Wyeth is a global pharmaceutical company dedicated to the discovery, development, manufacturer and sale of human and animal pharmaceutical products. Wyeth is the 7th largest pharmaceutical company based on sales in the UK.[156] Four of Wyeth's products are the subject of nine multiple health technology appraisals (MTAs).

  As a member of the Association of the British Pharmaceutical Industry (ABPI), Wyeth supports and endorses the submission to the Health Select Committee made by the Association. In addition, Wyeth welcomes the opportunity to submit evidence of its experience to inform the committee's inquiry into aspects of the work of the National Institute of Health and Clinical Excellence (NICE).

1.  Executive Summary

  In this submission Wyeth identifies a number of factors relating to; the challenge of NICE's decisions, NICE's evaluation process, the speed of publishing guidance, the appeal system and the implementation of guidance. To address the issues raised, Wyeth recommends:

—  A greater consideration of factors other than cost per QALY in decision making; eg acceptability, appropriateness, preference and innovativeness of the technology, degree of clinical need, consideration of national clinical priorities and a broader (societal) view of the costs and benefits associated with the technology.

—  Enabling NICE to commission work directly with the academic assessment groups thus giving them greater control over the quality of work carried out.

—  Reciprocal access to economic models between the Assessment Group and contributing Stakeholders.

—  Manufacturers should have the same opportunity to attend Appraisal Committee meetings as nominated members from other stakeholders.

—  Access to the ERG report should be given to stakeholders prior to the Appraisal Committee meeting.

—  There should be consultation over the Costing Templates and Costing Report.

—  In the event of little or no change to the FAD post appeal, the Guidance Executive should make the necessary changes and publish the guidance in accordance with section 4.6.9 of the NICE Guide to the Technology Appraisal Process.

—  An independent Appeal Committee, without NICE board members, hears appeals.

—  The opportunity, at appeal, for stakeholders to challenge the clinical rationale and the quality of the evidence upon which the recommendations are made.

—  Appropriate audit/measure of the implementation of NICE guidance and guidelines.

—  Incentives for the implementation of guidance and guidelines.

—  That subsequent guidance is placed in context with existing guidance.

—  Mandatory funding for clinical guidelines.

2.   WHY NICE'S DECISIONS ARE INCREASINGLY BEING CHALLENGED

  2.1  NICE's decisions are becoming increasingly reliant on the estimated cost effectiveness, expressed as cost per quality adjusted life year (QALY) gained, as the sole determinant of whether or not to recommend a therapy for use within the NHS. The cost per QALY gained frequently does not accord with both patients' and health care professionals' experience of the value of the therapy being appraised. For example the cost per QALY fails to account for the impact of disease and its treatment on carers and the immediate family of the patient.

  2.2  Cost per QALY also fails to account for the broader societal benefits derived from treatment such as ability to continue/return to work; with associated reduction in unemployment and/or disability benefits and increase in tax revenue from the individual maintaining or restarting work. This disparity in value is greatest in early onset, chronic, degenerative conditions such as Ankylosing Spondylitis (AS). Despite acknowledging that up to 30% of sufferers are unable to work, the recent Appraisal Consultation Document (ACD) for the use of TNF inhibitors in the treatment of AS, seeks to restrict the long-term use of these agents to the 6% of patients whom NICE consider achieve a cost per QALY of less than £20,000.

  2.3  There is variability in the quality and consistency of the Assessment Reports, commissioned on NICE's behalf from various academic centres within the UK and upon which the Appraisal Committee's base their recommendations. Our concerns relate to the adequacy with which the resultant Assessment Reports address the scope of the appraisals, the appropriateness of the structure and inputs to the economic models, the extent to which comments from stakeholders are addressed by the assessment groups and the handling of uncertainty with respect to the cost effectiveness analyses. Failure to address these issues during the appraisal process increases the likelihood of the final decision being challenged.

  2.4  The above concerns may be exacerbated in part by the system under which Assessment Groups are contracted to produce the reports that inform NICE decision-making. There are no direct agreements between NICE and individual Assessment Groups (with the exception of the Decision Support Unit). The Department of Health contracts with the umbrella organisation, the National Collaborating Centre for Health Technology Assessment, which is responsible for managing the contracts with individual Assessment Groups. The Institute thus has no direct contractual relationship with the Assessment Groups, although it is their ultimate customer. As such, NICE has limited ability to require and ensure that the reports produced by the Assessment Groups are fit for purpose.

  2.5  Wyeth are appealing the recent Final Appraisal Determination (FAD) for use of TNF inhibitors in the treatment of Rheumatoid Arthritis (RA). One of the aspects of this appeal relates to the Assessment Report failing to evaluate the earlier use of these agents despite the scope indicating that the appraisal should attempt to identify the stage in the pathway of care where these agents should be used. Another aspect of Wyeth's appeal relates to the failure of the assessment group to carry out the analysis of uncertainty defined in NICE's Guide to the Methods of Technology Appraisal.

  2.6  It is often difficult to determine why estimates of cost effectiveness derived by the assessment groups differ from those generated by the manufacturers and other stakeholders. Whilst the assessment groups have full access to the economic models produced by the manufacturers the assessment groups maintain their models in confidence in order to protect the intellectual property rights to their work. In the event that NICE negotiates release of the assessment groups' models they are "locked" to prevent stakeholders from re-running them, which thwarts stakeholders attempts to understand how they work. Given stakeholders concerns over the quality of the assessment groups' work, failure to fully disclose how their estimates of cost-effectiveness are derived further increases the likelihood of the final decision being challenged.

  2.7  Thus far despite concerns raised by both manufacturers and healthcare professionals over the construct of the assessment group's model for the appraisal of TNF inhibitors in the treatment of AS, neither the assessment group or NICE have attempted to address these issues.

  2.8  In conclusion, differences in the perceived value derived from the technologies being appraised and a lack of transparency regarding how decisions are reached results in an increasing number of challenges from patient, healthcare professional and manufacturer stakeholders.

  2.9  Wyeth recommend:

—  a greater consideration of factors other than cost per QALY in decision making; eg acceptability, appropriateness, preference and innovativeness of the technology, degree of clinical need, consideration of national clinical priorities and a broader (societal) view of the costs and benefits associated with the technology;

—  enabling NICE to commission work directly with the academic assessment groups thus giving them greater control over the quality of work carried out; and

—  reciprocal access to economic models between the Assessment Group and contributing Stakeholders.

3.   WHETHER PUBLIC CONFIDENCE IN THE INSTITUTE IS WANING, AND IF SO WHY

  3.1  The public's perception of NICE is informed to a large extent by the media coverage of its activities which focus on the frequent challenges to its decisions by patients, healthcare professionals and manufacturers. The media coverage is associated with the failure of the decisions taken by NICE to promote the faster uptake of innovative medicines and a failure to prevent postcode prescribing.

4.   NICE'S EVALUATION PROCESS, AND WHETHER ANY PARTICULAR GROUPS ARE DISADVANTAGED BY THE PROCESS

  4.1  Manufacturers, having developed and licensed the technologies, provide much of the evidence being appraised and yet they are excluded from the initial Appraisal Committee meeting when the evidence base is first discussed prior to the committee drafting its initial recommendations. This denies the Appraisal Committee the opportunity to have addressed any outstanding questions that can only be answered by those directly involved in generating the data. Enabling the manufacturer to hear the discussions would also increase the transparency of the subsequent decision-making and likely lead to a reduction in appeals brought about due to a failure to understand how decisions have been reached. Manufacturers are singularly disadvantaged as patients and healthcare professional organisations are asked to nominate experts who are invited to submit a personal view of the technology and to attend the first Appraisal Committee meeting.

  4.2  Within the newer Single Technology Appraisal (STA) process it is the critique of the manufacturers submission, performed by an academic Evidence Review Group (ERG) that is provided to the Appraisal Committee to inform their decision-making. As the report is not made available prior to the Appraisal Committee meeting and the manufacturer is not invited to attend the meeting, despite generating the original submission, the manufacturer remains unaware of the content of the final report until after the ACD or FAD has been issued. The lack of opportunity to correct any factual errors contained within the ERG's report clearly disadvantages the manufacturer and may lead to subsequent delays as these errors are addressed later in the process.

  4.3  The "Implications for the NHS" section of draft guidance has been replaced by reference to implementation tools, in particular a "Costing Template and Costing Report", which are not made available until after final guidance is issued. NICE invite stakeholders to comment on whether they consider that the preliminary views on the resource impact and implications for the NHS are appropriate. However the failure to release draft copies of these tools along with the ACD prevent stakeholders from commenting on this important aspect of the draft guidance. NICE have announced the intention to consult with stakeholders over the Costing Template and Report, however these tools have not been released with either the ACD or FAD for the previously mentioned AS and RA appraisals respectively.

  4.4  The variability of the quality of Assessment Reports has resulted in the need to issue addenda to correct errors in estimates of effectiveness, costs, utilities and additional benefits gained. In the event that the Appraisal Committee is not happy to make a recommendation on the strength of the evidence contained within the Assessment Report NICE have undertaken, or commissioned the Decision Support Unit (DSU) to undertake further analysis to address deficiencies. This results in delays in publication of Guidance and, as a consequence, delays in patient access to the appraised medicines. NICE have recently announced with regret that they have asked the DSU to undertake further analysis to inform the aforementioned AS appraisal. As yet NICE have not been in a position to provide stakeholders with a revised timeline for publication of guidance.

  4.5  Clinical specialists and patient experts whilst invited to attend the first Appraisal Committee meeting, often have, insufficient understanding of health economic methodology and NICE's processes and methods to effectively and fully engage in the HTA process. In addition, the groups that they represent often have limited resources, which further reduce their ability to make effective representations.

  4.6  Wyeth recommend:

—  manufacturers should have the same opportunity to attend Appraisal Committee meetings as nominated members of other stakeholders;

—  access to the ERG report should be given to stakeholders prior to the Appraisal Committee meeting; and

—  there should be consultation over the Costing Templates and Costing Report.

5.   THE SPEED OF PUBLISHING GUIDANCE

  5.1  Capacity to undertake appraisals, requirements for additional analyses and appeals to FADs all serve to reduce the speed with which guidance is published. As an example, despite advanced notification to the Department of Health of the anticipated license of etanercept for the treatment of AS in January 2004, the HTA for this technology is still ongoing. In October 2003, based on the extent of the burden of illness of AS, the likely budget impact and the anticipated funding issues, Wyeth requested that etanercept, along with infliximab, be included in the 8th wave of products referred to the Institute for appraisal. The topic was subsequently referred in the 9th wave with guidance anticipated in February 2006. NICE delayed the appraisal by 10 months to include the third TNF inhibitor adalimumab. There was a three-week delay in release of the Assessment Report, which was finally issued in June 2006 and a four-month delay in release of the draft guidance (ACD), which was finally released in December 2006. The delay in generation of the draft guidance was due to a request from the Appraisal Committee to the Assessment group for additional sub-group analysis. At this stage final guidance was anticipated in June 2007. However due to the repeated concerns expressed by all stakeholders as to the structure and inputs to the Assessment Group's model, NICE have asked the Decision Support Unit to conduct further analysis to inform generation of the FAD. At the time of this submission the extent of this further delay is not known.

  5.2  Until such time as NICE publish its final recommendation on the use of TNF ( inhibitors for the treatment of AS, funding is restricted to the few individuals for whom treatment can be negotiated on a case by case basis. In a recent survey of its consultant membership, the British Society of Rheumatology (BSR) identified that one third of respondents have no access to TNF inhibitors to treat patients with AS.[157] Only 25% of respondents reported the ability to prescribe in accordance with BSR guidelines. Clearly the delay in publication of NICE guidance is having a significant negative impact on patient access to these innovative treatments.

  5.3  Despite the vast majority of the appeal points being dismissed, and those upheld resulting in no substantiate change to the recommendations, the FADs for the Psoriasis and Psoriatic Arthritis appraisals were returned to the Appraisal Committee to be amended and reissued. This resulted in a lapsed time of 5-6 months from the appeal hearing to final publication of the guidance.

  5.4  Wyeth recommend:

—  in the event of little or no change to the FAD post appeal the Guidance Executive make the necessary changes and publish the guidance in accordance with section 4.6.9 of the NICE Guide to the Technology Appraisal Process.

6.   THE APPEAL SYSTEM

  6.1  Wyeth share the concerns raised by the ABPI regarding the deficiencies in the current appeal procedure. In particular, the role of the Chairman of the Appeals Committee in the initial scrutiny of appeals and the constitution of the Appeal Panel result in the lack of an independent review of the conduct of and decisions reached by the Appraisal Committee. The initial scrutiny of lodged appeals is intended to ensure that the appellant has a valid and arguable case. In practice, however, this review frequently addresses the merits of the appeal also. Given that the Chairman of the Appeals Committee subsequently sits on the Appeal Panel such initial scrutiny could prejudice the appeal. Two or three of the five members of the Appeal Panel, including the Chairman of the Panel, are members of NICE's own board. Such board members could be expected to have an inherent interest in defending the decision reached by the Appraisal Committee, which again one could argue would be prejudicial to the fair hearing of the appeal.

  6.2  As indicated throughout this submission, many of the concerns surrounding the NICE appraisal process relate to the quality of the evidence base upon which decisions are reached and the scientific merits of those decisions. However current interpretation of the very restrictive grounds for appeal prevent either of these aspects being challenged at appeal.

  6.3  The criteria for the successful appeal, made under the ground that the Institute has prepared a FAD that is perverse in the light of the evidence submitted, is so unrealistically high as to prevent any substantive review of the recommendations made.

  6.4  Wyeth recommend:

—  an independent Appeal Committee, without NICE board members, hears appeals; and

—  the opportunity, at appeal, for stakeholders to challenge the clinical rationale and the quality of the evidence upon which the recommendations are made.

7.   THE IMPLEMENTATION OF NICE GUIDANCE, BOTH TECHNOLOGY APPRAISALS AND CLINICAL GUIDELINES

  7.1  The extent of implementation of both HTA guidance and clinical guidelines is difficult to determine as they are not systematically assessed. Whilst the Healthcare Commission is responsible for assessing the performance of NHS organisations to ensure they conform to NICE technology appraisals, this currently consists of the self-assessment of whether an organisation has a procedure in place to ensure conformity, rather than a measure of the effectiveness of the procedure.

  7.2  From the various assessments of the implementation of individual health technology appraisals it is clear that the uptake of recommended therapies can be both slow and inconsistent across England and Wales. The BSR's survey of its membership identified that despite a positive NICE recommendation for the use of TNF inhibitors to treat RA patients published in 2002, 42% of respondents indicated that, four years on, they still had some form of restriction on the prescribing of these agents in line with NICE guidance. 70% cited some form of cap on funding whilst 21% and 9% cited lack of staff or facilities, respectively.

  7.3  With the advent of the STA process, there will be increasingly an MTA and a number of STAs covering the same patient population, as will be the case in the near future with TNF inhibitors for the treatment of psoriasis. If MTAs and STAs do not inter-relate it will be difficult for clinicians to identify which piece of guidance to follow.

  7.4  Wyeth are concerned that the replacement of HTA guidance, and associated mandatory funding, with clinical guidelines, for which funding is not mandated, may lead to restrictions in patient access to these medicines as NHS organisations prioritise the funding of guidance.

  7.5  Wyeth recommend:

—  appropriate audit/measure of the implementation of NICE guidance and guidelines;

—  incentives for the implementation of guidance and guidelines;

—  that subsequent guidance is placed in context with existing guidance; and

—  mandatory funding for clinical guidelines.

Wyeth Pharmaceuticals

March 2007

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