Memorandum by Campaign for Effective and
Rational Treatment (CERT) (NC 23)
SUMMARY
The drug approval process in the UK is governed
by the Medicines Control Agency and by the European Medicines
Evaluation Agency. These assess new drugs in terms of safety and
efficacy. However, the role of the National Institute for Clinical
Excellence (NICE) is uncertain, with its added value to the statutory
processes being unclear. Errors and inefficiency in the application
of health economics by NICE appear to decrease any added value.
CERT sees NICE as a short-term political solution
to the rationing of new health technologies within the NHS. Only
by reforming NICE can the Government live up to its promise to
provide an improved health service. In its present state, NICE
acts as a barrier to reform. Any credible assessment body must
be separate from the Government and the Department of Health if
it is to be seen as truly independent and credible.
HAS NICE
ACHIEVED ITS
KEY GOALS?
To date it is unclear whether NICE has achieved
the key goals envisaged in a First Class Service, thus:
— is providing clear and credible
guidance;
— has ended confusion by providing
a single national focus;
— is providing guidance that is
locally owned and acted on in the right way;
— is actively promoting interventions
with good evidence of clinical and cost-effectiveness that patients
have faster access to treatment known to work.
NICE appears to be actively hindering widespread
introduction of pharmaceutical interventions in its extremely
lengthy and flaw-ridden processes.
NICE uses health economics to be able to arrive
at decisions on cost effectiveness. This application of health
economics is fundamentally flawed by the organisation's apparent
inability to understand the data presented by stakeholders. Likewise
the material that NICE collects through its own offices is equally
problematic.
The NICE process as it stands can add up to
three years before a drug becomes available for use. The lengthy
and flawed appraisal process, the inevitable round of appeals
that occur following problematic NICE decisions, and the further
delays as new drugs only become available once their cost is covered
in the next Health Authority spending cycle, only serves to limit
the availability of vital new therapies.
Whilst NICE guidance remains clear, the credibility
of most of the organisation's appraisals for oncology agents that
are still in the appeal process, is negligible. At first sight,
it would appear that NICE has issued many recommendations that
should have improved patients' access to new and innovative treatments.
However for those familiar with the process and the delays that
have beset a number of appraisals, this apparent success has come
about in spite of that process.
NICE activities only serve to increase confusion
around provision of new treatments. Health Authority decision-making
manipulates and uses NICE rulings to prevent full treatment provision.
In some instances, Health Authorities have made drugs available
to the very few whilst claiming full provision. Some Health Authorities
provide funding for treatment for agents still under review by
NICE whilst other Authorities do not, thereby perpetuating the
accusations of inequitable access within the NHS.
PROBLEMS AND
RECOMMENDATIONS
1. Flexibility and delay
It is clear from recent appraisals that NICE
has little or no flexibility in assessing the advantages of a
treatment regime over existing therapies. In a recent assessment
of a "salvage therapy" for cancer (ie a treatment that
is used after all other treatment options have failed), NICE initially
attempted to refuse the new treatment saying it should be referred
to a randomised, controlled clinical trial, despite the fact that
it would have been unethical to do so.
The NICE appraisals process needs more flexibility
- with its first full appraisal, NICE set the precedent of splitting
the guidance on the use of taxanes for ovarian and breast cancer.
The appraisal of drugs for colorectal cancer has been the subject
of successful appeals against the proposal by NICE to limit the
first-line combination use of these agents to clinical trials.
The proposal by NICE to support the use of monotherapy in second-line
treatment of colorectal cancer is understood to be uncontroversial,
yet NICE have refused to separate out this section of the guidance.
As a result, thousands of patients with colorectal cancer continue
to be denied access to drugs that could extend their survival
by several months.
NICE also appears to move slowly. The whole
of the appraisal process is extremely laborious, taking at least
11 months from commencement to completion. However, experts have
commented that some appraisals of existing therapies could be
made in an afternoon by those that understand the particular field
of medicine and the evidence base from the relevant clinical studies.
There have been unplanned and unexplained delays
in some of the appraisals conducted by NICE. For instance, the
appraisal of Herceptin has been inexplicably delayed by six months,
even though this drug can have a dramatic effect on the survival
of women who have an aggressive form of breast cancer. How many
women with breast cancer have died prematurely as a result of
this delay alone?
There have also been unacceptable delays in
announcing the result of appeals and for setting dates for reassessment
by the Appraisals Committee following successful appeals. For
example, in the appraisal of treatments for colorectal cancer,
the appeal was held on 23 May 2001, yet it took until 2 July -
5 weeks and 5 days - for NICE to announce that this appeal had
been successful. Furthermore, the next Appraisals Committee meeting
to review the draft Guidance was held on 6 November; a delay of
almost six months. What was the reason for such an inordinately
long delay and how many patients with colorectal cancer have died
prematurely as a result of this delay?
There have also been delays in uncontested or
uncontroversial parts of an appraisal. This may not matter when
NICE appraises new treatments before the approval of a licence
(although there have been very few of these parallel reviews conducted),
but it is causing enormous problems for treaters who are already
using the medicines.
Health Authorities are also telling doctors
that they will refuse funding for drugs that doctors are already
using until NICE recommendations are published. This is not, however,
a problem with NICE but rather a criticism of the Health Authorities
using the NICE process as an excuse to curtail funding. In some
cases, doctors have been using the drugs for several years before
they were referred to NICE for appraisal. Despite having been
proven to be more effective than alternative treatments during
a NICE appraisal, Health Authorities are exerting pressure to
limit or prevent their use. Doctors are placed in a very difficult
position, perhaps even having to tell patients that they can no
longer treat them with their drug/s of choice.
Recommendations
— It is essential that time-scales
for appraisals are established to minimise delays.
— The results of appeals should be
announced promptly.
— Re-assessment following a successful
appeal should be conducted without undue or unnecessary delay.
— Where appropriate, NICE should look
to make more use of fast track procedures, particularly for treatments
that are believed to improve survival.
2. REFUSAL OF
NICE TO CONSIDER
KEY STAKEHOLDER
EVIDENCE
The method by which NICE accepts or refuses
the evidence and suitability of stakeholders appears arbitrary.
Lip service is given to incorporating the knowledge,
concerns and expertise of specialist health charities and patient
advocacy groups. NICE has failed to identify relevant patient
advocacy groups as being stakeholders in a particular appraisal
despite their expertise in representing the patient population
affected. Specialist doctors are also marginalised, with either
gross under-representation or a failure to represent at all the
concerns of the expert clinical community on the NICE assessment
panel.
The problems of expert witness's representation
in the review process are further compounded by systematic failures
in the administrative ethos of NICE. We are aware of several organisations
and individual experts who have not received correspondence from
NICE inviting them to participate. For example, NICE did not contact
the two specialist colorectal cancer patient advocacy groups in
the recent appraisal of colorectal drugs.
These problems of process may reflect problems
of resourcing of NICE. CERT shares the concern of other stakeholders
that patients' experience should play a greater role in the NICE
appraisal process.
NICE do not let health charities and patient
advocacy groups hear how their evidence is taken into account
by the Appraisals Committee in its deliberations, yet such transparency
would go a long way to reassure stakeholders of their contribution.
Recommendations
— It is in NICE's interest to ensure
that their processes and procedures always stand up to scrutiny.
To ensure this, full consideration must be given to stakeholders'
evidence in a much more inclusive way than at present.
— NICE could ensure that the deliberations
of the Appraisals Committee are open and transparent to all stakeholders.
— Many patient groups that possess
some of the most relevant patient-centred evidence are being denied
the opportunity to state the case on behalf of patients and their
families. Full account should be made by NICE of all those patient-centred
groups who have an interest in a therapeutic area.
— Furthermore, there are many other
professional organisations that work with the medical profession
who can provide a general overview of the position within health
care. Similarly these organisations should not be denied the opportunity
to present evidence to NICE without compelling reasons.
3. EXPERTS
This is perhaps one of the crucial areas in
the operation of NICE.
At the moment, a single expert is recruited
by NICE to advise an Appraisals Committee comprised of clinicians
and other individuals with no experience in the specific clinical
area. But how is the expert identified, and how does NICE ensure
that the clinician represents the expert opinion on current best
practice? Other problems relate to the Appraisal Committee trying
to interpret clinical trials in an area that is not their speciality,
rather than having expertise in the area being appraised.
We have heard of occasions when NICE have telephoned
experts to ask whether they would be available to advise the Appraisals
Committee on a particular date in two or three weeks time. When
the experts have said that they were not available on a particular
date, NICE have simply advised that they would find someone else.
This leads people to the conclusion that NICE are working at short
notice through a list of people to see who might be available
on a particular date, rather than identifying the experts in the
field with sufficient warning to ensure their attendance.
Medical consultants have said that they find
it "staggering" that treatments are being appraised
by clinicians who have no working understanding of the clinical
area they are investigating.
The medical profession remains critical of a
system that uses non-expert clinicians in its appraisals. Many
clinicians have said they will simply ignore NICE recommendations
if they run contrary to their own experience and practice.
The failure to use experts of suitable standing,
and the use of clinicians who do not operate within the therapeutic
area under investigation, has led to NICE being described as inadequate,
unrepresentative and lacking credibility within the medical profession.
Unless NICE uses experts who are widely recognised,
its credibility within the medical profession will remain suspect.
Furthermore, the over-emphasis on the role of
health economics undermines the clinical credibility of decision-making.
Recommendations
— Consideration should be given to
using a panel of experts to advise the Appraisal Committee, rather
than just a single clinician.
— NICE must ensure that it uses experts
of a suitable standing to advice the Appraisal Committee.
— NICE must also ensure that the experts
have appropriate input into the appraisal procedure.
4. PROBLEMS AND
ERRORS
A number of stakeholders have reported many
appraisals to be problematic.
Some stakeholders have reported substantial
errors in the evaluation reports on which the Guidance is based.
It is worrying that the quality of evaluation reports and of the
draft Guidance that is developed is variable or inconsistent.
Other errors in the evaluation reports have
been as great as two orders of magnitude with a complete reversal
of the result stated.
NICE arbitrarily decided to extend the appraisal
to include use of a drug for unlicensed indications even when
the drug is not being used for that purpose, and this has delayed
the appraisal of the licensed indication.
The following provide examples of some of the
problems encountered, but are not by any means an exhaustive list.
COX-2 Inhibitors:
— Experts reported that there were
numerous factual errors in the Assessment Report, and particularly
on the two coxibs where more clinical information exists - this
was in stark contrast with the data on the two older drugs that
was mainly accurate. Experts questioned whether different people
had prepared the Report for the older and the newer drug assessments.
Despite substantial errors being pointed out, no attempt was made
to correct the Assessment Report. When an Assessment Report is
patently inaccurate, it is difficult to see how the draft appraisal
that is developed from it can itself be accurate, and as a result
the credibility of the Guidance is undermined.
— Several patient groups invited to
submit to NICE never received a letter.
— NICE insisted on grouping four drugs
together for the appraisal process, even though there is evidence
to suggest that the two older agents may still cause the dangerous
gastrointestinal adverse events that the Guidance is designed
to stop, and these two agents also lack evidence from clinical
studies demonstrating that they reduce GI adverse events. NICE
appears to have lost sight of the original objective - to reduce
the number of people suffering dangerous GI adverse effects that
result in 12,000 hospitalisations and over 2,000 deaths a year.
Taxanes in Ovarian Cancer
— NICE substantially underestimated
the number of women who would be eligible for and benefit from
taxanes in ovarian cancer. They had estimated that approximately
a third of women with ovarian cancer would be eligible for treatment.
When investigated by CERT, the reference used by NICE was found
to be based solely on a local estimate from a single oncologist
who it is understood does not even treat ovarian cancer. The feedback
to CERT from experts in the field was that 60-80 per cent of women
with ovarian cancer would be eligible and benefit from taxane
treatment, and this figure was therefore supplied to NICE. The
final Guidance reflected this feedback.
Verteporfin in Age-related Macular Degeneration
(AMD)
— NICE extended the scope of the appraisal
on verteporfin to include patients with wet Age-related Macular
Degeneration (AMD) associated with occult choroidal neovascularisation
(CNV). This was outside the current licensed indications and in
spite of assurances from the Department of Health that "treatments
would only be considered in relation to their licensed indications".
— The inclusion within the appraisal
of verteporfin for wet AMD associated with occult CNV was not
discussed during the consultation rounds with stakeholders on
the remit and scope of the appraisal. Needless to say, the input
to the appraisal by the stakeholders would have differed if this
"off-label" indication had been raised.
— Patients with wet AMD associated
with predominantly classic subfoveal CNV will therefore continue
to be denied effective treatment with verteporfin pending the
licence approval for the other indication.
The NICE appraisal process appears to lack any
quality control or quality assurance procedures to prevent errors
in either the Assessment Report or draft Guidance from being issued.
Recommendation
— NICE should adopt appropriate quality
procedures into the appraisal process, but without introducing
delay.
5. RESOURCES
5.1 Resources within NICE
It is in all stakeholders' interest that NICE
not only works properly but is seen to work properly, and is fair
and open in its decision-making process. It is thought by many
that NICE lacks the proper resources to fully gain the confidence
of the medical profession and patients.
Some of the variability in appraisals may reflect
insufficient resources at NICE. The health technology groups commissioned
to develop the evaluation reports are paid only around £14,000.
Considering that this is a three-month project requiring detailed
analysis of all the relevant clinical data, it is to be expected
that at this level of funding the bulk of the work is being performed
by less-experienced staff, rather than by experts with detailed
knowledge of the relevant area. Assessments are carried out by
a limited number of academic units in England and Wales. These
units are comprised of health economists, with little or no input
from the clinical community. There is a degree of reflexivity
within this academic community, with personnel moving from one
unit to another repeating policy learned at their previous institution.
No use has been made of health technology resources outside of
the UK.
5.1 Resources within stakeholder groups
Many of the patient advocacy groups and research
charities, particularly those that are heavily reliant on voluntary
work, lack the resources and expertise to respond to the opportunity
that a NICE appraisal presents to their community. Those involved
in broad areas of interest (such as the elderly) receive numerous
requests from NICE to submit evidence, but are unable to respond
due to the sheer volume of work involved. Ideally, such funding
should be independent from NICE. One potential source could be
the National Lottery.
Recommendation
— Consideration should be given to
ensure that an appropriate level of funding is available for NICE
to meet the projected workload and ensure adequate quality.
— Consideration should also be given
for funding that is independent of NICE to allow patient advocacy
groups and research charities to respond to the requests for submissions
and participate as stakeholders.
6. ETHICS
NICE consistently disregards ethics in its appraisals.
It appears to have little concern for the ethical dilemmas which
specialists such as oncologists encounter in their working day.
For instance, a different emphasis is placed on survival times
for different tumour types. The breast cancer lobby has successfully
exerted significant pressure on available funds and political
focus. Colorectal cancer does not have such an active lobby; consequently
funding and political activity are less. If three months' survival
benefit from a taxane used to treat advanced breast cancer is
sufficient enough to be recommended by NICE, then why shouldn't
a similar survival advantage be sufficient to gain a recommendation
from NICE for the drugs used to treat patients with advanced colorectal
cancer?
As another example, in non-Hodgkins' lymphoma,
NICE recommended entry of patients into a randomised, controlled
clinical trial despite the fact that the treatment under appraisal
is a salvage therapy making an RCT unethical.
Rather than tackle the ethical issues directly,
NICE recently announced that they were to set up a panel of members
of the public as a "Citizen's Council" to advise it
on, amongst other things, ethical issues. The Council will not
include anybody in patient advocacy groups, those working in healthcare,
or even those working in ethics. CERT is concerned that the panel
is simply a way of enabling NICE to take unethical decisions whilst
having a group of the public without any expertise in ethics to
take the blame.
The concern that many stakeholders had regarding
NICE was that it was originally established by the Department
of Health to take unpalatable decisions that Ministers did not
want to make themselves in order to avoid being tarnished in the
public's eyes. Having found how difficult some of these decisions
are to substantiate, NICE now appears to be delegating these same
questions to another group—the Citizen's Council—in
order that NICE itself avoids criticism.
It is unclear whether the Citizen's Council
will have access to information from sources other than NICE in
order to reach their decisions, or whether their deliberations
will be open and transparent. If NICE is the only source of information,
there is a clear risk that the Council could be fed with unbalanced
information in order to reach a particular decision.
Recommendations
— The Appraisals Committees should
include an ethicist.
— The role of the Citizen's Council
should be examined to ensure it cannot be used by NICE as an unskilled
group that can be fed unbalanced information in order to reach
a particular decision. Where possible patient representatives
knowledgeable in clinical trial design, health economics and patient
advocacy should be recruited.
7. IMPLEMENTATION
OF NICE GUIDANCE
The NHS lacks an open and transparent means
by which stakeholders can easily assess whether particular treatments
are subject to inequitable access across the NHS. Most stakeholders,
particularly the patient advocacy groups, charities and professional
organisations, have to rely on anecdotal information on access
to particular treatments, although there are commercial sources
of information available which are actively used by both the Department
of Health and industry. An open and transparent mechanism of monitoring
would allow the NHS, Department of Health and stakeholders to
identify problem areas and respond at a local level rather than
waiting for a horror story to emerge through the media.
CERT welcomes the announcement from Lord Hunt
(5 Dec 2001, "New Statutory Obligations for the NHS to
fund treatments recommended by NICE"). We believe it
is important that the Health Select Committee ask how these recommendations
are to be enforced.
Some patients receiving drugs NICE have recommended
are still experiencing delays in treatment due to Health Authority
funding problems. These can extend beyond the end of the financial
year in which NICE Guidance is issued by (eg breast cancer, MND,
Alzheimer's disease). The situation appears to be slowly getting
better, but it is still unclear why there is such a disparity
between those Health Authorities who can immediately find the
money from increased Government investment in the NHS, whilst
others take much longer and require greater amounts of pressure
exerted on them. It is a pity that those Health Authorities who
do the job well don't get credit, and those who fail aren't held
to account.
It is unclear at this stage how the shift of
responsibility from Health Authorities to Primary Care Trusts
will impact the funding process and the uptake of NICE Guidance.
Recommendations
— There should be open and transparent
monitoring of the use of treatments recommended by NICE.
— Consideration should be given to
how the new statutory obligations are to be enforced.
— There should be open and transparent
monitoring of the transition of responsibility from Health Authorities
to Primary Care Trusts upon the uptake of NICE Guidance.
8. INDEPENDENCE
The general perception of NICE is that it is
a child of the Department of Health. Many of its staff have come
from the Department, and this wholesale importing of personnel
can only lead to a culture that "follows the Whitehall party
line". There is at least a perception that the culture is
dominated by the Department of Health, whereas the work of independent
personnel would be welcomed by stakeholders.
Furthermore, should any of the stakeholders
believe that there are problems with the draft Guidance developed
by NICE, the main route of recourse is through the appeal procedure.
However, the appeal board itself includes two members of NICE—the
chairman and a non-executive director—which does little
to reassure stakeholders and observers that the process is truly
independent and credible.
Recommendations
— CERT calls for the active recruitment
of senior personnel from overseas, industry and non-Department
of Health-aligned academia. Particularly welcome would be the
employment of health economic departments from overseas, facilitating
an increase in the number of assessments possible at any one time.
This would also minimise the bias of a UK academy that favours
a non-interventionist therapeutic policy.
— The appeal board should be truly
independent from NICE and the Department of Health.
January 2002
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