6 ms·

A question I rarely see addressed during double-blind placebo studies is: how do you ensure both groups encounter the same virus exposure during the study perio

A question I rarely see addressed during double-blind placebo studies is: how do you ensure both groups encounter the same virus exposure during the study period? Is it simply safe to assume nearly equal "average exposure" over say 90 days randomly, or are all participants encouraged to follow identical lifestyles.

joshgel 6y ago
This is the beauty of randomization and blinding. Because both the participants and the doctors (the ‘double’ in double blind) don’t know who got the vaccine or placebo, anything you tell them to do is told equally to both sides. You can’t alter the trajectory of one group over the other because you don’t know the groups.
- sokoloff 6y ago
  A close friend of mine is in one of the double-blind trials here in the US. He experienced symptoms 36-48 hours after the injection that have him convinced that he got an active vaccine dose. He has (by my judgment not his words) altered his routines as a result. That seems a mechanism by which the blinding can be undone (though in this case, it would seem to work against computed vaccine efficacy rather than for it).
  - disgruntledphd2 6y ago
    Yeah, ideally you'd use an active placebo (same side effects as the active drug) but that's hard to do well and presumably wasn't a priority.
    - tim333 6y ago
      For at least some of the Oxford trials they used a "widely available meningitis vaccine."
TomK32 6y ago
I guess you ensure exposure by having many test subjects during an ongoing pandemic... Now that the UK have already over 500k doses of the other vaccine administered we will see new data on the effectiveness and safety of the vaccine (in comparison to CoVid-19, don't forget that!).
mortehu 6y ago
Randomization will on average prevent confounding variables from being unbalanced. For known and suspected confounding variables you can use blocking on top of that. For example you can randomly split each age group in half in order to ensure the intervention and control arms have similar age distributions. Blinding and placebo control helps prevent behavior modification from the intervention itself, but it's possible that people who receive the saline placebos behave differently, since they don't get any side effects. I believe AstraZeneca's trial in the US uses a saline placebo, presumably because an active placebo might accidentally also work against the virus.
- radycov 6y ago
  Anecdotally, since March I have been travelling on public transport and going into crowded central city locations almost on a daily basis, yet appear to have (extremely fortunately) avoided infection. This includes over the past few weeks with new highly infections mutations. Equally anecdotally, I know of several friends who have caught it from young children in school settings or crowded groups.
  - deleted 6y ago
    [deleted]
  - kjakm 6y ago
    Given 1/3 people infected are asymptomatic there’s a decent chance you have had it and didn’t know.
    - ed25519FUUU 6y ago
      I wish they made antibody testing easier and more widespread. No reason taking a vaccine slot if we already have immunity.
      - tim333 6y ago
        Apparently a vaccine can still make your immunity better. That said, having antibodies, I'm not sure I'll bother unless there's some vaccination certificate type benefit. By the way in the UK at any rate if you donate blood they check it for covid antibodies for free.
randcraw 6y ago
The people who prepare and distribute the drug vials are obviously not blinded; each vial (or batch) has a serial number that is known to be positive or control. Only the drug's administrators in the clinic are blinded.
ulfw 6y ago
Of course not. You can't tell people what life to live. That's why the studies are generally 30,000+ people big to get enough randomisation in. I think the ChAdOx study wasn't quite as large. Someone know ?

joshgel 6y ago

This is the beauty of randomization and blinding. Because both the participants and the doctors (the ‘double’ in double blind) don’t know who got the vaccine or placebo, anything you tell them to do is told equally to both sides. You can’t alter the trajectory of one group over the other because you don’t know the groups.

sokoloff 6y ago
A close friend of mine is in one of the double-blind trials here in the US. He experienced symptoms 36-48 hours after the injection that have him convinced that he got an active vaccine dose. He has (by my judgment not his words) altered his routines as a result. That seems a mechanism by which the blinding can be undone (though in this case, it would seem to work against computed vaccine efficacy rather than for it).
- disgruntledphd2 6y ago
  Yeah, ideally you'd use an active placebo (same side effects as the active drug) but that's hard to do well and presumably wasn't a priority.
  - tim333 6y ago
    For at least some of the Oxford trials they used a "widely available meningitis vaccine."

TomK32 6y ago

I guess you ensure exposure by having many test subjects during an ongoing pandemic... Now that the UK have already over 500k doses of the other vaccine administered we will see new data on the effectiveness and safety of the vaccine (in comparison to CoVid-19, don't forget that!).

mortehu 6y ago

Randomization will on average prevent confounding variables from being unbalanced. For known and suspected confounding variables you can use blocking on top of that. For example you can randomly split each age group in half in order to ensure the intervention and control arms have similar age distributions. Blinding and placebo control helps prevent behavior modification from the intervention itself, but it's possible that people who receive the saline placebos behave differently, since they don't get any side effects. I believe AstraZeneca's trial in the US uses a saline placebo, presumably because an active placebo might accidentally also work against the virus.

radycov 6y ago
Anecdotally, since March I have been travelling on public transport and going into crowded central city locations almost on a daily basis, yet appear to have (extremely fortunately) avoided infection. This includes over the past few weeks with new highly infections mutations. Equally anecdotally, I know of several friends who have caught it from young children in school settings or crowded groups.
- deleted 6y ago
  [deleted]
- kjakm 6y ago
  Given 1/3 people infected are asymptomatic there’s a decent chance you have had it and didn’t know.
  - ed25519FUUU 6y ago
    I wish they made antibody testing easier and more widespread. No reason taking a vaccine slot if we already have immunity.
    - tim333 6y ago
      Apparently a vaccine can still make your immunity better. That said, having antibodies, I'm not sure I'll bother unless there's some vaccination certificate type benefit. By the way in the UK at any rate if you donate blood they check it for covid antibodies for free.

randcraw 6y ago

The people who prepare and distribute the drug vials are obviously not blinded; each vial (or batch) has a serial number that is known to be positive or control. Only the drug's administrators in the clinic are blinded.

ulfw 6y ago

Of course not. You can't tell people what life to live. That's why the studies are generally 30,000+ people big to get enough randomisation in. I think the ChAdOx study wasn't quite as large. Someone know ?