I heard this story on the radio last week, and the Italian physician working in Africa for a very long time said that the treatments have been provided for babies older than 6 months successfully. The new and important step (with Novartis) is to now safely treat babies younger than 6 months with the appropriate dosing. I wish I could find the link to the radio story.
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.
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.
The claim still holds then that there are no approved treatments for malaria in this age range. If we were already treating patients off book, and that were the reason we couldn't have a control group, then there is no real reason to do the study at all.
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.
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?
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?
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.
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.
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.
This particular one is mostly about dosing, the available medicines were weight based, with lowest dosages in the 5-15kg range. This brings dosages lower allowing more precise dosing for the lighter babies.
Edit: it's a very welcome addition. Limits side effects.
Are you taking the stance that no drug should ever be released on the basis that it is impossible for trials to cover literally the entire population? Like, what are you looking for here?
Probably as opposed to “approved for general use in the population because we’ve passed all of our tests”, which is what I’d assume “approved for use” means
Only for lab mice. Humans require making it clear that they are not being used as lab mice. But often, you see report saying that "After seeing the results for x years of use by populations, we found that it has y side effect which was not known earlier". A doctor literally said this to me last week.
> "After seeing the results for x years of use by populations, we found that it has y side effect which was not known earlier"
I would think that any reasonably intelligent adult could think about things for a few moments and come to the realization that... yeah, that's how things work. This is how we progress and learn. We develop, test, use, and learn about things - and if we learn that hey, turns out, this is bad over a long period of time... we change things.
And this of course doesn't apply to just medicine - it's just technological progress.
What's the alternative? "Oh, sorry, we would like to treat your baby's malaria, but that would disregard the baby's inherent dignity: we don't yet know the full side-effect profile up to 3 sigmas."
Most indignities are lesser than dying of malaria.
I heard this story on the radio last week, and the Italian physician working in Africa for a very long time said that the treatments have been provided for babies older than 6 months successfully. The new and important step (with Novartis) is to now safely treat babies younger than 6 months with the appropriate dosing. I wish I could find the link to the radio story.
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&ran...
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.
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.
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.
The claim still holds then that there are no approved treatments for malaria in this age range. If we were already treating patients off book, and that were the reason we couldn't have a control group, then there is no real reason to do the study at all.
a small study.... that then gets approved and released to everyone!
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.
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.
The famous comparison: you do not need a large N to test the effectiveness of parachutes.
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?
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?
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.
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.
It is pretty common to have a very small (and usually not exactly random) sample size.
Whether its common doesn't really matter. Are you arguing that a small, non-random sample size is acceptable in a scientific study?
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.
https://www.reuters.com/business/healthcare-pharmaceuticals/... | https://archive.today/Gsw4p
Good news! How do you safely develop medications for babies?
This particular one is mostly about dosing, the available medicines were weight based, with lowest dosages in the 5-15kg range. This brings dosages lower allowing more precise dosing for the lighter babies.
Edit: it's a very welcome addition. Limits side effects.
[flagged]
Approved for use means approved for testing on populations.
Are you taking the stance that no drug should ever be released on the basis that it is impossible for trials to cover literally the entire population? Like, what are you looking for here?
As opposed to what?
Probably as opposed to “approved for general use in the population because we’ve passed all of our tests”, which is what I’d assume “approved for use” means
Isn't that how medicine works?
Only for lab mice. Humans require making it clear that they are not being used as lab mice. But often, you see report saying that "After seeing the results for x years of use by populations, we found that it has y side effect which was not known earlier". A doctor literally said this to me last week.
What alternative process do you propose that will discover all side effects, including those with well under 1% occurence, without human use?
No one in the US is going to force you to take medication. You are free to die. You are also free to leave.
> "After seeing the results for x years of use by populations, we found that it has y side effect which was not known earlier"
I would think that any reasonably intelligent adult could think about things for a few moments and come to the realization that... yeah, that's how things work. This is how we progress and learn. We develop, test, use, and learn about things - and if we learn that hey, turns out, this is bad over a long period of time... we change things.
And this of course doesn't apply to just medicine - it's just technological progress.
What's the alternative? "Oh, sorry, we would like to treat your baby's malaria, but that would disregard the baby's inherent dignity: we don't yet know the full side-effect profile up to 3 sigmas."
Most indignities are lesser than dying of malaria.