On 22 Jan 2009, at 15:25, David Bevan wrote:
NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE
Single technology appraisal (STA)
Cetuximab for the treatment of metastatic and/or recurrent squamous cell carcinoma of the head and neck
Dear Consultees and Commentators
You are invited to comment on the attached appraisal consultation document (ACD) for the above appraisal. A hard copy of the ACD and evaluation report is being sent to you.
Following instructions of the Court of Appeal we will now distribute executable models to consultees and commentators in all technology appraisals. We will release the model if it does not contain information that was designated confidential by the model owner, or if the confidential material can be redacted by the model owner without producing severe limitations on the functionality of the model.
The economic model for this appraisal was developed by the manufacturer. We are still discussing with Merck Serono whether it is possible to release their model. If you would like to request a copy of this model, so that you can comment upon it, please contact the project manager for this appraisal.
The Appraisal Committee is interested in receiving your comments on the ACD under the following general headings.
i) Do you consider that all of the relevant evidence has been taken into account?
ii) Do you consider that the summaries of clinical and cost effectiveness are reasonable interpretations of the evidence, and that the preliminary views on the resource impact and implications for the NHS are appropriate?
iii) Do you consider that the provisional recommendations of the Appraisal Committee are sound and constitute a suitable basis for the preparation of guidance to the NHS?
iv) Are there any equality related issues that need special consideration that are not covered in the ACD?
If you wish to comment on the evaluation report, please do so under a separate heading from your comments on the ACD.
We prefer to receive comments in electronic format, either by email to email@example.com or on compact or floppy disk. Please use Microsoft Office software products. Comments sent by post should be addressed to Jeremy Powell, Technology Appraisal Project Manager, at the above address.
Please note that your comments, along with a summary table of these comments and the action taken in response to them, will be released to consultees and commentators with the final appraisal determination (FAD) for this appraisal, and published on the Institute’s website.
In line with the Guide to Technology Appraisals Process (April 2004; sections 126.96.36.199 and 188.8.131.52), we do not expect you to submit any information which is commercial in confidence or academic in confidence with your comments on the ACD and evaluation report.
In the light of comments received, the Appraisal Committee will reconsider the ACD at a meeting on 3 March 2009. In order for your views to be included in the papers for this meeting, your comments must be submitted before 5pm on 19 February 2009.
The ACD and evaluation report will be posted on the Institute’s website on 29 January 2009. People who are not formal consultees or commentators for this appraisal can comment on the ACD through an email link on the website. However, we do not wish to receive comments from formal consultees and commentators via the website. Please send your comments directly to the Technology Appraisal Project Manager, either by email or by post.
I must emphasise that the documents enclosed with this letter, and their contents, are confidential until they are published on the Institute’s website. They are released to you only for the purpose of informing the Appraisal Committee’s consideration of this technology. Accordingly, the documents and their contents should only be divulged to those individuals within your organisation who need to see them to enable you to prepare your response. You must ensure that anyone who sees these documents is aware of their confidentiality.
The use of any information contained in the ACD to make investment decisions regarding any shares or other securities, or the passing of such information to someone else for such use, may constitute insider dealing, which is a criminal offence under section 52 of the Criminal Justice Act 1993. It may also be an offence to encourage someone else to deal in shares or securities, the price of which would be affected by the disclosure to the public of any information contained in the ACD.
Dr Carole Longson
Director, Centre for Health Technology Evaluation
Dear Mr Powell
Thank you for giving the Mouth Cancer Foundation the opportunity to respond to the Appraisal consultation document (ACD)
and the supporting Evaluation Report (ER)
on Cetuximab for the treatment of recurrent and/or metastatic squamous cell cancer of the head and neck.
The Mouth Cancer Foundation is disappointed with the preliminary recommendation of the Appraisal Committee not to recommend the use of Cetuximab in combination with platinum-based chemotherapy for the treatment of recurrent and/or metastatic squamous cell cancer of the head and neck.
Here are our comments on the ACD, in response to the following general questions:
i. i. Do you consider that all of the relevant evidence has been taken into account?
ii. ii. Do you consider that the summaries of clinical and cost effectiveness are reasonable interpretations of the evidence, and that the preliminary views on the resource impact and implications for the NHS are appropriate?
The Mouth Cancer Foundation considers that while the relevant evidence has been taken into account, the ERG's reasoning is faulty in its interpretation of the material it considered. It appears to be biased and adversarial to material evidence in the manufacturer's submission. Our more detailed comments, keyed to various sections in the ACD, are below:
3.12 As a patient organisation, we would be disappointed if the manufacturer had not submitted clinical evidence to support the use of cetuximab plus platinum-based chemotherapy for the first-line treatment of patients with recurrent and/or metastatic SCCHN if its evidence shows that the added use of cetuximab improves outcome. Why does the ERG consider this a problem?
The ERG states that patients in the EXTREME trial may be younger and fitter (indicated by very high KPS scores) than patients with recurrent and/or metastatic SCCHN in the UK. However, perusal of the age categories in Table 4.6 of participants in the EXTREME trial shows that 82.4% were <65 years and 17.6% were >65 years. We would not read this to mean patients in the trial were younger unless ERG thinks those between 55 -64 are young! Our experience with patient members reflects very much the picture that most Head and Neck cancer patients are not over 65 years. There are increasing numbers of cases of younger patients in their 20’s – 40’s with recurrent and/or metastatic SCCHN and they should have access to this treatment that can prolong their life.
The ERG also expresses concern that no evidence was provided by the manufacturer to support the use of cetuximab plus platinum-based chemotherapy in patients with recurrent and/or metastatic SCCHN who were not cetuximab-naive. Is ERG not aware that the use of cetuximab for Head and Neck cancer patients is relatively new and not routinely available to them? One should expect that most patients with recurrent and/or metastatic SCCHN would inevitably be cetuximab-naive.
The ERG highlighted that for several subgroups, including metastatic disease, there appeared to be no survival benefit from cetuximab plus platinum-based chemotherapy. The corollary is that there is a survival benefit for some subgroups. As a patient organisation, we expect the ERG to support the use of cetuximab for these groups of patients but do not find the ERG doing this.
3.13 We feel that the ERG's own critique of the economic model submitted by the manufacturer is badly flawed. The ERG felt that the average BSA value of 1.7m2 used was incorrect and worked out a higher mean BSA of 1.83m2 to use in their own model from a 'recent survey of three UK cancer centres.' The reference (no 20) given in its Evaluation Report is to a BMJ awareness article on "Squamous Cell Carcinomas of the Head and Neck", not a survey. However, the average UK male BMA is 1.98 (based on average height of 178cm and weight of 80kg) and the average UK female BMA is 1.72 (based on average height of 162cm and weight of 67kg) and the average of the two gives 1.85. However derived, we would like to know if this 'survey' was of (1) Head and Neck cancer patients and (2) whether their BSA was recorded after initial treatment (surgery, radiotherapy) or before. Our patient members' experience is that they lost a lot of their normal weight after surgery and radiotherapy and their BSA was most definitely below the average UK male or female figure.
3.14 We feel that for rarer cancers like recurrent and/or metastatic SCCHN where patient numbers are smaller, the ERG should not readily dismiss data presented by saying that "some of the subgroups were too small to yield reliable projection models, casting doubt on the credibility of the cost-effectiveness results for those subgroups." If so dismissed, rarer cancers will always be disadvantaged by the approach employed.
We submit that exploratory analysis done using the ERG model amendments on all the patient subgroups were flawed and its conclusion that the use of cetuximab plus chemotherapy may not be cost effective at any price is perverse.
iii. Do you consider that the provisional recommendations of the Appraisal Committee are sound and constitute a suitable basis for the preparation of guidance to the NHS?
The Mouth Cancer Foundation is of the opinion that the Appraisal Committee's decision is unsound especially when it says in the ACD that:
4.2 Overall the Committee accepted the evidence from the clinical specialists that the results of the EXTREME trial would be applicable to the UK population.
4.3 The Committee accepted that the trial demonstrated the efficacy of cetuximab plus platinum-based chemotherapy in patients with recurrent and/or metastatic SCCHN
4.4 The clinical specialists and a patient expert advised the Committee that the adverse events reported for the trial were consistent with those seen in clinical The practice where cetuximab had been used for locally advanced SCCHN and colorectal cancer.
The Mouth Cancer Foundation hopes that the Appraisal Committee's will reconsider its decision as the concerns raised by the ERG in relation to its exploratory analyses undertaken by the ERG using alternative assumptions and parameters in the economic model (see section 3.16) are flawed. It is important that the Appraisal Committee recognise that oncologists who provide the treatment always consider the individual patient on a case-by-case-basis as not all patients will be suitable for this treatment. We are not sure if the model of costs reflects this.
iv. Are there any equality related issues that need special consideration that are not covered in the ACD?
The Mouth Cancer Foundation considers that all the following criteria in the supplementary advice from the Institute when appraising treatments which may be life-extending for these patients with short life expectancy, and which are licensed for indications affecting small numbers of patients with incurable illnesses, were met:
o The treatment is indicated for patients with a short life expectancy, normally less than 24 months.
o No alternative treatment with comparable benefits is available through the NHS.
o The treatment is licensed, or otherwise indicated, for small patient populations.
o In addition, when taking these into account the Committee must be persuaded that the estimates of the extension to life are robust and the assumptions used in the reference case economic modelling are plausible, objective and robust.
o There is sufficient evidence to indicate that the treatment offers an extension to life, normally of at least an additional 3 months, compared with current NHS treatment.
We would argue that the criteria that the treatment offers an extension to life, normally of at least an additional 3 months, compared with current NHS treatment is only guidance and so should be applied flexibly. The Committee observed that the trial data suggest that cetuximab plus platinum-based chemotherapy extends survival relative to platinum-based chemotherapy alone. The EXTREME trial showed a statistically significant increase in median overall survival for cetuximab plus chemotherapy of 2.7 months or 81 days. It would be perverse if this treatment is denied just because patients in the trial failed to live for an additional 9 days longer in order to meet this criteria. This is the first time in 30 years that a study has shown an increase in overall survival for these patients. The Committee should consider that the magnitude of this benefit is in keeping with the spirit of the supplementary advice for consideration of life-extending, end-of-life treatments. The Committee should conclude that cetuximab for recurrent and/or metastatic SCCHN be recommended.
The Mouth Cancer Foundation feels that it is important that clinicians are able to provide this current treatment modality if they decided it as most appropriate for their patient.
Dr Vinod K Joshi
BDS(Singapore) DRDRCS(Edinburgh) FDSRCPS(Glasgow) FDSRCS(England)
Consultant in Restorative Dentistry
Restorative Dentistry Oncology Clinic
St Luke’s Hospital, Bradford
Pinderfields Hospital, Wakefield
Founder and Chief Executive
Mouth Cancer Foundation