole of the UK. In lieu of having a truly national body, where the SMC or the AWMSG have already assessed a drug, let their recommendations be applied in the interim in England.

—  Establish an independent Appeals Panel, put measures in place to speed up both the publishing of guidance and the appeals process, and a more realistic turnaround should be granted to appellants to submit their appeal evidence.

—  PCTs should be directed with clearer guidance, both as to their obligations during an ongoing NICE appraisal process, but also as to what the guidance does and does not mean.

MYELOMA UK

  Myeloma UK is the only organisation in the UK dealing exclusively with myeloma and its related disorders. We have been involved with two NICE technology appraisals—erythropoietin for cancer treatment-induced anaemia and bortezomib (Velcade) for treatment of relapsed/refractory myeloma. Evidence presented in this submission derives from our extensive knowledge of patient issues; submitting evidence to NICE appraisals and appeals; and ongoing organisational research into the role and workings of NICE and how new drugs are accessed in the UK.

Why NICE's Decisions are Increasingly being Challenged

  1.  Primarily, NICE's decisions are increasingly being challenged because there is growing recognition of the fact that NICE's recommendations frequently do not translate into the clinical excellence they are striving for, or even reflect current clinical practice. The limitations of NICE's appraisal methods when interpreting evidence (for example using data in their analyses that was never intended to provide answers of clinical and cost effectiveness that can be extrapolated to the wider NHS, and only reviewing drugs within the limits of their licensed indication) means that their recommendations are out of kilter with current UK practice and can perversely subject patients to treatments that lack the gold standard evidence base which they insist scrutinised drugs possess. Consequently there is a real possibility that the NHS is wasting money on less effective treatments rather than investing in treatments backed by sound clinical evidence.

  2.  The recent brunt of negative decisions cannot be ignored: NICE are increasingly giving negative recommendations to new treatments. Examination of the eleven published NICE recommendations for cancer medications since January 2006 and the further eleven technology appraisals currently in development with a published ACD or FAD indicates that more than half (13 out of 22) have received a negative decision. Ten of the eleven preliminary decisions are negative at time of writingi (Appendix 1). The majority of these are for less common cancers and conditions: head and neck cancer, glioma, myeloma, lymphocytic leukaemia, mesothelioma and cancer-treatment induced anaemia. Whilst these recommendations are still in draft format, it does not seem unreasonable to construe that the future looks uncertain for patients with less common cancers awaiting guidance on new treatments. This is neither right nor sustainable, thus NICE decisions are being publicly challenged.

  3.  Each negative decision inevitably breeds anger in the affected patient sectors which catalyses further dispute with the Institute's decisions, and it is evident that unless reform is initiated particular groups of patients will continue to be disadvantaged with regard to access to novel treatments.

Whether Public Confidence in the Institute is Waning, and if so Why

  4.  Public confidence is waning after several high-profile negative NICE decisions. As part of our ongoing work and to help substantiate our views, we surveyed the opinions of those who visit Myeloma UK's website (including patients, families, healthcare professionals and the general public) on the role and workings of NICE. 131 people completed the survey (a full transcript of the responses can be made available if the Committee wish to see it). The following views were collected:

—  Only 11% of the 131 respondents were confident that NICE generally makes the right decisions when assessing treatments for use on the NHS, compared with 70% who disagreed or strongly disagreed with this statement.

—  70% of respondents disagreed or strongly disagreed that NICE operates as an independent organisation free from political intervention. Our experience from talking with patients is that there is a strong perception of government interference in NICE decisions that are deemed more `worthy' than others; the Herceptin example and Patricia Hewitt's intervention is frequently cited by patients.

—  63% believed cost considerations to be the most important consideration in NICE analysis, compared to 19% believing that equal consideration is given to both cost and clinical effectiveness evidence. Patients consider that the principles underlying NICE decisions, namely the role that cost and government funding of the NHS play in the evaluations, should be made explicit and communicated honestly to patients and the wider society. There is a lack of transparency within the appraisal process which generates suspicion of the motives behind the process.

—  64% disagreed or strongly disagreed that NICE should decide which treatments are made available on the NHS. 46% believed that it should be doctors responsible for patient care that should be making the decisions. If a drug is not approved by NICE, then it is down to the tenacity of the patient to either get themselves on a trial, persuade their PCT to pay for the drug or finance their own care privately. This causes immeasurable stress, worry and frustration. Having similar bodies in Scotland and Wales reaching different conclusions about the same drugs further diminishes public confidence in the decisions of NICE.

NICE's Evaluation Process, and Whether any Particular Groups are Disadvantaged by the Process

  5.  As outlined in section 2 above, there has been a recent wave of negative decisions assigned to treatments for less common cancers (Appendix 1). It is the opinion of Myeloma UK that patients with rare diseases, and in particular rare cancers, who could be treated with highly effective orphan medicines, are disadvantaged by the NICE process.

  6.  NICE, in a formal response to the Department of Health in March 2006ii, wrote that they did not consider that any changes are required to its methods for the appraisal of orphan drugs (those for treatment of an orphan disease with a prevalence of < 5 per 10,000). NICE state that orphan drugs referred to the Institute have been appraised successfully "suggesting that for these drugs it was possible to apply NICE methodology". The Institute does, however, advise adoption of different methods for appraising their self-appointed "ultra-orphan" drugs as they "encompass all products that appear, both now and in the foreseeable future, to be particularly problematic".

  7.  There are important issues to raise in response to this assertion:

—  Analysis of Appendix 1 of the NICE responseii reveals a considerable number of errors and omissions (including erroneous inclusion of products which are not for rare diseases, erroneous classification of EMEA and FDA orphan designation, and omitted orphan medicines) (see Appendix 2). These are misleading to their overall recommendation to the Department of Health. Furthermore, the incremental cost effectiveness ratio (ICERs) for each drug was provided and those that were considered to be cost ineffective (and thus not recommended) are highlighted in bold text. The inference is that the remainder of the products were considered cost effective and were recommended for usage. However, 6 (46%) of the 13 medicines inferred as cost-effective and recommended were in fact recommended for use by a restricted subgroup only (see Appendix 2 of this submission).

—  Independent research undertaken by the Office of Health Economics (OHE) reveals that as of January 2007, NICE had appraised 16 EMEA/FDA designated orphan medicines, of which it has rejected 4 (25%), recommended 9 (56%) for restricted use and only recommended 3 (19%) for general use. By way of comparison, of the 116 non-orphan drugs appraised by NICE only 7 (6%) were rejected, 56 (48%) were recommended for restricted use, and 53 (46%) were recommended for general use. There is statistically significant difference between the outcomes of NICE appraisals for orphan and non-orphan medicines (p value 0.013) iii.

—  Further 6 of the 8 orphan medicines currently under NICE appraisal have reached a preliminary decision (as of January 2007). All 6 are orphan medicines for the treatment of rare cancers; myeloma (bortezomib), mesothelioma (pemetrexed disodium), head and neck cancer (cetuximinab), malignant glioma (temozolomide and carmustine implant). Of these appraisals 5 (83%) were rejected, 1 (17%) was recommended for use in a restricted subgroup only, none were recommended for general use (Appendix 3). For bortezomib and pemetrexed disodium, the negative recommendations were based primarily on cost-effectivenessi. It should also be pointed out that 4 of the 5 that have reached the FAD stage have been subject to lengthy appeals, which further delays access to effective treatment for patients with high unmet need.

—  Thus, NICE have no basis on which to make their claim that orphan drugs have been appraised successfully. Indeed, compelling evidence exists to support our position that patients with rare diseases who could be treated with highly effective orphan medicines are disadvantaged by the NICE process.

  8.  It is illogical that after measures are put in place by EU licensing legislation (which safeguards research and development of orphan drugs) patient access is stymied by NICE assessing their cost effectiveness in the same manner as "conventional" therapies. Indeed the slow uptake of orphan medicines in the UK is of concern to the EMEA (Appendix 4). Many EU countries have special arrangements to facilitate fast patient access to orphan medicines. For example, in the Netherlands orphan medicines can be exempt from economic evaluation.

  9.  It is artificial to apply the same quality-adjusted life years (QALY) parameters to treatments for rarer and more common diseases. Indeed, this approach is at odds with the fundamental NHS principle of equity of access to treatments for all patients based on clinical need:

—  The existing parameters of cost effectiveness do not make allowance for the smaller financial burden on the NHS from fewer patients accessing the treatment, or indeed the higher per-patient costs in developing novel drugs for rarer illnesses and the frequency with which these development opportunities arise.

—  The cost per QALY threshold has been untouched by inflationary uplifts let alone the much higher NHS inflationary uplifts: extra investment in the NHS is growing by an average of 7.4% a year; drugs costs are rising even faster yet the QALY threshold has stayed unaffected.

—  The QALY does not capture all that is valued in a health outcome eg it cannot adequately and sensitively capture improvements in quality of life, much to the disadvantage of those with debilitating and incurable diseases to whom this is a precious outcome.

—  By the Institute's own admission, many orphan drugs have ICERs at the "high" end of what the appraisal committee consider to be cost effectiveii. Patients with rarer diseases are being disadvantaged as a result of an inappropriate costing exercise.

The Speed of Publishing Guidance

  10.  The introduction of the rapid Single Technology Appraisal process in November 2005 set out to improve the NICE approval system. Bortezomib (Velcade), a myeloma treatment, was one of the first drugs to be appraised by this rapid assessment process. At the time of writing, 16 months on, the outcome is still subject to an appeal decision and patients remain exposed to discretionary access to an effective drug. There must be faster and timely decisions made on new and novel treatments because for patients, time is of the essence.

  11.  It is nonsensical that different bodies exist across the UK applying the same efforts and resource to interpreting the same evidence for the effectiveness of a treatment. This represents a massive duplication of effort. It is also disheartening for patients to feel like a second-rate citizen to their neighbour across a UK border.

The Appeal System

  12.  There is no independent appeal process to NICE's appraisal system. Engaging with a process where the deciding body is both judge and jury limits confidence in the end result.

  13.  Whilst stakeholders have 14 days to submit their appeal evidence after the release of a Final Appraisal Determination (substantially encroaching on staff time and resource for smaller organisations) the ensuing appeals process can take months. A lengthy appeal process exacerbates the delay in access to effective medicines for patients that may have already high unmet need.

Comparison with the Work of the Scottish Intercollegiate Guidelines Network (SIGN)

  14.  Myeloma UK has no comment to make on this sub-section.

The Implementation of NICE Guidance, both Technology Appraisals and Clinical Guidelines (Which Guidance is Acted On, Which Is Not and the Reasons For This)

  15.  It is difficult for us to comment fully on this section as with regards to specific myeloma guidance, the Velcade appraisal has not yet reached completion so has not been distributed out to the Service for implementation. However, we have started a scoping exercise to obtain ongoing snap shots of how the provision for patients is being affected by draft guidance:

—  In an ongoing surveyv of 39 haematology doctors working in the field of myeloma in England, 56% have experienced a lack of consistency among Primary Care Trusts when seeking funding for the myeloma treatment Velcade. 46% have found it more difficult to obtain Velcade for NHS patients since its negative FAD was made public on the Institute's website in October 2006. This indicates that there is both widespread inequity in access to this treatment and confusion out in the Service as to the protocol when awaiting final NICE guidance, both of which disadvantage patients.

—  We know from other published reviews that there is still considerable variation of spending on cancer drugs by PCTsvi and in the implementation of NICE guidancevii. This knowledge, coupled with the existing variation in access to drugs in use pre-1999 and the establishment of NICE, stresses the urgent need for reform.

  16.  The December 2006 Good Practice Guidance on Managing the Introduction of New Healthcare Interventions makes strides to consolidate the advice in HSC 1999/176 which seeks to explain the responsibilities of PCTs throughout the NICE appraisal process. More could be done, however, to clarify that when guidance is draft or subject to appeal it should not be used to inform local decision making.

Eric Low

REFERENCES

i	http://www.nice.org.uk/guidance/topic/cancer/?View=All&template=diseasetax.aspx
ii	http://www.nice.org.uk/page.aspx? o = 286850.
iii	OHE Working paper by the OHE : "HTA for orphan drugs: A review of the Issues and of NICE and SMC Decisions.
iv	http://ec.europa.eu/health/ph_threats/non_com/docs/EMEA_chart_en.pdf accessed March 2007.
v	Independent study carried out on behalf of the myeloma community by Dr Mehta, Royal Free Hospital, London.
vi	Local variations in NHS spending priorities, King's Fund Briefing, August 2006.
vii	Usage of Cancer Drugs approved by NICE, Report of Review by the National Cancer Director, September 2006.