Annex 1
1. INTRODUCTION
1.1 The principle of a national decision-making
body producing clear guidance on the use of evidence-based interventions
was seen to be a sensible approach to eliminate post-code prescribing.
It was recognised that a national decision was sometimes necessary
for the use of some expensive pharmaceutical agents and/or highly
emotive areas of prescribing where the evidence-base was limited
but patient expectations were high. There were also the perceived
advantages that there would be less duplication of effort across
the country in terms of Health Technology Assessments and an improved
prioritisation system for those technologies to be funded. It
was assumed that the guidance would inform national and local
budget-setting processes to ensure adequate service provision.
1.2 Specific concerns have been raised by
local general practitioners following the publication of a number
of the guidance documents and the recent change to the National
Health Service Act 1977 making implementation of NICE guidance
mandatory within a limited timescale.
2. PROVISION
OF CLEAR
AND CREDIBLE
GUIDANCE
2.1 Clarity—guidance is presented
in a concise manner and is, in general, relatively clear on the
use of individual agents or drug groups when considered in isolation—eg
riluzole, drugs to treat mild to moderate Alzheimer's disease,
methylphenidate. What is less clear is the use of some pharmaceutical
interventions in relation to conventional/alternative agents or
treatment regimens available, or where the agent should be considered
as part of an overall treatment strategy. Examples include:
2.1.1 Zanamivir in the treatment of influenza—compared
to placebo not to the current practice of rest, fluids and simple
analgesia. The use of amantadine was also not considered for this
indication.
2.1.2 Selective Cox-II inhibitors in treatment
of rheumatoid arthritis and osteoarthritis—not compared
to ibuprofen 400mg three times a day, or a "lower risk"
anti-inflammatory agent co-prescribed with gastroprotection.
2.1.3 Sibutramine and orlistat for treatment
of obesity in adults—their place in an overall obesity strategy
was unclear.
2.2 Credibility—many of the concerns
expressed by local GPs have been with regard to the clinical and
cost-effectiveness of the technologies appraised, these are outlined
in more detail in paragraph 5. Other specific concerns raised
are in relation to:
2.2.1 Intervention recommended despite limited
diagnostic accuracy—zanamivir to treat influenza—guidance
recommended that clinical guidelines for the diagnosis of influenza
should be developed to improve diagnostic accuracy and enable
effective targeting of appropriate therapy.
2.2.2 Prescribing guidance in conflict with
the Summary of Product Characteristics (SPC)—zanamivir to
treat influenza —when prescribing any new drug with limited
safety data, prescribers are recommended to prescribe only within
the parameters of the current SPC. This was not the case with
the guidance issued. This concern would appear to have been addressed
in more recent guidance—sibutramine for treatment of obesity.
2.2.3 Safety concerns—zanamivir to
treat influenza—Glaxo Welcome revised warnings during July
2000 in the US; zanamivir should not generally recommended for
treatment of influenza in patients with known airways disease.
Despite this and limited evidence of clinical effectiveness, these
patients were considered to be appropriate candidates for therapy
in the NICE guidance. Locally the decision was made that the supply
of zanamivir via a Patient Group Direction was inappropriate due
to limited clinical and safety data.
2.2.4 The implications of guidance on the
workload in primary care—zanamivir to treat influenza—increased
pressure on access to GP services, potential for increased consultations
due to the common cold. Sibutramine and orlistat for the treatment
of obesity—lack of clinicians specialised in the treatment
of obesity, pressure to prescribe falls to GP.
2.2.5 Concerns raised over data suppression
and selective reporting of results by one manufacturer—use
of selective Cox-II inhibitors for the treatment of rheumatoid
arthritis and osteoarthritis.
2.2.6 Disparity between the translation
of the Health Technology Assessment report to guidance issued
by the Appraisal Committee—riluzole for the treatment of
Motor Neurone Disease.
2.2.7 Emphasis of unpublished data on conclusions
of Health Technology Assessment reports and subsequent appraisal—zanamivir
to treat influenza
2.3 Recommendations for consideration:
2.3.1 Where necessary, develop clinical
guidelines in conjunction with guidance in order to place the
technology into an overall treatment strategy to encourage appropriately
targeted therapy thereby maximising health gain. Consider all
treatment options for the indication.
3. HAS ENDED
CONFUSION BY
PROVIDING A
SINGLE NATIONAL
FOCUS
3.1 Unfortunately not. NICE guidance has
become an "additional" national focus for pharmaceutical
and non-pharmaceutical technologies alongside National Service
Frameworks (NSFs) and the numerous national and locally agreed
treatment guidelines. As of January 2002, mandatory NICE guidance
has effectively become another "must do" that competes
with other national policies, including clinical governance and
waiting lists and access targets, in terms of implementation and
priority for resource from the unified allocation. By making NICE
guidance mandatory, there is also the potential to divert funds
from other technologies with a sound evidence-base and improved
health gain but which are not to be reviewed by NICE and are effectively
not a "must do". In addition to this local flexibility
is lost with regard to planning service provision to ensure appropriate
prescribing eg development of a strategy to manage obesity. GPs
will be forced to fund the prescribing before support services
are in place.
3.2 In an environment where there are numerous
policy documents with limited funding available, it is necessary
to "prioritise the priorities". Inevitably this will
result in a postcode service provision through either the decision
not to fund a drug therapy or the need to suspend services in
order to fund an overspend. Locally, the latter is currently the
case.
3.3 There is a degree of confusion locally
over the place of NICE clinical guidelines in relation to NSFs
eg Post-MI clinical guidelines versus NSF for Coronary Heart Disease,
Mental Health NSF local treatment guidelines for the management
of schizophrenia and depression versus future NICE guidelines.
In addition to this, guidance issued is often in conflict with
the Drugs and Therapeutics Bulletin (zanamivir, pioglitazone,
rosiglitazone and sibutramine), a publication held in high regard.
3.4 Recommendations for consideration:
3.4.1 Publish guidance that is already pre-prioritised
and includes more realistic timescales. For those interventions
that require immediate implementation (within 6 months), funding
should be allocated in year. Guidance allowing longer-term implementation,
reflecting the health gain achieved from the intervention, would
enable planning of services and an assessment of the budgetary
implications. Although this would have the potential to result
in postcode prescribing, it would allow some local flexibility
to reflect local population health needs and services.
3.4.2 If national policy (NICE and NSFs)
continues to be issued with targets for implementation then this
must be reflected by realistic budgetary uplift to the unified
allocation.
4. PROVISION
OF GUIDANCE
THAT IS
LOCALLY OWNED
AND ACTED
ON IN
THE RIGHT
WAY
4.1 It is widely accepted that ownership
of guidelines is highest in those who have been involved in the
development of such guidance. For a number of years, the local
Prescribing Committee has brought together general practitioners,
public health specialists, pharmaceutical advisers and secondary
care consultants to appraise the evidence base of chosen drugs
and plan implementation. Whilst it is recognised that national
guidance is a sensible approach to avoid duplication of effort,
some loss of local ownership is inevitable.
4.2 Whether NICE guidance has been acted
upon in an appropriate manner will obviously depend on the person/organisation
asked ie NICE or a general practitioner with overall clinical
responsibility for prescribing.
5. IS ACTIVELY
PROMOTING INTERVENTIONS
WITH GOOD
EVIDENCE OF
CLINICAL AND
COST-EFFECTIVENESS
SO THAT
PATIENTS HAVE
FASTER ACCESS
TO TREATMENTS
KNOWN TO
WORK
5.1 As mentioned previously there have been
concerns raised locally regarding the clinical significance and
quality of evidence on which some of the guidance has been based
and how transferable these results are to general practice.
5.2 Zanamivir to treat influenza:
5.2.1 The initial Health Technology Assessment
report concluded that there was an insufficient evidence base
in "at risk" patients to recommend the routine use of
zanamivir. The data was suggestive of a benefit but did not reach
statistical significance.
5.2.2 An additional submission, in confidence,
studied the use of the drug in only one group of "at risk"
patients, those with asthma and COPD. The primary outcome measure,
time to alleviation of symptoms, did not reach statistical significance
when analysed by intention to treat. Despite this and safety concerns
highlighted in the US for this patient group, NICE guidance endorsed
the use of zanamivir in such patients.
5.2.3 The majority of patients in the trials
considered were under the age of 65 years. However, zanamivir
was recommended for use in the over 65 year age group.
5.2.4 Patients participating in the trials
presented well within 48 hours duration of symptoms, it is unclear
whether this would happen in general practice.
5.2.5 Trials documented a high prevalence
of influenza (unclear in supplemental report) and low vaccination
rate, again questioning the validity of results outside the trial
environment.
5.2.6 The overall reduction in duration
of symptoms was small and the reduction in use of antibiotics
(of borderline significance) was seen as an inappropriate indicator
for assuming a reduction in hospital admissions and death.
5.3 Orlistat and sibutramine in the treatment
of obesity:
5.3.1 Although the trials have shown statistically
significant differences in weight loss compared to placebo, the
mean differences between treatment groups were sometimes small
and therefore may not be clinically significant. This may also
apply to secondary outcomes measured eg changes in lipid levels
and indicators of glycaemic control. It is therefore left to the
prescribing GP to decide whether these differences are of clinical
significance to their patients.
5.3.2 A positive result reported in one
trial may have been over-emphasised due to the failure to analyse
by intention-to-treat.
5.3.3 Both drugs have not been shown to
be effective and safe in the longer-term.
5.3.4 Weight loss following cessation of
therapy is usually regained over time and therefore the use of
anti-obesity drugs may detract from patients making long-term
healthy lifestyle changes.
5.3.5 Many contraindications, potential
drug interactions and stringent requirements for monitoring make
sibutramine difficult and impractical to use—Drugs and Therapeutics
Bulletin 2001; 39(12): 89-91.
5.4 In terms of cost-effectiveness of guidance
issued, it is recognised that pharmacoeconomic analysis is a relatively
new science and is only as robust as the data included. Much of
the evidence on cost-effectiveness of newer interventions remains
inconclusive due to insufficient information and therefore it
is recommended that these data models be viewed with caution.
Despite this, the Institute has issued guidance that requires
vast sums of investment for drugs where the cost-effectiveness
of such interventions is uncertain (riluzole, zanamivir, drugs
to treat Alzheimer's disease).
6. INDEPENDENCE
OF NICE
6.1 It is unclear from the guidance documents
whether Appraisal Committee members have interests to declare
and, if they do, there is no indication as to how the Institute
deal with these potential conflicts of interest or if the individual
is distanced from the appraisal process in any way.
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