LONDON - Mild Alzheimer’s Patients Continue to be Denied Treatment

Eisai Limited, the licence holder of Aricept(R) (donepezil hydrochloride) and Pfizer Limited, its co-promotion partner, have been notified by the National Institute for Health and Clinical Excellence (NICE) of their decision to continue to deny vulnerable patients the use of anti-cholinergic medicines in the treatment of mild Alzheimer’s disease.

At the recent Appraisal Committee meeting it was recognised that the current model contained four significant errors, and that NICE had failed to undertake appropriate checks of their calculations in three separate areas.

Disappointingly, despite recognising these errors in the NICE model, and the availability of a new model which showed conflicting results, the NICE Appraisal Committee still consider the current guidance remains ‘fit for purpose’ and that these flaws are insufficient to warrant any change in their recommendation to the way anti-cholinergic medicines are used in the treatment of mild Alzheimer’s disease.

The new model submitted to the Appraisal Committee incorporated the latest techniques for determining cost effectiveness in Alzheimer’s disease and shows a cost saving to the NHS and society by treating mild Alzheimer’s disease patients. NICE recognised the existence of this model and the implications of its results, but chose not to incorporate them into its review of the Guidance.

Serious concerns remain about the quality of the economic models developed by NICE and their own quality assurance processes. That NICE sought to keep these calculations from independent scrutiny fails to serve well either themselves or the integrity of the decision-making process.

Eisai and Pfizer remain frustrated that patients suffering from mild Alzheimer’s disease will continue to be denied treatment after such a lengthy process, but welcome the opportunity of working with NICE in the new review that has been recommended, and call on NICE to start this process as a matter of urgency and conduct an expedited review.

Notes to Editors:

As part of the review process, Eisai commissioned United BioSource Corporation (UBC) to conduct an independent assessment of the NICE model. The UBC team was lead by Professor Jamie 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 the duration of disease to diagnosis is on average seven years and from onset of symptoms to diagnosis can average more than 3 years (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.

Source: Eisai and Pfizer

For further information please contact: Andrew Day, Eisai, +44-(0)7973-411-419. Andrew Thomas, Pfizer, +44-(0)7814-528-928