Medical DevicesEisai And Pfizer Decide Not To Appeal NICE Decision And Call For An Expedited Review Of Guidance For Alzheimer's Disease
On June 11, the National Institute for Health and Clinical Excellence
(NICE) announced that, following consultation with stakeholders on the
economic model that underpinned NICE"s 2006 guidance on the use of drugs to
treat Alzheimer"s disease, the guidance remains unchanged despite recognising
significant errors within their model.
While the process afforded Consultees the right to appeal against this
decision, Eisai Limited, the licence holder of Aricept(R) (donepezil
hydrochloride) and Pfizer Limited, its co-promotion partner, today confirm
that they do not intend to pursue an appeal in the interests of patients.
Nick Burgin, Managing Director of Eisai Ltd., commented: "While we shared
the disappointment of many on hearing NICE"s decision, we have decided today
not appeal. The fundamental reason for this is that on June 11th, Andrew
Dillon, NICE Chief Executive, committed to commence a review of the existing
guidance "as soon as possible", as long as no appeals were received. It is
therefore right that Eisai and Pfizer do all we can to allow NICE to honour
its stated commitment and to take into account new data that have become
available as well as advances in economic modelling techniques."
Eisai and Pfizer are committed to working with NICE and call upon the
Institute to provide a timeline for review as a matter of urgency.
As part of the review process, Eisai commissioned United Bio
Corporation (UBC) to conduct an independent assessment of the NICE model. The
UBC team was lead by Professor Jaime Caro, who developed the original "AHEAD"
economic model, which was modified by NICE for use in this appraisal. The UBC
team"s main findings were:
- The model incorrectly assumes that the likelihood of a patient dying in
any year is the same despite evidence that it varies according to
factors such as patient"s age or the severity of Alzheimer"s" disease
(Xie 2008). Correcting this error would lead to lower (better) cost-
effectiveness estimates than those that were reported by NICE,
especially for patients with milder disease.
- The model incorrectly assumes that the annual cost of caring for
patients prior to entering full time care is the same for each patient
despite evidence that these costs depend on the extent to which the
disease has progressed. For example, patients with very mild cognitive
deficits are known to be less expensive to care for than those with
more severe cognitive deficits (Knapp 2007). Correcting this error
would lead to lower (better) cost-effectiveness estimates than those
that were reported by NICE, especially for patients with milder
disease.
- The model incorrectly assumes that apart from cognitive level, the
baseline characteristics are the same for patients with mild disease
and with moderate disease: they have the same age, behavioural symptoms
and so on, despite evidence that these aspects also relate to disease
severity (Knapp 2007, Chatfield 2007, Piccininni 2005, Steinberg 2008).
By not taking into account the real difference in baseline
characteristics between patients with mild and moderate disease, the
model generates results that make treatment of mild patients look less
attractive (less cost-effective) than treating patients with moderate
disease.
- The model incorrectly assumes that the mean duration of Alzheimer"s
disease prior to treatment is one year in all analyses, even though
studies have shown that from onset of symptoms to diagnosis can
approach 3 years in the UK (Bond 2005). The consequence of this
assumption is that the model estimates that relatively few patients
will show signs of deterioration, including in patients who are not
treated. As a result the model makes treatment appear to be less
clinically and cost-effective than if it focuses on when treatment is
actually started in the UK (between three and seven years from onset of
disease) when the rate of deterioration is greater.
- The model incorporates treatment effect estimates derived from
six-month clinical trials and ignores information available from
randomised, placebo-controlled trials of greater duration. By
effectively limiting treatment benefit to a maximum of six months, the
model makes treatment appear much less clinically and cost-effective.
- The model assigns a single utility for patients who are not yet in full
time care, thus ignoring the slower deterioration with treatment.
Rather than addressing this error, the model incorporates a "fix" by
adding a quality of life ("augmented") benefit but no justification is
made for the significant number of arbitrary assumptions that were
made. Despite the significant uncertainty in these assumptions, none of
them was varied in the sensitivity analyses.
Eisai and Pfizer