2002/025 Reactive press release - appraisal of imatinib for chronic myeloid leukaemia

NICE 2002/025

Issued: 15 May 2002

REACTIVE PRESS RELEASE

Appraisal of imatinib (Glivec) for chronic myeloid leukaemia

One of the reasons NICE was established to look at technologies where there is genuine uncertainty regarding their value and to end this uncertainty by providing clear authoritative guidance for the NHS in England and Wales.

The Department of Health and the National Assembly for Wales have asked the National Institute for Clinical Excellence (NICE or the Institute) to conduct an appraisal of imatinib for chronic myeloid leukaemia and provide clear guidance to the NHS as to where the evidence suggests it should be used.

NICE has not yet issued guidance on the use of imatinib for chronic myeloid leukaemia to the NHS. The guidance is in an early stage of development and has not been finalised.

The process NICE follows to develop its guidance involves patients, health professionals, the manufacturers of the technology and an independent advisory committee. It provides organisations representing patients, professionals and manufacturers with the opportunity for consultation and appeal. In line with the Institute's commitment to transparency, consultation documents are published on the NICE web site at www.nice.org.uk.

In developing its guidance NICE commissions an independent review of the published evidence and the manufacturers own data, this 'Assessment Report', together with evidence submitted by patient/carer organisations, health professionals and manufacturers, is considered by an independent appraisal committee. Patient/carer and professional representatives, nominated by their own organisations, attend and inform the committee meeting.

After their first consideration of the evidence the independent appraisal committee consult on their initial thoughts with all of the stakeholders including the patient/carer and professional groups. This consultation document is called an ACD (Appraisal Consultation Document). The ACD is also published on the NICE web site and it is important to note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in it are preliminary and may change after consultation.

The feedback from the consultation process is considered by the appraisal committee at a further meeting and they then draft a further document which is sent to NICE. NICE considers the committee's recommendations, and sends their proposed guidance to the same stakeholder groups who have the opportunity to appeal. If there are no appeals this guidance is issued to the NHS.

Andrew Dillon, NICE Chief Executive and Executive Lead for the appraisal of imatinib said: "NICE have not made any recommendations on the use of imatinib. In fact we are weeks away from even receiving the independent appraisal committee's final thoughts. As a part of the NHS we are committed to transparency, and we publish in full the committee's initial evaluation of the evidence so that people can send us their views.

"We are quite clear that the document contains preliminary views that may change after consultation. From their consideration of the evidence so far it appears that the Committee are minded to advise NICE that: imatinib should be recommended for the treatment of patients with the accelerated phase of chronic myeloid leukaemia (CML), but that the evidence does not support the use of imatinib for the routine treatment of people in the chronic or blast-crisis phase. The Committee are also considering recommending to NICE that until adequate clinical and cost effectiveness data become available, the use of imatinib for these indications should be restricted to ongoing or new clinical trials. This would mean that patients would be fully informed of the current evidence supporting the technology, and that patients and the NHS together would be collecting data to help end these uncertainties"

Ends

Notes for editors
1. The appraisal committee's consultation document is published on the NICE web site http://www.nice.org.uk/article.asp?a=31915. Note that this document does not constitute the Institute's formal guidance on this technology. The recommendations made in Section 1 are preliminary and may change after consultation.
2. Patients and professionals can send the appraisal committee their views on the document through the web site.
3. Closing date for comments is Tuesday 4 June 2002 and the Appraisal Committee will meet again on Thursday 13 June 2002, they will prepare the final draft guidance that will be sent to consultees to consider whether they wish to appeal. The final draft guidance will also be published on the NICE web site.
4. In summary the considerations section of the consultation document explains that:
• The Committee reviewed the evidence on both the clinical effectiveness and the cost effectiveness of imatinib. They have considered evidence from people with CML, those that represent them, and clinical experts, on the nature of the condition and the value placed by users on the effects of imatinib treatment. The Committee was also mindful of the need to ensure that its advice took account of the efficient use of NHS resources.
• The Committee carefully considered the indirect comparisons (made by the Group that conducted the independent assessment of the published evidence and manufacturers submissions). between the effectiveness of imatinib and other therapies for CML. The Committee were aware that indirect comparisons of this kind are not an ideal way of assessing comparative effectiveness, as they are very prone to bias. However, the Committee were also mindful of the current absence of Randomised Control Trial (RCT) data on imatinib and of the difficulties of undertaking RCTs in this clinical field.
• In the chronic phase of CML, the Committee concluded that there was not enough evidence to be certain of the effects of imatinib therapy on overall survival. Most of the evidence presented was based principally on intermediate outcomes. The Committee was not convinced that these intermediate outcomes could be used as robust surrogates for long-term survival of patients in chronic-phase CML who were interferon resistant/intolerant and were treated with imatinib.
• For the chronic phase, the Committee concluded that the effectiveness of imatinib treatment in terms of survival at 1 year did not seem to differ from the effectiveness of other treatments, in particular hydroxyurea, which would be the usual treatment in this interferon refractory/intolerant group. However, HR and CR were better with imatinib than with other treatments.
• Bearing in mind all the limitations of indirect comparisons made by the Assessment Group, the Committee accepted that overall the evidence base suggested a survival advantage for imatinib over alternative treatments in the accelerated phase. This advantage was also apparent in the blast-crisis phase, though the magnitude of the advantage was smaller. In addition, expert view presented to the Committee indicated that the observational evidence for this survival advantage in the blast-crisis phase was less robust.
• The Committee accepted that the current evidence on the effectiveness of imatinib may suggest a survival benefit with imatinib treatment in the chronic and blast-crisis phases. However, the Committee concluded that, overall the currently available evidence of the clinical and cost effectiveness of imatinib was not sufficient to recommend its routine use for either of these indications.
• The Committee considered that the survival advantage in patients with accelerated phase of CML demonstrated by the indirect comparisons of imatinib with other treatments was sufficient to establish that the use of imatinib in accelerated phase CML was likely to be cost effective.
• The Committee was aware of an ongoing trial, which investigates the efficacy of imatinib versus IFN-a combined with cytarabine in newly diagnosed, previously untreated CML patients in the chronic phase. However this trial is not relevant to the remit of this appraisal, as imatinib is not currently licensed for first-line use in chronic-phase CML.