2 ms·

How? The vaccinated individuals would come into contact with lots of people who are not vaccinated. How do you track all of them to determine if vaccinated indi

by runako 6y ago

How? The vaccinated individuals would come into contact with lots of people who are not vaccinated. How do you track all of them to determine if vaccinated individuals can transmit the disease? That seems like a much larger logistical problem that differs from the existing (and challenge) trials in very material ways.

Closi 6y ago
Well you observe transmission within a controlled environment - ie you keep people in the lab and don’t let them go home. You could take 50 people, vaccinate half and give half a placebo, infect them with Covid, then put them in 50 rooms with 50 other unvaccinated people (so each has two people) for 2 weeks and see what happens. The reason you can’t do it without a challenge trial is exactly because of what you said - you can’t track infections in the community.
- runako 6y ago
  I wonder how big such a trial would need to be in order to generate any meaningful confidence in the results, especially given the unpredictability of this pathogen. Also note that had this been run last spring you've doubled the size of the trial and therefore the number of hospitalized patients who would not have life-saving therapeutics. By comparison, the BioNTech/Pfizer vaccine had over 40,000 people in its trial. Not sure you could even run a trial that big with even a tenth as many people.
  - Closi 6y ago
    You should need less people in a challenge trial - the reason 40,000 was so high is because only a small amount of those people was expected to be infected, e.g. maybe only a few hundred of those actually got infected even in the control group. (Eg in a control group of 20k maybe 1% got infected = 200 people). In a challenge trial you can make people cough in each other’s faces, or literally inject them with Covid depending on the study, which raises your chance of getting people infected and seeing the impact. You would expect the control group to have a very high infection rate, and to see the difference in the study group much more easily. I’m not saying 100 people would be enough, but you would need significantly fewer people fewer to get a good level of confidence.
    - sudosysgen 6y ago
      You can't measure immediate response. You'd have to wait 3-6 weeks to see if protection against transmission still works. It would be maybe a 2-3 weeks faster but not yield as useful of data.
    - runako 6y ago
      You need a lot of participants because the expected outcome is that you inject a novel foreign substance into billions of people. At some point, you have to test for safety too, and very small trials are not good for that. And again -- the backup therapeutics that enable any challenge trial were not broadly available until a month or two before vaccines went into wide deployment. (You will note that nobody is volunteering for a challenge trial for any drugs or vaccines for our other ongoing pandemic, HIV. Lack of backup therapeutics is a big reason for that.)
      - Closi 6y ago
        You still need to test for safety, that's definitely true. At least you know you have a viable candidate though I guess. People were actually volunteering for a challenge trial for Covid prior to theraputics being available - because Covid actually is low-risk for the groups in the challenge trial (young people) and the vast majority of people recover. I don't think theraputics are necessary for a challenge trial, as long as there is sufficient benefit, the risk is sufficiently low, and volunteers are aware of the personal risks (aware this criteria is ambiguous!). HIV is incurable, however there are excellent therapeutics. Despite this, the prognosis of HIV is much worse than someone with Covid.

by runako 6y ago

Closi 6y ago

Well you observe transmission within a controlled environment - ie you keep people in the lab and don’t let them go home. You could take 50 people, vaccinate half and give half a placebo, infect them with Covid, then put them in 50 rooms with 50 other unvaccinated people (so each has two people) for 2 weeks and see what happens. The reason you can’t do it without a challenge trial is exactly because of what you said - you can’t track infections in the community.

runako 6y ago
I wonder how big such a trial would need to be in order to generate any meaningful confidence in the results, especially given the unpredictability of this pathogen. Also note that had this been run last spring you've doubled the size of the trial and therefore the number of hospitalized patients who would not have life-saving therapeutics. By comparison, the BioNTech/Pfizer vaccine had over 40,000 people in its trial. Not sure you could even run a trial that big with even a tenth as many people.
- Closi 6y ago
  You should need less people in a challenge trial - the reason 40,000 was so high is because only a small amount of those people was expected to be infected, e.g. maybe only a few hundred of those actually got infected even in the control group. (Eg in a control group of 20k maybe 1% got infected = 200 people). In a challenge trial you can make people cough in each other’s faces, or literally inject them with Covid depending on the study, which raises your chance of getting people infected and seeing the impact. You would expect the control group to have a very high infection rate, and to see the difference in the study group much more easily. I’m not saying 100 people would be enough, but you would need significantly fewer people fewer to get a good level of confidence.
  - sudosysgen 6y ago
    You can't measure immediate response. You'd have to wait 3-6 weeks to see if protection against transmission still works. It would be maybe a 2-3 weeks faster but not yield as useful of data.
  - runako 6y ago
    You need a lot of participants because the expected outcome is that you inject a novel foreign substance into billions of people. At some point, you have to test for safety too, and very small trials are not good for that. And again -- the backup therapeutics that enable any challenge trial were not broadly available until a month or two before vaccines went into wide deployment. (You will note that nobody is volunteering for a challenge trial for any drugs or vaccines for our other ongoing pandemic, HIV. Lack of backup therapeutics is a big reason for that.)
    - Closi 6y ago
      You still need to test for safety, that's definitely true. At least you know you have a viable candidate though I guess. People were actually volunteering for a challenge trial for Covid prior to theraputics being available - because Covid actually is low-risk for the groups in the challenge trial (young people) and the vast majority of people recover. I don't think theraputics are necessary for a challenge trial, as long as there is sufficient benefit, the risk is sufficiently low, and volunteers are aware of the personal risks (aware this criteria is ambiguous!). HIV is incurable, however there are excellent therapeutics. Despite this, the prognosis of HIV is much worse than someone with Covid.