1.  INTRODUCTION

1.1  Roche in the UK

  1.1.1  Roche aims to improve the health and quality of life of people in the UK through the research, development and supply of innovative medicines and services for the early detection, prevention, diagnosis and treatment of disease. As part of one of the world's leading healthcare groups, Roche in the UK employs over 2,000 people in pharmaceuticals, diagnostics and clinical development.

  1.1.2  Our portfolio of medicines includes treatments for cancer, rheumatoid arthritis, osteoporosis, obesity, anaemia and virology. Further information about Roche in the UK can be found at www.rocheuk.com

1.2  Roche and NICE

  1.2.1  Roche fully supports the aims and objectives of NICE. Over the course of the past eight years, Roche UK has submitted 24 technology appraisal dossiers to NICE on almost all of our key medicines. This record of engagement is substantially more than most other pharmaceutical companies. Details of these appraisals are provided in the accompanying Appendix.[124] Of these, four have been undertaken using the new Single Technology Appraisal (STA) process through which NICE intends to appraise most medicines in the future. At present, Roche therefore has a greater level of experience of the STA process than other manufacturers.

  1.2.2  The first ever STA which was conducted for Herceptin in early breast cancer was described by the Chair of the Appraisal Committee which reviewed it as "setting the gold standard for all subsequent STA appraisals".

  1.2.3  Roche has continuously engaged with NICE, the ABPI and other key stakeholders in sharing learnings and experiences of undertaking health technology appraisals in the UK from both NICE and the Scottish Medicines Consortium (SMC) and would be pleased to provide further evidence in this regard at an oral hearing of the Committee.

2.  EXECUTIVE SUMMARY

  2.1  As part of one of the world's leading healthcare groups, Roche in the UK employs over 2,000 people in pharmaceuticals, diagnostics and clinical development. Our portfolio of medicines includes treatments for cancer, rheumatoid arthritis, osteoporosis, obesity, virology and anaemia.

  2.2  Roche fully supports the aims and objectives of NICE. Over the course of the past eight years, Roche UK has submitted 24 technology appraisal dossiers to NICE. Of these, four have been appraised using NICE's new Single Technology Appraisal (STA) process through which most medicines will be reviewed in the future. At present, Roche therefore has a greater level of experience of the STA process than other manufacturers and we would therefore be pleased to provide further evidence in this regard at an oral hearing of the Committee.

3.  SUBMISSION

3.1  Whether public confidence in the Institute is waning and if so why?

  3.1.1  NICE has recently declined to give a number of innovative medicines approval and these cases have received high profile and significant media attention. When drugs are rejected by NICE, significant negative publicity often follows with generalised media statements being made about NICE being overly focussed on cost. Whether this is true or not, these perceptions may be serving to undermine the confidence of the general public and patients alike that NICE is simply an organisation put in place to contain NHS costs. However, the reasons that NICE reject drugs are varied and often not related to matters of cost at all. For example, perceived issues with the evidence base may often mean that a particular medicine might not be endorsed. This was the case recently for example with Roche's oral medicine Tarceva for non-small cell lung cancer. It may therefore be helpful for NICE in the future to be more specific about its precise reasons for rejecting medicines in its dealings with both the general and medical media.

  3.1.2  It does appear though that NICE's rejection rate for medicines may be increasing. The Inquiry might therefore usefully investigate whether the approval rate for drugs has changed year-on-year since NICE's inception and if so what the reasons are for this. It might also investigate what the approval rate is across the different independent Appraisal Committees (two being chaired by Professor David Barnett and one being chaired by Professor Andrew Stevens) in case different approval standards are being inadvertently applied across different Appraisal Committees.

  3.1.3  Such an analysis would be particularly timely given the introduction of the new rapid STA process which is currently being used to appraise a good number of medicines and in the future will be the primary mechanism for appraising almost all medicines. There are issues with the STA process which we outline in section 3.2 below which may be contributing to the apparent increasing large number of negative NICE appraisals. It is essential that these issues are resolved quickly if all stakeholders, including patients, are to maintain faith in both NICE and the STA process overall. Due to the increasing importance of the STA process for appraising medicines, we have limited our comments in the question below to the STA evaluation process.

3.2  NICE's evaluation process, and whether any particular groups are disadvantaged by the process?

  3.2.1  The premise of the new STA process, akin to that of the Scottish SMC, is that the manufacturer has to provide the majority of the evidence to be used in the appraisal. The role of University-based Evidence Review Groups (ERGs) being to provide a balanced critique of the manufacturers submission rather than to produce an independent assessment report or undertake additional analysis or new economic modelling as is the case with the original multiple technology appraisal (MTA) process. Many of the ERG reports which have been produced to date involving Roche drugs have been unfair and unbalanced in their perspective. Roche has significant issues with the ERG reports produced for three out of the four STAs in which we have participated to date, namely:

—  MabThera for Non-Hodgkin's Lymphoma.

—  Tarceva for Non Small Cell Lung Cancer.

—  MabThera for Rheumatoid Arthritis.

  3.2.2  Despite now being the primary evidence provider to support the STA process, manufacturers are significantly disadvantaged in the STA process as follows:

3.2.2.1     The manufacturer is not given sight of the ERG report to correct any inaccuracies, factual errors or major misinterpretations of the manufacturer's submission by the ERG group prior to it being seen and utilised by the Appraisal Committee for decision making. In three out of the four STA appraisals to date involving Roche drugs (listed above) there have been issues with ERG reports which we believe could have been corrected and addressed had we been given sight of the ERG report before being utilised by the Appraisal Committee for decision making.

3.2.2.2     The manufacturer is excluded from being present at the first STA Appraisal Committee meeting to answer questions or provide clarification about its evidence submission. In contrast, patient groups and clinical experts are present and representatives from the ERG group are in attendance to answer questions and provide clarification. It is our understanding that often there are questions raised during Appraisal Committee meetings regarding the manufacturer's submission to which the answers are "second guessed" since the manufacturer is not present to provide any direct response.

3.2.2.3     The manufacturer is excluded from being present at the second STA Appraisal Committee meeting to answer questions or provide further clarification. Notably the ERG group also attends this second meeting even though it is the manufacturer which will inevitably be providing the primary response to issues raised after the first Appraisal Committee meeting.

  3.2.3  As well as manufacturer attendance at Appraisal Committee meetings, Roche also believes that Appraisal Committee meetings should be held in public (as at present are meetings of the All-Wales Medicines Strategy Group (AWMSG), the NICE Board and NICE appeal hearings).

  3.2.4  Furthermore, it is clear that there is significant variation in the approach being taken to critiquing manufacturer submissions across the different Evidence Review Groups. NICE should provide ERGs with clearer requirements and expectations regarding their role in the STA process in the same way that manufacturers are provided with specific and detailed guidance about the contents of their submissions. Greater quality control and quality assurance of the work undertaken by ERGs is urgently required.

  3.2.5  In the current arrangements this is difficult, if not impossible, for NICE to engineer since it does not hold the direct contractual relationship with academic Evidence Review Groups nor does it fund their NICE related work directly. Commissioning of ERG work is done via the national HTA R&D Programme which is funded directly by DH and this limits the ability of NICE to properly direct the work of ERGs.

3.3  The speed of publishing guidance

  3.3.1  The introduction of the STA process has provided NICE with the opportunity to significantly improve the speed with which technology appraisal guidance can be produced. For example, the STA appraisal of Herceptin for adjuvant breast cancer was not only one of the fastest appraisals undertaken by NICE but also one which produced guidance within weeks of EMEA licensing.

  3.3.2  However, as more STAs are referred to NICE it will be important to ensure that NICE is appropriately resourced in its Technical Teams to ensure an acceptable turnaround time for appraisals. Regular performance metrics should be collected and made available detailing key milestones in the NICE appraisal process such as the time which medicines spend in the topic selection process; time in appraisal; time in appeal; and time to publish final guidance.

  3.3.3  Whilst the speed of publishing and communication of NICE guidance is generally more acceptable with the STA process, the speed of implementation of guidance by the NHS remains problematic. There remain significant variations in the speed with which some NHS organisations choose to fund and implement guidance. Roche regularly audits the implementation of NICE guidance relating to its medicines and consistently we see that there remain large variations in uptake across different parts of the NHS in England and Wales. This is true for primary care medicines such as Xenical used to treat obesity; for specialist medicines such as Pegasys used to treat Hepatitis C; and for Roche's portfolio of NICE appraised cancer medicines: Herceptin for breast cancer, MabThera for Non-Hodgkin's Lymphoma and Xeloda for breast and colorectal cancer.

  3.3.4  Implementation issues are described further in section 3.5 below.

3.4  The appeal process

  3.4.1  Roche has participated in five appeals, most recently for the use erythropoetins in cancer related anaemia and for Tarceva for the treatment non-small cell lung cancer (to be heard at oral hearing in April 2007). In general though, Roche believes that the appraisal process should facilitate the early resolution of issues through dialogue and up front engagement in order to prevent lengthy, resource and time consuming appeals being lodged. At present around 30% of technology appraisals go to appeal and we believe this figure is too high; spending this level of resource on appeals does not represent good value for money for taxpayers or patients. The high level of appeals is demonstrative of the fact that the appraisal process is not sufficiently focussed on early resolution of disputes and issues emerging during the appraisal process. In the case of the STA for Tarceva for non-small cell lung cancer which Roche is presently appealing, many of the issues raised in the appeal could have been dealt with earlier in the appraisal process, had Roche, for example, been given sight of the ERG report for the appraisal before it went to Committee. Such engagement would in fact also be consistent with the recommendations made in the Cooksey Report for earlier dialogue with manufacturers.

  3.4.2  Our observations and recommendations for change regarding the appeal process are:

3.4.2.1     Many of the issues raised in appeals relate to health economics issues and yet there is no qualified person on appeal panels to deal with such issues, ie a health economist and this deficiency should be remedied.

3.4.2.2     Stakeholders at appeal hearings are often in practice not treated equally, whilst all discussion at appeal hearings is directed through the Chair it is usually the case that attendees from NICE, the Appraisal Committee or academic groups working on an appraisal are permitted to engage in greater dialogue or communication than the appellants, and with less hostility, and this is unfair. This may open up the appeal process to accusations of imbalance and unfairness and should be remedied.

3.4.2.3     The appeal process should be administered and undertaken by an independent body unconnected with NICE. The fact that NICE can be its own "judge and jury" seems inappropriate to any outside and fair minded observer and leaves NICE open to the perception of potential bias. This is of course a long standing issue which the Committee has investigated previously in its first Inquiry about NICE.

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

  3.5.1  Whilst the speed of delivering NICE Guidance has improved with the STA process, the speed at which the NHS implements guidance remains highly variable across England and Wales. The establishment of the ERNI database by NICE to bring together in one place information about the uptake of NICE guidance across the NHS is very welcome.

  3.5.2  Roche conducts quarterly audits into the implementation of NICE guidance relating to our medicines which show significant regional variations in uptake for Xenical (obesity), Pegasys (hepatitis C), Herceptin (breast cancer), MabThera (non-Hodgkin's lymphoma) and Xeloda (colorectal breast cancer). We would be pleased to make the latest results of these NHS audits into the uptake of NICE guidance available to the Committee to support the Inquiry if requested to do so.

  3.5.3  More needs to be done to join-up thinking to ensure that improved access to medicines follows rapidly on from the publication of positive NICE guidance. The Ministerial Industry Strategy Group's (MISG) Long-Term Leadership Strategy makes helpful and practical recommendations on how to improve access to medicines, including those which have been appraised by NICE and the Committee may wish to review these as part of it's Inquiry.

  3.5.4  The Committee may also wish to investigate ongoing issues relating to so-called "NICE blight" where treatments are being withheld from patients and access is being denied until final NICE guidance to the NHS is published. Although DH has recently clarified for the NHS in its Good Practice Guidance that in the absence of NICE guidance, other local and national sources of evidence should be used to inform local decision making about treatment availability, this practice is not being consistently applied across the service. The issue of NICE blight is now also being reinforced through the use of "minded rejections" utilised by the Appraisal Committee in the new STA process as a mechanism to obtain further analysis to support appraisals.

  3.5.5  Key factors affecting implementation and recommendations are:

3.5.5.1     The availability of a local NHS champion motivated to pick up and drive the local NICE implementation agenda.

3.5.5.2     The buy-in of clinicians to embrace and implement guidance rapidly, including the need to embrace stopping those practices and treatments which are to be replaced by the guidance.

3.5.5.3     The making available of timely funding by PCTs to ensure that every eligible patient (as opposed to only a locally selected sub-set f patients) is able to receive treatment when they need it (as defined in the implementation tools produced by NICE and captured in NICE Costing Templates issued at the time of guidance publication).

3.5.5.4     The timely, accurate and sensitive reflection of NICE guidance in payment by results tariffs such that there are no disincentives to local implementation built in through inappropriate or lower drugs costs being reflected in the tariff.

3.5.5.5     The removal of any disincentives in commissioning and payment systems which do not support NICE guidance. For example, NICE guidance for Xeloda in breast and colorectal cancer endorses that patient's should be given the choice of replacing an IV treatment option with oral Xeloda (which can save pharmacy, nurse and IV infusion time) but there are sometimes local disincentives for NHS Trusts in place (eg loss of income from day case episodes) to making such switches and implement the NICE guidance.

3.5.5.6     Roche believes that such perverse incentives, as well as undermining NICE guidance implementation, are damaging to patients and run counter to the choice agenda, preventing patients from having access to treatment options which have been judged to be both clinically and cost effective.

3.5.5.7     Regarding NICE clinical guidelines, there is comparatively little information available to determine whether or not guidelines are being implemented by the NHS and particularly what affect they have on access to medicines in the UK and research is urgently needed in this area.

Paul Catchpole

Healthcare Management Director

Roche Pharmaceuticals

March 2007