3 ms·

Unless I'm reading the original study [1] wrong, I'm surprised the study only used a population size of 28. They did do a 12 month check-in which is good, but

Unless I'm reading the original study [1] wrong, I'm surprised the study only used a population size of 28. They did do a 12 month check-in which is good, but why such a small group of study participants, especially when malaria is so widespread? [1] https://clinicaltrials.gov/study/NCT04300309?term=CALINA&rank=1 https://clinicaltrials.gov/study/NCT04300309?term=CALINA&ran...

_heimdall 1y ago
Also they apparently didn't use a control group, the study was terminated early, and after the 43 day test window 9 of the 28 participants are listed as having the adverse event of malaria. I'm particularly confused by that last one. How is malaria considered an adverse event when testing an anti-malaria treatment? Other data in the study shows that 1 participant had malaria again with matching DNA, meaning the original infection likely came back. 6 others were reported as getting malaria again but with different DNA. So what does it mean to have 9 with the adverse event of malaria?
- deleted 1y ago
  [deleted]
- refulgentis 1y ago
  Think you're over-parsing a bit: adverse events ~= something we should mention, not Bad Things The Treatment Did. "What does it mean?" is a qualitative question, not a quantitative one. Taking that question more colloquially, in this case, I'd say it means "the vaccine did not prevent infections in 9 of 28 cases and / or they had an infection before the vaccine was taken" I'm sure you mean well -- since your post, the thread got cluttered up with outright know-nothing-type comments. I am being very literal in order to help teach people in despair what we expect when we read these.
  - _heimdall 1y ago
    I did mean well, thanks for assuming good intent here. I still don't understand how 9 of 28 could have the adverse event of malaria, though, given that other data in the results show that 1 participant had what seemed to be a reinfection with a genetic match and 6 others were infected again with a parasite that didn't match their original infection's genetic makeup. That is 7 individuals, where do the other 2 come from? My uncertainty is that I may be misunderstanding the meaning of malaria as an adverse event entirely here - I don't get how reinfection would be an adverse event rather than a potential failure of treatment.
freeone3000 1y ago
Statistical power. Malaria doesn’t go away on its own. They know the treatment should be overwhelmingly effective if dosed correctly, it’s merely a measure of determining dosage vs negative effects.
- 3eb7988a1663 1y ago
  The famous comparison: you do not need a large N to test the effectiveness of parachutes.
- _heimdall 1y ago
  Right, in this case my concern really wouldn't be with efficacy as much as safety. When the test group is only 28 participants how can we assume that we would have found most of the safety concerns? Is the assumption being made that the only concerning factor is age and that there are no other contribution factors that could lead to negative outcomes?
BugsJustFindMe 1y ago
Ethics dictate always using the smallest viable cohort to show that giving the treatment regimen (in this case dosage for a drug known to be effective) isn't obviously worse than the thing it's supposed to treat, even if we're already pretty sure. This also keeps the costs of running the studies down so we can effectively conduct more studies for more treatments. We also already have data about its use in babies over 11 lbs, and this is just going even smaller to 4.4 lbs, so a strong baseline has already been demonstrated.
- verisimi 1y ago
  a small study.... that then gets approved and released to everyone!
  - refulgentis 1y ago
    A little dull assertion can't hurt you, individually, and I bet it feels fun. I assume you're well-aware the process for something like this doesn't fit in a sentence. Additionally, there's context in the comment you're replying to, this isn't the only study.
- _heimdall 1y ago
  What do you mean "ethics dictates?" We define ethics and they generally reflect the current culture, ethics aren't universal and can't dictate anything. The scientific method, though, would dictate that a cohort size should be large enough to show a high probability of safety and efficacy, assuming that is what is being tested. It would also dictate that a control group would be needed to compare against the test group. I totally understand the ethical concerns of potentially allowing children to be harmed while part of a control group, but when the test is being done specifically because there is currently no treatment the only change is that they would pick a group of untreated children that are a valid control group for the study. Either way those children wouldn't be treated and there really isn't an ethical issue to deal with.
  - roywiggins 1y ago
    There is a treatment, but it's done ad-hoc: > Until now there have been no approved malaria drugs specifically for babies. > Instead they have been treated with versions formulated for older children which presents a risk of overdose.
dev_l1x_be 1y ago
It is pretty common to have a very small (and usually not exactly random) sample size.
- _heimdall 1y ago
  Whether its common doesn't really matter. Are you arguing that a small, non-random sample size is acceptable in a scientific study?
  - standardUser 1y ago
    I think if we take off our pedant caps we can easily understand that the nature of scientific research on living people is rife with unique restrictions and circumstances. And, more mundanely, that when a medication is proven through widespread use over decades in one population, the standards to study the impact on other, very similar populations does not always require the most onerous approach.
    - _heimdall 1y ago
      I'm not sure how this would fall under a pedantry label. If we are okay assuming that a medication used widely for other age groups is safe for infants, why bother with an incomplete study that was never designed to produce statistically significant results? The study is only useful if it can show safety and efficacy of the dosage levels for the test population. I'm not trying to argue that the study was even necessary if the safety and efficacy can be implied, only that if the study is to be done it should at least be setup with a chance of proving the needed results.

_heimdall 1y ago

Also they apparently didn't use a control group, the study was terminated early, and after the 43 day test window 9 of the 28 participants are listed as having the adverse event of malaria. I'm particularly confused by that last one. How is malaria considered an adverse event when testing an anti-malaria treatment? Other data in the study shows that 1 participant had malaria again with matching DNA, meaning the original infection likely came back. 6 others were reported as getting malaria again but with different DNA. So what does it mean to have 9 with the adverse event of malaria?

deleted 1y ago
[deleted]
refulgentis 1y ago
Think you're over-parsing a bit: adverse events ~= something we should mention, not Bad Things The Treatment Did. "What does it mean?" is a qualitative question, not a quantitative one. Taking that question more colloquially, in this case, I'd say it means "the vaccine did not prevent infections in 9 of 28 cases and / or they had an infection before the vaccine was taken" I'm sure you mean well -- since your post, the thread got cluttered up with outright know-nothing-type comments. I am being very literal in order to help teach people in despair what we expect when we read these.
- _heimdall 1y ago
  I did mean well, thanks for assuming good intent here. I still don't understand how 9 of 28 could have the adverse event of malaria, though, given that other data in the results show that 1 participant had what seemed to be a reinfection with a genetic match and 6 others were infected again with a parasite that didn't match their original infection's genetic makeup. That is 7 individuals, where do the other 2 come from? My uncertainty is that I may be misunderstanding the meaning of malaria as an adverse event entirely here - I don't get how reinfection would be an adverse event rather than a potential failure of treatment.

freeone3000 1y ago

Statistical power. Malaria doesn’t go away on its own. They know the treatment should be overwhelmingly effective if dosed correctly, it’s merely a measure of determining dosage vs negative effects.

3eb7988a1663 1y ago
The famous comparison: you do not need a large N to test the effectiveness of parachutes.
_heimdall 1y ago
Right, in this case my concern really wouldn't be with efficacy as much as safety. When the test group is only 28 participants how can we assume that we would have found most of the safety concerns? Is the assumption being made that the only concerning factor is age and that there are no other contribution factors that could lead to negative outcomes?

BugsJustFindMe 1y ago

Ethics dictate always using the smallest viable cohort to show that giving the treatment regimen (in this case dosage for a drug known to be effective) isn't obviously worse than the thing it's supposed to treat, even if we're already pretty sure. This also keeps the costs of running the studies down so we can effectively conduct more studies for more treatments. We also already have data about its use in babies over 11 lbs, and this is just going even smaller to 4.4 lbs, so a strong baseline has already been demonstrated.

verisimi 1y ago
a small study.... that then gets approved and released to everyone!
- refulgentis 1y ago
  A little dull assertion can't hurt you, individually, and I bet it feels fun. I assume you're well-aware the process for something like this doesn't fit in a sentence. Additionally, there's context in the comment you're replying to, this isn't the only study.
_heimdall 1y ago
What do you mean "ethics dictates?" We define ethics and they generally reflect the current culture, ethics aren't universal and can't dictate anything. The scientific method, though, would dictate that a cohort size should be large enough to show a high probability of safety and efficacy, assuming that is what is being tested. It would also dictate that a control group would be needed to compare against the test group. I totally understand the ethical concerns of potentially allowing children to be harmed while part of a control group, but when the test is being done specifically because there is currently no treatment the only change is that they would pick a group of untreated children that are a valid control group for the study. Either way those children wouldn't be treated and there really isn't an ethical issue to deal with.
- roywiggins 1y ago
  There is a treatment, but it's done ad-hoc: > Until now there have been no approved malaria drugs specifically for babies. > Instead they have been treated with versions formulated for older children which presents a risk of overdose.

dev_l1x_be 1y ago

It is pretty common to have a very small (and usually not exactly random) sample size.

_heimdall 1y ago
Whether its common doesn't really matter. Are you arguing that a small, non-random sample size is acceptable in a scientific study?
- standardUser 1y ago
  I think if we take off our pedant caps we can easily understand that the nature of scientific research on living people is rife with unique restrictions and circumstances. And, more mundanely, that when a medication is proven through widespread use over decades in one population, the standards to study the impact on other, very similar populations does not always require the most onerous approach.
  - _heimdall 1y ago
    I'm not sure how this would fall under a pedantry label. If we are okay assuming that a medication used widely for other age groups is safe for infants, why bother with an incomplete study that was never designed to produce statistically significant results? The study is only useful if it can show safety and efficacy of the dosage levels for the test population. I'm not trying to argue that the study was even necessary if the safety and efficacy can be implied, only that if the study is to be done it should at least be setup with a chance of proving the needed results.