NICE follows an open, structured and widely publicised process for all its technology appraisals. The process was developed following consultation and is the process we are following for the Interferon beta/glatiramer review. The details of the process and the dates for all appraisals are published in the technology appraisal section of this site.
To date NICE has not issued any guidance to the NHS on the use of Interferon beta or glatiramer in Multiple Sclerosis.
The current situation is that the Department of Health (DH) has reminded the NHS that existing guidance to the NHS on drug treatments for multiple sclerosis (MS) remains in place pending publication the Institute’s guidance. This guidance is contained in DH documents EL(95)97 and HSC 1999/176 both of which can be accessed from the DH website at www.doh.gov.uk/multiplesclerosisdrugsguidance.
In summary they ask purchasing authorities and providers to develop and implement local arrangements to manage the entry of such drugs into the NHS, in consultation with other key interests; and in particular, to initiate and continue prescribing of beta-interferon through hospitals. HSC 1999/176 asks NHS bodies to continue with these local arrangements until the NICE guidance becomes available.
What’s happened so far in the NICE appraisal?
The Department of Health (DH) and the National Assembly for Wales (NAW) asked NICE to appraise Beta Interferon/glatiramer for MS on the 6 August 1999, at the same time the DH and NAW entered into consultation with the manufacturers of the products.
NICE wrote to interested parties (manufacturers, national patient/carer groups and professional bodies) on the same day asking that any submissions they wished to make should be made by the 1 November 1999.
Following the consultation between the manufacturers and the DH / NAW they allowed an extension to the submission date to NICE until February 2000.
During this time NICE commissioned a review of the published material in this area from the Northern and Yorkshire Drug and Therapeutic Centre.
In February 2000 NICE received submissions from the manufacturers, patient/carer groups and the professional bodies involved. These submissions contain both published and unpublished information.
The submissions from the manufacturers were assessed and combined with the review of the published literature into an Assessment Report.
The Assessment Report, and the original submissions from patient/carer organisations and the professional groups, together with the manufacturers’ submissions were made available to the Appraisal Committee.
The first meeting of the Appraisal Committee (membership published in the technology appraisal section of this site) for Interferon beta/glatiramer in MS was held on the 30 May 2000. In addition to the written submissions the committee also had ’experts for the day’ at its meeting. They represented a patient/carer organisation and health professionals with experience in this area. These individuals were nominated by their own organisations. The minutes of this meeting are published in the technology appraisal section of the site.
Following the committee meeting, the Appraisal Committee prepared their provisional views on the evidence – known as a PAD (Provisional Appraisal Determination). The PAD is always sent for consultation to the groups involved.
NICE sought feedback on the PAD from patient/carer groups, professional groups and the manufacturers involved. These are the consultees. During this consultation phase NICE also sought the views of the Department of Health and the National Assembly for Wales who are also consultees. The organisations that represent pharmaceutical and medical device manufacturers had previously informed the Institute that a PAD, (which may vary from the final guidance) could have a significant impact on their share price and the stock market and asked that it should be treated as confidential material, therefore for appraisals that commenced before February 2001 the PAD is circulated to consultees as strictly confidential material.
The Appraisal Committee met again on the 27 July 2000 to consider its provisional determination in the light of the feedback received from the consultees. The minutes of this meeting are published in the technology appraisal section of the web site. At this meeting the Appraisal Committee made their final determination (Final Appraisal Determination – FAD) and submitted it to NICE. At this point the appraisal for glatiramer in the treatment of MS was put on hold until the manufacturer received its UK Marketing Authorisation (license for sale in the UK) from the licensing authority.
NICE recieved the FAD and as part of the process in developing the final guidance circulated it to the patient/carer groups, professional groups and the manufacturers at which point they could decide if they wanted to appeal.
Eight appeals were received against the draft guidance (FAD) for interferon beta. An independent appeal panel considered the appeals on the 22 and 23 September 2000.
Their decision was published on 8 November 2000. Parts of the Appeal were rejected and parts were upheld. Full details of the appeal are published in the technology appraisal section of the site.
NICE asked the Appraisal Committee to reconsider the original evidence in the light of the Appeal Panel’s decision. NICE also asked the committee to look at a new economic model submitted, by a manufacturer (Shcering) as commercial in confidence, at the Appeal Hearing.
The Appraisal Committee met to reconsider the evidence on 13 December 2000. The committee considered the original evidence in light of the appeal panel’s decisions, in addition they considered the new evidence and heard again from the groups that represent people with MS and their carers. The groups were the MS Society and the MS Research Trust and their representatives included people with MS. The minutes of this meeting are also published in the technology appraisal section of this site.
In the meantime glatiramer was granted its UK license and the details were made available to the Institute. The Appraisal of this technology has recommenced and the Appraisal Committee considered this technology alongside Interferon beta at their meeting on 13 December 2000.
During this appraisal the Committee has considered evidence that included economic models supplied by manufacturers and independent researchers. The models are used to inform their judgement on the cost effectiveness of these drugs.
At the meeting on December 13 a review of the economic models was presented which raised a number of concerns (refer to the published minutes). The Committee gave careful consideration to each of these concerns and then reflected generally on the evidence relating to cost effectiveness for both medicines. During this discussion, it was noted that the economic models for both medicines had been challenged on methodological grounds and had doubts cast on the reasonableness of the assumptions they used.
Having considered the evidence and comments made by the people with MS and the patient organisations and having reflected on the analysis of the existing and new economic modelling, the Committee considered the merits of preparing an appraisal determination for either interferon beta or glatiramer. Serious reservations were expressed about the economic models. Given the importance of the advice which the Committee was being asked to provide it was suggested that if the flaws which had been identified in the models presented so far were capable(in whole or part) of being rectified, there would be benefit in doing so. If there was no opportunity to undertake any further work on the economic modelling, the Committee would need to prepare an appraisal determination.
On the basis of the information in front of it the Committee asked their Chairman to prepare an appraisal determination which reflected that, on the basis of the evidence presented, the Committee did not consider that either the beta interferons or glatiramer acetate had demonstrated that their use in the NHS in England and Wales could be considered to be cost effective. The Chair agreed to do so and indicated that he would advise the Institute of the Committee’s serious reservations over the economic modelling.
The evidence relating to the cost effectiveness of these medicines is critically important in this appraisal. Therefore the Institute carefully considered the Appraisal Committee’s concerns and decided to commission further economic modelling on the beta interferons and glatiramer acetate.
The commissioning, construction and evaluation of the new modelling will take some months and therefore the timeline for the appraisal process for both medicines was extended. Although the Institute accepted this would delay production of the final guidance, it considered that this action was in the best interests of people with MS and those who care for them. It is of the utmost importance that the Institute’s guidance is both evidence-based and seen to be fair by those effected by it.
In January 2001 the Institute wrote to the consultees on 3 issues:
1. Consulting on its proposals for the process for commissioning the development of the new economic modelling and identifying where stakeholders would be involved (the draft process document is attached to press release 2001/04 published on this site -search MS)
2. Asking if stakeholders were prepared to release data they may have, including patient specific data from clinical trials, that is likely to be of use to the modellers. Data would be made available through the Institute and treated in accordance with the Institute's standard arrangements for handling data supplied by consultees.
3. Requesting nominations of individuals or organisations that consultees' consider have the capability and experience to undertake the economic modelling.
The Institute asked for consultation feedback, and responses by the 9 February 2001.
The Institute’s Research and Development Committee met in February 2001 to consider the consultation feedback and agree the process and timetable for commissioning the new economic model. Following this meeting the Institute also advertised for health economic modellers, with experience in this sector, to undertake the work.
The Institute appointed a consortium based on the Sheffield School of Health and Related Research (ScHARR) and the Department of Mathematics and Statistics at the University of Sheffield working with colleagues from Oxford, City, Newcastle, Nottingham and York Universities to undertake the work.
What stage is the process at?
The Institute, the
consortium and the consultees met on 30 March 2001. The meeting was constructive
and provided an opportunity for a useful exchange of views on the approach
being taken by the Institute to the final phase of the appraisal. Work
is now underway to construct the new economic model and the Institute has
asked principally the manufacturers to provide relevant clinical trial
data to the consortium. This request is being considered by them.
What happens next?
A further meeting with consultees is planned for a date in the second half of May, following which there will be an opportunity for all consultees to examine the completed model in detail.
The Institute anticipates that the Appraisal Committee will reconsider the evidence, which will consist of the new modelling and any other new evidence available at the time, in July 2001.
The Institute has not yet issued guidance on the use of interferon beta or glatiramer for MS and will not do so until later in 2001. As the process allows for further consultation the earliest the guidance could be issued is September 2001, this is a provisional date pending the outcome of the consultation.
Consultees in this appraisal are:
Copyright ©2001 National Institute for Clinical Excellence.