APPENDIX 29
Letter from the Deputy Editor, and Managing
Editor, Drug and Therapeutics Bulletin to the Chairman of the
Committee (NC 132)
HEALTH COMMITTEE INQUIRY INTO THE NATIONAL
INSTITUTE FOR CLINICAL EXCELLENCE (NICE)
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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