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Comment by radycov | Hacker News Reader

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.

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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.

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.

> I know of several friends who have caught it from young children in school settings

I guess there’s no way for them to be certain. But I’ve been wondering if we’ve been too quick to believe that kids are less susceptible to Covid or the virus that causes it.

Imagine that children do contract it as regularly as adults, but are usually asymptomatic. No symptoms = no suspicion = no reason for them to be tested.

Kids not being tested regularly could be the reason why we believe “they don’t get it”. I fear we’ve come to an unsound and dangerous conclusion on this. And I think it’s partly due to the way we confounded the variables when we shut schools in spring. Closed schools probably helped keep kid cases down at first. And from there we leaped to “kids don’t get it”.

Meanwhile, the CDC has published more data on that shows kids do transmit. But their updates seem to have a hard time breaking through the noise. https://www.cdc.gov/mmwr/volumes/69/wr/mm6939e2.htm

Same with their update last week to acknowledge that Covid is mainly airborne. How many are now aware of this? Checking air ventilation? Or still focused on surface wipedowns? https://twitter.com/first10em/status/1341121947682418691?s=2...

Given 1/3 people infected are asymptomatic there’s a decent chance you have had it and didn’t know.

I wish they made antibody testing easier and more widespread. No reason taking a vaccine slot if we already have immunity.

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.

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 ?

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!).

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.

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.

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).

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.

For at least some of the Oxford trials they used a "widely available meningitis vaccine."

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