Epistemic status: not sure.
People comparing Mackenzie Scott's charitable donations to EA charities to dunk on them for "being ineffective" on a health basis seem to be arguing in pretty bad faith.
A large portion of those donations weren't health-focused at all, but rather cause-focused. This doesn't seem more out of line to me than (say) EA focus on x-risk non-profits: Both have nebulous return in a quantifiable sense, but both do (for better or worse) make noticeable impacts in the world on a long enough timescale.
Sometimes a person cares about a thing that isn't about saving as many immediate-now lives as possible, and this seems... kind of critical? When EA was initially pitched to me, part of that pitch was, "More flashy stuff will likely get funded without you, so you can aim to spend as effectively as possible without worrying about the things you personally care about going underfunded."
Things like the YMCA, LGBT advocacy groups, jazz arts funding (all taken from the Yield site) - I don't feel like any of these are bad things to fund. If charitable spending was only malaria nets and chemoprevention, I feel like it'd be a worse world.
I'd go as far as to say that the current giving strategy Scott is undertaking is probably optimal for building soft power in the United States, though I don't think she's actually trying to at the moment.
Soft power breeds hard power in time. Who will society look more fondly on in twenty years, the people who allocated all of their funds to abstract figures overseas and constantly talked of how virtuous they were for it, or the person who grabbed the drowning child out of the lake, got them a good education, and then left them alone?
And who has more capability to be effective or damaging, the person who chooses who gets to control USAID, or the person who has $26bn to throw around?
I don't actually know the sum and substance of her charitable donations; I haven't paid that much attention, and I'm a pretty strong believer in malaria nets, so I'm weighted toward "probably pretty suboptimal," especially in the immediate-now.
It just seems wrong to me to go after her in the specific way a lot of EAs are, though; yeah, she's giving ineffectively. Giving most effectively in a cause-blind manner wasn't her goal. But now a lot of the things you and people with capital care about domestically are taken care of for a while, and you can make more persuasive arguments for reallocating a bunch of funding to be genuinely optimal.
Not everyone is going to be a strict, Singer-style utilitarian; the world would be a lot worse if they were. Very few people are solely spending money on shrimp, even though from a utilitarian standpoint, it's way more effective to improve the lives of shrimp than to save human lives, or to give to Lighthaven. You pick issues to care about, and you care about them; if nobody cares about the local problems, it seems likely that there'll be no one to care for the shrimp after long enough.