Select Committee on Health Appendices to the Minutes of Evidence


Letter from the Deputy Editor, and Managing Editor, Drug and Therapeutics Bulletin to the Chairman of the Committee (NC 132)


  We write on behalf of Consumers' Association's Drug and Therapeutics Bulletin (DTB) in relation to evidence given to the Health Committee by the National Institute for Clinical Excellence (NICE) on 30 January 2002.

  1.  In both written and oral evidence given to the Health Committee, DTB indicated that it had not received any formal response from NICE to a detailed report on the Institute's revised guidance on use of zanamivir (Relenza), a treatment for influenza. Having listened to the oral evidence NICE gave to the Committee, we are unclear as to whether the Institute was accepting or denying that it had not responded to the report. With this in mind, we would like to put on record the sequence of relevant correspondence between DTB and the Institute.

  1.1  DTB circulated a draft of an article entitled Why not zanamivir? to NICE (and commentators) in late January 2001. The Institute sent a reply to this draft on 29 January 2001 (Appendix 1); this letter included both comments about the draft itself and criticisms of the role of DTB's editor in producing the article. It is crucial to note that DTB has received no further correspondence on zanamivir from the Institute.

  1.2  In the course of producing Why not zanamivir?, DTB became aware of several issues of concern (in addition to those discussed in the DTB article) relating to the revised NICE guidance. This led DTB to compile a 10-page report detailing these issues (Appendix 2). This report was not completed until 12 February 2001; on 13 February, the Institute was sent (and acknowledged receipt of) a copy of the report along with a pre-publication final copy of Why not zanamivir?, which was published on 15 February 2001 (Appendix 3). Accompanying the report was a note inviting the Institute to discuss DTB's position (Appendix 4).

  1.3  On 4 April 2001, the editor of DTB (in the absence of any further correspondence from NICE) wrote to the Institute, primarily to address the Institute's criticisms of his role in the production of Why not zanamivir? (Appendix 5). He enclosed with this letter another copy of the 10-page report on the revised NICE guidance; to date, DTB has received no formal response to this second copy of the report.

  2.  In oral evidence given on 30 January 2002, NICE suggested that its guidance on medicines has always been in keeping with the manufacturer's recommendations as detailed in the summaries of product characteristics for such treatments. This position seems at odds with the following:

  2.1  The revised NICE guidance on zanamivir (Relenza) recommends the use of the drug in at-risk adults with suspected influenza when influenza is circulating in the community. This at-risk group includes those with "chronic respiratory disease (including chronic obstructive pulmonary disease and asthma) requiring regular medication" and "immunocompromised" patients. The current summary of characteristics for zanamivir offers the following warnings about use of the drug in such people: "Due to the limited number of patients with severe asthma or with other chronic respiratory diseases, patients with unstable chronic illnesses or immunocompromised patients who have been treated, it has not been possible to demonstrate the efficacy and safety of Relenza in these groups." It also states that "Due to the limited experience, patients with severe asthma require a careful consideration of the risk in relation to the expected benefit, and Relenza should not be administered unless close medical monitoring and appropriate clinical facilities are available in case of bronchoconstriction." The summary of product characteristics also includes the following safety advice: "Should zanamivir be considered appropriate for patients with asthma or chronic obstructive pulmonary disease, the patient should be informed of the potential risk of bronchospasm with Relenza and should have a fast acting bronchodilator available. Patients on maintenance bronchodilating therapy should be advised to use their bronchodilators before taking Relenza". Neither the revised NICE guidance on zanamivir nor its accompanying patient information makes any reference to these safety concerns or recommendations as described in the summary of product characteristics.

  2.2  The NICE guidance documents on rosiglitazone and pioglitazone state clearly that each of these drugs "should be used in accordance with the manufacturer's recommendations." However, both documents contradict this advice by advocating uses outside the licensed indications detailed in the summary of product characteristics for the two drugs. The manufacturers advise that pioglitazone and rosiglitazone are "indicated only in oral combination treatment of type 2 diabetes mellitus in patients with insufficient glycaemic control despite maximal tolerated dose of oral monotherapy with either metformin or a sulphonylurea"; they also advise that the drugs can be given in combination with the drug metformin only in obese patients, and in combination with a sulphonylurea drug in patients who are intolerant of metformin or for whom this drug is contraindicated. Going beyond these licensed indications, the NICE guidance suggests that patients whose blood glucose remains high despite an adequate trial of metformin plus sulphonylurea combination therapy "may be offered pioglitazone in combination with metformin or sulphonylurea as an alternative to injected insulin." The NICE guidance on rosiglitazone offers a stronger recommendation, suggesting that such patients "should be offered rosiglitazone combination therapy as an alternative to injected insulin." We should point out that, in citing both of these recommendations, paragraph 7.1.1 of our written evidence to the Committee slightly misquoted the relevant NICE guidance documents. (For the Committee's information, we enclose another copy of our written evidence with the appropriate amendments to paragraph 7.1.1; Appendix 6). Please accept our apologies for these discrepancies, which do not affect the central point of paragraph 7.1.1: neither recommendation from NICE is among the licensed indications in the summaries of product characteristics for pioglitazone and rosiglitazone. It is worth noting that the British National Formulary includes the following cautions against these NICE recommendations: "Inadequate response to a combination of metformin and sulphonylurea may indicate failing insulin release; the introduction of pioglitazone or rosiglitazone has a limited role in these circumstances and insulin treatment should not be delayed. Long-term benefits of the thiazolidinediones (ie pioglitazone and rosiglitazone) have not yet been demonstrated."

  2.3  The NICE guidance on use of proton pump inhibitors includes the following recommendations: "For patients with a documented non steroidal anti-inflammatory drug (NSAID)-induced ulcer, who must unavoidably continue with NSAID therapy (eg those with severe rheumatoid arthritis), an acid supressor, usually a protein pump inhibitor (PPI), should be prescribed. After the ulcer has healed, the patient, where possible, should be stepped down to a maintenance dose of the acid suppressor." Whatever the basis and merits of this advice to reduce the dose, it does not appear in the summaries of product characteristics of the proton pump inhibitors specifically licensed for treating patients with NSAID-induced ulcers. Again, it is worth noting that the British National Formulary offers a caution against the NICE advice: "In patients who need to continue NSAID treatment after an ulcer has healed, the dose of proton pump inhibitor should normally not be reduced because asymptomatic ulcer deterioration may occur."

  Appendices not printed

4 February 2002

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