3 ms·

So, I know people involved in COVID vaccine trials (I can't remember which, I think it was Pfizer or Moderna), and also work with people who have been involved

So, I know people involved in COVID vaccine trials (I can't remember which, I think it was Pfizer or Moderna), and also work with people who have been involved with other sorts of trials involving sensitive populations. Awhile ago, we had a conversation about the issue you're referring to. Basically what was happening was that people in the control group were getting vaccinated, increasingly so, after the trials showed efficacy. It wasn't even so much they were leaving the study, they were just violating the inclusion criteria. They were very aware of this, and discussed all sorts of ways of trying to get around it, too many to note here, including some weird designs with a new sample that at the time didn't really make logical sense to me from an efficacy RCT standpoint, but did from an ethical standpoint. There were at least two things on their mind. First, you can't force participants to remain in the trials long-term. So if they want to go get vaccinated, they're going to get vaccinated. You can't keep them from doing that. So if you lose 95% of your participants to that, and your power goes through the floor, what can you do? Second, there's a strong argument to be made that if you show strong efficacy of an intervention that prevents a world-crippling disease, it is highly unethical to keep the intervention from the control participants. It's not just unethical to encourage them not to get the vaccine, it's unethical to not offer it to them. There are many RCTs my colleagues have been in, of much more inconsequential treatments, where they ended up giving the treatment to controls because of this issue. So what about a COVID vaccine? Yes, long-term findings are necessary and/or desirable, but this can't really be done while circumventing ethical issues about withholding a highly effective intervention. There's lots of scenarios where this happens all the time -- where you'd like to get more and/or any RCT data but doing so raises ethical obstacles that are difficult to overcome. Maybe you could scrounge together enough people across trials but then you run into another issue: are the people who choose to remain in the control group long term really comparable to treatments on average anymore? You lose your randomization in an important sense, so it's all moot anyway. It's a difficult issue.

peteradio 5y ago
How do you make sure we don't inadvertently fuck over a huge population in a black swan event? It's like the establishment is using small scale tactics at totality scale which is certainly a critical point to be concerned about.
- FjolsvithAase 5y ago
  Watch the elimination of the control group. With a control group, it is easy to see the adverse effects.
angelzen 5y ago
Thanks for taking the time to write an in-depth informative mini-article. It is a difficult issue. Usually the following would be none of my business, but we are in a pandemic that affects billions of people around the world. It is uncomfortable to navigate uncharted waters without a depth line. A lingering unclarity is that in practice there is no shortage of people willing to weather covid with no vaccine. I suspect such people are unlikely to participate in a RCT, but perhaps the recruitment process can be adjusted to attract more conservative (in the psychological sense) types.
landemva 5y ago
World-crippling _political_ response to the disease. My experience is that being in OK physical shape I was sick for a few days and recovered with no medical intervention. I have the antibody test results and Dr. letter to prove it. The ongoing political response and mask wearer social signalling is over the top.
- kadoban 5y ago
  So the real world-crippling result of Covid is that some people are wearing masks?
native_samples 5y ago
There are more than enough people who don't want to take the vaccine for pre-existing reasons that they could have formed a control group who promised not to take it, and would stick to it.
- thisiszilff 5y ago
  For a double blind randomized trial, no one can know who's in what group. If an individual isn't willing to get the vaccine then they'd be excluded by default.
blindmute 5y ago
While a blind trial is preferable, we can and should still gather data based on unblinded trials. Using the voluntarily unvaccinated in trials as a control group will yield meaningful data at scale, just not as good as it could be. For example, are they being diagnosed with heart problems less often? That is not likely to be placebo.

peteradio 5y ago

How do you make sure we don't inadvertently fuck over a huge population in a black swan event? It's like the establishment is using small scale tactics at totality scale which is certainly a critical point to be concerned about.

FjolsvithAase 5y ago
Watch the elimination of the control group. With a control group, it is easy to see the adverse effects.

angelzen 5y ago

Thanks for taking the time to write an in-depth informative mini-article. It is a difficult issue. Usually the following would be none of my business, but we are in a pandemic that affects billions of people around the world. It is uncomfortable to navigate uncharted waters without a depth line. A lingering unclarity is that in practice there is no shortage of people willing to weather covid with no vaccine. I suspect such people are unlikely to participate in a RCT, but perhaps the recruitment process can be adjusted to attract more conservative (in the psychological sense) types.

landemva 5y ago

World-crippling _political_ response to the disease. My experience is that being in OK physical shape I was sick for a few days and recovered with no medical intervention. I have the antibody test results and Dr. letter to prove it. The ongoing political response and mask wearer social signalling is over the top.

kadoban 5y ago
So the real world-crippling result of Covid is that some people are wearing masks?

native_samples 5y ago

There are more than enough people who don't want to take the vaccine for pre-existing reasons that they could have formed a control group who promised not to take it, and would stick to it.

thisiszilff 5y ago
For a double blind randomized trial, no one can know who's in what group. If an individual isn't willing to get the vaccine then they'd be excluded by default.

blindmute 5y ago

While a blind trial is preferable, we can and should still gather data based on unblinded trials. Using the voluntarily unvaccinated in trials as a control group will yield meaningful data at scale, just not as good as it could be. For example, are they being diagnosed with heart problems less often? That is not likely to be placebo.