OVERVIEW

  GlaxoSmithKline (GSK) welcomes the opportunity to contribute to the Health Select Committee inquiry into NICE. GSK is one of the world's leading research-based pharmaceutical and health care companies, developing and supplying medicines to improve patients' quality of life. We make prescription medicines, vaccines, over-the-counter medicines and oral care and nutritional healthcare products. We are proud of our strong, open relationship with the NHS and our British heritage. We employ more than 20,000 people across the United Kingdom and spent £1.3 billion on Research and Development (R&D) in the UK in 2006.  This equates to over 40% of our global R&D spend.

1.  EXECUTIVE SUMMARY

  1.1  Historically, the environment for medicines in the UK has struck a good balance between delivering value for the NHS and stimulating innovation to deliver the medicines for the future. Mechanisms such as PICTF, the Ministerial-Industry Strategy Group (MISG), the MISG Long-Term Leadership Strategy (LTLS) and the UK Clinical Research Collaboration have allowed the perspectives of all stakeholders to be considered.

  1.2  As a result of sustained dialogue between industry, government and other stakeholders, the government has been able to develop and implement policies that have delivered a stable environment that is broadly supportive of innovation. NICE is a contributor to an environment which is recognised across the world, aiming to ensure that patients have timely access to new medicines as they become available.

  1.3  NICE has developed a positive international reputation, with its processes and methods evolving over an eight year period. These include efforts to consult with stakeholders, particularly patient groups, and inclusion of expertise from a wide range of professional groups.

  1.4  The recent reports by Sir David Cooksey on Research Funding and the Office of Fair Trading (OFT) study into the Pharmaceutical Price Regulation Scheme (PPRS) envisage a broader role for NICE. GSK is open to an increased role for NICE, but urges caution against implementing radical changes to the system which may lead to unintended consequences. It is essential that any such changes are pragmatic in nature and continue to ensure that patients gain access to new medicines, the NHS continues to get value for money and the UK-based pharmaceutical industry receives appropriate reward for innovation.

  1.5  The UK environment is attractive for a number of reasons, not least its stability and predictability. It will be important to retain, or replicate these attributes to continue to give industry the confidence to invest here and not unduly harm the competitiveness of the UK. Therefore, we believe that there are a number of aspects of how NICE operates today that would need to be reviewed before any broadening of its remit takes place:

—  A broader definition of value should be developed. The cost per Quality Adjusted Life Year (QALY) should not be used as the only criteria for decision-making. A broad range of clinical outcomes and societal factors that have a real impact on patients and carers should also be part of the formal assessment.

—  In addition, the current cost-effectiveness threshold (£20,000 to £30,000) should be reviewed. Consideration should be given either to increasing it, or assessing how it is applied, perhaps considering other aspects such as areas of significant unmet medical needs, UK health priorities, or a convergence with other government targets such as increasing the number of patients being treated in Primary Care as opposed to in hospital.

—  The decision-making process should acknowledge inevitable uncertainty in the evidence base at the time of launch. The benefit of the doubt should favour the patient who should not be unreasonably denied access to the medicine under review when there is uncertainty.

—  The opportunity for levels of consultation and dialogue during the current evaluation process should be increased. This could include improved dialogue between manufacturers and academics performing the reviews, and the possibility for manufacturers to present and answer questions at the Appraisal Committee meetings.

—  An independent review of the appeals process should be carried out to ensure that it inspires confidence that the decisions reached are fair and based on the evidence available.

—  Further measures should be introduced to increase implementation of NICE guidance.

—  NICE should work with industry to develop a capacity for early dialogue to inform medicine development.

2.  WHAT WORKS WELL WITHIN THE CURRENT SYSTEM

The remit of NICE

  2.1  Since the inception of NICE, GSK has endorsed its objective to promote faster and more equitable access to modern treatments, as well as recognising the right of government to use a mechanism to inform rational decisions about the use of medicines and other health technologies. We believe we enjoy relatively good levels of engagement in the process, in terms of participation as a stakeholder, providing expert membership of its key committees, and constructive contribution to consultations and dialogue to help develop its processes and ways of operating. However, as we outline later in this submission, there is room for improvement in some areas.

  2.2  GSK believes that NICE should be supported in its efforts to ensure fairness across the country's health system. We endorse its remit to produce robust, workable evidence-based guidance which is free from political interference. We also support its core principles, which represent an attempt to place measured consideration of both clinical effectiveness and value for money at the centre of NHS decision-making.

Ways of working

  2.3  GSK recognises that there is much within NICE's approach that is praise-worthy. In 2005, the European trade body EFPIA produced a set of principles (see appendix 1) on the criteria for an effective Health Technology Appraisal (HTA) system and the NICE process fulfils many of these. In particular, we welcome its active involvement of key stakeholder groups including patients and professionals.

  2.4  GSK welcomes NICE's decision to base one of its reviews, the Single Technology Appraisal (STA) on a submission from manufacturers. This often takes place in parallel with licensing, a stage where the vast majority of the evidence reviewed will in any case be held by the manufacturer. GSK also welcomes the small but important steps NICE has taken to improve dialogue through the STA process to help ensure that the manufacturer's submission will meet the needs of the appraisal process.

NICE prioritisation

  2.5  GSK supports the current approach of NICE which focuses on areas of greatest importance to the NHS. Hence NICE balances its resources to continue to develop clinical guidelines that may arguably have the greatest impact on patient care. It would seem impractical for NICE to review all medicines currently available, or indeed all new indications of those medicines, as this would inject considerable bureaucracy into the system and would not be a good use of either taxpayer's money or industry resources and expertise.

  2.6  A further challenge is the need to balance the desire to put into the public domain all evidence that informed the decision-making process, and the desire of companies and researchers to retain the opportunity to initially communicate new evidence via the recognised mechanism of presentation at medical congresses and peer-review publication. GSK took a key role within the Association of the British Pharmaceutical Industry (ABPI) in developing an approach with NICE to address this issue, and now fully subscribes to an agreed policy that minimises the extent and the time that evidence can be maintained as confidential.

3  WHAT COULD BE IMPROVED

Broadening the definition of value

  3.1  GSK recognises the desire of governments to develop mechanisms to assess the cost-effectiveness of medicines. There are examples of evaluation leading to increased uptake and patient choice in areas such as cancer and cardiovascular disease. However, in a cost-driven climate, there is a risk that evaluation mechanisms will run counter to what should be their key objective: identifying medicines that bring the greatest benefit to patients, ensuring early access to these medicines, allowing choice among medicines of value and ensuring efficient healthcare through objective, high-quality assessments.

  3.2  GSK believes that there is a case for broadening the definition of value. In assessing value, NICE relies on the cost per QALY as its tool. This has some merits but is not an exact science and can be a crude measure of value, in that it imposes an arbitrary, population-based barrier to access for individual patients with varying needs.

  3.3  The QALY also finds it difficult to fully capture all the benefits likely to be important to patients, such as an improved safety profile or providing therapy in an oral rather than intravenous form, which may allow a cancer patient to be treated at home. Similarly, the value of a new medicine may lie in improved tolerability, reduced potency or improvements that increase patient compliance that may not be fully reflected in the QALY. This is demonstrated by the EQ5D questionnaire which is the preferred approach for generating QALY's (see appendix 2.) The questionnaire is relatively insensitive to incremental changes in quality of life and may not fully reflect the range of benefits that are important to patients. An example is the reduced impact on cognitive function of newer epilepsy treatments compared to older ones. Any subsequent improvement in educational performance would not register on the EQ5D. Likewise, no validated instruments exist for young children, and for some mental health conditions such as psychosis or depression, measurement is difficult or impossible.

  3.4  The benefits and costs of a medicine beyond that of the NHS and Personal Social Services are not currently taken into account in the QALY. For example, the potential to alleviate the stress, anxiety and burden of care imposed on relatives and carers in Alzheimer's disease is a significant benefit not routinely included in decision making. Similarly, the potential to enable people to return to work and therefore contribute to society.

  3.5  GSK has particular concerns around oncology medicines, where increasingly the QALY threshold (£20,000 to £30,000) does not appear to take into account the unique challenges of developing medicines in this area. This appears to result in a number of situations where new oncology medicines, with demonstrable benefit in terms of improved survival, are not being made available in the UK due to a delayed or negative NICE appraisal, whereas they have become standard of care in mainland Europe and the United States. An example is Avastin for Colorectal Cancer (made by Roche) which is now used widely in the European Union but not in the United Kingdom. It has been rejected by NICE on the grounds that it does not represent a good use of scarce NHS resources. This decision appears to unfairly disadvantage UK patients and is contrary to the principles of providing a world-class national health service. It also has the potential to develop an inequitable system where a patient's access to medicines is dependent on their ability to pay. This is in contrast to the French philosophy for example, which recognises the value of improvements in survival even in the late-stages of cancer, to both patients and their relatives. Medicines such as Avastin have received high ratings for additional medical benefit (ASMR) leading to rapid uptake in patients in France.

  3.6  In addition, it should be considered whether the cost-effectiveness threshold should be increased or applied flexibly within the current system. One example is for "orphan medicines" to allow for the higher cost per patient. Orphan medicines are defined as those to treat diseases which are serious, life-threatening or seriously debilitating and with a prevalence of less than 5 per 10,000 population. These treatments are often the only medicines available for these rare diseases and it is therefore important to ensure that the system does not preclude impacted patients.

  3.7  GSK recognises that the QALY provides a common currency for measuring the extent of health gains that result from an intervention, and therefore can be used to assess their relative worth from an economic perspective. However this common currency is by nature inflexible, which means that it is difficult to give greater weighting to defined therapeutic areas even if they have been identified by government as a public health priority. Therefore, GSK believes that if the QALY is to be retained, consideration should be given to introducing a flexible system, where certain agreed disease areas fall into different bands with varying thresholds. Areas of greater need could attract a higher threshold, thereby further aligning the concept of rewarding innovation with meeting the objectives of public health policy.

Developing greater dialogue between NICE and industry in the development phase

  3.8  The development of a medicine takes between 10 to 12 years, but there is little dialogue between government, NICE and industry until the medicine has been granted a licence. Increasing dialogue early in the process of a new medicine would be of benefit to all parties if it could be achieved without adding to development times.

  3.9  GSK supports Sir David Cooksey's recommendations on the subject of improved dialogue, which have been accepted by the Government. What is needed by pharmaceutical companies is advice and guidance about the sort of dataset that would be required for a positive NICE review at launch, in order that this can be built into clinical development plans. We do not want NICE to propose trial designs or to be overly prescriptive about what trials need to be done, to avoid data needing to be generated for the UK market alone.

  3.10  Even with earlier NICE dialogue in place, there will be some medicines where value cannot be demonstrated at launch but for which collection of additional data through usage in clinical practice is likely to prove value. In these circumstances, greater flexibility is needed by both industry and NICE to agree a temporary solution that facilitates patient access to the medicine.

The Evaluation Process

  3.11  The process of appraising health technologies remains embryonic and its quality is variable. It is often based on a number of assumptions, particularly in the assessment of new medicines, when all of the data is unlikely to be available. NICE relies upon a number of Assessment Groups (AGs) and Evidence Review Groups (ERGs) to produce independent assessment reports in the case of Multiple Technology Appraisals, or critiques of the manufacturer's assessments in the case of Single Technology Appraisals. The groups are at liberty to take different approaches to their assessment of the evidence and to the production of their reports, often applying varying academic methodologies. This has led to inconsistency and corrections in a number of cases.

  3.12  To increase confidence in the decision-making process, GSK advocates a more collaborative approach between industry and the Assessment Groups. This should allow more discussion and potential resolution of any technical or factual issues prior to the Appraisal Committee. In addition, stakeholders should have the opportunity to fully critique the analysis on which the report is based. This would include complete access to working copies of the economic models used by Assessment Groups and the opportunity to provide feedback on the ERG critique prior to the Appraisal Committee within the STA process.

  3.13  Currently, clinicians and representatives of patient groups are invited to attend Appraisal Committee meetings to share expertise and respond to questions. This invitation is not extended to manufacturers, who have spent on average a decade amassing the evidence upon which NICE guidance is based. We believe the process would benefit from constructive engagement throughout appraisal, including attendance at the Appraisal Meetings to ensure a fair and balanced hearing.

  3.14  NICE has recognised a need to issue guidance on some new medicines more quickly than the original process allowed. GSK broadly welcomed the launch of a "fast-track" process known as Single Technology Appraisal (STA) that allows the NHS to issue guidance nearer to the time that a medicine launches. However, as raised with NICE during the consultation on these proposals, there is again a need for the committees to recognise what evidence can practically be expected at the time of launch. They should not therefore unreasonably deny access to medicines which may in fact be cost-effective, based on a full dataset that can only be generated post-launch. Although we recognise this process is at its early stages, GSK is concerned that this is not being taken into account and therefore some new medicines are being turned down.

The Appeals Process

  3.15  GSK recognises that NICE invests considerable resources into its appeals process. However, we would raise questions about its effectiveness. In the 12 appeals undertaken since the process has been made public, no substantive changes have yet been made to the guidance in any particular case. This is despite the fact that 4 cases had points upheld. This discrepancy appears to be a result of the permitted grounds for appeal which are highly restrictive and do not allow a substantive review of the evidence on which the decisions were made. We would recommend a review of the process and consideration be given as to whether the grounds could be broadened. A more robust appeals procedure would ultimately increase confidence that decisions are reached fairly and are based on the presented evidence.

Implementation

  3.16  Demonstration of cost-effectiveness will increasingly be required to allow widespread use of new medicines in patients. If a medicine does demonstrate value at launch, the system should facilitate wide and rapid uptake to all appropriate patients, at a price that rewards the value delivered.

  3.17  Failure to implement NICE guidance remains a key issue. Since 2001, clinicians have been officially required to implement NICE guidance, but take-up is inconsistent which disadvantages patients. This is largely due to poor horizon-scanning combined with capped budgets within Primary Care Trusts and a sense that some clinicians are cautious to introduce new and innovative medicines. This has led to the perception that whilst all negative NICE decisions are routinely picked up by Primary Care Trusts, some positive ones are blocked. The UK remains one of the slowest adopters of new medicines in Europe which means that patients continue to be denied new medicines which could enhance the quality of their lives.

  3.18  Access to, or denial of, a new medicine frequently depends on where a patient lives. The principal barrier to more uniform implementation appears to relate to poor financial planning within NHS Trusts, rather than financial shortages per se. GSK believes that this poor implementation of NICE guidance is the most important issue for the government to address in this area, particularly if the new fast-track process is to have any impact.

  3.19  Given the impact of poor financial planning on the implementation of guidance, it is critical to retain the statutory requirement for the funding of NICE approved medicines (including when it is incorporated into NICE guidelines following a review) and to ensure a clear and rapid mechanism for the incorporation of the costs of these medicines into the tariffs operated as part of Payment by Results (PbR.)

  3.20  Further implementation of NICE guidance could be driven through the Healthcare Commission reviews, which currently focus on process, but could be extended to monitor and track levels of implementation within Primary Care Trusts. Existing mechanisms such as the Quality Outcomes Framework (QOF) could also be used to drive uptake of guidance. This was introduced as part of the new General Medical Services (GMS) contract in April 2004 and has been instrumental in changing prescribing behaviour. GSK believes that the implementation of NICE guidance could be incorporated into the QOF, which would then reward doctors for implementing good practice in their surgeries. As the criteria are designed around best practice and have a number of additional points for achievement, it follows that this mechanism would drive doctor's behaviour to ensure they implement NICE guidance, as essentially they would be incentivised to do so. This in turn would benefit patients, who would be granted better access to appropriate innovative medicines.

  3.21  The government has introduced policy measures which could further help to address issues of implementation. The recent White Paper "Our Health, Our Care, Our Say" (2006) directs more resources towards the Primary Care sector and empowers local healthcare providers by giving them greater control of resources. This could help to overcome poor NICE implementation by providing incentives to adopt NICE guidance quickly and completely. Transparency of process will therefore be critical, as will much improved dialogue and trust.

4.  CONCLUSION

  NICE plays an important and integral role in the UK healthcare system, which seeks to balance the need to provide patients with access to affordable new medicines while encouraging high-risk innovative research by UK-based pharmaceutical companies. As with all systems which seek to measure value, there are strengths and there are areas for improvement. GSK believes there is a need to review the work of NICE, as outlined above, in advance of NICE taking on an important role in providing guidance to industry early in medicine development. Any reform should be gradual and practical and it should be guided by a range of stakeholders. Due to the UK's leadership in this area, decisions reached in the UK will have ramifications at a European and global level. The challenge is significant, but we are confident that over time it will be possible to come to a system that provides proper alignment between ensuring timely access to medicines for patients, value for money for governments and appropriate reward for companies that discover and develop innovative medicines. GSK looks forward to playing its part.

GlaxoSmithKline

March 2007