RECOMMENDATIONS

  1.  The Health Select Committee needs to critically evaluate the impact of health technology assessment (HTA) as currently practised by NICE on the sustainability of pharmaceutical innovation in the UK.

  2.  NICE should commit to establishing a process for defining the evidence, expected to be necessary at the time of approval, to demonstrate cost-effectiveness and value. That process must include the pharmaceutical company and allow for collaborative interaction in defining the target evidence for promising new technologies.

  3.  Pharmaceutical companies should be permitted to attend appraisal committee meetings with the same rights as all other stakeholders.

  4.  Appraisal committee hearings should be held in public and all calculations and models should be made available to stakeholders in advance in a format that enables full and proper independent audit.

  5.  NICE should revise its appeal process so that it considers the merit of the decision, as well as the process, and the appeal process should be conducted and chaired by an independent panel.

  6.  NICE needs explicitly to recognise the inherent limitations of using quality adjusted life years (QALYs) to measure the value of medicines.

  7.  Further research is required to develop more robust, inclusive and transparent methodologies for valuing medicines. These need to acknowledge the variations in patient response to medicines and the limitations of applying population level models to individuals.

  8.  NICE needs to broaden the perspective of appraisals so that they include costs and savings that accrue to patients, caregivers, and wider society.

  9.  NICE needs to recognise the inherent uncertainty in all economic evaluations and not to place undue emphasis on these results when developing guidance.

INTRODUCTION

  1.  The National Institute for Health and Clinical Excellence (NICE) was created in 1999, and has established a reputation as one of the leading HTA organisations in the world. Pfizer supports the objective of NICE to raise the standards of health care in the UK and its stated aim of supporting the diffusion of innovation.

  2.  NICE has appraised approximately one hundred technologies, of which, approximately 70% have been medicines. However, despite the often high profile and controversial nature of these appraisals, they cover a relatively small percentage of annual NHS spending or activity.

  3.  Pfizer has been involved in over a dozen NICE appraisals, including the ongoing assessments of treatments for Alzheimer's disease and age-related macular degeneration.

  4.  The theory of Health Technology Assessment (HTA) has intuitive appeal—the NHS clearly needs to use its resources wisely, and Pfizer recognises that NICE can play an important role in guiding healthcare professionals towards treatments that offer the most value to patients and the NHS.

  5.  However, there remains a significant gap between the theoretical benefits of HTA and the reality of medicines' development. Indiscriminate application of HTA has the potential to have a significant and adverse impact on public health and pharmaceutical innovation in the UK.

  6.  Pfizer welcomes this opportunity to contribute to the Committee's inquiry. In this short submission, we outline reasons why Pfizer believes that NICE's decisions are often contentious, outline significant ongoing concerns and make proposals that would better safeguard the interests of patients, the National Health Service (NHS), taxpayers and the research based pharmaceutical industry.

REMOTE DECISION MAKING AND LACK OF ACCOUNTABILITY

  7.  The allocation of public money will always have a significant political dimension. In healthcare, where the consequences of treatment being provided or withheld can have profound implications for individuals, these decisions are often highly emotive.

  8.  Historically, treatment decisions in the UK were made by physicians, often with input from patients. The approach that NICE has introduced makes greater use of population level assessments of health gain, predominantly undertaken by health economists. While population assessments can be useful, they do have significant limitations including their failure to reflect the specific needs of individual patients.

  9.  NICE attempt to include the views of patients and doctors in their appraisals. However, the processes for doing so have been regularly criticised as being insufficient (Milewa, 2005; Bridges 2007). Importantly, it is often difficult for patients to present information in a form that is able to be fully incorporated into highly data driven methods adopted by NICE appraisal panels. As a result, concerns have been raised that decision making relies too heavily on the academic assessments. This has an adverse impact on the relationship between patients and their doctors who are charged with implementing NICE guidance.

  10.  Another concern with over-reliance on economic assessments is that wider implications of decisions about which groups of patients to treat are not formally scrutinised through any political process. Lines of accountability are unclear and are a cause of frustration when patients are denied access to treatments.

IMPACT ON INNOVATION

  11.  Pfizer believes that given the substantive costs and time required to develop new medicines, any system of medicines assessment should be stable and lead to predictable outcomes. Despite NICE being in existence for eight years, many of its appraisal decisions remain contentious and unpredictable; leading to high levels of frustration for patients, professional groups, patient groups and pharmaceutical companies.

  12.  One of the principles of HTA is to compare new medicines with current standards of care. New classes of medicines must bear significant research and development costs in order to satisfy the requirements of regulatory and HTA organisations. Generic medicines have no such requirements and therefore, can be provided to the NHS at a significantly lower price. Thus, in disease areas where current practice is a relatively cheap, off patent medicine, such as in many areas of cardiovascular disease, mental health and respiratory illness, HTA discriminates against pharmaceutical innovation.

  13.  One argument put forward for this approach is that it creates incentives for pharmaceutical companies to concentrate their research efforts in areas of unmet clinical need rather than in areas where cheaper older medicines are already available. This thinking appears to have underpinned recommendations in the recent Cooksey Report into Medical Research in the UK as well as the Office of Fair Trading's market study into the Pharmaceutical Pricing and Regulation Scheme (PPRS). However, it is flawed for two reasons and, as such, risks damaging the future of medical innovation to the detriment of both industry and patients.

—  First, the notion that if treatments exist within a given disease area, then there is no longer clinical need, is simply false. Cardiovascular disease is still the biggest killer in the Western world—and is increasingly a major problem in the developing world—and yet, treatments exist. We need more and better treatments in cardiovascular medicine, not fewer.

—  Second, associating value only with breakthrough pharmaceutical innovation is fundamentally flawed. History shows that disruptive pharmaceutical innovations are rare and that medicines normally evolve incrementally over time (Wertheimer, 2005; Williams 1999). Furthermore, and perhaps most importantly, within a new area of medical innovation, the first medicine is rarely the best.

  14.  Unless this is addressed, then there is a real prospect that no new medicines will be introduced in the UK into disease areas where common practice is to use off patent medicines. By 2020, this could realistically extend to all disease areas.

Recommendation 1

NICE EVALUATION PROCESS

  15.  The credibility of NICE guidance relies on there being open, transparent decision making during the appraisal process that involves all stakeholders. Pfizer recognises the appraisal process has evolved considerably in recent years, for which NICE should be commended. We do believe that despite these changes, there remain a number of areas where further improvements should be made. These include:

EARLY ENGAGEMENT WITH PHARMACEUTICAL COMPANIES

  16.  Unlike the regulatory authorities, NICE does not engage with pharmaceutical companies in early dialogue concerning the data needed to conduct a NICE appraisal. Without this dialogue, there remains a risk that NICE will reject a medicine because the pharmaceutical company did not collect data required by NICE.

  17.  We welcome the indication from NICE that it may be willing to engage in early discussions with pharmaceutical companies to clarify future data needs in the event of a NICE evaluation. We strongly urge NICE to implement this change in order to help reduce the likelihood of negative recommendations due to different expectations of required data. It should also lead in return to faster decision-making and a more timely issue of appraisals.

  18.  NICE needs to recognise that it may not always be possible to conduct clinical trials to meet their specific information requests, especially before and around the time the medicine is licensed. NICE, therefore, needs to adopt a pragmatic approach to assessing new medicines, and not unduly punish a pharmaceutical company if these data are not forthcoming.

  19.  Given the limited scope of clinical trials, the real value of a medicine to the NHS can only be confirmed after launch following sufficient and appropriate use in a real world setting. There is clearly a trade-off between the need for NICE to provide early advice on new medicines, and our ability to provide the type of data required to make such decisions. We believe that earlier engagement between NICE, pharmaceutical companies and other key stakeholders such as patients, carers and clinicians, would enable a more informed dialogue about the optimal time to conduct any appraisal given that the evidence base for new medicines evolves over time.

Recommendation 2

PHARMACEUTICAL COMPANY PARTICIPATION IN APPRAISAL COMMITTEE MEETINGS

  20.  Pharmaceutical companies are currently the only stakeholder group not represented at appraisal committee hearings, despite knowing most about the medicine under review. We believe this is fundamentally wrong and increases the chances of arbitrary decision making by NICE. Addressing this shortcoming would also have a number of practical benefits, including quicker responses to any questions or uncertainties about submitted data, and reducing the likelihood of decisions going to appeal as a result of factual errors and omissions.

  21.  We note that other HTA agencies, including the All Wales Medicines Strategy Group, have managed to successfully include pharmaceutical companies in their meetings and would request NICE consider this option.

Recommendation 3

TRANSPARENCY

  22.  Pfizer believes the NICE appraisal process should be fully transparent. We note that other HTA agencies, including the All Wales Medicines Strategy Group, hold their hearings in public. We believe NICE appraisal committee hearings should adopt this approach.

  23.  We remain particularly concerned that NICE does not make available to stakeholders its cost effectiveness calculations in a format that enable independent audit. This is unreasonable and in contrast to the requirement of pharmaceutical companies to provide all of their calculations with unlocked, fully operational versions of the models that are developed as part of their submission.

Recommendation 4

THE APPEAL PROCESS

  24.  The current NICE appeal process focuses almost exclusively on whether the appraisal process has been followed correctly. It provides insufficient opportunity to review whether the appraisal decision is fair and balanced in light of the available evidence. The range of data chosen to be included, and the fundamental assumptions in the cost-effectiveness model are not subject to appeal, yet these are likely to be at the heart of flawed guidance. The consequences of flawed guidance can be profound for patients and their carers. As such the development of a fair appeal process, where the evidence reviewed and value judgements adopted by the panel can be critically examined, is long overdue.

  25.  Failings of the current appeal process include:

—  The definition of perversity adopted by NICE serves no practical use as no guidance could realistically meet the NICE definition of "perverse".

—  The current appeal process is conducted by NICE itself with no external consultation as to its form or judgements. Essentially, NICE members act as judge and jury on their own decisions.

—  The level of input from affected stakeholders appears to be arbitrary.

—  Certain groups of stakeholders such as patients may be excluded by the complexity of the process.

Recommendation 5

METHODOLOGICAL ISSUES

  26.  Pfizer remains concerned that the methodological approaches adopted by NICE systematically underestimate the value of medicines to patients and the NHS. This is primarily due to the failure of currently available tools to capture the full value of medicines to patients along with the systematic exclusion of important costs and benefits for appraisals. Pfizer is also concerned that NICE fails to publicly recognise the wide range of plausible cost-effectiveness estimates that exist in many appraisals and instead, places undue emphasis on individual estimates.

LIMITATIONS OF EXISTING TOOLS FOR ASSESSING HEALTH GAIN

  27.  NICE has adopted the quality-adjusted life year (QALY) as the standard basis for assessing the value of medicines. It is widely acknowledged that the QALY has very significant limitations and does not produce reliable estimates of health gain (McDonough, 2007). For example, NICE recommends the use of a generic tool for assessing health gain, the EQ-5D, for incorporation in QALY analyses. This instrument is simplistic and relatively insensitive to important changes in quality of life that are important to patients (Krahn-Murray et al, 2007).

  28.  In practice, the tendency to under-report the impact of a medicine on a patient's quality of life actively disadvantages those medicines where the benefit is in improving quality of life rather than extending life expectancy, such as medicines for pain relief and neurological conditions. By implications, patients with chronic conditions and elderly patients are most likely to be disadvantaged (Harris, 2005).

Recommendations 6 and 7

FAILURE TO INCLUDE THE FULL COST AND SAVINGS ATTRIBUTABLE TO MEDICINES FROM A TOTAL HEALTHCARE SYSTEM PERSPECTIVE

  29.  NICE currently only includes the financial impact of medicines on NHS and social services budgets. It excludes the impact on social security payments and costs borne by patients and carers. For example, residential care costs borne by patients were excluded in the appraisal of medicines for the treatment of Alzheimer's disease, which has the effect of systematically under-estimating the value of these medicines. In addition, focusing on new technologies and medicines in isolation risks ignoring the potential implications for increasing costs elsewhere in the system.

  30.  Pfizer believes NICE appraisals should reflect the full value of medicines to UK society, rather than the NHS alone. An approach would be to focus on "episodes of care" as a way to recognise the full cost and value of an intervention, the overall patient outcome, and the corresponding costs and benefits incurred across the healthcare system. By expanding the perspective from one of evaluation in isolation to a broader systemic look, it is possible to better integrate the cost and value of medicines and focus the comparison of all treatment options on their ability to affect overall outcomes. Hence, NICE needs to review how the perspective taken in its cost effectiveness analysis can be broadened to allow additional relevant costs and benefits delivered outside the NHS to be formally taken into account.

Recommendation 8

OVER-RELIANCE ON ECONOMIC ASSESSMENTS

  31.  Pfizer is concerned that NICE does not fully respect the limitations of current economic analyses methodologies and resulting imprecision of these assessments. Economic modelling often results in a wide range of plausible cost-effectiveness estimates, depending on which data and assumptions are used. Despite this uncertainty NICE appraisal committees appear to place undue weight on the certainty of economic analyses when developing guidance.

  32.  The complexity of evaluation methods employed by NICE have increased considerably in recent years. However, despite adding the appearance of advanced science, these methods do not obviate the need for pragmatism in handling data, particularly those derived from recently launched products.

  33.  While economic assessments can legitimately generate a wide range of plausible value for money estimates, these should be seen as contributing to the decision making. Pfizer believes NICE places undue emphasis on a single result within this range and does not adequately recognise the high degree of variability of these results.

Recommendation 9

FUTURE ROLE OF HTA

  34.  Despite the progress NICE has made since 1999, there remain a number of important areas where NICE reform is required to ensure that it properly fulfils its current role. However, even if these issues are addressed, the fundamental limitations of HTA will remain—it provides only one of a number of perspectives on the value of health technologies, it is conducted at a distance from the vital conversations between patients and their doctors, and it cannot foresee how medical advances will develop in practice.

  35.  Sir David Cooksey's report on medical research in the UK and the Office of Fair Trading's market study into the Pharmaceutical Pricing and Regulation Scheme (PPRS) suggest far wider roles for HTA in priority setting and pricing. The range of problems with these ideas are out of the scope of the Committee's current inquiry, but the suggestions are worth noting since they reflect an over-enthusiasm for what can be achieved by bodies like NICE. We have advocated greater pragmatism and more realistic expectations throughout this submission; this applies with even greater force to any suggestions about extending NICE's remit into these areas.

  36.  Pfizer notes that the current focus of NICE activities accounts for a relatively small proportion of NHS activity and expenditure. If NICE is truly to realise its role in achieving a better use of NHS resources, then it needs actively to consider broadening its current assessments beyond a narrow subset of medicines and other technologies. One possibility would be to look more broadly at the effectiveness and efficiency of the NHS and how it delivers care.

Pfizer

March 2007

REFERENCES

  Milewa, T. Barry, C. Health Policy and the Politics of Evidence. Social Policy and Administration. 2005; 39(5): 498-512

  Bridges, J. Jones, C. Patient-based health technology assessment: a vision of the future. International Journal of Technology Assessment in Health Care, 23:1 (2007), 30-35

  Wertheimer, A, Santella T, Pharmacoevolution: The advantages of incremental innovation, IPN Working papers on intellectual property, innovation and Health, International Policy Network 2005.

  Williams, J.W. Jr., et al. (1999). Treatment of Depression: Newer Pharmacotherapies. Publication No. 99-E014. Agency for Health Care Policy and Research, US Department of Health and Human Services, Rockville, MD.

  McDonough-Christine-M, Tosteson-Anna-N-A. Measuring preferences for cost-utility analysis: how choice of method may influence decision-making. PharmacoEconomics, 2007; 25 (2): 93-106.

  Krahn-Murray, Bremner-Karen-E, Tomlinson-George, Ritvo-Paul, Irvine-Jane, Naglie-Gary, Responsiveness of disease-specific and generic utility instruments in prostate cancer patients. Quality of life research, 2007; 16 (3): 509-22

  Harris, J, It's not NICE to discriminate. Journal of Medical Ethics, 2005; 31: 373-375