EXECUTIVE SUMMARY

—  Public confidence in NICE is being eroded owing to a growing perception that it is an arm of Government to cut costs rather than a force for improving clinical care: This perception has been reinforced by some recent decisions that appear to be incompatible with common sense, eg the decision not to recommend pharmacological treatment for patients with mild Alzheimer's disease but to let them progress to a moderate to moderately-severe disease state before offering treatment.

—  The perception that NICE decisions are driven by economics is supported by its apparent over-reliance on cost-QALY as the over-arching decision-making variable: Whilst cost/QALY values are useful, they should be used as an aid, and not the sole basis for decision-making with regard to patients' access to medicines. Other factors, such as clinical need and availability of other effective treatments should be given relevant weight in the decision-making process. We would welcome a broader debate on exactly how the value of medicines should be assessed.

—  Flaws in the quality of evidence assessment have resulted in the need for further analysis and unnecessary delays. Two examples have been provided which relate to Novartis products.

—  Some patient groups are disadvantaged by the methods used by NICE: in particular those who derive quality (rather than quantity) of life benefits from treatment, eg the elderly, people at the end of life, or with chronic conditions and those with rare conditions. This is contrary to the increasing attention of Government on management of long-term conditions and the focus on care and dignity for the elderly and equality of access to care.

—  The perspective taken by NICE in assessing value is perhaps incompatible with that of the public. NICE examines value to the NHS, whereas the public may feel it should look at value to patients, carers and wider society.

—  These factors are leading to an increasing number of appeals using an appeals process that is seriously flawed and which is weighted heavily against appellants achieving any significant changes to guidance.

—  Implementation of NICE guidance is highly variable, with differing interpretations of what implementation means. Technology appraisal guidance is often perceived as a necessary evil that contributes to cost pressures, although evidence has shown that good financial planning removes funding as the major barrier to implementation. "Wait-for-NICE" policies are common and often written into local policy documents.

—  Collaborative and constructive dialogue with industry is lacking thereby preventing significant information and arguments on patient benefit from forming part of the appraisal process.

  Novartis recommends that:

—  Factors other than cost/QALY are given sufficient weight by NICE when making decisions and it makes clear how these factors have been balanced in its guidance.

—  NICE works with industry to broaden this definition of value and to adopt a more holistic approach to evaluation of benefits and costs of treatment, to include societal benefits and costs beyond NHS and personal social services.

—  is given direct accountability for the quality and consistency of the assessments of evidence it receives from the academic centres commissioned to provide Assessment/ERG Reports.

—  NICE; academic centres and companies engage in a truly constructive dialogue throughout the appraisal on such issues as identifying the most appropriate population for whom treatment would be deemed cost effective, methods and assumptions to be used, data quality and modelling techniques.

—  A root-and-branch review of the appeal process is conducted.

—  Implementation of NICE guidance is given more attention in the Healthcare Commission's Annual Health Check and that an implementation component is included in the Quality and Outcomes Framework.

INTRODUCTION

  1.  Novartis Pharmaceuticals UK Limited has a long track-record of researching, developing and supplying innovative medicines in areas of major unmet medical need. In the past five years, we have launched more chemical entities than any other major pharmaceutical manufacturer, including significant advances in the fields of medicine which include cancer, ophthalmic medicine, transplantation and asthma. Furthermore, our interactions with NICE are likely to increase in the coming years with an unprecedented programme of new launches planned.

  2.  During this period, we have been involved in 15 NICE appraisals and 1 review for products which include imatinib (Glivec®), verteporfin (Visudyne®), rivastigmine tartrate (Exelon®), letrozole (Femara®), clozapine (Clozaril®) and ranibizumab (Lucentis®). We therefore have considerable experience of working with NICE, of its processes and its effects on patient care. Whilst NICE does much good work, we feel that there is scope to improve the consistency and quality of some assessments conducted by the independent assessment groups.

Why are NICE decisions increasingly being challenged?

  3.  There are a number of factors that may contribute to the increasing number of challenges to NICE guidance. The first is that there is an impression that NICE is increasingly focusing its decision-making on the cost/QALY and whilst the cost/QALY is a useful measure, it should not be used as the sole basis for decision-making. Although we recognise that QALYs provide a useful measure to compare cost-effectiveness across a wide range of different treatments, it is important that all relevant factors are given due consideration to ensure fair, balanced and evidence based guidance to the NHS. Cost/QALY as it is today is too narrow, excluding such factors as societal costs and some of the qualitative costs to the patient.

  4.  An area that appears to have diminishing importance when reaching a decision is the opinion of patients, carers and clinicians. These stakeholders have direct experience of living with and managing the condition in question, yet it appears that their opinions are often given relatively less emphasis in comparison to economic considerations. Such an approach undermines the confidence of NHS staff and patients in the quality of guidance produced, resulting in increased challenges to guidance as well as poor implementation.

  5.  NICE's policy on the use of QALYs was outlined in 2005 in its valuable paper on social value judgements. NICE states "that while it endorses the use of cost-utility analysis in the economic evaluation of particular interventions, such information is a necessary, but not sufficient, basis for decision-making". We believe that if this policy were fully implemented that a more well informed and patient focused decision making process would be the result.

  6.  Another reason for NICE decisions increasingly being challenged is the sometimes questionable quality of the work undertaken for it by the academic centres commissioned to produce Assessment Reports and Evidence Review Group Reports. Whilst economic models submitted by manufacturers of technologies are criticised heavily during the appraisal process, NICE is reluctant to accept any criticism of the models developed by the ERGs. This situation is further exacerbated by not allowing manufacturers access to fully working versions of the models developed by the ERGs. For example, in the case of Alzheimer's disease, the economic model developed by SHTAC[118] only used two disease states (plus death)—full-time care and pre-full-time care—contradictory to the medically recognised and identifiable stages of the disease (mild, moderate, moderately severe, severe, as measured by MMSE[119] scores). The criteria used to define these states were taken from a small US study, where clinical practice and availability of full-time care are substantially different from the UK. Moreover, drug treatment is licensed for use dependent on MMSE scores, not on care setting.

  7.  In the COX-II appraisal in 2004, concomitant use of aspirin was included in the meta-analyses for COX-II users but not in users of NSAIDs. Given that the benefits of COX-IIs reside in their ability to reduce gastro-intestinal side-effects, which can be found with aspirin, this decision immediately biased the results of the meta-analyses and subsequent economic models against the use of COX-IIs.

  8.  In both cases further cost-effectiveness analyses were required resulting in major delays to guidance and patients' access to the medicines.

  9.  The work from Assessment/Evidence Review Groups is commissioned via the National Coordinating Centre for Health Technology Assessment. This puts NICE in a difficult position in that it is not directly accountable for the quality of the work upon which it relies for its decision-making. It is also difficult for NICE to ensure consistency of methods, standards and approaches across, in particular, the different Evidence Review Groups, who wish to exercise some degree of academic freedom.

  10.  We believe the degree of challenge to NICE decisions would be reduced considerably if a more inclusive approach were taken during the assessment process, enabling a dialogue from the beginning on the appropriate patient population in whom treatment may be cost effective, on methods, on assumptions, on data quality and on modelling techniques. Currently interaction is generally limited to the manufacturer's submission of its dossier. We believe that such an approach is not incompatible with NICE maintaining its independence.

  11.  In contrast, it is not uncommon to collaborate with other Health Technology Appraisal bodies as the assessment progresses on such issues as the assumptions to be used and appropriate patient populations. This type of approach enables a more rigorous and robust evaluation of the evidence base thus more effectively serving the needs of the patient. Importantly, it assures that misunderstandings in a submission are removed, thereby ensuring a more balanced judgement.

  12.  We would therefore recommend that NICE considers constructive dialogue throughout appraisal, to clarify issues and prevent unnecessary misunderstandings. This would also seem a sensible means to reduce the number of appeals.

Are any particular groups disadvantaged by the NICE evaluation process?

  13.  Uncertainty in cost-effectiveness calculations is particularly marked when estimating quality of life. Quantity of life is more tangible, but quality of life measurement is highly subjective and approximate, and the generic instruments preferred by NICE to measure quality of life are relatively simplistic and insensitive to incremental changes.

  14.  Over-reliance on cost/QALY as the major decision-making criterion therefore disadvantages patients where treatment benefits enhance rather than lengthen life, eg in the elderly, end-of-life therapies and chronic diseases where small improvements can make a big difference to patients.

  15.  Patients suffering from rare conditions are another group disadvantaged by the NICE process. Development costs for therapies in such conditions are relatively high, and the price per patient appears to be high (while the budget impact is often relatively low). It can therefore be difficult to make the economic case using the criteria required by NICE. Proportionately fewer orphan medicines receive a positive recommendation than non-orphan medicines. Patients are therefore being denied effective treatments for severe, often life-threatening conditions, simply because those conditions are rare.

Is public confidence in the Institute waning and if so why?

  16.  We believe that public confidence is waning because NICE's role appears to be moving away from clinical excellence to cost containment. The decisions referred to above, eg denying access to drug treatment for patients with mild Alzheimer's disease, runs counter to what most people would deem as common humanity and sense. Such decisions lead to a perception that NICE exists as an arm of Government to cut costs, rather than to promote good patient care. The current attention given to NHS deficits only strengthens this view.

  17.  A contributing factor to lack of confidence is that the balance of factors taken into account by NICE in deciding on guidance is not made clear. We believe that a clear rationale for how NICE reached its decisions should be given when guidance is issued.

  18.  One question the Committee may wish to explore is what is meant by value when NICE makes its decisions—value to whom: the NHS, the patient, or wider society? NICE's remit is to focus on the costs and benefits to the NHS and Personal Social Services. However, medicines can confer benefits and savings beyond the health budget, eg in social services costs (for which people with mental health problems account for a significant proportion) in improved educational outcomes in children, enabling them to contribute to society through adult life, and in reduced disability enabling people to continue to work.

  19.  Calculations of such benefits and costs can make a significant difference to cost-effectiveness assessment: in the Alzheimer's disease appraisal, 30% of the costs of institutionalisation were attributed to carers. The exclusion of this 30% from the costs of NHS care artificially inflated the cost/QALY estimates of the medicines under review.

  20.  Costs and benefits beyond the health system are included in the assessment of clinical and cost effectiveness in HTA systems in Sweden and the Netherlands. In Sweden 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". Whilst we understand this is challenging, we would call on NICE to work with industry to improve its methodology in this respect.

The speed of publishing guidance

  21.  The aim of the NICE Single Technology Appraisal (STA) process was to address concerns that the Multiple Technology Appraisal process was too long and delaying patients' access to important new medicines. Regrettably, only two of the 10 STAs commenced to date have been completed within the target six months. Whilst early teething problems are inevitable, it appears that very few STAs will not be subject to consultation, which is initiated when the Appraisal Committee's preliminary recommendations are "substantially more restrictive that the terms of the licensed indication being appraised".

  22.  A further delay is being caused by a disproportionate number of appeals resulting from NICE appraisals and the numbers and rates of appeals appear to be increasing.

The appeal system

  23.  Embarking on an appeal against a Final Appraisal Determination is not to be undertaken lightly because the chances of any significant change to NICE decisions are minimal. Appeals are costly, taking a significant amount of management time on the one hand and delaying market access on the other.

  24.  The majority of appeals are the result of disagreement with the interpretation of the evidence and the resulting evaluation of cost-effectiveness. NICE procedures do not allow for challenge on the basis of a differing view of the interpretation of evidence, unless the appellant can show that the NICE decision was "perverse," which is defined as "to be obviously and unarguably wrong, to be in defiance of logic or so absurd that no reasonable Appraisal Committee could have reached such conclusions". This is a very high hurdle. It is not helped by the fact that there is no health economics expertise on the Appeal Panel.

  25.  The NICE appeal process is not independent: the Chairman of the Appeal Committee undertakes the initial scrutiny of appeals to assess admissibility (which appears in many cases to constitute an early assessment of the merits of the appeal) two or three members of the Appeal Panel (including the Chairman) are members of the NICE Board and following an upheld appeal the same Appraisal Committee is asked to review the original decision. NICE is therefore acting as judge and jury over its own guidance.

  26.  The lack of success in appealing NICE decisions is a barrier to companies—but it is an even bigger barrier to other stakeholders, in particular patient groups, who are deterred from making appeals by the highly legalistic nature of the process, the complexity and expense and who, in many cases, do not have the resources available.

  27.  For all these reasons we would support the ABPI's call for a root-and-branch review of the appeal process.

The implementation of NICE guidance, both technology appraisals and clinical guidelines (which guidance is acted on, which is not and the reasons for this)

  28.  In common with most other stakeholders, our experience is that implementation of NICE guidance is highly variable. Whilst some NHS organisations have well-developed systems to horizon scan, plan for and implement NICE guidance, this is far from the general picture. Some organisations "cherry pick" parts of guidance, especially where they conform with their existing practice or audit programmes.

  29.  The interpretation of what "implementation" means varies—in some organisations it means circulation of the guidance and the allocation of funding (without necessarily effectively communicating the existence of that funding) to others it means identifying a clinical lead and project manager who work with colleagues to draw up a plan and reconfigure services in order to deliver the guidance with appropriate funding to support it.

  30.  Implementation of NICE technology appraisal guidance is more straightforward and more developed than implementation of clinical guidelines and has been subject to more focus as it is associated with mandatory funding. It is our belief that understanding of how guidelines are implemented is universally poor and a lot of research needs to be done to get a clearer picture before the Committee's questions can be answered.

  31.  NICE technology appraisal guidance is often perceived by PCTs and Trusts to be a necessary evil that has to be funded and adds to cost pressures, rather than a means to improve patient care. However, the Audit Commission Study, Managing the Implementation of NICE Guidance (September 2005) showed that where good financial planning systems are place, funding is not the major barrier to implementation.

  32.  "NICE blight" is a common phenomenon. The inclusion of a medicine on the NICE work programme frequently triggers processes whereby funding is only released on a case-by-case basis, necessitating individual "business cases" to be generated by clinicians for patients. This is bureaucratic and time-consuming and increases the problem of post-code prescribing. To quote one PCT's Local Development Plan for 2007-08: "The PCT will not fund any drugs that are not NICE approved unless prior agreement has been reached. Drugs handling costs, overhead costs, admin and packaging costs will also not be funded unless prior agreement has been reached."

  33.  The major drivers for effective implementation are good financial and project planning, clinical engagement, clear lines of accountability and a commitment at senior level to the importance of NICE guidance as a means to improving patient care. The major influence to ensure that implementation is effective is Healthcare Commission assessment, and we would call for the Commission to put in place measurement and inspection systems that provide a clear picture of both the quality and extent of implementation. A further lever in primary care would be to include implementation of guidance as a component in the Quality and Outcomes Framework.

Novartis Pharmaceuticals UK Ltd

March 2007

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