6 ms·

This is of course exactly what was expected, and why First Dose First was so clearly the right strategy until countries had plenty of supply. Good for the UK re

This is of course exactly what was expected, and why First Dose First was so clearly the right strategy until countries had plenty of supply. Good for the UK recognizing this early. The US hasn't.

peytn 5y ago
It’s unethical to gamble your citizenry on untested medical interventions regardless of outcome. There was enough time to sponsor a trial.
- moultano 5y ago
  Come on, we didn't even have time for the trials we actually ran. Thousands died while we waited for rubber stamps.
- tnorthcutt 5y ago
  So was it ethical to gamble on a four week interval when it wasn’t proven to be the best option?
  - nradov 5y ago
    No one ever claimed that it was the best option, just that it was the only option clinically tested. It would have been irresponsible to recommend a different option without at least some limited clinical trials. Sometimes you can't wait for perfect data.
  - ttul 5y ago
    Gamble is the wrong word for this. It was a calculated risk as is everything in a pandemic or other evolving threat to public health.
  - inglor_cz 5y ago
    I still think that something else was unethical: not running challenge tests. There were enough volunteers for them.
- ttul 5y ago
  This is easy to say if one is living in the country with all the vaccine supply. Canada bought more doses per capita than any other country, yet US prohibitions on vaccine export meant Canada could not get enough supply in the first few months of the vaccine rollout. A calculated risk was taken to give first doses while waiting for supply to come online, which did eventually happen. This was not some random experiment on the population. While the gold standard of a phase three trial was not available to support the longer interval, there was plenty of data about the performance of prior vaccines, and interim data about immunogenicity with a longer interval for the COVID-19 vaccines.
- Daishiman 5y ago
  No. It is ethical to do that which maximizes life-saving outcomes. Saying that something is an "untested medical intervention" lacks the nuance of saying that some interventions are completely unknown, while others have fairly predictable and understandable effects. The effects of a single dose were reasonably well understood as well as the impacts on transmission. Reducing transmission is a potentially more relevant goal than individual health outcomes in the grand scheme of things.
  - bakuninsbart 5y ago
    While I agree with you on the overall sentiment, it is very hard to apply sometimes. Here in Germany there were a lot of calls to start handing out Curevac doses. They had a few million ready to go, but we were still awaiting trial data. Our government decided against the emergency usage in the end, and it was the right decision in hindsight, as it turns out that the vaccine is far less effective than its competitors, and could very well have had similar problems as AZ or Biontech.
- 7952 5y ago
  The alternative could people taking their chances with covid. The do nothing option is not a neutral outcome.
- deleted 5y ago
  [deleted]
Wowfunhappy 5y ago
What if it had gone the other way, and longer intervals made the vaccine significantly less effective? I do agree with you on the whole, but for me it’s a very difficult choice, not an obvious one.
- derbOac 5y ago
  A few months ago I remember there were interviews and articles with immunologists and virologists. There seemed to be a consistent sentiment with many of them at least that the Pfizer and Moderna protocol intervals were kind of suboptimal from an immunology perspective. The conclusion was that many in the field saw it as obvious that the two companies were trying to maximize the probability of vaccine efficacy in as short of period of time as possible (I don't think they saw the companies as acting immorally, just that they saw it as not making sense unless you understood the time constraints). Many of the people interviewed commented that with unlimited time and lack of public health constraints, they would have expected smaller doses given longer apart. I guess my point is, I'm not an expert in this area but there was a lot of chatter earlier that this was kind of predictable or something.
- smnrchrds 5y ago
  That would be unexpected. Not impossible, but improbable. Think about it this way: do you know of any other vaccines with 4-week intervals? If all other vaccines use longer intervals, what are the chances that this particular vaccines needs a shorter interval? The decisions made in UK and Canada to delay the second dose were not a random choice. They were expected to work based on the body of knowledge we have from other vaccines and what we know about the immune system. It was by no means a certainty, but a strong probability. And it paid off.
  - areyousure 5y ago
    Bexsero (MenB) is two doses given 4 weeks apart. For children receiving their first vaccines for the flu (whether inactivated or live), it is recommended they receive two doses 4 weeks apart. Lots of the early childhood vaccines have minimum spacings of 4 weeks, but are given at 2, 4, and 6 months simply because of standard pediatric followup visit schedules: DTaP, Hib, IPV, PCV13, and Rotavirus. HepB has a first dose at birth and the second at 4 weeks -- 2 months. HPV is available in a 3-dose series with 4 weeks between the first two doses.
rsynnott 5y ago
I think you could argue that it has broken down a bit with Delta, as the first dose provides very little protection there.
- jaytaylor 5y ago
  Edit: Nevermind, I was wrong- apologies! https://www.forbes.com/sites/carlieporterfield/2021/07/21/study-finds-pfizer-and-astrazeneca-vaccines-effective-against-the-delta-variant---as-long-as-you-get-both-doses/ https://www.forbes.com/sites/carlieporterfield/2021/07/21/st...
  - rsynnott 5y ago
    From the article you posted: > Two doses of the Pfizer vaccine had an effectiveness of 93.7% at preventing symptomatic alpha infections, and 88% for the delta variant. [..] > However, the effectiveness of the vaccines plummeted if a patient had only received one dose of either vaccine: the study found both to be just more than 48% effective against alpha and only about 30% effective against delta. I'm a little confused as to what your point is? The vaccines are highly effective after two doses, but not very effective after only one dose.
    - jaytaylor 5y ago
      I don't see 50% as "very little", but that's just semantics and not worth fussing over. I concede to you :) Thank you for following up- I appreciate it.
      - rsynnott 5y ago
        50% (48%) is for Alpha (I'm actually a little surprised it's that low; IIRC it was a lot better in the initial studies, though those were on the ancestral variant, not Alpha). For Delta, it's 30%, per that article. I'd call that pretty low. That said, other studies are available, and some have shown decent performance against Delta after one dose.

This is of course exactly what was expected, and why First Dose First was so clearly the right strategy until countries had plenty of supply. Good for the UK recognizing this early. The US hasn't.

peytn 5y ago

It’s unethical to gamble your citizenry on untested medical interventions regardless of outcome. There was enough time to sponsor a trial.

moultano 5y ago
Come on, we didn't even have time for the trials we actually ran. Thousands died while we waited for rubber stamps.
tnorthcutt 5y ago
So was it ethical to gamble on a four week interval when it wasn’t proven to be the best option?
- nradov 5y ago
  No one ever claimed that it was the best option, just that it was the only option clinically tested. It would have been irresponsible to recommend a different option without at least some limited clinical trials. Sometimes you can't wait for perfect data.
- ttul 5y ago
  Gamble is the wrong word for this. It was a calculated risk as is everything in a pandemic or other evolving threat to public health.
- inglor_cz 5y ago
  I still think that something else was unethical: not running challenge tests. There were enough volunteers for them.
ttul 5y ago
This is easy to say if one is living in the country with all the vaccine supply. Canada bought more doses per capita than any other country, yet US prohibitions on vaccine export meant Canada could not get enough supply in the first few months of the vaccine rollout. A calculated risk was taken to give first doses while waiting for supply to come online, which did eventually happen. This was not some random experiment on the population. While the gold standard of a phase three trial was not available to support the longer interval, there was plenty of data about the performance of prior vaccines, and interim data about immunogenicity with a longer interval for the COVID-19 vaccines.
Daishiman 5y ago
No. It is ethical to do that which maximizes life-saving outcomes. Saying that something is an "untested medical intervention" lacks the nuance of saying that some interventions are completely unknown, while others have fairly predictable and understandable effects. The effects of a single dose were reasonably well understood as well as the impacts on transmission. Reducing transmission is a potentially more relevant goal than individual health outcomes in the grand scheme of things.
- bakuninsbart 5y ago
  While I agree with you on the overall sentiment, it is very hard to apply sometimes. Here in Germany there were a lot of calls to start handing out Curevac doses. They had a few million ready to go, but we were still awaiting trial data. Our government decided against the emergency usage in the end, and it was the right decision in hindsight, as it turns out that the vaccine is far less effective than its competitors, and could very well have had similar problems as AZ or Biontech.
7952 5y ago
The alternative could people taking their chances with covid. The do nothing option is not a neutral outcome.
deleted 5y ago
[deleted]

Wowfunhappy 5y ago

What if it had gone the other way, and longer intervals made the vaccine significantly less effective? I do agree with you on the whole, but for me it’s a very difficult choice, not an obvious one.

derbOac 5y ago
A few months ago I remember there were interviews and articles with immunologists and virologists. There seemed to be a consistent sentiment with many of them at least that the Pfizer and Moderna protocol intervals were kind of suboptimal from an immunology perspective. The conclusion was that many in the field saw it as obvious that the two companies were trying to maximize the probability of vaccine efficacy in as short of period of time as possible (I don't think they saw the companies as acting immorally, just that they saw it as not making sense unless you understood the time constraints). Many of the people interviewed commented that with unlimited time and lack of public health constraints, they would have expected smaller doses given longer apart. I guess my point is, I'm not an expert in this area but there was a lot of chatter earlier that this was kind of predictable or something.
smnrchrds 5y ago
That would be unexpected. Not impossible, but improbable. Think about it this way: do you know of any other vaccines with 4-week intervals? If all other vaccines use longer intervals, what are the chances that this particular vaccines needs a shorter interval? The decisions made in UK and Canada to delay the second dose were not a random choice. They were expected to work based on the body of knowledge we have from other vaccines and what we know about the immune system. It was by no means a certainty, but a strong probability. And it paid off.
- areyousure 5y ago
  Bexsero (MenB) is two doses given 4 weeks apart. For children receiving their first vaccines for the flu (whether inactivated or live), it is recommended they receive two doses 4 weeks apart. Lots of the early childhood vaccines have minimum spacings of 4 weeks, but are given at 2, 4, and 6 months simply because of standard pediatric followup visit schedules: DTaP, Hib, IPV, PCV13, and Rotavirus. HepB has a first dose at birth and the second at 4 weeks -- 2 months. HPV is available in a 3-dose series with 4 weeks between the first two doses.

rsynnott 5y ago

I think you could argue that it has broken down a bit with Delta, as the first dose provides very little protection there.

jaytaylor 5y ago
Edit: Nevermind, I was wrong- apologies! https://www.forbes.com/sites/carlieporterfield/2021/07/21/study-finds-pfizer-and-astrazeneca-vaccines-effective-against-the-delta-variant---as-long-as-you-get-both-doses/ https://www.forbes.com/sites/carlieporterfield/2021/07/21/st...
- rsynnott 5y ago
  From the article you posted: > Two doses of the Pfizer vaccine had an effectiveness of 93.7% at preventing symptomatic alpha infections, and 88% for the delta variant. [..] > However, the effectiveness of the vaccines plummeted if a patient had only received one dose of either vaccine: the study found both to be just more than 48% effective against alpha and only about 30% effective against delta. I'm a little confused as to what your point is? The vaccines are highly effective after two doses, but not very effective after only one dose.
  - jaytaylor 5y ago
    I don't see 50% as "very little", but that's just semantics and not worth fussing over. I concede to you :) Thank you for following up- I appreciate it.
    - rsynnott 5y ago
      50% (48%) is for Alpha (I'm actually a little surprised it's that low; IIRC it was a lot better in the initial studies, though those were on the ancestral variant, not Alpha). For Delta, it's 30%, per that article. I'd call that pretty low. That said, other studies are available, and some have shown decent performance against Delta after one dose.