Malaria vaccine trial procedures

[IvanV]

While it is exciting to read of a promising early trial of an innovative malaria vaccine, and Nature is a highly respected journal, I was rather surprised to read the third paragraph in the quoted extract below. Is it normal to deliberately infect vaccine trial subjects with the disease? What happens to those people who were not protected when they are infected? They get falciparium malaria? Or am I misunderstanding what happened - the "infection" perhaps was applied to a blood sample, not in their bodies.
Nature news article: Vaccine made of live malaria parasites shows early success
Nature academic article summarised in news article

An experimental malaria vaccine that contains live parasites protected nearly all recipients from infection in a small clinical trial.

Participants in the study, published on 30 June in Nature1, were given a shot containing live Plasmodium falciparum parasites, along with drugs to kill any parasites that reached the liver or bloodstream, where they can cause malaria symptoms. Participants were then intentionally infected with malaria three months later to test the vaccine’s efficacy.

The vaccination protected 87.5% of participants who were infected after three months with the same strain of parasite that was used in the inoculation, and 77.8% of those who were infected with a different strain. This is a significant improvement on earlier efforts to use live parasites in a malaria vaccine, which did not perform as well against different strains.

[bolo]

It's called a challenge trial. It's common enough that there's a WHO statement:

https://www.who.int/biologicals/expert_ ... _final.pdf

Others will know better than I do whether this is considered "normal".

[tom p]

Since there are perfectly good treatments for malaria, just ones which many people at risk of malaria don't have access to, there should be no ethical problem with a challenge trial like this.

[IvanV]

Since there are perfectly good treatments for malaria, just ones which many people at risk of malaria don't have access to, there should be no ethical problem with a challenge trial like this.

When I read bolo's link, pointing out that there is an ethical issue with challenge studies, I was surprised that the only ethical declaration in the paper related to financial interests of the researchers.

They are working on falciparium malaria. I think "there are perfectly good treatments..." is an oversimplification when talking about falciparium. And what are these relapses that people who had malaria in the past tend to experience from time to time?

Cases of severe and complicated malaria are almost always caused by infection with P. falciparum. The other species usually cause only febrile disease....When properly treated, people with malaria can usually expect a complete recovery. However, severe malaria can progress extremely rapidly and cause death within hours or days. In the most severe cases of the disease, fatality rates can reach 20%, even with intensive care and treatment.

[tom p]

Since there are perfectly good treatments for malaria, just ones which many people at risk of malaria don't have access to, there should be no ethical problem with a challenge trial like this.

When I read bolo's link, pointing out that there is an ethical issue with challenge studies, I was surprised that the only ethical declaration in the paper related to financial interests of the researchers.

They are working on falciparium malaria. I think "there are perfectly good treatments..." is an oversimplification when talking about falciparium. And what are these relapses that people who had malaria in the past tend to experience from time to time?

Cases of severe and complicated malaria are almost always caused by infection with P. falciparum. The other species usually cause only febrile disease....When properly treated, people with malaria can usually expect a complete recovery. However, severe malaria can progress extremely rapidly and cause death within hours or days. In the most severe cases of the disease, fatality rates can reach 20%, even with intensive care and treatment.

Good, point; however being part of a challenge trial in the USA means that you're gonna get treated as promptly and properly as anyone else in history & will have access to intensive care facilities next door in case anything goes horribly wrong.

[WFJ]

When I read bolo's link, pointing out that there is an ethical issue with challenge studies, I was surprised that the only ethical declaration in the paper related to financial interests of the researchers.

They are all that should be listed in the ethical declaration of a paper. There are all sorts of ethical considerations that can go into any research project plan, but there is no reason to list them upfront in an article like that. If they were to be mentioned in the paper, the intro, methods or discussion would be a more suitable place.

[tom p]

When I read bolo's link, pointing out that there is an ethical issue with challenge studies, I was surprised that the only ethical declaration in the paper related to financial interests of the researchers.

They are all that should be listed in the ethical declaration of a paper. There are all sorts of ethical considerations that can go into any research project plan, but there is no reason to list them upfront in an article like that. If they were to be mentioned in the paper, the intro, methods or discussion would be a more suitable place.

Yes, this too.
The ethical considerations of performing such a study will have been put before an ethics committee, where they will have experienced people who are suitably trained and educated to be able to debate the ethics of performing such a trial

[monkey]

When I read bolo's link, pointing out that there is an ethical issue with challenge studies, I was surprised that the only ethical declaration in the paper related to financial interests of the researchers.

They are all that should be listed in the ethical declaration of a paper. There are all sorts of ethical considerations that can go into any research project plan, but there is no reason to list them upfront in an article like that. If they were to be mentioned in the paper, the intro, methods or discussion would be a more suitable place.

Yes, this too.
The ethical considerations of performing such a study will have been put before an ethics committee, where they will have experienced people who are suitably trained and educated to be able to debate the ethics of performing such a trial

I can't read the paper, but I bet there's a bit in the meathods that goes "The research was approved by [the institution's Ethics Board] and followed the tenets of the Declaration of Helsinki. Consent was obtained from all subjects after the risks involved were explained to them."

That's what it looks like in my field, anyway, your field may vary.

[tom p]

That's the sort of thing I'd expect to see too. Basic boilerplate meaning an awful lot of background was done.

[shpalman]

It says

The study adhered to Good Clinical Practice guidelines and US NIH guidelines and procedures. All participants provided written informed consent. The study was reviewed and approved by the US National Institute of Allergy and Infectious Diseases, NIH institutional review board and conducted under an FDA IND application.

It might say other things too, I haven't read the whole thing.