Memorandum by the Association of the British
Pharmaceutical Industry (NC 118)
SUMMARY OF KEY POINTS
The ABPI fully supports the objectives of NICE.
It has the potential to play a key role in improving the quality
of care in the NHS but NICE cannot achieve its objectives on its
The pharmaceutical industry has been in regular
dialogue with NICE to resolve many issues and progress has been
made. However, the process leading to selection of technologies
for appraisal and implementation of guidance post NICE review
are issues that cannot be addressed without action from the Department
of Health and NHS.
Analysis of prescribing data shows there are
still wide variations in uptake of medicines that have been appraised
by NICE: postcode prescribing still persists. Overall increases
in uptake have rarely resulted from NICE guidance.
NICE's own estimates of increased uptake in
its guidance predicted a total annual addition of £93 million.
This figure compares with an actual increased uptake of, at most,
£32 million, i.e. only a third. There is also evidence that
predicted savings accruing from NICE decisions have not been realised.
In addition, NICE is leading to reduced access
to modern effective treatments through a phenomenon known as "NICE
A major consideration is the NHS's capacity
to comply with NICE guidance and limitations of NHS ability to
redesign and adapt services to meet many priorities.
The Government's recent announcement requiring
HAs and PCOs to fund NICE recommendations is implicit confirmation
that they not currently being implemented satisfactorily. While
we very much welcome this move as a step in the right direction,
additional sufficient funding needs to be made available to enable
such compliance if "Peter is not going to be robbed to pay
Paul", diverting funding from other important areas of clinical
ABPI believes that NICE is being asked to focus
too much on technology appraisals and with little impact as a
result. We believe that the development of sound, evidence-based
clinical guidelines, which address the full range of care for
particular conditions, will improve the quality of NHS care far
more than a narrow assessment of the cost-effectiveness of individual
interventions and will have far greater influence.
Recommendations made by NICE in some circumstances
are being made too early on the basis of immature evidence. NICE
is currently relying heavily on a methodology that is based on
a one-size-fits-all measure of cost effectiveness. In practice
this has a profound impact on patients, who can be denied treatment
on the basis of theoretical assumptions.
Perceptions prevail among many stakeholders
that NICE is not independent of Ministerial intervention and is
not yet perceived as a genuine force for improving the quality
of NHS care rather than as a tool to control costs.
ABPI believes that NICE, as an important area
of health policy, should evolve with the help of an ongoing, systematic
and independent review.
1. THE ASSOCIATION
1.1 The Association of the British Pharmaceutical
Industry (ABPI) represents the majority of the companies in Britain
engaged in the research, development, manufacturing and supply
of prescription medicines. The ABPI brings together companies
producing such medicines, whether branded or generic, many smaller
organisations involved in pharmaceutical and bio-pharmaceutical
R&D, and those with an interest in the pharmaceutical industry
operating in the UK. ABPI member companies manufacture and supply
more than 80 per cent of the medicines prescribed through the
NHS and are major exporters to countries all over the world.
1.2 The pharmaceutical industry in the UK
is a world leader in medicines research, and patients in the UK
have the potential to benefit from this research by the early
introduction of new medicines developed in their own country.
2. THE ROLE
2.1 Annex 1 responds to the specific questions
posed by the Select Committee. The ABPI fully supports the objectives
of NICE to encourage faster uptake of effective new treatments,
to promote more equitable access to treatments, to improve the
use of NHS resources and to promote the longer-term interests
of the NHS in the development of innovative treatments for the
future. NICE has the potential to have a key role to play in improving
the quality of care in the NHS. The ABPI has sought constructive
dialogue with both NICE and the Department of Health (DH) to support
NICE in achieving its objectives.
2.2 NICE has an important and difficult
job to do. The postcode lottery of care still exists, and patients
in the UK have some of the poorest access to modern effective
treatments in Western Europe. The Wanless Report made some unflattering
international comparisons, concluding that the UK lags behind
other countries in the adoption and diffusion of new technologies,
and confirming that the uptake of new drugs is at best half of
that in Germany and a third of France. Another study, jointly
undertaken by the ABPI and DH, published in December 2001, shows
that in comparison with 12 countries in Europe, North America
and Asia, new medicines in the UK achieve only about a quarter
of the average level of international use one and three years
after launch. These facts highlight the need for NICE to encourage
the uptake of medicines in the UK.
2.3 NICE needs to be seen in context, as
part of a complex web of interweaving factors. NICE cannot achieve
its objectives on its own.
The policy framework within which
NICE operates is determined by Ministers, Parliament and the National
Assembly for Wales (NAW).
Ministers and the NAW determine the
work programme for NICE technology appraisals and clinical guidelines.
NICE's ability to develop guidance
and guidelines on clinical and cost effectiveness is also affected
the quality of the evidence base
other regulatory assessments
- medicines pass through several hurdles before becoming available
to patients, including assessment of safety, quality and efficacy
by the Medicines Control Agency (MCA).
other regulations, for example
the pharmaceutical price regulation scheme.
Having received NICE guidance, it
is the role of local NHS organisations to develop supportive infrastructure,
allocate funding and enable implementation by clinicians.
2.4 Many of the observations below, therefore,
identify weaknesses in the overall system, of which NICE is but
a part, rather than specific criticisms of NICE. The process leading
up to selection for technology appraisal and the post NICE review
implementation of guidance both have weaknesses that are beyond
the remit of NICE yet both have a critical influence on the value
and effectiveness of NICE itself. The pharmaceutical industry
has been in regular dialogue with NICE to resolve issues within
its own remit and progress has been made on many fronts but some
remaining issues cannot be rectified without action from the DH
2.5 ABPI believes that NICE is being asked
to focus too much on technology appraisals and with little impact
as a result. We believe that the development of sound, evidence-based
clinical guidelines, which address the full range of care for
particular patients in areas of high morbidity and mortality,
will improve the quality of NHS care far more than a narrow assessment
of the cost-effectiveness of individual interventions and will
have far greater influence. This concords with Professor Kennedy's
recommendation in his Bristol Inquiry report that NICE manages
a comprehensive programme of standard setting through the development
of clinical guidelines.
3. "NICE BLIGHT"
3.1 The very existence of NICE is leading
to reduced access to modern effective treatments through a phenomenon
known as "NICE blight". There are two kinds of blight.
The first is when Health Authorities (HAs) and Primary Care Organisations
(PCOs) hold back decisions on funding of a product on the NICE
work programme pending a decision by NICE, which is often issued
months or even years after grant of a licence. The second is when
HAs/PCOs hold back funding for new treatments that are not short-listed
for consideration by NICE on the assumption that they will at
some stage be the subject of an appraisal. This clearly runs against
the objective of NICE to bring patients faster access to modern
3.2 NICE blight is having a profound effect
on patients. Two examples illustrate a much bigger problem. The
first of these relates to a treatment, Visudyne, for age-related
macular degeneration, an aggressive disease that is the most common
cause of blindness in the elderly. Poor vision not only leads
to loss of quality of life and independence, it is also a major
cause of falls in the elderly, and blindness consumes considerable
health and social care resources. Some 4000 patients per year
could benefit from treatment; yet despite the facts that Visudyne
has been available in the UK for 16 months, that 100 hospitals
have the ability to offer Visudyne treatment, and that the DH
has issued guidance that NHS patients should be offered Visudyne
before NICE guidance is published, only 500 patients have received
treatment. Novartis, the licence holder for Visudyne, estimates
that 9000 patients in the UK will have been denied the opportunity
to have their vision saved by the time NICE's guidance is published.
3.3 Another important example of blight
is in the area of breast cancer. Herceptin has been licensed and
available to UK patients since September 2000. It represents a
major advance for the treatment of a particularly aggressive form
of breast cancer. In combination with chemotherapy, it can induce
disease remission and extend survival, and does so in a way that
enhances the quality of the life remaining to patients. NICE guidance
is still awaited. Since its launch, Herceptin has only been used
in a very small number of hospitals in the UK (with significant
postcode prescribing as a result). Even some of the largest cancer
centres do not make it routinely available to patients. A reason
given by Health Authorities and Primary Care Organisations for
non-funding of Herceptin is that they are waiting for NICE guidance.
3.4 These examples illustrate that the very
existence of a NICE technology appraisal process is having an
effect opposite to the very purpose of NICE. ABPI would like to
recommend that a robust mechanism be put in place to ensure that
patients are not denied access either because a treatment has
not been subjected to NICE appraisal or because an appraisal has
not yet been published.
OF NICE GUIDANCE
4.1 Even once NICE guidance is issued, implementation
is poor. Further detail on this is provided in response to the
Select Committee's questions in Appendix 1 (Question 3) and in
the examples shown in Appendix 2. ABPI would be happy to share
additional data with the Committee.
4.2 A major consideration is the NHS's capacity
to comply with NICE guidance. Clinicians and managers are being
deluged with directions and guidance on a daily basis, and have
many competing priorities, such as implementation of National
Service Frameworks, organisational change, and managing day-to-day
patient care. We would recommend that the Health Select Committee
consider the practical issues around implementation and the limitations
NHS organisations face in their ability to redesign and adapt
services to meet many priorities. This is especially true in the
field of cancer, where lack of staff is often given as a reason
for denying patients modern treatments.
4.3 If NICE is to recommend individual technologies,
adequate money needs to be provided to cover the funding of all
aspects of compliance with NICE guidance. The Secretary of State
is seeking to address non-compliance by the issue of Directions
set out in Statutory Instrument 2001/74. This is a step in the
right direction, but unless there is adequate funding an inevitable
outcome of the new directions will be that "Peter is going
to be robbed to pay Paul", diverting resources from other
important areas of clinical need. Whilst postcode prescribing
may reduce in areas covered by NICE, it is likely to increase
in areas not subject to NICE guidance.
5. THE TECHNOLOGY
5.1 While a change of focus should be the
priority issue as described in 2.5 above, NICE has been instructed
by the DH to concentrate the majority of its resources on new
medicines. ABPI has had discussions with the DH and NICE on the
process for the selection of topics for NICE appraisal, the decision
on when is the best time to conduct an appraisal, and NICE's appeals
process. We await the outcome of those discussions. We have also
made good progress through regular meetings with NICE to highlight
areas where process improvements can be made.
5.2 ABPI believes that NICE should only
appraise a new medicine where there is an adequate evidence base
to do so. At launch, the evidence base for a new medicine is founded
on a highly scientific clinical trials process, the results of
which are used as the basis for the granting of a product licence
by the licensing authorities, which make a rigorous assessment
of quality, safety and clinical efficacy. At this stage in a medicine's
life, there is a detailed understanding of its use only in a scientifically
restricted patient population.
5.3 NICE is examining clinical effectiveness.
Clinical efficacy and clinical effectiveness are different; the
latter is a broader assessment of whether a medicine helps people
and is usually demonstrated by examining evidence on the medicine
in routine clinical useuse that is prohibited until a product
licence is granted. In many cases, therefore, the true effectiveness
of a medicine cannot be assessed at the time of launch when there
has been little or no use in a "natural" clinical setting.
To fill this gap, NICE generally uses economic modelling to estimate
effectiveness on the basis of efficacy data. This is not an invalid
approach; however, it is important to remember that the quality
of a model is only as good as the assumptions upon which it is
based, which by definition are more uncertain the less that is
known about the product's use. This is particularly true where
innovative medicines lead to significant changes in the design
and delivery of care.
5.4 NICE rightly believes that it can only
have the confidence of its stakeholders if it delivers authoritative
guidance, which is based upon robust evidence. But frequently
NICE is being asked to appraise treatments before it is possible
to have an adequate effectiveness evidence base, with some decisions
therefore based on health economic models for which assumptions
are highly uncertain.
5.5 NICE and the DH are in a difficult situation:
ABPI understands that the NHS needs information on new products
at the time of launch, but we are concerned that recommendations
made by NICE in some circumstances are being made too early on
the basis of immature evidence. We would recommend that for those
treatments where an appraisal at launch is inappropriate, an information
bulletin be issued by a respected body skilled in doing this work.
Our recommendation would be that a format is adopted, based on
the current output of the National Prescribing Centre, and that
the medicine is made fully available to the NHS while better evidence
5.6 Issuing definitive guidance on a medicine
too early can have damaging consequences - it can deny opportunities
for discovery of valuable therapeutic potential in the form of
new uses. Indeed, as Gelijns et al commented in the New England
Journal of Medicine in 1998 (NEJM, 1998, Vol 339, No 10, pp693-698),
"Unanticipated uses of diagnostic and therapeutic interventions
are often identified many years after their introduction. Indeed,
widespread use is often an essential precondition for the identification
of new applications, and clinical practice itself is thus a particularly
important source of medical innovation." Examples of
important breakthroughs attributed to medicines initially used
for other indications are many, and include ACE Inhibitors and
beta blockers in the treatment of heart failure and acute myocardial
infarction, and antibiotics for the treatment of peptic ulcer
5.7 ABPI, DH and NICE have agreed that a
"one size fits all" approach to the timing of an appraisal
is not appropriate. We have recommended that a dialogue between
the manufacturer and a reformed Technologies Advisory Group take
place on when is the best time to appraise on a case-by-case basis.
ABPI and the DH have worked together to develop a checklist of
factors that could form the basis of this discussion. Our proposals
for a process to undertake this dialogue, and the checklist, are
given in Annex 3. We look forward to hearing how the DH
and NICE intend to incorporate these proposals into their processes.
6. DEFINING COST-EFFECTIVENESS
6.1 Determining cost effectiveness is a
challenging task. We would like to suggest that the Committee
consider whether the methods used to determine cost effectiveness,
and which drive recommendations as to whether a treatment should
be funded by the NHS, are appropriate. By assessing medicines
at launch, and basing many of its decisions upon models that are
based on theoretical assumptions for newly developed medicines
that have not yet found their place in clinical practice, NICE
is likely to reach false conclusions. NICE is currently relying
heavily on a methodology that is based on a one-size-fits-all
measure of cost effectiveness, an Incremental Cost Effectiveness
Ratio (ICER) based upon a cost per Quality of Life Year gained
(QALY), which attempts to apply the same parameters to a wide
range of health interventions and subjective outcomes such as
quality of life. While such a measure has a role, it is but one
of a number of parameters. Over-reliance on this single measure
may have a profound impact on patients, who can be denied treatment
on the basis of theoretical assumptions.
6.2 QALY values can change over time, as
more is learned about the optimum use of a medicine. The best
example of this is erythropoietin (EPO), a treatment for patients
with kidney failure, which improves red blood cell count, reduces
anaemia, reduces the need for blood transfusions and improves
patients' well being. At the time of EPO's launch in 1990, the
estimated cost per QALY was £103,000, a value which does
not represent cost effectiveness under NICE's methodology. Over
time, management of kidney failure using EPO has changed, as more
has been learned about the drug and benefits, including improved
quality of life for patients, have been found. Current estimates
of cost per QALY for EPO show a dramatic reduction from the initial
value to £3,000-9,000. If usage of EPO had been rejected
or highly restricted at its launch both patients and NHS would
have been the losers.
FOR NICE WORK
7.1 The DH has acknowledged that the current
procedures to select topics for NICE appraisal are unsatisfactory
and not transparent. In a presentation at the annual NICE conference
in December 2001, a DH speaker indicated that current selection
criteria are vague and open to broad interpretation, and the selection
process, including the reasons topics are chosen, needs to be
made clearer to stakeholders. ABPI concurs with these views and
believes that the skills base of the body that makes recommendations
to Ministers on topic selection (the Technologies Advisory Group
(TAG)) needs to be more appropriate for this complex task. It
is even unclear who sits on TAG. We believe that a broad range
of stakeholders should be represented, including industry. We
have discussed these points with the DH (see Annex 3) and
look forward to hearing their views.
8. ONGOING REVIEW
8.1 ABPI believes that NICE, as an important
area of policy, should evolve with the help of an ongoing, systematic
and independent review.
8.2The review should be open and inclusive of
all stakeholders, with appropriate consultation. It should examine
whether NICE is achieving its objectives, the impact it is having
on its stakeholders, and should make tangible recommendations
for improvement in consultation with those affected. This should
not detract from ongoing improvement in the working of NICE's
processes. Such a review should also examine implementation of
NICE guidance by HAs/PCOs once the new arrangements under SI 2001/74
have bedded down.
8.3 We would recommend that the review suggest
appropriate performance indicators, so that the progress of NICE
against its objectives can be continuously monitored, and that
the review should answer the following questions:
Is the existence of NICE adding value
to healthcare provision and benefits to patients?
Were the technologies chosen for
appraisal of most relevance to improving patient care?
Has NICE eliminated post-code prescribing?
Is there evidence of increased post-code
prescribing in areas not covered by NICE guidance?
How does the uptake of medicines
appraised by NICE compare with the recommendations in NICE guidance?
How does the uptake of innovative
medicines in the UK compare with those in comparable European
Does NICE have the confidence of
its stakeholders, including patients, professionals, the wider
NHS and the pharmaceutical industry?