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All-cause mortality is easier to measure, it also takes into account any deaths caused by the vaccine, and any deaths caused by non-malaria proximate causes tha

All-cause mortality is easier to measure, it also takes into account any deaths caused by the vaccine, and any deaths caused by non-malaria proximate causes that would nevertheless have been averted by the vaccine. Malaria is really bad for you even if you survive it, and probably makes you more vulnerable to dying of other things: "For instance, clinical malaria is known to exhaust T cells, he says, and vaccination, by preventing infection, might therefore leave T cells readier to combat other pathogens. Such a general survival benefit has been documented for measles and tuberculosis vaccination. Other leading causes of death in the young children in these areas include pneumonia and diarrhea caused by pathogens including Streptococcus pneumoniae and rotavirus." So, surviving malaria could very easily make it harder to survive your next encounter with rotavirus; vaccinating against malaria would then reduce deaths from rotavirus.

timr 3y ago
Yeah, but...it's also subject to sample bias. Especially in a place like east Africa, having enough resources (not just money -- time, transport, etc.) to get a crazy expensive new vaccine could easily have co-variates that affect all-cause mortality. It's great to report it, but you definitely want to see the cause-specific numbers, too.
- deleted 3y ago
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- roywiggins 3y ago
  They used two sets of controls: 1, an entire set of communities where the vaccination wasn't offered at all, and 2, children who were not eligible due to age. They weren't just comparing children who got the vaccine with children who didn't, they were comparing children who were eligible for the vaccine and those who weren't, and that couldn't have been so easily confounded: "79 areas where the RTS,S vaccine was administered and 79 comparator areas where it was not available" "Researchers then compared the death rates of babies whose age made them eligible to receive three doses of the vaccine with those of young children who were not age-eligible for three doses, in both RTS,S areas and unvaccinated areas." This is obviously not foolproof, but it seems like a substantial bulwark against obvious confounders. If you can show that 1) the mortality rate in the vaccinated communities was lower in the age-eligible children than not-age-eligible[0] and 2) this effect was absent in unvaccinated communities that seems like it goes quite far towards proving that it's real and not an artifact. It probably even underestimates how protective it is at an individual level. (communities which had the vaccine offered also had fewer cases of severe malaria recorded in their hospitals, so there's a straightforward reason to think it does something) [1] okay probably age-ineligible children have a different mortality rate regardless. You'd be taking the difference between those two groups of children and comparing it to the same difference in communities without the vaccination offered. This difference-of-difference would tell you whether the vaccine is doing anything. It wouldn't matter if only the richer children received the vaccine if the communities have basically the same distribution of wealth since you're comparing differences between age cohorts, not between vaccinated and unvaccinated.
  - timr 3y ago
    > This is obviously not foolproof, but it seems like a substantial bulwark against obvious confounders. I mean...they had controls? That's good. But otherwise, there's no way you can tell from what is written. Even if the controls are perfect (which I don't grant without more detail), the implementation of the controls can still allow for confounding. > they were comparing children who were eligible for the vaccine and those who weren't, and that couldn't have been easily confounded You can trivially get confounding based on that. Just pick the kids who are healthier, and call them "eligible". Or pick the ones who are older (which they did, as you note), and voila...infinite time bias! Kids who make it to age N are more likely to survive to age N+1 than kids who make it to age N-1 (I mostly disregarded the between-group differences based on age, for this exact reason. It's too easily confounded.) More commonly, bias of this form sneaks into a study. Particularly in a place like sub-saharan Africa, the set of people who are even willing to engage with you, mysterious doctor-magician, are of a fundamentally different nature than the ones you never see. They probably do all sorts of things that make them a little bit healthier, on average. It's hard to correct for that, and it's a real problem when the primary metric is "community survey of all-cause mortality". For example: are the community surveyors also magical stranger doctor-magicians, or are they just regular people? It matters.
    - roywiggins 3y ago
      > Just pick the kids who are healthier, and call them "eligible". Sure, yeah. Or whatever. But there's no evidence for that in the article, it says it was done based on age, and then matched between comparable communities. You'd have to not only mess with the eligibility, but only do so in the vaccinated communities. Because they compared eligible and ineligible children in the unvaccinated communities, too. And again, the cohorts were split apart by age. Maybe a bunch of unhealthy children didn't get the vaccine for that reason, but they'd be included in the age-cohort anyway. Of course they could maliciously juice the study but the "what if richer, healthier children were the ones that got the vaccine" just doesn't seem a reasonable criticism at least as described. It seems like a perfectly good design to avoid being confounded that sort of thing.
      - 3y ago

timr 3y ago

Yeah, but...it's also subject to sample bias. Especially in a place like east Africa, having enough resources (not just money -- time, transport, etc.) to get a crazy expensive new vaccine could easily have co-variates that affect all-cause mortality. It's great to report it, but you definitely want to see the cause-specific numbers, too.

deleted 3y ago
[deleted]
roywiggins 3y ago
They used two sets of controls: 1, an entire set of communities where the vaccination wasn't offered at all, and 2, children who were not eligible due to age. They weren't just comparing children who got the vaccine with children who didn't, they were comparing children who were eligible for the vaccine and those who weren't, and that couldn't have been so easily confounded: "79 areas where the RTS,S vaccine was administered and 79 comparator areas where it was not available" "Researchers then compared the death rates of babies whose age made them eligible to receive three doses of the vaccine with those of young children who were not age-eligible for three doses, in both RTS,S areas and unvaccinated areas." This is obviously not foolproof, but it seems like a substantial bulwark against obvious confounders. If you can show that 1) the mortality rate in the vaccinated communities was lower in the age-eligible children than not-age-eligible[0] and 2) this effect was absent in unvaccinated communities that seems like it goes quite far towards proving that it's real and not an artifact. It probably even underestimates how protective it is at an individual level. (communities which had the vaccine offered also had fewer cases of severe malaria recorded in their hospitals, so there's a straightforward reason to think it does something) [1] okay probably age-ineligible children have a different mortality rate regardless. You'd be taking the difference between those two groups of children and comparing it to the same difference in communities without the vaccination offered. This difference-of-difference would tell you whether the vaccine is doing anything. It wouldn't matter if only the richer children received the vaccine if the communities have basically the same distribution of wealth since you're comparing differences between age cohorts, not between vaccinated and unvaccinated.
- timr 3y ago
  > This is obviously not foolproof, but it seems like a substantial bulwark against obvious confounders. I mean...they had controls? That's good. But otherwise, there's no way you can tell from what is written. Even if the controls are perfect (which I don't grant without more detail), the implementation of the controls can still allow for confounding. > they were comparing children who were eligible for the vaccine and those who weren't, and that couldn't have been easily confounded You can trivially get confounding based on that. Just pick the kids who are healthier, and call them "eligible". Or pick the ones who are older (which they did, as you note), and voila...infinite time bias! Kids who make it to age N are more likely to survive to age N+1 than kids who make it to age N-1 (I mostly disregarded the between-group differences based on age, for this exact reason. It's too easily confounded.) More commonly, bias of this form sneaks into a study. Particularly in a place like sub-saharan Africa, the set of people who are even willing to engage with you, mysterious doctor-magician, are of a fundamentally different nature than the ones you never see. They probably do all sorts of things that make them a little bit healthier, on average. It's hard to correct for that, and it's a real problem when the primary metric is "community survey of all-cause mortality". For example: are the community surveyors also magical stranger doctor-magicians, or are they just regular people? It matters.
  - roywiggins 3y ago
    > Just pick the kids who are healthier, and call them "eligible". Sure, yeah. Or whatever. But there's no evidence for that in the article, it says it was done based on age, and then matched between comparable communities. You'd have to not only mess with the eligibility, but only do so in the vaccinated communities. Because they compared eligible and ineligible children in the unvaccinated communities, too. And again, the cohorts were split apart by age. Maybe a bunch of unhealthy children didn't get the vaccine for that reason, but they'd be included in the age-cohort anyway. Of course they could maliciously juice the study but the "what if richer, healthier children were the ones that got the vaccine" just doesn't seem a reasonable criticism at least as described. It seems like a perfectly good design to avoid being confounded that sort of thing.
    - 3y ago