LAUSR

In Gustavsson et al, we discussed the ethical issues that arise when identifying the relevant population for diseasemodifying drugs targeting Alzheimer disease (AD). More specifically, we focused on novel immunotherapies aimed at amyloid β and tau, two relevant biomarkers. The commentaries to our paper 3 acknowledge our conclusion: screening for AD involve ethical costs that cannot be justified unless a drug with clinically relevant effect (with acceptable safety) becomes available. Since Aduhelm is the only immunotherapy targeting AD currently approved by the Food and Drug Administration, we use that as a case in point. Our commentators also agree that the documented effect of Aduhelm is scarce, to say the least. With scarce data on clinical effect, Aduhelm has poor prospects of providing benefits that can justify the current pricing of the drug. The uncertainties regarding the effect should also be seen in light of the risk of adverse effects, the most prominent one being the risk for amyloidrelated imaging abnormalities (ARIA). The risk of ARIA should, according to current guidelines for Aduhelm, be regularly monitored by MRI. The uncertainties regarding the effect and the nature of the adverse effects (and the way in which they should be monitored) as well as the current pricing of Aduhelm raise two pressing questions regarding priority setting ethics. First, the reimbursement issue. Priority setting in healthcare is primarily an ethical question. A crucial reason for that is the alternative use of resources —the opportunity cost. Therefore, decisionmakers should be asking whether the relation between the cost and the clinical effect is reasonable. There may be cases when higher costs per health gain can be justified. For example, there is fairly wide support for accepting higher costs for treatments targeting severe conditions, even if it is contentious how this should be accounted for more specifically. While AD is considered a very severe condition, and even on more generous interpretations about the data sets, the cost of reimbursing Aduhelm exceeds, by far, any reimbursement decision so far. Second, the pricing of the drug aside, the infrastructure needed for monitoring adverse effects would put severe strain on any healthcare system. Access to MRI is, like any other healthcare resource, a limited resource, therefore, making room for the infrastructure needed for monitoring patients on Aduhelm means further opportunity costs (in terms of forgone health). For ethical reasons, the alternative use of these resources should be carefully considered when making reimbursement decisions for new drugs targeting AD.