Comment on NATSEM’s report on the economic and societal cost of Alzheimer disease in Australia

To the Editor: The socio‐economic modelling of the impact of a hypothetical disease‐modifying treatment (DMT) for Alzheimer disease by the National Centre for Social and Economic Modelling (NATSEM)1 is an interesting contribution to what is a critical question for policymakers: how effective does a new antidementia treatment need to be to justify a given cost to the community?

1. • The disease progression pathway lacks backwards transitions. It is commonly understood that mild cognitive impairment is an unstable diagnostic state; individuals are at higher risk for transition to dementia, but a predictable proportion also spontaneously revert back to cognitive normality.2
2. • The durability of DMT efficacy is unrealistic. It is implausible to assume that a 12‐month treatment with an anti‐amyloid will deliver lifelong cognitive benefits after cessation. In the EMERGE and ENGAGE trials,3 the treatment was for the duration of the trials (18 months), and it is generally accepted that this form of treatment will require infusions for years.
3. • The clinical efficacy of DMT is unfounded. Scientific opinion is divided as to whether modification of cerebral amyloid burden has clinical benefits on cognition or daily function. Further, there is no good reason to assume that a 23% relative difference on the continuous measure of cognitive decline observed in EMERGE — incidentally, not replicated in the identically designed ENGAGE trial3 — will translate to a relative difference in categorical transitions between mild cognitive impairment and mild or moderate dementia. Given this is the main driver of projected cost savings, assuming a 25% reduction in such transitions is unrealistic4 and, surprisingly, not subject to sensitivity analysis.
4. • The adverse costs of DMTs are not modelled. It is not appropriate to model presumed clinical benefits of a hypothetical DMT without accounting for the personal, medical and social cost of their documented adverse effects, including cerebral oedema, brain haemorrhage, and falls.2,5

Given that the list price of any such DMT to the health system was also deliberately not modelled, NATSEM is encouraged to address these concerns in a revised report.