The National Institute for Clinical Excellence was established recently to promote clinical- and cost-effectiveness in the National Health Service. This article outlines the NICE's structure and its processes, and provides examples of the sort of work the institute is carrying out. Its content is drawn from the official documents listed
The National Institute for Clinical Excellence (NICE) was established to provide clinical guidance, and guidance on the clinical- and cost-effectiveness of new and existing clinical interventions, to the National Health Service (NHS) in England and Wales. Proposals for setting up the NICE were first described in the Government's White Paper, "The new NHS: modern, dependable",1 and further developed in the consultation paper, "A first-class service: quality in the new NHS",2 and a follow-up discussion paper, "Faster access to modern treatment: how NICE appraisal will work".3
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The building at 90 Long Acre in London's Covent Garden, where the NICE has an office |
The NICE will appraise 30 to 50 new and existing interventions each year and issue guidance by which it will help to:
The results of the NICE's deliberations and its recommendations are to be sent to clinical professionals and commissioners in health authorities, health trusts, and primary care groups. The NICE will also develop guidance for patients and carers on the implications to them of its recommendations.
Timely guidance is deemed necessary on individual treatments and products, and in particular clinical innovations. Frequently, when new treatments are introduced into general NHS practice, evidence of clinical- and cost-effectiveness is unclear or incomplete. This can cause:
In theory, it would be beneficial to consider all kinds of clinical intervention on an equal basis. This should include:
However, priorities have to be set for the work programme, and consideration made of how different health sectors (eg, the medical device industry) may be able to respond to the programme. Other sectors may already have effective arrangements in place (eg, population screening is covered by the work of the National Screening Committee).
Promotion of clinical- and cost-effectiveness The NICE promotes clinical- and cost-effectiveness by providing guidance and audit in support of staff dealing with patients. It advises on best practice in using existing treatment options, appraising new health interventions, and advising the NHS on how they can be implemented and how best these might fit alongside existing treatments.
Dissemination of information The NICE also has a key role in co-ordinating the range of current activity in both the active dissemination of information and in responding to specific inquiries. It provides a single reference point for information on standards and audit methodologies, and supports and complements the new NHS information strategy (intended to provide universal desktop access to NICE guidance, along the lines of the Prodigy computer-aided, decision-support system for GPs).
Implementation methodologies The NICE is to develop a role in providing information about implementation methodologies to help local clinical teams. It will also ensure that its clinical guidance is integrated into other appropriate activities (eg, professional education and training, seminars and workshops, patient education and information, and audit).
A new partnership The NICE creates a new partnership between the Government, the NHS, and clinical professionals. Through NICE, the Government's objective is to help clarify, for patients and professionals, which treatments work best for which patients and those which do not. The Government, working with clinical bodies, will systematically appraise clinical interventions before their introduction into the NHS. Thus, the NICE gives doctors, nurses, and midwives more support than previously available to facilitate their making the complex decisions about individual patient care. It will also assist in the decisions made by those commissioning care.
Network of relationships In support of its work, NICE is developing a network of relationships:
Other responsibilities The NICE is also taking over the funding, commissioning, and oversight of a range of functions currently undertaken by a number of different groups funded by the Department of Health and the National Assembly for Wales. These functions include:
The functions of the NICE apply to the NHS in England and Wales. The NICE was set up as a special health authority in April, 1999 (following the Establishment Order laid before Parliament on January 2, 1999), and is accountable to the Secretary of State for Health in England and the National Assembly for Wales for its resources, delivery of its work programme, and for the guidance it produces for the NHS. The NICE is funded out of the money currently being spent on similar organisations and activities to those whose roles it will take on. Its annual budget is about £9.8m.
Executive board The executive board reflects a range of expertise, including the clinical professions, patients and user groups, NHS managers, and research bodies. Members are appointed on merit, not as representatives of a particular organisation or interest. As a small body of executives and non-executives, the board will ensure that the NICE conducts its business on behalf of the NHS in the most effective way. The chief executive will be accountable to the board for progress on the agreed programme and the use of resources.
Although the NICE's executive board will not be involved in the detail of each individual appraisal, it will give final authorisation for the issue of all guidance prepared by the appraisal group and direct the work of the appraisal group to ensure consistency with the NICE's other work.
In addition, the board will have to decide how best to handle cases in which sponsoring companies feel that the process operated by the appraisal group has not allowed them the to put their evidence in full.
Appraisal group The appraisal group is a subcommittee of the NICE's executive board. Therefore, the chairperson of the group is accountable on all matters of policy and professional judgment to the chairperson of the NICE. The head of the secretariat is also accountable to the NICE's chief executive for the performance of the appraisal group. All appraisal group advice is channelled through the NICE and will be issued with the NICE's authority.
The appraisal group will also (through the secretariat) have access to a wide range of subject specialists. These specialists will be invited to comment, usually in writing, but also at the committee's deliberations if required. They do not contribute to the appraisal group's final decisions, but advise on specialist aspects of procedures under discussion.
Partners' council The NICE partners' council comprises representatives of all the key stakeholder groups (patients and carers, the health professions, including the professional Royal Colleges, academics, NHS service interests and the pharmaceutical and other health care industries). The council is appointed by the Secretaries of State for Health and Wales. Its role includes reviewing the NICE's annual progress report and contributing to the development of the work programme, commissioned by the Department of Health and the Welsh Office.
Secretariat The NICE secretariat initially consists of staff from the Department of Health who provide technical and administrative support. It also has professional, academic, and managerial skills to commission and manage the guidance and audit programmes and to support the national appraisal function. The secretariat will have a wider role in the co-ordination of the NICE's work programme across a range of organisations.
The secretariat prepares initial evaluations of evidence for the appraisal group, to allow discussion to focus on key issues. The secretariat will also assist in drafting the appraisal group's recommendations and in handling inquiries about its work, both generally and in individual cases. The secretariat is intended to comprise the following expertise:
A memorandum of understanding on appraisal of health interventions sets out the rules under which the NICE is to carry out its appraisals. Appraisals are intended to promote the appropriate use of interventions which offer good value to patients and to discourage the use of those which do not. It builds on the proposals set out in the discussion paper "A first-class service: quality in the new NHS",2 modified in the light of comments received and further discussion with stakeholders.
The responsibility for selection of topics to be referred to the NICE lies with the Department of Health, in consultation with the National Assembly for Wales, the NICE itself, and other interested parties. In practice, new interventions are selected from those innovations which it is deemed are likely to have significant impact on the NHS. This appraisal is carried out on behalf of the Department of Health by the National Horizon Scanning Centre at the University of Birmingham. Selection criteria include topics covered by national service frameworks or those where there is widespread variation in clinical practice or uncertainty over best practice.
Once the process is mature, the Department of Health intends to give final notification of referral of interventions to the NICE no later than nine months before the point at which guidance is to be ready for dissemination. Exceptionally, a shorter notice period may be necessary (eg, when a technology is changing rapidly or when new evidence radically alters the perception of an existing technology).
The National Horizon Scanning Centre and the National Prescribing Centre for medicines have been commissioned to carry out horizon scanning on behalf of the NHS Executive.
To do this, they will scan published material, maintain contacts with similar groups in other countries, and establish informal contacts with clinicians and researchers, patient groups, sponsoring companies, and industry associations.
A standing "short-list" will be produced, summarising areas of application, possible benefits, and the likely impact on NHS resources. For medicinal products under development, bulletins based on these summaries will be published by the National Prescribing Centre and Drug Information Pharmacists Group about six to 12 months before the medicinal product is expected to receive a marketing authorisation.
The Department of Health will regularly and systematically examine all the interventions on the shortlist, focusing in particular on those expected to be launched in about six years' time or less. Where an intervention will probably be selected for appraisal, the Department will notify the sponsoring company and invite comments. The judgment that a particular intervention is likely to qualify for appraisal will be reviewed annually, and the sponsoring company notified of any changes. The Department will notify the NICE of its provisional judgments to enable forward planning of the programme of appraisals.
If there is no obvious sponsoring company, the Department will decide whether any research should be commissioned through the NHS R&D programme.
When an intervention has been provisionally selected for appraisal and it is likely to be marketed to the NHS within the subsequent 12 months, the Department will finalise its selection decision and give the sponsoring company a final opportunity to make representations. Subject to this:
Initial work programme In August, 1999, the NICE published the initial batch of technologies that Ministers wish it to start appraising in autumn, 1999. It has written to the following, inviting them to submit evidence for the appraisal:
The list of interventions is given in Table 1 (p872).
Table 1: List of NICE interventions |
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| Treatment | Notes |
| Hip prostheses/hip replacement | There was no evidence of additional benefit from using more expensive prostheses from two recent studies in the NHS health technology assessment programme. The NICE will examine this and other evidence and produce an assessment of the issue. The NICE will also advise how the NHS could obtain best value for money without reducing quality of patient care |
| Advances in hearing aids/hearing disability | There have been significant recent developments in hearing aid technology, but provision both of new and conventional aids is variable. Guidance from the NICE will establish basic standards, and may assess any additional benefits from newer aids. |
| Routine extraction of wisdom teeth/dental care | Professional opinion is increasingly stating that routine extraction of non-symptomatic wisdom teeth is unnecessary (and some related procedures involve the risk of actual harm). This is supported by guidelines from the Faculty of Dental Surgery and from the Scottish Inter-Collegiate Network, and by a critical review from York university. Nevertheless, a significant number of dentists continue to carry this out. NICE guidance will give clear standards, possibly leading to the phasing out of many unnecessary and potentially harmful treatments |
| Liquid-based cytology/cervical screening | This is one of a number of current developments in screening technology, and the one most likely to have early impact on the NHS. This technique should improve the quality and readability of slides, thus reducing the number of false negatives. Its use, however, involves significant capital investment, a major reorganisation of the service, and a significant increase in running costs. The NICE will consider the evidence and advise whether this technology offers worthwhile benefits |
| Coronary artery stent developments/ treatment of coronary heart disease | Stent insertion, to reduce the risk of coronary arteries blocking up again after angioplasty, is common. However, there are doubts over its appropriate use, especially in view of the variations to the basic technique being developed. The NICE has been asked to survey these developments as well as the underlying case for using stent technology |
| Taxanes: paclitaxel (Taxol) ovarian cancer, breast cancer; docetaxel (Taxotere) breast cancer | The taxanes are existing drugs with well-established uses in treatment of a range of cancers. The current uncertainty concerns the use of paclitaxel as a first-line treatment in ovarian cancer. Both drugs may be newly indicated in the treatment of advanced breast cancer. Because of their relatively high cost and some difficulties over interpreting the clinical evidence, the NICE will give definitive advice on the available evidence |
| Inhaler systems (devices) for childhood asthma | A wide range of devices has been developed to enable patients to inhale effective doses of anti-asthma drugs. There is much debate over the clinical- and cost- effectiveness of more sophisticated systems, and therefore much variation in practice. The issues are particularly problematic in very young children (up to five years), who may have difficulty in using simpler, cheaper devices |
| Proton pump inhibitors (PPIs) for treatment of dyspepsia | PPIs are very clinically- and cost-effective for some patients, but there is good evidence of their inappropriate use in two instances: treatment of minor disease, which would have responded to less expensive treatments; and failure to attack the underlying cause of ulcers by using Helicobacter pylori eradication therapy after initial treatment of symptoms with a PPI. Clear guidance from the NICE offers the potential for significant savings while enhancing quality of care |
| Interferon beta (relapsing remitting/secondary progressive multiple sclerosis); glatiramer (relapsing remitting MS) | Beta interferon is a controversial treatment for patients with a poor prognosis and no effective alternative, and upon which high patient hopes have developed. Many clinicians have major doubts over the cost-effectiveness of this treatment and the scope for successful targeting of patients most likely to benefit. On the available evidence, the new product glatiramer (expected to receive a marketing authorisation imminently) will raise similar issues. It is proposed that the NICE should consider pharmaceutical treatment in the context of services for MS patients generally; the NICE may subsequently be asked to follow up this appraisal of the role of the two pharmaceuticals by developing a more wide-ranging guideline to set standards for care in MS |
| Zanamivir/oseltamivir for influenza | Evidence suggests these two new drugs can shorten the duration of influenza by up to two days if taken soon after symptoms appear. Effective use will depend critically on how successfully they could be targeted at those most likely to benefit, without increasing the pressure on primary care services at what is already a difficult time of year. The NICE guidance could help set the evidence of clinical benefit in its proper context, including the appropriate use of preventative measures such as vaccination |
Future work programme The Department of Health has also determined the future work programme for the NICE, and those technologies it is required to consider in early 2000 (see Table 2, p873).
Table 2: The NICE's future work programme |
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| Treatment | Notes |
| Laparoscopic surgery: various applications, including for hernia and colorectal cancer | Keyhole surgery techniques have been widely taken up in the NHS. But apart from concerns over safety and training issues, recent evidence suggests that keyhole surgery for at least these two conditions is more expensive than conventional surgery and offers only marginal benefits. A review by the NICE would be timely. |
| Wound care: various applications | This is a highly significant area of NHS care in terms of morbidity, quality of life, and impact on NHS resources. There is continuing widespread uncertainty over the appropriate use of innovations in wound care (eg, use of complex bandages), and a lack of good evidence of clinical effectiveness. In consultation with the NICE, the Department of Health will define more clearly the areas on which an appraisal should initially focus |
| Implantable cardioverter defibrillators: arrhythmias | This technology involves administering an electric shock to control a heart beating abnormally fast or slow. It has developed rapidly since its introduction in the 1980s. Following publication of a key trial in 1997, uptake in the UK is likely to grow rapidly. It is significantly more costly than equivalent treatment by medication. The NICE could give guidance on its appropriate use and the scope for targeting patients likely to derive most benefit |
| Autologous cartilage: transplantation for treatment of cartilage injury | This is a novel technique which takes a patient's cartilage cells, cultures them, and reimplants them. If early results are confirmed the potential clinical benefits could be significant. So far, there appears to be a lack of good evidence on which to judge cost-effectiveness. The NICE could advise on the need for further structured research and on whether the technique could in the meantime have a role in routine practice |
| Riluzole: for motor neurone disease | Riluzole was first launched in 1996 for treatment of this highly distressing condition. There has been considerable debate over the extent of the clinical benefits which it offers, and as a result widespread variations in availability. The NICE guidance could help end this uncertainty by a clear assessment of the available evidence |
| Ritalin: for hyperactivity in childhood | Ritalin, a treatment for attention deficit hyperactivity disorder, is another drug in which there is wide variation in access. Some practitioners strongly advocate its use while others question its value, or consider that it should be prescribed only in conjunction with other interventions such as cognitive and behavioural work. Prescriptions have increased dramatically over the past 10 years, probably as the result of better identification. There are uncertainties over the available clinical evidence. The NICE could review the situation, identify issues requiring further research, and make recommendations for routine practice |
| Ribavarin and alpha interferon: for hepatitis C | Ribavarin is expected to be authorised for marketing in the very near future, in combination with alpha interferon, for treatment of hepatitis C. Available evidence suggests that it may achieve a significantly higher cure rate than alternative therapies. NICE guidance based on the evidence should help to ensure a consistent uptake in the NHS if this is found to be appropriate |
| COX-2 inhibitors: for musculoskeletal disorders | The COX-2 inhibitors are a new class of drugs which promise similar benefits to other non-steroidal anti-inflammatory drugs, but with much lower risk of causing ulcers. Of the two leading products, one is already licensed and the other is likely to follow later this year. There is likely to be some uncertainty over the appropriate use of these products, especially in relation to simple alternatives (for some conditions) (eg, paracetamol). NICE guidance could prevent possible variations in uptake and ensure that usage is appropriately targeted |
| Orlistat/sibutramine: for obesity | The consensus view of professionals is that the new anti-obesity drugs are likely to have some clinical benefit if appropriately used. There is, however, a risk of inappropriate use outside their (fairly narrow) indications. A fast track HTA is under way on the relative cost effectiveness of anti-obesity drugs compared with other preventative measures, and will report in time to inform an appraisal by the NICE |
| Glitazones: for Type II diabetes | This new class of compounds, for which the lead compound is likely to be licensed late in 1999, is expected to offer significant benefits to a substantial proportion of patients with Type II diabetes. Careful targeting may, however, be needed to ensure cost-effective use |
| Glycoprotein IIb/IIIa receptor inhibitors: for unstable angina and acute coronary syndrome | This is a new group of pharmaceuticals intended for patients admitted to hospital with unstable angina or acute coronary syndrome, as an adjunct to existing therapies such as low molecular weight heparin. The earliest compounds (administered by intravenous injection, ie, suitable only for hospital use) are expected to be licensed around the middle of the year, with oral preparations later in the year. Again, careful targeting on patients most likely to benefit may be needed |
| Galantamine/propentofylline: for Alzheimer's disease | These may be the next two licensed drugs (late 1999) for treatment of Alzheimer's disease. Galantamine is in the same chemical class as donepezil (Aricept) and rivastigmine (Exelon). Referral of the two new drugs would give the NICE the opportunity to review treatments for Alzheimer's disease more generally |
The appraisal process to be used by the NICE has been set out in a memorandum of understanding, published in August, 1999, (see above) and in "Appraisal of new and existing technologies: interim guidance for manufacturers and sponsors."4 The memorandum outlines arrangements for submitting evidence, consulting on draft guidance, and instigating appeals in the event of dispute over final recommendations from the NICE. If it is necessary to modify the appraisal process in the light of experience, the NICE will consult on proposed changes and will give due notice of bringing them into effect.
It is intended that the appraisal process will have no effect on requirements for medicinal products obtaining a marketing authorisation or on safety requirements for medical devices (determined by the application of a CE mark). The process will be formally independent of the processes operated in each case by the UK Medicines Control Agency and the UK Medical Device Agency.
Detailed methodology will be developed for judging the evidence, and reaching an overall view on the clinical cost-effectiveness of the intervention. The appraisal will consider some or all of the following points:
Evidence submitted will be appraised by the NICE, in consultation with interested parties. The NICE aims to apply equal rigour to its appraisal of all types of intervention.
Data and evidence required from a single sponsoring company The appraisal process will be mature about three years after launch. The data submitted by a sponsoring company will be analysed, and the company contacted to clarify points. The secretariat will append a commentary to the data which reviews the robustness of the evidence submitted, and adds to the analysis as needed (eg, supplying an analysis of the impact on NHS resources if the sponsoring company has not included this in its submission).
The commentary will be sent to the sponsoring company, which can add comments. Comments will also be invited from any relevant patient groups, either on their own initiative or in response to the industry submission and/or secretariat comments. The Department of Health, National Assembly for Wales, or NHS bodies (eg, the NHS Confederation) will also be invited to submit views.
When the process is complete, the full set of papers (containing the sponsoring company's submission, any other initial submissions, secretariat commentary, and further comments from the company and other interested parties) will be given to the appraisal group.
Data and evidence required when there is no sponsoring company If there is no sponsoring company (eg, as for most surgical procedures), the NICE will invite the Department of Health to commission an assessment. This will typically be from academic groups (eg, those who already have experience of similar work on behalf of the regional development evaluation committees). The assessment will review existing and new research as appropriate. Patient groups will also be invited to submit views. The process will then continue as above.
Data and evidence required from several sponsors If there are a number of alternative devices for a single procedure, or there are a number of alternative treatments (none of which have been previously appraised), more than one sponsor may be involved.
To deal with this situation, the Department might commission research on the clinical effectiveness of the procedure in generic terms. This would consider variations associated with particular products, drawing as far as possible on research already carried out by individual sponsoring companies. Combined with information on the cost of individual products, this would create an assessment of the relative clinical cost-effectiveness of each product. The submission to the NICE would be made by the group carrying out the research, but each company (and relevant patient groups) would be able to add comments on the overall assessment or on aspects relating to its individual product.
Confidentiality issues The NICE has to bear in mind issues of confidentiality very carefully. Ideally, the NICE's processes should be as transparent as possible and the evidence underlying its recommendations accessible. However, the NICE recognises that, to operate effectively, it has be supplied with information from sponsors which is not in the public domain at the time of appraisal. In many cases, this information will be commercially confidential. Sponsors will be reluctant to make it available unless they can be assured that it will not be disclosed outside the NICE.
The NICE will adopt policies which reflect these objectives. Such policies must take into account current legal requirements (including any future freedom of information legislation) and prevailing understandings between Government, industry, and the general public on information in regulatory submissions.
The initial appraisal and guidance from the NICE might be reviewed at which time limited approval is given to a health intervention, allowing further research or development. Subsequently, the sponsoring company will be invited to make a further submission, describing how their new data amend the original decision.
Review may also be necessary when further information on benefits or costs (eg, concerning either an intervention or comparison treatments) becomes available which changes the basis of a previous appraisal. The additional data may come from the appraisal secretariat, an individual member of the appraisal group, or from the sponsoring company. The appraisal group considers whether to review its earlier guidance. If necessary, it invites the sponsoring company to make a full submission.
It is not intended that the appraisal process should delay the introduction of innovations into clinical practice. Indeed, it is likely that appraisals will expedite the use of beneficial new interventions throughout the NHS. The process described in "Appraisal of new and existing technologies: interim guidance for manufacturers and sponsors"5 suggests an overall timetable of up to eight months from submission of evidence to issue of guidance.
Additional time might be allowed at the sponsor company's request if the company wished to submit further evidence in the light of the secretariat's commentary.
The appraisal period incorporates time for the sponsoring company, patient groups, the Department of Health, and the National Assembly for Wales to receive the draft recommendations and make final comments. The appraisal group will then review its recommendations before they are issued in their final form.
In both the programmes described below, the appraisal process will be essentially the same as for new interventions. However, the appraisal group will also have to consider those patients who are established on treatments subsequently shown not to meet the criteria of clinical- and cost-effectiveness. The group should advise on when clinicians should be encouraged to attempt to switch such patients to alternatives. There are two elements to the "catch up" programme for existing health interventions.
Assessments completed under the Department of Health's health technology assessment (HTA) programme Upon completion of each HTA, the Department of Health will use the same selection criteria as those for new interventions. Interventions meeting the criteria will be automatically referred to the appraisal group, with the HTA forming the central platform of evidence (supplemented as required by further analysis, commissioned from the original research group or from one of the regular assessment providers). The Department will ensure that this does not inadvertently give a competitive advantage to one product, although application of the suggested selection criteria should normally avoid this.
Systematic, prioritised, catch-up programme Over several years, the Department will prioritise the most significant existing interventions for appraisal, using a modified version of the selection criteria. Interventions are more likely to be selected if there is evidence of significant variations in NHS use, or of use not in accordance with generally accepted good clinical practice. Where necessary, the Department will commission an assessment of the selected intervention through the NHS R&D programme.
The guidance documents form the crux of the output from the NICE. They will include the primary appraisal assessment, giving the NICE's guidance on when an intervention is recommended for routine NHS clinical use.
Format and content of the NICE's guidance If the advice is to succeed in enhancing resource use and reducing disparities in the uptake of the intervention, the recommendations must be clear and precise. The recommendations should be expressed as a limited number of categories, which are likely to be:
A. Recommended as clinically cost-effective for routine NHS use (for all indications, for specific indications, and/or only for particular patient subgroups). (This could be further qualified as recommended for use by all GPs and specialists, in hospitals and for GPs with particular expertise [and agreed by joint formulary or shared care arrangements], or only in specialist [tertiary referral] centres)
B. Recommended only for use in clinical trials set up to research cost-effectiveness and targeting
C. Not recommended for routine use
The NICE's advice might also incorporate indications for use, training, issues to raise with patients in seeking informed consent, monitoring and evaluation, indications for stopping treatment, any priorities for treatment, and an assessment of any wider implications for the NHS. A summary of the evidence on which the appraisal is based, giving the reasoning behind the NICE's recommendations, will be part of the guidance. As far as practicable, all evidence sources should be made available for inspection.
Legal status of guidance All guidance must be fully reasoned and written in terms which make clear that it is guidance. Guidance for clinicians does not override their professional responsibility to make an appropriate decision in an individual's circumstances, in consultation with the patient, guardian or carer and in the light of any locally agreed policies.
Similarly, guidance to NHS trusts and commissioners does not take away their discretion under administrative law to take account of individual circumstances.
Implications for guidelines and other information Where appropriate, the NICE will ensure that the implications of its recommendations are carried through to:
The guidance from the appraisal process is to be different in nature and purpose from clinical guidelines. To prevent confusion, however, the NICE will ensure that the appraisal group considers any guidelines relevant to the intervention they are appraising. Conversely, any future clinical guideline development must incorporate the results of the NICE appraisals of any relevant interventions.
This will be facilitated by regular liaison between the respective secretariats, some common membership of the appraisal group and the professional advisory group overseeing the NICE's guidelines programme, and overview of the final outcomes by the NICE board. The same principles will apply to the relation between the appraisal process and the Department's initiative on computerised decision support (Prodigy).
Dissemination of information to patients and carers Patients and carers have a right to information on the patient's condition and its treatment, so that they can discuss treatment choices on an informed basis with their clinicians. This information needs to be unbiased, authoritative, and intelligible. Patients and carers also have a right to information on the basis of recommendations adopted by the NICE which could affect the available treatment options.
To enable this, the NICE will consult with appropriate patient groups and bodies such as the Centre for Health Information on the best format and means of dissemination. This guidance should inter alia explain the nature of the clinical recommendations, the implications for the standards which patients can expect, and the broad nature of the evidence on which the recommendations are based.
It is possible that the appraisal group may decide that a proposed intervention is potentially of value, but there is insufficient evidence to justify an unqualified positive recommendation by the NICE. This is most likely to arise during the three-year maturation period. To deal with this, the NICE can:
Exceptionally, and during the maturation period only (and where uncertainty relates only to details of clinical practice, not to the assessment of clinical- and cost-effectiveness), the NICE may recommend wider adoption of the treatment, as long as the necessary research is to be carried out.
Sponsoring companies will fund further research advised by the NICE. They will also be encouraged to discuss with the Department of Health's R&D directorate the best way of organising this research. If there is no sponsoring company for a particular intervention, the Department of Health will consider whether it should fund the required research.
Transitional arrangements are needed. For medicinal products, any clinical research needed to satisfy requirements to obtain a marketing authorisation will already be under way. It is, therefore, unreasonable to require information which was not obtainable from this research, since additional research might delay product launch.
The medical device industry faces different problems. Current European legislation (Directive 90/342/EEC, which covers about 90 per cent of all medical devices) requires evidence only of quality and safety, not clinical efficacy (all three are required for medicinal products). Assessment of clinical- and cost-effectiveness is not easy or cheap. Some of the smaller medical devices companies may find it difficult to fund clinical trials to produce evidence of clinical- and cost-effectiveness. It is also much more likely that a number of medical device companies will be developing similar products for the same procedure. In recognition of this, it is planned that:
A standard reporting format will assist both preparation of submissions and the secretariat of the appraisal group. It acts as a checklist, ensuring essential information is not omitted, and helping organisation of the work involved in producing the submission and in appraising its contents.
Summary and introductory remarks The sponsors must provide an executive summary. Results are to be compared with alternative therapies and describe limitations of the analysis, and appropriate recommendations for NHS use. An introduction to the main submission should follow the summary. It should describe the disease, its epidemiology, current practice, and its significance in terms of ill health and resource costs to treat it. It should describe the intervention being assessed and the indications for which a recommendation is sought.
For medicinal products, the description should include therapeutic classification, brand and generic name, dosage form and route, and all indications for which a marketing authorisation is being sought or has been obtained. Specific patient subgroups to which the analysis is being applied should be defined. Sponsors should disclose their relationship with the author of the study. It should be clear how much of the submission the author agrees with, and to what extent the author is independent of the sponsor.
Methods Study design The submission should specify whether the study design was prospective, retrospective, modelled, or a mixture. The analytical framework and reasons for adopting the study design should be set out. Departures from incremental cost-utility analysis should be justified.
Timescale The choice of timescale of the assessment should also be justified, by showing that significant costs or benefits beyond the chosen horizon are unlikely.
Related and comparative studies All related studies of the therapy and its comparators (and especially all randomised clinical trials) should be reviewed and fully referenced. If the results of any of these are excluded from the analysis, reasons should be fully given. The choice of comparator therapy should be explained together with any reasons for not following guideline recommendations.
The method adopted for comparing clinical efficacy should be given (eg, randomised control trial, meta-analysis, or other specified methods).
Outcome measurement The approach used should be detailed. All outcome variables considered should be mentioned. Reasons should be given for rejecting any outcomes considered and for ignoring any outcomes measured. For all outcomes included, the method of measurement should be given. The methods, evidence base, and assumptions used in deriving clinical efficacy results should be described. Other clinical and sociodemographic data collected in trials should also be listed.
Methods used to assess quality of life These should be described and justified where quality of life is a significant factor in the assessment. If an attempt has been made to measure quality of life directly, the focus will be on the performance of the measuring instrument. When quality of life is modelled indirectly from clinical endpoints, it will be more important to demonstrate the evidence underpinning the modelling.
Costs It should be clear how costs have been estimated and who bears them. The sources should be given for both resource use and price data, and assumptions should be stated explicitly.
Uncertainty Major sources of uncertainty should be highlighted. Do they arise from sampling error or from the range of plausible assumptions? Any major assumptions and limitations contained in the analysis should also be highlighted.
Results - outcomes The analysis should be reported step by step proceeding from the base data, through any systematic review, meta-analysis and modelling, to final estimates of efficacy and effectiveness relative to comparator therapy. The structure for reporting should therefore be:
The level of detail required is the minimum necessary to enable replication of the results from base data. Additional data may, however, be requested.
Results - costs related to health treatment Sufficient information should be given to enable sources of all cost estimates to be traced. The following items should be separately identified:
A wider range of costs and benefits may be relevant in particular cases. The secretariat will advise in individual cases how costs and benefits arising outside the NHS should be handled.
Results - sensitivity and subgroups Sources of uncertainty not deriving from sampling error should be presented in a sensitivity analysis. A decision tree should be considered where there are several important sources of uncertainty. Cost-effectiveness results for each identified sub-group should be set out, identifying any economically significant differences.
Aggregate cost impacts The submission should estimate the number of patients for whom the therapy is likely to be clinically cost-effective, and derive from this an estimate of the total cost to the NHS of adopting it. A profile of costs over time should be given. A sensitivity analysis will show how these estimates are affected by extending treatment to all patients with indications for which the therapy has, or will have, regulatory approval.
Equity issues The sociodemographic characteristics of the beneficiaries should be noted where they are a non-representative sample of the UK population. It is important to highlight treatments which could have a significant impact on health inequalities by gender, ethnic group, or socio-economic category, or on a group particularly disadvantaged due to the nature of their disease.
Other unquantifiable factors Any other unquantifiable factors should be described. These will include factors which cannot be reflected in quantified assessment of health gain, but which the sponsoring company believes are relevant to the final assessment of clinical cost-effectiveness. Any relevant details should also be given which would help the appraisal group judge their significance. The appraisal group might issue further guidance at a later stage on the factors which are likely to be relevant.
Conclusions The final part of the submission should draw together the main results, assumptions, limitations, and uncertainties. These should be in the context of relevant alternative therapies, and present a reasoned conclusion based on the estimated increase in health gain and any other relevant factors.
Robin J. Harman is a freelance pharmaceutical and regulatory consultant based in Farnham, Surrey