How are vaccines for children tested and approved?
September 15, 2020 8:46 AM Subscribe
I think I understand the process for approving vaccines for adults - the 3 phases and the purpose of each, and the fact that adults can consent to being in a trial. But it seems testing vaccines to be given to children has both substantial ethical issues (how do we ethically pick someone to go first?) and recruitment issues (can you really find parents willing to have their kids participate?). So how do vaccine researchers navigate this?
Obviously this has SARS-CoV-2 implications, but I'm interested in learning more generally how vaccines (e.g., for influenza) have been approved for use in kids.
It's also possible I'm not thinking about this in the right way — do vaccines even have specific approvals for use on children?
Obviously this has SARS-CoV-2 implications, but I'm interested in learning more generally how vaccines (e.g., for influenza) have been approved for use in kids.
It's also possible I'm not thinking about this in the right way — do vaccines even have specific approvals for use on children?
Assent is the term used for ethically involving children in clinical research of any kind. Parents or guardians need to consent; assent is the term used for getting the child’s permission to involve them in research as well.
posted by MadamM at 9:42 AM on September 15, 2020 [6 favorites]
posted by MadamM at 9:42 AM on September 15, 2020 [6 favorites]
I can talk about this a little bit from the ethics review perspective, if that's useful. The overall process of approving a child vaccine study is not *super* different from an adult vaccine study. It's more that there are ethical considerations and options that are always present for any study but they're applied with a heavier hand in approving a child study. A few points of variance are:
- Probably, unless it's a child-specific illness somehow, we'd really like to see some research done in adults first before we start testing on kids. I'm not sure that's a hard-and-fast rule but it's certainly something that makes the people in the review room a lot more comfortable with the study. (Before it gets an adult study, a similar thing happens with asking for animal data or very small pilot data or modelling data or whatever the investigator can provide to convince the ethics review people that they're not just throwing things at the wall to see what sticks. The IRB wants to know that there's a reasonable justification for the risks you're asking people to take.)
- We always talk a lot about risk level in approving any study, but for child studies in particular (vaccine related or not) there's a lot of detailed discussion of the interaction between risk level and whether the study might provide direct benefit to the child themselves vs. benefit to humanity. By regulation, these factors determine how consent works - can one parent consent? Is two-parent consent required? can the child consent for themselves? There's a decent rundown here from CHOP. Exceptions can be requested but are not the easiest thing to get, where children are concerned.
- Your typical review board is going to look carefully at how those children are being found/recruited. You don't want either the risks or the potential benefits of study participation to be limited to a particular population. That's fuzzy and hard to balance out sometimes, but it's certainly taken into account - the researcher doesn't just get free rein to go pick on any particularly desperate population that they want. They have to justify how and why they're choosing their participants, and as the study goes along they have to report back to the ethics review board about things like whether their demographics are shaking out as expected, any unusual side effects they're seeing, etc. That's true for all studies but the scrutiny is a lot more intense in child studies.
- Age-appropriate assent is important, as MadamM noted. As a reviewer I spend a lot of time on this one. Sometimes researchers try so hard to make things simplified and not-scary for a child that they end up coming out the far end of making them sound fun in a way that can end up being coercive. (Not all that long ago I had an assent on my desk for a study involving children with disabilities that basically said "if you like science and want to help people you'll do [XYZ that involves letting the researchers experiment on your disability assistance device]" and I sent that one back with extreme red-lines; you can't make it sound like "if you say no to this you are being mean and not helping people.")
- Any given risky study probably will be required to have an independent monitoring board that will meet (monthly/quarterly/after every 5 patients/whatever is deemed appropriate by investigator and IRB.) But on top of that, the ethical review board can unilaterally impose any additional safety overview. They can say that instead of a standard annual report, they want the researcher to come back for ethics review in three months, or one month, or after the first patient, or whatever they feel is appropriate to the risk level. The extent to which that happens is going to be really dependent on the study; they may demand really frequent monitoring when a vaccine study is in the early basic-safety portion, but ease way off once the safety is established and researchers turn more to effectiveness. This is all true for all research, but in my experience ethics review boards lean way harder on this ability for a child study with an unknown safety risk, than they would for a similar adult study.
Generally speaking, in times before the last few years, when people had a greater tendency to trust that the CDC/FDA/NIH were doing actual science and not being railroaded by an anti-science government, it was not too difficult to find parents to enroll children in various moderately risky studies. (I can't speak to vaccines specifically but maybe someone else will.) A lot of people feel very strongly about contributing to science and to the community, or they have a family member who has [x] disease and they want to contribute to studying/treating it, or they need the pocket money. Although hopefully if the ethics review people have done their job right the cash isn't an inordinately coercive amount. Or they have a relationship with a set of researchers from other studies, and maybe they wouldn't join just any study but they will do a new one for this researcher they know and trust. None of that is across the board; populations that have traditionally been treated unethically by researchers are a lot less willing to cheerfully sign up for new risky studies. It's a real challenge. But it has been, to at least some extent, possible in the past. I suspect the climate is a bit different now but as it's been several years since I was involved in study recruitment myself, that's really just speculation.
posted by Stacey at 12:01 PM on September 15, 2020 [16 favorites]
- Probably, unless it's a child-specific illness somehow, we'd really like to see some research done in adults first before we start testing on kids. I'm not sure that's a hard-and-fast rule but it's certainly something that makes the people in the review room a lot more comfortable with the study. (Before it gets an adult study, a similar thing happens with asking for animal data or very small pilot data or modelling data or whatever the investigator can provide to convince the ethics review people that they're not just throwing things at the wall to see what sticks. The IRB wants to know that there's a reasonable justification for the risks you're asking people to take.)
- We always talk a lot about risk level in approving any study, but for child studies in particular (vaccine related or not) there's a lot of detailed discussion of the interaction between risk level and whether the study might provide direct benefit to the child themselves vs. benefit to humanity. By regulation, these factors determine how consent works - can one parent consent? Is two-parent consent required? can the child consent for themselves? There's a decent rundown here from CHOP. Exceptions can be requested but are not the easiest thing to get, where children are concerned.
- Your typical review board is going to look carefully at how those children are being found/recruited. You don't want either the risks or the potential benefits of study participation to be limited to a particular population. That's fuzzy and hard to balance out sometimes, but it's certainly taken into account - the researcher doesn't just get free rein to go pick on any particularly desperate population that they want. They have to justify how and why they're choosing their participants, and as the study goes along they have to report back to the ethics review board about things like whether their demographics are shaking out as expected, any unusual side effects they're seeing, etc. That's true for all studies but the scrutiny is a lot more intense in child studies.
- Age-appropriate assent is important, as MadamM noted. As a reviewer I spend a lot of time on this one. Sometimes researchers try so hard to make things simplified and not-scary for a child that they end up coming out the far end of making them sound fun in a way that can end up being coercive. (Not all that long ago I had an assent on my desk for a study involving children with disabilities that basically said "if you like science and want to help people you'll do [XYZ that involves letting the researchers experiment on your disability assistance device]" and I sent that one back with extreme red-lines; you can't make it sound like "if you say no to this you are being mean and not helping people.")
- Any given risky study probably will be required to have an independent monitoring board that will meet (monthly/quarterly/after every 5 patients/whatever is deemed appropriate by investigator and IRB.) But on top of that, the ethical review board can unilaterally impose any additional safety overview. They can say that instead of a standard annual report, they want the researcher to come back for ethics review in three months, or one month, or after the first patient, or whatever they feel is appropriate to the risk level. The extent to which that happens is going to be really dependent on the study; they may demand really frequent monitoring when a vaccine study is in the early basic-safety portion, but ease way off once the safety is established and researchers turn more to effectiveness. This is all true for all research, but in my experience ethics review boards lean way harder on this ability for a child study with an unknown safety risk, than they would for a similar adult study.
Generally speaking, in times before the last few years, when people had a greater tendency to trust that the CDC/FDA/NIH were doing actual science and not being railroaded by an anti-science government, it was not too difficult to find parents to enroll children in various moderately risky studies. (I can't speak to vaccines specifically but maybe someone else will.) A lot of people feel very strongly about contributing to science and to the community, or they have a family member who has [x] disease and they want to contribute to studying/treating it, or they need the pocket money. Although hopefully if the ethics review people have done their job right the cash isn't an inordinately coercive amount. Or they have a relationship with a set of researchers from other studies, and maybe they wouldn't join just any study but they will do a new one for this researcher they know and trust. None of that is across the board; populations that have traditionally been treated unethically by researchers are a lot less willing to cheerfully sign up for new risky studies. It's a real challenge. But it has been, to at least some extent, possible in the past. I suspect the climate is a bit different now but as it's been several years since I was involved in study recruitment myself, that's really just speculation.
posted by Stacey at 12:01 PM on September 15, 2020 [16 favorites]
Response by poster: Interesting, thanks. Follow-up: are there any cases where a treatment would be approved for use in children after it's approved for adults, or would it always require study in pediatrics? I realize pediatrics covers a lot of ages so this question might have different answers for 17 y.o. vs 3 y.o. patients.
posted by Tehhund at 1:44 PM on September 15, 2020
posted by Tehhund at 1:44 PM on September 15, 2020
Most drugs prescribed for children have not been tested in children.
Off-Label Medication use in Children, More Common than We Think: A Systematic Review of the Literature
posted by Iris Gambol at 7:29 PM on September 15, 2020 [1 favorite]
Off-Label Medication use in Children, More Common than We Think: A Systematic Review of the Literature
posted by Iris Gambol at 7:29 PM on September 15, 2020 [1 favorite]
Hi! 10 years ago my newborn twins participated in a vaccine study. We were contacted through the hospital where they were born, as were all the babies born that week (maybe month?). We read the material, and decided it was a good idea, it was a combination vaccine made up of two tested parts. We believe that studies like this are important. Our doctor recommended participating, and so did my father, also a doctor.
The babies received a full checkup for each vaccine, before and after, from 2 months until they were 2. We received: free parking. A $5 coffee card. A book or toy for each kid at each appointment.
We are in Canada.
posted by Valancy Rachel at 7:29 PM on September 15, 2020 [2 favorites]
The babies received a full checkup for each vaccine, before and after, from 2 months until they were 2. We received: free parking. A $5 coffee card. A book or toy for each kid at each appointment.
We are in Canada.
posted by Valancy Rachel at 7:29 PM on September 15, 2020 [2 favorites]
This thread is closed to new comments.
In the past, it was not hard to get parents to volunteer their kids to be the first to take an approved vaccine. My mother-in-law is still proud of having been a Polio Pioneer. Their parents and the kids themselves had watched their siblings and playmates die of these diseases. The opposition to vaccines that we see in some modern societies can only exist because that society is so far removed from that experience of watching so many children die.
posted by hydropsyche at 9:07 AM on September 15, 2020 [25 favorites]