The Velcade Three

Following our meeting on 24 January 2008, I promised to write to you to confirm our discussions and to provide written clarification of the points you raised. Please accept my apologies for the delay in responding but I have only recently returned from business in the US.

I have taken each issue in turn, which I hope you will find helpful.

Change of wording between the Appraisal Consultation Document (ACD) of June 4th 2007 and the Final Appeal Document (FAD).

The wording did change between the ACD and the FAD, and I very much regret the confusion this has caused. We changed the wording to make our recommendation clearer, not because the actual recommendation changed. We realised that the wording on the ACD led to misinterpretation, and rectified this with the revised wording in the FAD.

The intention of the committee was always to issue positive recommendations of bortezomib only for people who have experienced a first relapse, and throughout this appraisal our recommendations have only applied to this group of patients. The supporting documents for the ACD shows that the Appraisal Committee’s wish to allow the use of bortezomib only in those patients at first relapse; this is what the evidence base allowed for, what the responder scheme was calculated upon, and finally the rebate agreed for by the Department of Health and the manufacturer.

Studies considered, and evidence supporting use only at first relapse.

As part of the development process for the guidance we commissioned the National Coordinating Centre for Health Technology Southampton, Southampton Health Technology Assessment Centre (SHTAC) to gather and review all available evidence relating to the effectiveness of bortezomib at first relapse. This reflected the remit passed to us by the Department of Health. We have published their findings on our website at: [link]

We have also published the other evidence we considered, such as the manufacturers submission and the expert evidence statements, and you can find these at: [link]

Following the appeal in 2007, we requested further analysis on the cost-effectiveness of bortezomib at first relapse, and these documents are all available on our website at: [link]

Difference between the schemes that the manufacturer put forward, and the recommendations that NICE’s independent appraisal committee made.

The scheme put forward by the manufacturer proposed that all suitable patients would be offered treatment. Patients showing a minimal or better response to the drug would be kept on it and funded by the NHS. Patient showing little or no response would be taken off the drug and the drug costs refunded by the company.

In advising on the use of the drug and the proposed scheme, our independent advisor committee recommended that the NHS should only pay for those patients classified as having a full or partial response. The cost of the drug for ‘minimal responders’ should be refunded by the manufacturer, and ‘minimal responders’ should not continue with treatment after four cycles. The committee based their decision on the evidence presented to it in terms of time in to progression and overall survival in people only a minimal response compared with people achieving complete or partial response. The Committee concluded that, in the absence of evidence to show that outcomes are comparable for people with different degrees of initial response a decision to include people with a minimal response could not be supported.

Ampule size

You raised concerns about the size of ampule used and suggested that if the ampule was smaller, and only contained the amount needed for a single dose, this could save money and reduce the cost. Unfortunately this is not something which NICE can comment on. I suggest taking this issue up directly with the manufacturer.

Revamid

I can confirm that we do not have Revamid in our current work programme. If you think we should be looking at it, you can put this forward as a topic suggestion. You can find out more about our topic selection process on our website at: [link]

I hope this written clarification if helpful to you. I do appreciate that the recommendations we made in the guidance were not what you had hoped for. When we review our guidance we will consider any new evidence about the clinical and cost-effectiveness of bortezomib, including that from the response-rebate scheme and, as is the case for all our appraisals, the views of patients and their carers.