EXECUTIVE SUMMARY

  1.  The BIA supports the work of the NICE and its objective of allowing "Faster Access to Modern Medicines",[41] and welcomes this opportunity to make constructive comments to build on NICE's strengths.

  2.  Feedback from BIA members indicates that NICE's decision-making process is not fully transparent; this in itself is a highly likely reason why NICE decisions are being increasingly challenged. A system comparable to the US FDA with open and public advisory committee outcomes would be highly preferable.

  3.  NICE currently relies heavily on a methodology that is based on a one-size-fits-all measure of cost effectiveness.

  4.  NICE's approach to cost-effectiveness analysis is often based on limited data generated at too early a stage in a product's growth. This can lead to higher levels of uncertainty, especially in highly innovative products. There needs to be agreement on the criteria against which therapeutic progress (or value) can be identified throughout a product's lifecycle.

  5.  Provision for early dialogue between companies and NICE would ensure a more efficient process. It would ultimately speed up the appraisal process, reduce inaccuracies and, consequently, reduce the number of appeals.

  6.  Once NICE guidance is issued, prescriber uptake implementation is poor and patchy.

  7.  Investing in NICE, and ensuring it has the resources it needs to do its job properly, is pointless if its guidance is not implemented.

INTRODUCTION

  8.  The BIA is the trade association for innovative enterprises in the UK's bioscience sector. We represent over 300 members, the majority of which are involved in realising the human health benefits that bioscience promises.

  9.  The UK is a world leader in biomedical research, second only to the United States. More than 250 million patients worldwide have already benefited from approved biotech medicines and therapies to treat or prevent conditions including heart attacks, multiple sclerosis, breast cancer, cystic fibrosis and leukaemia.

  10.  The BIA recognises the focus of this Inquiry but wanted to take this opportunity to highlight the fact that aspects of NICE's work impact on the bioscience sector and result in lower levels of uptake of innovative medicines.

  11.  The Ministerial Industry Strategy Group "Long Term Leadership Strategy Report", published in February 2007, reported NICE as having the most influence (in secondary care) in driving different uptake patterns. "The work of NICE can be one of the single biggest factors influencing uptake of new technologies in the NHS, and warrants a specific focus in the context of work to improve uptake."

  12.  The BIA hopes that the outcome of this Inquiry, and the Government response, will contribute to increasing the uptake of new medicines for improved patient health.

Why Are NICE'S Decisions Increasingly Being Challenged?

  13.  There is evidence that NICE is turning down an increasing number drugs, so it is perhaps unsurprising that the rate of challenges is also increasing.

  14.  Out of 15 recent decisions classified as appraisals under development, eight drugs were not recommended in all indications because they were not considered cost effective (most Incremental Cost Effectiveness Ratio (ICER) values were higher than £40,000)".[42] A central question here is the threshold for ICER values. The range is given between £20,000 and £30,000; this needs to be debated moving forward.

  15.  In addition, there are concerns over NICE's decision process. Feedback from BIA members is that the process is not fully transparent; this in itself is a likely reason why NICE decisions are being increasingly challenged.

Is Public Confidence in the Institute Waning, and If So, Why?

  16.  It would be uncommon for the public to fully understand NICE's activity beyond what is reported in the media. At a recent NICE Roundtable discussion in Birmingham it was suggested that an "FDA-like" open and public evaluation before an advisory committee could help increase the transparency of reviews by allowing all stakeholders to "have their say", which could improve transparency and trust in the NICE process and decisions.

Nice's Evaluation Process, and Whether Any Particular Groups are Disadvantaged by the Process

  17.  In this section the BIA has chosen to examine four different patient groups by way of examples. The BIA's comments on improvement the NICE evaluation process are covered in the section below on "Improving the Health Technology Assessment Process".

EPO

  18.  Quality Adjusted Life Years (QALY) values can change over time, as more is learned about the optimum use of a medicine. A good example of this is erythropoietin (EPO), a treatment for patients with kidney failure, which improves red blood cell count, reduces the need for blood transfusions and improves patients' quality of life. At the time of EPO's launch in 1990, the estimated cost per QALY was £103,000, a value which does not represent cost effectiveness under NICE's methodology. Over time, management of kidney failure using EPO has changed, as more has been learned about the drug and benefits, including improved quality of life for patients, have been found. Current estimates of cost per QALY for EPO show a dramatic reduction from the initial value.  

  19.  On a related note, erythropoetin (alpha and beta) and darbepoetin for the treatment of cancer-treatment induced anaemia have been undergoing NICE appraisal, and is scheduled to be considered by the NICE appraisal committee for the fourth time in June 2007, with Guidance expected in November 2007. Preliminary Guidance from NICE does not recommend the use of EPO for patients with cancer-treatment induced anaemia. In the appraisal, NICE did not properly consider quality of life as they only used Quality of Life (QoL) estimates derived from clinical trials. RCT data is difficult to generalise to real life clinical practice and this may lead to an underestimate of the QoL benefits associated with EPO in the real treatment setting.

  20.  In the NICE health economic estimate of EPO, it was assumed blood transfusion would only be considered in patients whose Hb level fell below 10g/dl. The National Blood Service (NBS) have confirmed that transfusion is actually considered when the Hb level is approximately 8-9g/dl. Using the NBS estimates reduces the cost-effectiveness ratio by about one third. NICE did not consider the impact on cost-effectiveness that some patients with lower Hb levels would require more blood transfusions. Including published estimates of the amount of blood that would be used in a real life situation, halves the cost-effectiveness ratio.

  21.  NICE's decision ignores internationally recognised evidence based guidelines which are supported by a wealth of research. The European Organisation for Research and Treatment of Cancer (EORTC), the American Society of Clinical Oncology (ASCO) and the US National Comprehensive Cancer Network (NCCN) all recommend EPO for patients with chemotherapy-induced anaemia within the licensed indications for the products. As it currently stands, NICE's interim decision is also at direct odds with the Government's core objective of improving a patient's quality of life and a variety of further objectives laid out in the National Cancer Plan.

Gliomas

  22.  Every year, nearly 2,000 people in England and Wales are diagnosed with high grade glioma, a life-threatening form of malignant brain tumour which accounts for 2% of all cancers in the UK. This highly aggressive brain cancer has a devastating effect on patients (many of whom are very young) with at least half dying within 12 months.

  23.  Gliadel implants, produced by BIA member Archimedes Pharma, are used at the time of surgery. Clinical data show these implants can prolong meaningful quality of life and significantly increase survival rates. The use of Gliadel can increase the numbers of high grade glioma patients surviving three years from surgery by four- to five-fold.

  24.  Gliadel is the only treatment which allows patients to start chemotherapy immediately following surgery and prior to radiotherapy. This is particularly important as patients frequently face a five to six week delay for radiotherapy rather than the recommended two weeks post-surgery. Gliadel is also the only treatment that can be used in patients with grade 3 or grade 4 glioma; other treatments are indicated only for patients with grade 4 glioma.

  25.  The cost of Gliadel is just over £5,000 per patient. If all patients suitable for Gliadel received treatment the cost to the NHS would be around £2 million per annum. All the leading European countries and the US have approved and reimbursed Gliadel and Scotland has also approved Gliadel for reimbursement.

  26.  In January 2007, NICE issued a negative appraisal on Gliadel. If this negative appraisal is implemented, then around 25% of patients with high grade glioma will have no access to drug therapy.

  27.  It is of concern that the process of assessing Gliadel appears to have been significantly flawed—NICE have twice used the wrong data, producing inaccurate cost effectiveness ratios and have used incorrect assumptions about the neurosurgery involved. There also appears to have been limited discussion with experts on high grade glioma, particularly around the treatment of those specific groups of patients who have most to gain from Gliadel.

Orphan diseases

  28.  The EMEA's definition of orphan disease is a serious, life-threatening or chronically debilitating disease affecting fewer than five in 10,000 people in the EU.

  29.  Patients with rare diseases who could be treated effectively with orphan medicines are disadvantaged by the NICE process. Orphan medicines appear expensive because the cost of developing them is relatively high on a "per-treated patient" basis. There is also only limited data available on such medicines at launch. These factors combine to make it particularly difficult for orphan medicines to meet the ICER threshold. As a result they appear to be expensive but an adequate return is necessary to sustain research and medical progress in areas of high unmet patient need.

  30.  Simply because these patients are suffering from rare diseases, they are being denied an effective treatment for severe, often life-threatening conditions, which is at odds with the fundamental NHS principle of equity of access to treatments for all patients based on clinical need. Indeed, the slow uptake of orphan medicines in the UK is of concern to the EMEA.[43]

  31.  As of January 2007, NICE had appraised 16 EMEA/FDA designated orphan Medicines, of which it rejected four (25%), recommended nine (56%) for restricted use and recommended three (19%) for general use. In comparison, of the 116 non-orphan drugs appraised by NICE, seven (6%) were rejected, 56 (48%) recommended for restricted use, and 53 (46%) recommended for general use.[44]

  32.  The current methodology therefore needs to be re-assessed, with more emphasis attached to unmet need, innovation, clinical effectiveness and budget impact, and less on cost/QALY.

Ultra-orphan diseases

  33.  Ultra-orphan medicines are described by NICE as medicines for the treatment or prevention of a disease affecting fewer than 1,000 people in the UK.

  34.  The conventional NICE evaluation process disadvantages individuals with ultra-orphan diseases, for which products that are available for treatment are characterised by:

—  high acquisition costs;

—  high ICER;

—  use is limited to an ultra-orphan disease that are chronic, severely disabling and/or life-threatening; and

—  potential for life-long use.

  35.  Currently there is no process outside the conventional evaluation for this class of products. It has been suggested that NICE establish an Ultra-Orphan Drugs Evaluation Process and Committee. The process would be modeled on the existing conventional process but be tailored for ultra-orphan drugs. The reference ICER would be developed from currently marketed ultra-orphan drugs that are in the range of £200-£300K per QALY. The BIA would support such a development, and would also support a similar development for orphan drugs.

Improving the Health Technology Assessment Process

Definition of value

  36.  A broader definition of value is needed in the NICE evaluation process. NICE currently relies heavily on a methodology that is based on a one-size-fits-all measure of cost-effectiveness, an ICER based upon a cost per QALY. This attempts to apply the same parameters to a wide range of health interventions and subjective outcomes such as quality of life.

  37.  While such a measure has a role, it is but one of a number of parameters. Over-reliance on this single measure can have a profound impact on patients, who can be denied treatment on the basis of theoretical assumptions.

  38.  Not only are QALYs not always objective, they can also change over time and, importantly, they do not take into account the indirect benefits of a new therapy, such as productivity gains, reduction in caregiver and personal time costs, shorter hospitals stays, enabling people to return to work and contribute to the economy. The priorities of the patient population, the nature of the therapeutic market and availability of alternative treatments, the perspective of medical specialists, affordability concerns and effects on macro-economic growth should all be recognised in decisions about price and reimbursement.

  39.  A particular concern for innovative companies is that NICE's approach to cost-effectiveness analysis is often based on limited data generated at too early a stage in a product's growth. This can lead to higher levels of uncertainty, especially in highly innovative products. There is a real risk that smaller companies will either be penalised for failing to generate insufficient health economic data, or forced to use limited data from RCTs that will give uncertain outcomes.

  40.  There needs to be agreement on the criteria against which therapeutic progress (or value) can be identified throughout a product's lifecycle—this can include mortality and morbidity data, side-effects, tolerability, predictive surrogate parameters, pharmaceutical form, route of administration, compliance, ease of use, impact on the healthcare service, disease severity, medical need, quality of life and patient preferences. Improvements under any of these headings may constitute innovation that is of value to sub-groups of patients.

Early interaction

  41.  The BIA welcomes the recommendation in the recent Cooksey review of UK health research funding to involve NICE earlier in the process of development to accelerate assessment of clinical and cost-effectiveness.

  42.  Provision for early dialogue between companies and NICE would ensure a more efficient process. It is likely that the burden of more reviews will mean that more companies will be impacted by the NICE process, and it is important that companies gain an early understanding of what is expected of them.

  43.  Engaging with companies from the start of the appraisal would allow discussion on methods and data. This would ultimately speed up the appraisal process, reduce inaccuracies and, consequently, reduce the number of appeals.

Speed of publishing guidance

  44.  There are significant concerns over the speed of publishing decisions. For example, one BIA member company has been waiting NICE's guidance on Osteoporosis Primary Prevention which has been in progress since March 2002.

  45.  Certainty, to which positive NICE guidance contributes, is important for innovative companies to grow. A long wait for NICE guidance will not create an overall innovation-friendly environment. Many emerging biotechnology companies are working largely on single product development, so delay, not to mention negative appraisals, can be catastrophic for such companies.

  46.  The BIA welcomed the announcement in November 2005 of a new NICE Single Technology Appraisal, which will be used initially to produce faster guidance on certain life-saving drugs which have already been licensed and on new medicines referred to NICE.

  47.  Two of the first five medicines to go through the new process are biotech medicines—Herceptin, for breast cancer, and MabThera, for non-Hodgkin's lymphoma. This is a positive step towards ensuring that patients have the best possible access to innovative medicines. It is important that the new procedure is extended to other medicines for debilitating and life-threatening diseases.

  48.  The take-up of innovative drugs would be improved by the further improvements to the fast-track system of NICE appraisals for innovative medicines. For example, the STA submission word limit makes it difficult to ensure the submission is sufficiently comprehensive, and creates a risk that the appraisal committee cannot adequately understand and correctly analyse the data.

The Implementation of Nice Guidance, Both Technology Appraisals and Clinical Guidance (Which Guidance Is Acted On, Which Is Not and the Reasons For This)

  49.  Negative appraisals almost certainly result in non-implementation, however, positive appraisals do not mean universal implementation within NICE timelines.

  50. There are two kinds of "NICE blight" that are leading to reduced access to modern effective treatments:

(a)  where PCTs hold back decisions on funding of a product on the NICE work programme pending a decision by NICE, which is often issued months or even years after grant of a licence; and

(b)  when PCTs hold back funding for new treatments that are not short-listed for consideration by NICE on the assumption that they will at some stage be the subject of an appraisal.

  51.  Government policy is that patients should not automatically be denied funding for medicines that are awaiting NICE guidance. NHS organisations are supposed to use local arrangements for the managed introduction of new technologies where NICE guidance is not yet available. However, funding decisions are routinely delayed until guidance is available, meaning that patients are often denied access to medicines for months or years.

  52.  A good example is the use of bortezomib for multiple myeloma, which was licensed in April 2004 and received CHMP positive opinion for the expanded indication in March 2005, although final NICE guidance on the expanded authorisation has still not been issued. In the meantime, patients are dependent on decisions made by local PCTs which leads to inequality of access across the UK.

  53.  In this, as in other instances, even once NICE guidance is issued, prescriber uptake implementation is patchy. The reasons for this are varied, but do not simply relate to the cost of implementing NICE guidance—factors such as poor NHS financial management and clinical resistance are key.

  54.  Investing in NICE, and ensuring it has the resources it needs to do its job properly, is pointless if its guidance is not implemented. The BIA would support more joined-up financial incentives and measures to measure tangibly the extent and quality of guidance implementation, eg by including this in the Healthcare Commission's Annual Health Check, which is not currently the case.

The Appeal System

  55.  The BIA would like to bring to the Committee's attention an issue with the appeal process insofar as companies have to deal with the same people that actually made the decision in the first place, so it is questionable whether it is an objective process.

Laura Gilbert

Public Affairs Director, Bioindustry Association

March 2007

42   Office of Fair Trading. Annexe B, Review of NICE, SMC and AWMSG. February 2007. OFT885bb Back

43   http://ec.europa.eu/health/ph_threats/non_com/docs/EMEA_chart_en.pdf Back

44   "Working paper by the OHE: `HTA for orphan drugs: A review of the Issues and of NICE and SMC Decisions". Back