Ref: NICE 2000/043 Issued: 8 November 2000

The facility for consultees to make an appeal is part of the Institute's process for developing its guidance for the NHS. The manufacturers and the nationally based patient and professional organisations that are invited to make a submission to an appraisal are provided with the opportunity to make an appeal.

An Appeal Panel considered the appeals against the Institute's proposed guidance on the use of beta interferons in the treatment of multiple sclerosis on the 22 and 23 September 2000 and they have today made their decision public.

There were 8 appellants and each appealed a number of points during the hearing. Some of these points were rejected and some were upheld.

In addition during the hearing Biogen and Schering asked the Appeal Panel to receive some new data that had not been placed before the Appraisal Committee. They requested that the Appeal Panel submit this new data back to the Appraisal Committee for consideration.

Andrew Dillon, Chief Executive of NICE said " Appeals are a part of the process for developing our guidance for the NHS and they are designed to give our technology appraisal process added objectivity and strength.

As the Appeal Panel upheld certain points from this appeal the Institute is following its usual process and has asked the Appraisal Committee to reconsider the original evidence in light of the panel's decision.

I have also taken this opportunity to ask the Appraisal Committee to consider the new evidence that was submitted during appeal hearing. The committee will do both at their December meeting."

Ends

For further information contact:

Anne-Toni Rodgers

Notes for Editors:

Background

1. NICE follows the same open, structured and widely publicised process for all its technology appraisals. This process was developed following consultation and is the process the Institute is following for the Interferon beta/glatiramer review. The process involves the relevant manufacturers and organisations representing patients/carers, as well as health professionals. All these groups:

  • prepare and submit information on the technology and its use,
  • comment on the emerging (provisional) views of the Appraisal Committee; and
  • can lodge an appeal against the Appraisal Committee's final conclusions.

Appeals can either be upheld or rejected. If appeals are upheld, the Appraisal Committee are asked to revisit the evidence and reconsider their Appraisal Determination in light of the appeal panel's findings. If appeals are rejected the draft guidance becomes final and is issued to the NHS.

2. The three grounds upon which an appeal can be heard:

  • The Institute has failed to act fairly and in accordance with the Appraisal procedure set out in the Interim Guidance for Manufacturers and Sponsors.
  • The Institute has prepared guidance that is perverse in the light of the evidence submitted.
  • The Institute has exceeded its powers.

3. The Appeal Panel considered the appeals against the Institute's final draft guidance on the use of beta interferons in the treatment of multiple sclerosis on the 22 and 23 September 2000

4. The Appeal Panel comprised

  • Dr. Susanna Lawrence (Chair of Appeal Panel and non-executive member of the Institute's Board),
  • Professor Tony Culyer (Deputy Chairman of the Institute),
  • Professor Parveen Kumar (non-executive member of the Institute's Board)
  • Ms Mercy Jeyasingham (patient representative)
  • Professor Peter Stonier (industry representative)

5. Appeals were lodged by the following:

  • Association of British Neurologists
  • Biogen Limited
  • Multiple Sclerosis Research Group
  • Multiple Sclerosis Research Charitable Trust
  • Multiple Sclerosis Society
  • The Neurological Alliance
  • Royal College of Nursing
  • Schering Health Care Limited

Appeal Decision

6. The full decision of the Appeal Panel (25 pages) is published on the NICE web site (www.nice.org.uk)

7. In summary the Appeal Panel was satisfied regarding the following points and rejected the appeals in these areas:

a. No specific threshold (cut off point) for cost effectiveness had been set by either NICE or the Secretary of State / National Assembly for Wales.

b. The evidence of all the clinical benefits of beta interferons in the broadest sense, including the impact on the quality of life and estimates of associated costs had been considered and assessed by the Appraisal Committee

c. It was not perverse for the Guidance to state that a major reduction in the cost of beta interferons would be needed before they could be considered cost effective.

d. The Appeal Panel did not accept that the Appraisal Committee should specify the cost at which the beta interferons would become cost effective as the cost of the products is only one element in their cost effectiveness

e. All the economic models and data submitted, including the Biogen model, (recently published by Kendrick and Johnson and referred to in the national press), had been considered by the Appraisal Committee.

f. The Appeal Panel accepted the Committee's conclusion that the Biogen model (recently published by Kendrick and Johnson) was flawed and decided that it was not unreasonable or unfair to reject this economic model.

g. The Appraisal Committee made their judgement by considering the clinical effectiveness, cost effectiveness and the wider implications for the NHS.

h. The Appraisal Committee did consider non-NHS costs.

i. The Appraisal Committee did consider the broad balance of benefits and costs.

j. The Appeal Panel was satisfied that the Appraisal Committee did not reach its conclusions on a consideration of cost effectiveness alone.

k. The Appeal Panel was satisfied that the Appraisal Committee, in referring to management strategies for MS in the Guidance, had wished to underline the importance of providing adequate therapy and rehabilitation services for patients with MS.

l. The Appeal Panel was satisfied that the Appraisal Committee had considered the patient survey conducted by the MS Research Trust

m. The Appeal Panel believed that an appreciation of this need and of the seriousness of the symptoms of multiple sclerosis for patients is implicit in the recommendations for further research, and review of the Guidance.

n. The Appraisal process had followed the Institute's Interim Guidance for manufacturers.

o. The Appraisal Committee was aware of the National Guidance on NHS Priorities, and was not required to seek further specific guidance from the Secretary of State.

p. The Appraisal Committee's awareness of the need to encourage innovation is evident in the Guidance.

q. The Appraisal Committee did demonstrate transparency in the process.

r. The Appeal Panel rejected the assertion that the Institute had not followed an evidence-based approach, and recognised that the Appraisal Committee had not only considered all the evidence submitted, but had also assessed the limitations of the models used within the submissions received from consultees.

s. The Appeal Panel was satisfied that as data submitted by Schering and Serono Pharmaceuticals Limited was submitted to the Institute as confidential, it was therefore legitimate that the Institute did not disclose this to the other consultees.

t. The Appeal Panel did not accept the appellants' assertion that the sole basis for the Appraisal Committee's conclusion was the calculation of QALYs for beta interferons. Moreover, the Panel did not accept that the Appraisal Committee was required to consider the effects of the PPRS (Prescription Pricing Regulation Scheme).

u. The Appeal Panel rejected the assertion that undue emphasis was placed on the side effects of the beta interferons

v. It is an inherent part of the appraisal process that changes may occur between the PAD and FAD stages as a result of the consultation exercise. The Appraisal Committee is not obliged to provide reasons for any changes.

8. In summary the Appeal panel upheld the appeal on the following points:

a. The Institute wrote to the MS Society in January 2000 inviting the Society to send a representative to the Appraisal Committee meeting on 30 May. Due to an administrative error the letter mistakenly asked for a clinical expert when it should have asked for a patient advocate, the Society responded by nominating its Medical Director. Mr. Cardy (MS Society) wrote to NICE on the 25 May 2000 asking why the MS Society had not been asked to send a patient advocate. Realizing the error, Andrew Dillon responded on the same day, apologising and inviting Mr. Cardy, the Chief Executive, to attend the meeting or to send a senior colleague in his place. In the event, four representatives from the MS Society attended the meeting on 30 May.

The Institute accepted that there had been an administrative error and although this error was discovered in time to allow a patient advocate nominated by the MS Society to attend the Appraisal Committee's meeting, the short notice restricted the MS Society's choice as to whom to nominate as the patient advocate and did not give the patient advocate adequate time to prepare. The Panel concluded that the Appraisal Committee's understanding of the perspective of patients might have been adversely affected as a result.

The Appeal Panel was satisfied that the Appraisal Committee had considered the patient survey conducted by the MS Research Trust, however the appeal panel concluded that the decision by the Institute to regard the MS Research Trust as a professional rather than a patient group had a similar effect.

b. The Appeal Panel concluded that because general information on the cost effectiveness of other treatments was widely available it was not necessary to set out direct cost comparisons in the Guidance. Nevertheless, the Panel concluded that the Appraisal Committee had not explained the basis of its conclusion that the beta interferons are not cost effective, when compared with alternative uses of current resources and therefore the reasoning in this part of the proposed Guidance was not sufficiently transparent.

c. The Appeal Panel accepted the Appraisal Committee's conclusion that the Kendrick and Johnson model (Biogen model) was flawed; however, the reasoning given in the Guidance for rejecting the model is misleading.

d. The Appeal Panel questioned whether the issues relating to the long-term benefits of treatment with beta interferons had been fully considered by the Appraisal Committee.

e. Whilst the Appeal Panel recognised that the decision to allow patients already on treatment with interferon beta to continue, and those on the placebo arm of a clinical trial to be treated with beta interferons after the trial, was made on compassionate grounds, it considered this to be insufficient justification for selecting these patient groups over others.

f. The Appeal Panel noted that the European Transparency Directive requires the Institute to ensure that its Guidance contains a full statement of the reasons supporting its decisions. The Appeal Panel felt that the explanation in the Guidance as to why the beta interferons are not cost-effective when compared with alternative uses of NHS resources, did not fully comply with this requirement.

g. The Guidance gives insufficient weight to the significance of MRI data, in particular evidence of correlation with disease activity in early relapsing remitting MS.

h. Although it was clear from the wording recommending further clinical trials in the Guidance that the Appraisal Committee was simply making a recommendation, the Appeal Panel did not consider that this was the case with regard to the audit section of the guidance. The audit section appeared to be more directive and the panel was concerned that this may lead some Health Authorities to believe that they had no discretion in the matter.

New Data

9. During the hearing Biogen and Schering asked the Appeal Panel to receive some new data that was not placed before the Appraisal Committee. They requested that the Appeal Panel submit the new data back to the Appraisal Committee for consideration. Having upheld parts of the appeals, the Appeal Panel would expect this appraisal to be referred back to the Appraisal Committee for reconsideration. The Appraisal Committee should consider these new data at that time.

What happens next?

10. The Institute has asked the Appraisal Committee to reconsider the original evidence in the context of the Appeal Panel's decision. They have also taken the opportunity to ask the committee to look at the new economic model submitted, by Schering as commercial in confidence, at the Appeal Hearing.

11. The Appraisal Committee will meet to reconsider the evidence on 13 December 2000. It will then issue a new Final Appraisal Determination (FAD), to those who submitted evidence, for appeal.

12. Since it may take up to a week after the Committee's meeting to prepare the final version of the FAD and in recognition that we will, by then be very close to Christmas, the usual 10 working day deadline for appeals will not apply. The Institute has decided to extend the deadline for submission of appeals against the new FAD will be extended to 5.00 pm on Monday 15 January 2001.

13. Following the Appeal Panel's decision resulting from the administrative error that led to the MS Society not receiving the correct letter of invitation and the Institute's decision to regard the MS Research Group as a professional rather than a patient organisation, the Institute has offered these organisations the opportunity of joining the Appraisal Committee at its meeting on 13 December 2000. The choice of representatives is a matter for the organisations to decide.

14. The Institute has not yet issued guidance on the use of interferon beta for MS and will not do so until 2001.

Update on the appraisal of glatiramer

15. The Institute is appraising another technology (glatiramer) for the treatment of MS.

16. The Institute's Appraisal Committee has two meetings. Following the first meeting the Committee produces a Provisional Appraisal Determination (draft view) that is sent to manufacturers, the groups that represent patients and professional organisations, the Department of Health and the National Assembly for Wales for consultation.

17. The feedback from this consultation is reviewed at the second committee meeting. Following this second meeting the committee produces a Final Appraisal Determination (FAD) that is sent to the same groups providing them with an opportunity to appeal.

18. The technology appraisal of Interferon beta and glatiramer in the treatment of MS was conducted together until the production of the FAD (Final Appraisal Determination).

19. The Final Appraisal Determination on the use of glatiramer in the treatment of MS was placed on hold until the product received its full Marketing Authorisation in the UK and the full terms of the licence were available to the Institute.

20. Glatiramer now has its UK licence and the details have been made available to the Institute. The Appraisal of this technology has recommenced and the Appraisal Committee will consider this technology alongside Interferon beta at their meeting on 13 December.

21. Following this meeting the Appraisal Committee proposes issuing a combined Final Appraisal Determination and guidance document for interferon beta and glatiramer in the treatment of MS for appeal.