Guidance on the use of riluzole (Rilutek) for the treatment of motor neurone disease

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Riluzole - Appeal against guidance dated December 2000

NATIONAL INSTITUTE FOR CLINICAL EXCELLENCE

RILUZOLE APPEAL

Appeal against Guidance dated December 2000

Decision of the Appeal Panel

Introduction

1. The Appeal Panel met at 11.00am on 4 January 2001 to consider appeals by the Motor Neurone Disease Association (MNDA) and the Association of British Neurologists (ABN) against the Institute's Guidance to the NHS on the use of Riluzole for the treatment of Motor Neurone Disease dated December 2000.
   
2. The Appeal Panel was composed of Professor Sir Michael Rawlins (Chairman of the Appeal Panel and Chairman of the Institute), Mr Roy Luff (non-executive Board Member) Dr Peter Read (industry representative and former President of the ABPI and former Chairman, Hoechst UK),and Ms Ruth Carlyle (independent member and patient representative on the Institute's Partner's Council). Ms Mary McClarey (non-executive board member) was unavoidably detained and sent her apologies. The appellants agreed to the appeal continuing in her absence. Ms Victoria Long (Administration Co-ordinator for the Institute) in the capacity of minute-taker, Ms Kathleen Dalby (Administration Assistant for the Institute) and Mr Stephen Hocking, the Institute's legal advisor were also in attendance.
   
3. Dr Read declared that he had previously been employed by and chairman of Hoechst UK, and was an occasional adviser to Aventis, although he had had no involvement with Riluzole. Ms Carlyle declared that she had previously been employed by the MNDA.
   
4. The Appeal Panel had considered the prior written submissions made by the Motor Neurone Disease Association and the ABN. They also considered submissions at the hearing for the MNDA from Mr George Levvy, Ms Alison Morris, Professor Michael Swash and Mr Richard Stein (legal advisor) and the ABN from Dr Richard Orrell.
   
5. In addition, representations were also considered from Professor David Barnett, Chairman of the Appraisal Committee; and Mr Andrew Dillon, Chief Executive of the Institute.
   
6.

The three grounds upon which the Appeal Panel can hear an appeal are:

  • The Institute has failed to act fairly and in accordance with the Appraisal Procedure set out in the Institute's Interim Guidance for Manufacturers and Sponsors;
  • The Institute has prepared guidance which is perverse in the light of the evidence submitted;
  • The Institute has exceeded its powers.
7. The MNDA appealed on the second ground and the ABN on the first ground. The Appeal Panel suggested that the ABN might wish to treat their appeal as being made on both the first and the second ground, to which the ABN agreed.
 
Ground 1: Fairness and Process
   
8. The representative of the ABN alleged that the Institute had failed to conduct the appraisal in accordance with its published procedures. In particular, the Institute had failed to provide the ABN with a copy of the Provisional Appraisal Determination (the PAD) for its comments; or a copy of the Final Appraisal Determination (the FAD) until specifically requested.
   
9. The Institute's Interim Guidance for Manufacturers and Sponsors provides, under the heading "Evaluation Process" that a PAD "will be released in confidence to ...relevant professional organisations." It is the Institute's practice to release a FAD in the same way.
   
10. In response to questions from the Appeal Panel Mr Andrew Dillon (Chief Executive) explained that the ABN had not, originally, been a formal consultee. A letter from the Registrar, Royal College of Physicians of London (dated 22 February 2000) indicated that the College was acting together with the ABN in preparing a joint submission in relation to riluzole. A letter from the President of the ABN (dated 13 July 2000), accompanying the submission on riluzole, indicated that the accompanying document was a joint submission of the ABN and the College. Consequently, the Institute had confined its communications to the College. The College had been provided with and subsequently responded to both the PAD and the FAD, and the Institute had therefore continued to assume that these represented the views of both organisations. Mr Dillon accepted that, in retrospect, it would have been preferable for the Institute to have regarded the two organisations as separate consultees.
   
11. Findings The Panel accepted that all parties had acted in good faith. The Panel also agreed that it might have been preferable for the two organisations to be treated as separate consultees. Nevertheless, the Panel did not consider that the Institute had failed to act in accordance with its published processes. The initial approach to the College had in fact elicited the joint views of the ABN and the College, and the Panel concluded that the Institute was acting fairly and within its procedures to assume that this joint approach by the ABN and the College would continue during consultation on the PAD and circulation of the FAD. The Panel found that the Institute had genuinely considered that consultation with the College was also consultation with the ABN. The Panel considered that it was reasonable to make this assumption and that it was for the College or the ABN to have corrected the Institute on this point.
   
12. Decision The Panel rejected the appeal on this point.
   
Ground 2: Perversity
   
13. Both the ABN and the MNDA claimed that the proposed guidance was perverse.
   
14. The MNDA alleged that it was confusing since it restricted the use of riluzole to patients with amyotrophic lateral sclerosis (ALS). The guidance failed to define ALS; and a strict interpretation would deny patients with the clinical variants primary lateral sclerosis (PLS) and progressive muscular atrophy (PMA) riluzole's benefits. The MNDA's clinical expert explained that British neurologists had largely abandoned the terms ALS, PLS and PMA since these were clinically and neuropathologically variants of a single disorder "motor neurone disease" (MND); and that most patients with variant forms of MND ultimately developed features of ALS. He explained that the terminology was further confused by the differences in terminology used in the UK and mainland Europe: whilst the UK had adopted the terminology described above, neurologists in many (if not most) other EU states used ALS to describe MND.
   
15. The ABN's representative confirmed the MNDA's statements about terminology, and also regarded the guidance as consequently confusing.
   
16. In response to questions Professor David Barnett (Chairman, Appraisal Committee) sympathised with the appellants' claims about the nomenclature of MND, but emphasised that the Appraisal Committee had considered this fully when drawing up its guidance. The Committee, however, were also aware that the indications for riluzole were restricted to "patients with amyotrophic lateral sclerosis"; and that the Summary of Product Characteristics for riluzole included the phrase "should not be used in any other form of motor neurone disease". The Committee had attempted to draw up its guidance in manner that would allow some flexibility in its interpretation, but were conscious of the need to give advice that was compatible with the terms of its marketing authorisation.
   
17. The appellants' clinical experts expressed the view that since the marketing authorisation had been granted through the Centralised Procedure (i.e. authorised by the European Medicines Evaluation Agency) the nomenclature reflected the terminology used in mainland Europe; and that "amyotrophic lateral sclerosis" as used in the Summary of Product Characteristics should be interpreted (in UK nomenclature) as MND. The statement about "other forms of motor neurone disease" in the Summary of Product Characteristics referred, in the opinion of these experts, to other unrelated motor neurone diseases such as Spinal Muscular Atrophy.
   
18. Mr Dillon explained that when the Department of Health and the National Assembly for Wales referred a pharmaceutical product to NICE for appraisal, the Institute was normally expected to base its advice in relation to the product's authorised indications. The only exceptions were either when the Institute was specifically asked to consider other indications; or when substantial new evidence to support wider indications had become available only after the granting of marketing authorisation. In the case of riluzole, neither of these conditions applied.
   
19. Findings The Appeal Panel appreciated the problems arising from the international differences in neurological terminology. However, the Panel considered that the Appraisal Committee was aware of and had given full consideration to the issue; and that it could not be said to be perverse for the Committee to have decided not to re-interpret the authorised indications on its own authority.
   
20. Decision The Panel rejected the appeal on this point.
   
The Appeal
   
21. The Appeal Panel having found against the ABN and MNDA on both grounds, dismissed the appeals.
   
Further Appeal
   
22. There is no possibility for further appeal within the Institute against this decision of the Appeal Panel. The decision of the Appeal Panel and the Institute's decision to issue the Guidance may be challenged by an interested party by an application to the High Court for permission to bring an application for Judicial Review. Any such application must be made promptly and in any event within three months of the receipt of this decision, or the issue of the Guidance to the NHS, as applicable.

 

 

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