EXECUTIVE SUMMARY

—  The ABPI supports the objectives set out for NICE at its inception. It has built up some core strengths over the years that we value and would not wish to lose: its focus on clinical excellence in public health priority areas; the breadth and coherence of its work programme; inclusion in its remit of support for diffusion of innovation; independence from pricing negotiations and decisions; its systematic engagement of stakeholders, including industry representation on many of its committees and regular dialogue with the ABPI; its respect for commercial-in-confidence information; and the ability to appeal its decisions.

—  However, there are shortfalls in the way NICE operates that have compromised public confidence, and which need to be addressed. This need would become more acute were any expansion in its reach to be considered, eg as envisaged in the Cooksey Review and implementation of the OFT's recommendations. We believe these shortfalls are leading to a situation where patients in England and Wales may be permanently disadvantaged in their ability to benefit from major and incremental medical innovation, available in other countries, because the bar to positive recommendation is becoming unrealistically high or there is pressure to take decisions on the basis of very limited clinical effectiveness or cost-effectiveness data.

—  This submission outlines these concerns in particular:

—  Over-reliance on cost/QALY, a mathematical prediction of potential future benefit, in making (rather than informing) decisions

—  Expectations of certainty in decision-making that cannot be achieved, particularly early in a product's lifecycle

—  Issues of quality and consistency in the work commissioned from Assessment Groups/Evidence Review Groups (AGs/ERGs), including transparency issues

—  An unnecessarily adversarial approach to industry within some AGs/ERGs, which can colour assessment and appraisal

—  These issues result in an increasing trend to resort to an appeal process that is itself seriously flawed, and which has resulted in the past two years in no significant changes to NICE guidance.

—  No doubt there are frustrations for all in the relationship between NICE, AGs/ERGs and industry. The ABPI wishes to constructively address these through engagement with NICE and the ERGs from the outset of appraisal.

—  NICE has devoted significant resource to helping the NHS improve implementation of its guidance, which after eight years since NICE was created remains slow and patchy. Reasons for this include poor local financial planning, clinical resistance, and little in the way of sanctions if guidance is not implemented. The major levers in improving implementation are joined-up commissioning and financial incentives, removing prolonged and duplicative local evaluation processes, and more robust HCC assessment. The latter focuses on process rather than outcome, and implementation is not high in the HCC's priorities.

RECOMMENDATIONS

—  More evenly-balanced NICE decision-making to recognise the imprecision in cost/QALY calculations and to encompass broader factors than cost/QALY. Final guidance to contain a clear explanation of how these factors were taken into account

—  NICE to include broader parameters and costs when calculating value: eg societal benefits and costs, including carer and return-to-work factors; social security costs

—  Industry to be invited to participate in Appraisal Committee meetings to answer questions and provide clarification on areas of uncertainty

—  An independent review of the quality of Assessment/ERG Reports with recommendations including:

—  accountability for quality being brought under NICE;

—  production (for STAs) of a detailed methods manual setting out standards, expectations, and approaches;

—  introduction of more robust quality control systems

—  A joint committee of industry, NICE and AGs/ERGs to contribute to the above review and to identify and address quality and process issues on an ongoing basis

—  A more constructive, and less adversarial, approach to be taken to appraisal, including dialogue, from the outset of each appraisal, between manufacturers, NICE and AGs/ERGs on methods, data quality and sources used

—  A root-and-branch review of the appeal process, which examines the grounds for appeal, its independence and its operation

—  A review of NICE guidance implementation with recommendations that result in tangible action, eg greater HCC attention; "joined-up" commissioning and financial incentives; NICE-approved medicines automatically included in local formularies; mandatory funding for medicines, where reviews of technology appraisals have been moved into clinical guidelines and where positive recommendation remains

INTRODUCTION

  1.  The ABPI welcomes this Inquiry into NICE. Whilst we support the objectives set for NICE when it was created and recognise much good practice, we share with other stakeholders concerns about aspects of its methods and decision-making—recently made even more acute by recommendations in the reports by the OFT on the PPRS and by Sir David Cooksey on research funding. Both envisage broader roles for NICE that could have a major impact on the future health of the nation and the UK pharmaceutical industry.

NICE DECISION MAKING

Use of Cost/QALY

  2.  NICE decisions have become overly reliant on one parameter: the cost/QALY, an assessment of the incremental cost-effectiveness of a new technology compared to that of standard practice. Although the ABPI recognises the usefulness of this approach as a means of comparing the cost-effectiveness of a broad range of technologies, it is generally derived from a complex mathematical prediction of potential future benefits and costs, and therefore should be used as one important factor to inform decisions rather than make them, in line with Principle 4 of NICE's social value judgements.[32] More balance should be struck between cost/QALY and other important factors (listed in Appendix 1),[33] such as clinical need.

  3.  There are a number of issues in the application of QALYs:

—  Cost-effectiveness assessment is an imprecise and emerging science and is usually reliant on complex economic modelling, incorporating data and assumptions from a wide range of sources. Modelling results in wide-ranging estimates of cost-effectiveness depending on the methodology and assumptions used. For example in the appraisal of Exubera@, cost/QALY estimates presented to the committee ranged from £24,184 to £1,260,325 and for Alimta@ in Lung Cancer from £9,010—£1.8 million.

—  The QALY is based on the measurement of two key elements of benefit: quantity and quality of life. Although not without challenges, given time, quantity-of-life estimates are relatively straightforward; but measurement of quality of life is much more difficult, subjective and approximate. The wide range of methodological approaches and definitions results in significant uncertainty in the accuracy of absolute values or reproducibility between different appraisals. Also, the generic (rather than disease-specific) approach required by NICE (as illustrated by its preferred questionnaire, EQ5D (Appendix 2))[34] is relatively insensitive to incremental changes in quality of life and does not fully reflect the range of benefits that are important to patients.

—  Other aspects of value may not be fully reflected in the QALY estimate, eg the impact of an improved safety profile, the benefits of an oral product that may reduce pressure on hard-pressed hospital services, or the advantages of improvements that enhance compliance.

  4.  In practice, these limitations mean that it is generally more difficult for medicines which deliver quality rather than quantity of life to demonstrate a large enough incremental benefit to be deemed cost-effective, eg in treatments at the end of life, for the elderly, and for long-term conditions, where apparently small quality-of-life benefits can make a significant difference to patients.

  5.  In some cases, it may never be possible to demonstrate cost-effectiveness at a price that secures a return on investment, particularly in areas that have suffered from historically low levels of innovation and where comparators used are old, generic, and very inexpensive. In the recent Velcade@ appraisal, the main comparator cost £74/patient/year. In osteoporosis, new provisional guidance compares innovative treatments with generics. This approach means that innovative treatments, available in other European countries, may never be available to patients in England and Wales. Comparing medicines with novel mechanisms and/or better side-effect profiles to the cheapest available therapy in a disease area would effectively halt further innovation. Were such an approach to have been followed historically, few of today's "best-in-class" medicines would be available.

  6.  The perspective of cost-effectiveness taken by NICE is limited to the NHS and Personal Social Services; this excludes important benefits such as the impact on carers or enabling people to return to work and contribute to society. In Sweden, for example, LIF economic evaluation guidelines state " . . . all relevant costs and revenues for treatment and ill health, irrespective of the payee (county council, local authority, state, patient, relation) should be considered." The current approach is inappropriate in diseases such as Ankylosing Spondylitis, which can strike patients in their 30s, lead to progressive disability, and have major effects on people's ability to work, resulting in incapacity benefit, sick leave and loss of employment.

  7.  Patients with rare diseases treated with orphan medicines[35] are disadvantaged by the NICE process. Orphan medicines appear expensive on a "per-treated-patient" basis because development costs are relatively high and an adequate return is necessary to sustain research.

  8.  As of January 2006, NICE had appraised 16 EMEA-designated orphan medicines, of which four (25%) were rejected, nine (56%) recommended for restricted use, and three (19%) recommended for general use. This compares to 6% rejected, 48% restricted-use, and 46% recommended-for-general-use rates in the 116 non-orphan medicines appraised over the period, a statistically significant difference.[36]

  9.  The combination of limited data at launch and relatively high per-patient prices means it is challenging for orphan medicines to meet NICE cost/QALY criteria. The current methodology requires re-evaluation, with distinct decision rules focusing more on unmet need, innovation, clinical effectiveness and budget impact, and less on cost/QALY.

CONSISTENCY AND QUALITY OF ASSESSMENT

  10.  In order to produce credible and defensible guidance NICE requires top-quality analysis of the evidence submitted to it. This is synthesised in the assessment report, for MTAs a review of clinical and cost effectiveness based upon a systematic review of the literature, a review of the manufacturer/sponsor submissions, and frequently a de-novo assessment of cost-effectiveness, involving the generation of an economic model; and for STAs in the ERG Report, which is a critique of the manufacturer's submission. NICE obtains these reports from a number of AGs/ERGs, commissioned via the NHS R&D HTA Programme. The assessment reports are the property of the AGs/ERGs, and their quality is the responsibility of the authors.

  11.  The approaches taken, particularly by ERGs, are inconsistent—most likely because there is no comprehensive STA "methods manual" to ensure consistency of standards and methods, and ERGs wish to exercise academic freedom. Concerns include the adequacy with which assessment reports address the scope of appraisals; the appropriateness of the structure and inputs to economic models; and the extent to which comments from stakeholders are addressed.

  12.  A key issue is how the Groups handle uncertainty, which is greatest early in a product's lifecycle. Given that effectiveness and cost-effectiveness data are derived from highly structured clinical trials and economic models based on a wide range of assumptions and inputs, it is inevitable that different conclusions will be reached by different assessors. It is how these uncertainties are managed and the transparency with which they are addressed that are important. Rather than seeking to constructively outline and address them, some centres present them as fatal flaws in the manufacturer's case.

  13.  Quality control is another important issue. Addenda correcting errors in original assessment reports have been required for six (30%) of the 20 MTAs published since the beginning of 2006. These addenda have corrected errors in the modelling of costs and utilities; amended (increased) the value placed on clinical effectiveness, and included additional benefits not originally modelled. NICE or its Decision Support Unit were required to undertake further analysis and/or address deficiencies in the assessment report in half of these cases.

  14.  One simple, but essential, quality control step is missing in the STA process. The ERGs prepare a report which is considered by the Appraisal Committee to formulate draft guidance. No opportunity is provided to stakeholders to comment on its technical accuracy before the Appraisal Committee uses it to make recommendations. Apart from being inconsistent with the MTA process, the opportunity for manufacturers to correct inaccuracies in an STA is particularly important, as the ERG report is based solely on the company's submission. Factual errors are translated into draft and final guidance leaving appeal as the only route to make corrections. NICE has resisted this step on the grounds that it leads to unequal treatment of stakeholders.

  15.  The consequence of poor quality assessment reports is a delay in issuing appropriate guidance at best and the production of non-transparent and possibly incorrect guidance at worst. Without doubt, more appeals result.

  16.  The situation is exacerbated by the inability to challenge the methods and models developed by the AGs/ERGs. Whilst the AGs/ERGs have access to the full working models produced by manufacturers, manufacturers sometimes do not have access to the models created by the AGs/ERGs, the results from which form the primary evidence upon which the Appraisal Committee decides on cost-effectiveness and patient access. If the model is made available, it may be "locked", which significantly hinders the ability to understand the basic assumptions upon which the cost-effectiveness calculation is made.

  17.  The ABPI believes that, underlying these issues, there is an adversarial approach to industry in appraisal, which is not helpful. The ABPI would prefer a more collaborative approach, with a constructive dialogue between the AG/ERG, NICE and the company from the outset of appraisal, allowing discussion and debate on methods, data quality and sources used. This would reduce inaccuracies, address unnecessary misunderstandings, speed up the process, and reduce the number of appeals.

WORKINGS OF THE APPRAISAL COMMITTEE

  18.  Currently clinicians and representatives of patient organisations are invited to attend Appraisal Committee meetings to give their views and respond to questions. This invitation is not extended to manufacturers, who have spent years amassing the evidence upon which NICE guidance is based. This is inherently inequitable, can lead to misunderstandings and, in some cases, unnecessary re-work and appeals. In STAs, where appraisal is based on the manufacturer's submission, a level playing field should be adopted so manufacturers can help clarify areas of uncertainty and answer questions.

  19.  NICE has consistently rejected the industry view (particularly for STAs) that the Appraisal Committee should give proper consideration to the lack of maturity of the evidence for products early in their lifecycle. Unreasonable expectations of clinical and economic certainty lead to "all-or-nothing", "yes-no" decisions. This is dangerous for two reasons: 1) patients are being denied access to important treatment advances; and 2) denying access so early in the life of the product means that learning and incremental innovation through normal clinical experience will not happen.

  20.  In the case of MTAs, the assumption in "class" appraisals is that all products are essentially similar. This is done to enable cost comparison, but fails to take into account that some products may have more robust evidence than others. This opposes NICE's principle of evidence-based assessment and can lead to patients being denied access to a technology which has the best evidence, merely because it is more expensive. The approach is anti-innovative because the innovator entrant demonstrates clinical and cost-effectiveness only to have their evidence translated across the class, negating their advantage on price alone.

APPEAL PROCESS

  21.  The deficiencies described above are leading to an increasing number of costly and time-consuming appeals, which further delay patients' access to medicines.

  22.  Of the 279 appeal points heard since NICE appeal hearings became public, not one has resulted in any significant change to guidance.[37] One reason for this is that the grounds for appeal are based on procedure rather than a difference of scientific opinion. Ground 2 (perversity) allows an appeal where the conclusion in the FAD is so unarguably wrong as to be "perverse", which is a very high hurdle. NICE procedures explain that it is theoretically possible for two Appraisal Committees to reach different conclusions based on the same facts, without either being perverse. There is no scope, therefore, to challenge where a conclusion appears to be incorrect, but is not frankly perverse.

  23.  The process is not independent, with NICE deciding which grounds for appeal can be heard, constituting the Appeal Panel (which includes at least two NICE directors including the chair), and administering the process. NICE is therefore sitting as judge and jury over its own guidance. Appendix 3 sets out these concerns and others relating to how appeals are conducted. A root-and-branch review of the process is required.

IMPLEMENTATION OF NICE GUIDANCE

  24.  NHS implementation of NICE guidance remains slow and patchy, in spite of considerable efforts by the NICE Implementation Team to improving it, and the inclusion of implementation in NHS core and developmental standards, against which local NHS organisations are assessed by the HCC. A number of factors contribute to this, the most important being poor NHS financial management, clinical resistance, and lack of sanctions against poor implementation.

  25.  Two studies commissioned by NICE looked at financial planning,[38] and found inappropriate use of allocated funding, lack of horizon scanning for future NICE guidance, and poor planning. Organisations perceived that NICE guidance was unaffordable, but where robust implementation systems were in place funding was found not to be the biggest barrier.

  26.  In contrast to implementation of technology appraisals, there is very little understanding of how clinical guidelines are implemented. Research is needed.

  27.  Implementation of guidance is not an HCC priority in its Annual Health Check. Assessment takes the form of ensuring that processes are in place rather than measuring tangible evidence of implementation.

  28.  There is little point in investing in NICE, and the resources required to meet its requirements, if its guidance is not implemented. The major levers to improve implementation are more rigorous HCC measurement and inspection systems that provide a clear picture of both the quality and extent of implementation, and "joined-up" commissioning and financial incentives, eg inclusion of an implementation component in the QOF, automatic inclusion of NICE approved medicines on local formularies.

REVIEWS OF TECHNOLOGY APPRAISALS (TAS)

  29.  TAs are accompanied by mandatory funding within three months of guidance being published. There is no such mandatory funding for Clinical Guidelines. There has been a recent trend for reviews of TAs to be carried out "within the context of a clinical guideline", with express information from NICE that mandatory funding will be removed, even if the guideline continues to recommend use. An example of this policy is given in Appendix 5.[39]

  30.  The reason given by NICE is that the average length of time for a TA to be reviewed (about three years) should be sufficient for the NHS to embed it into clinical practice. However, as we discuss above, implementation is patchy and slow, and three years are simply not sufficient for use of a (new) intervention to have become routine. We call for continued mandatory funding for a medicine whose use remains recommended when reviewed as part of a guideline.

David Fisher

ABPI

March 2007

BEFORE THE APPEAL HEARING

Lack of Transparency

  A recurrent difficulty in relation to NICE appraisals is the lack of proper reasoning to explain the conclusions reached in the FAD. It is therefore difficult for consultees to assess the content of the FAD and whether the conclusions reached may be characterised as perverse. The result of this is that:

(a)  where consultees seek to argue a point as lack of transparency, NICE will frequently rule that, by seeking to engage with the issue, consultees have demonstrated an understanding of the matters raised and the question should therefore be considered under perversity (even though insufficient reasoning is provided to enable a consultee fully to understand the basis for the Appraisal Committee's conclusion and therefore to prepare a perversity argument);

(b)  where an argument is presented under perversity, a further explanation is then provided by the Appraisal Committee verbally at the Appeal Hearing, often in a way that cannot be anticipated, therefore prejudicing the ability of the Appellant to respond.

The Initial Scrutiny of Appeals

  The initial scrutiny of appeals by the Chairman of the Appeals Committee is intended to confirm that an appeal (a) falls under one or more of the permitted grounds; and (b) whether sufficient detail is provided to demonstrate an arguable case. In practice, however, the initial scrutiny often appears to go beyond the requirement that an arguable case be demonstrated and to constitute an assessment of the merits of the appeal.

  This is particularly the case in relation to points argued as a lack of transparency and brought under Ground 1, where the Chairman of the Appeal Committee will frequently form a view of the adequacy of the reasoning provided in the FAD and conclude that the point should be brought under Ground 2. In our view, the adequacy of the reasoning provided in the FAD should not be determined at the admissibility stage.

  The rulings made at the initial scrutiny stage with respect to admissibility are not always consistent, suggesting that greater guidance needs to be provided by the Institute in relation to the admissibility of appeals.

The Involvement of the Chairman of the Appeal Committee

  The Chairman of the Appeal Committee undertakes the initial scrutiny of appeals, to assess admissibility. As indicated above, this appears to involve a preliminary assessment of the substantive merits of the appeal and further correspondence about whether or not the Appellant's points are admissible. In these circumstances, we believe it is unfair for the Chairman of the Appeal Panel to participate in the appeal hearing as a member of the Panel.

THE APPEAL HEARING

Constitution of the Appeal Panel

  Concern has been expressed regarding the constitution of Appeal Panels and, in particular, the fact that two or three members of the five person Appeal Panel (including the Chairman of the Panel) will be members of NICE's own Board. (It should be noted that the 2004 procedures introduced a change in this respect. The previous procedures, issued in 2001, provided that three members of the five person Panel would, in all cases, be members of NICE's Board. The 2004 procedures however raise the possibility that one of those three persons may instead be an NHS representative.)

  In spite of the fact that the majority of appeal points relate to interpretation of cost-effectiveness evidence, there is no Health Economist on the Panel, suggesting a deficiency in expertise in addressing the complex points raised.

Lack of any Substantive Review of the Recommendations

  NICE appeal procedures do not allow for any review of the scientific merits of its recommendations. While appeals are permitted under the three identified grounds these do not include a challenge based simply on a difference of scientific opinion.

  Ground 2 (Perversity) allows an appeal to be brought where a conclusion expressed in the FAD is so unarguably wrong as to be perverse, but this is a very high hurdle. NICE procedures explain that the Appeal Panel will not substitute its own view for that of the Appraisal Committee and that it is theoretically possible for two Appraisal Committees to reach different conclusions based on the same facts, without either being perverse.

  The effect of this limitation is that there is no possibility within NICE procedures for any challenge to be brought where a conclusion appears to be incorrect, but is not frankly perverse. This unsatisfactory situation is exacerbated in the following circumstances:

(a)  In some cases, guidance is changed between the ACD and FAD and, in those circumstances, there may be no possibility to submit a challenge to the substantive scientific conclusions that are expressed for the first time in the FAD;

(b)  The position described in (a) above is particularly acute in circumstances where new evidence is obtained by the Appraisal Committee and disclosed to consultees for the first time within the FAD (eg as occurred in the appraisals of Alzheimer's Disease Treatments and Erythropoetins for the Treatment of Cancer Treatment Induced Anaemia). In these circumstances, a consultee has no opportunity to challenge the new evidence or, in view of the fact that new evidence may not be introduced at the appeal stage, to introduce its own new material to counter it;

(c)  The fact that a challenge to the substantive conclusions expressed in the FAD is not possible at appeal is particularly unfair to manufacturers who, in contrast to other consultees, have had no opportunity to attend earlier meetings with the Appraisal Committee to ensure that their case is fairly and accurately represented;

(d)  The absence of any review of the substantive conclusions expressed in the FAD is not corrected by the fact that Judicial Review is available, because the Courts will also not review the substantive merits of the Institute's decision, but only the procedure by which it was reached.

  Some of these concerns might be ameliorated if the appraisal process was more transparent and if manufacturers were permitted a greater opportunity to participate in the appraisal by attending Appraisal Committee meetings. In addition, the practice of disclosing new evidence together with the FAD should be discontinued and there should be a requirement that in all cases where there is significant change following consultation on an ACD, a second ACD should be issued for consideration rather than a FAD.

Approach to Issues of Transparency

  In many cases, where an Appellant raises a point of appeal based on lack of transparency, the Appeal Panel will then give the Appraisal Committee an opportunity to explain its reasoning. The reasons provided by the Appraisal Committee at the hearing are often wholly new and have not been addressed at any previous part of the appraisal. When these reasons are provided for the first time at the appeal hearing, the Appeal Panel may accept them as providing justification for the conclusions reached, without apparently considering that the mere fact that further explanation was necessary supports an Appellant's appeal that the FAD, as drafted, lacked transparency. It is self-evident that the Appellant is unable to give a fully considered response to reasoning provided for the first time by the Appraisal Committee at an appeal hearing.

Way in which the Appeal Hearing is Conducted

  The way in which appeal hearings are conducted is variable. While Appellants are permitted 10 minutes at the commencement of the hearing in which to make a short oral presentation, whether or not Appellants are then permitted to introduce each point of appeal varies. Appellants should be permitted to introduce each point of appeal, especially where the scientific arguments may be complex; without such an explanation the questioning from the Appeal Panel may not address the point raised by the Appellant.

  In addition, it is a standard approach at appeal hearings that, where more than one Appellant is present, each Appellant may respond to the questioning, only when its particular point of appeal is under consideration. In circumstances where several Appellants may raise similar points of appeal, this may mean that an Appellant is prevented from engaging with issues relevant to its own appeal. The issue is highlighted by the circumstances of the Alzheimer's Disease Treatments Appeal where issues relevant to the clinical trial data of one manufacturer were raised by one of the professional groups. In that case, the manufacturer concerned was prevented from responding or commenting on their own clinical trial data because the Appeal Panel was not, at that time, considering their appeal.

  Similarly, in some cases, particularly where there have been several Appellants present at an appeal hearing, the Panel has not given adequate time for all the issues to be adequately explored. There is no reason why an appeal hearing should be rushed and the Institute should be required to set aside adequate time so that each appeal point may be properly considered.

  Overall, we believe that NICE should adopt a more flexible approach towards the hearing of appeals, with a willingness to hear submissions from other Appellants in response to points of appeal, in the format that is used for the Hearing and in the time permitted for considering the issues raised.

AFTER THE APPEAL HEARING

The fact that, following an Appeal, the same Appraisal Committee is asked to Review the Appraisal

  Following a successful appeal, an appraisal will be returned to the Appraisal Committee for further consideration. However, the Appraisal Committee asked to perform this task is the same as the one that previously produced the unfavourable FAD, raising the possibility of lack of impartiality.

Timing between communication of Appeal Decision and publication of Guidance

  Irrespective of whether an Appeal is successful or unsuccessful, the decision is provided to Appellants only two days prior to publication. This allows little opportunity for preparation of communication materials by companies. Furthermore, if an appeal is unsuccessful, the Appeal Decision will be published together with Guidance to the NHS and the two day period allows little opportunity for consideration of any legal challenge, including injunctive proceedings, prior to publication. We believe the two day period could be increased without detriment to the Institute.

The Guidance itself is not issued to consultees prior to publication

  Following an appeal hearing, minor changes to the FAD may be effected by the Guidance Executive, without the appraisal returning to the Appraisal Committee, as a result of the decision of the Appeal Panel or on the Guidance Executive's own initiative. However, irrespective of such changes, the Guidance itself is not provided to consultees prior to publication. This means that changes to the FAD, made by the Guidance Executive, will be published with no advance notice to companies and no opportunity for challenge—even if they may not reflect the decision of the Appeal Panel or be otherwise controversial.

  We believe there is no reason why a copy of the Guidance should not be issued to consultees together with the Appeal Panel decision for consideration in advance of publication.

The role of the Guidance Executive is poorly defined

  NICE procedures merely state that the Guidance Executive will review Guidance before it is issued. There is no indication as to precisely the measures that the Guidance Executive may properly take and NICE's website includes no procedures for this body. We believe that NICE should be required to specify in more detail the purpose of the Guidance Executive review and the modifications that may be authorised by this body.

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35   The EMEA defines orphan medicines as those to treat rare diseases which are serious, life-threatening or chronically debilitating, with prevalence <5 per 10,000 population. NICE defines "ultra-orphan" diseases as those affecting up to 1000 people in the UK. Back

36   Working paper by the Office of Health Economics: "HTA for orphan drugs: A review of the Issues and of NICE and SMC Decisions (to be made available in April 2007) Back

37   ABPI can supply a detailed analysis of appeal decisions from the period October 2004-November 2006 (since hearings were held in public) on request. Back

38   Audit Commission, 2005, Managing the financial implications of NICE guidance; Howard S and Harrison L, 2005, NICE Guidance Implementation Tracking, Data Sources, Methodology & Results. Back

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