10 ms·

What’s the timeline for Phase III trials? The article doesn’t seem to say. I don’t feel reassured that those won’t be rushed.

deelowe 6y ago
It's a moving target, so it's hard to say. Phase 3 trials depend entirely on the number of infected in the control group. Current estimates seem to indicate we may start seeing preliminary results in early Q4 with vaccines on target for an early 2021 date for implementation. These are the most aggressive schedules of course. Few are giving conservatives estimates right now, but I've seen June floated for more reasonable timelines.
dmarchand90 6y ago
My impression is that this was done to specifically counter Donald Trump rushing a vaccine prior to the election. I don't think it was really made to give any security beyond that
- saiya-jin 6y ago
  Any increase in testing time will give some, albeit hard to measure, improvement in safety of the vaccine. Or am I missing something?
  - marcosdumay 6y ago
    Trump has made some very worrisome statements intended on either rushing a vaccine or placing the blame for the lack of it into whoever refuses to rush it. Then the FDA answered with a non-statement that said basically "there's no conspiracy, we are fully invested into doing our job". And, of course, that gave a clear signal that the FDA felt pressured and was reported worldwide with that bias. So, I read the GP saying that the manufacturers are telling the FDA "we know better than you" in an attempt to conserve their own credibility. Notice that this is a very bad message to pass into their own regulator, and worrisome for different reasons. But as long as it's only PR, it's not a real problem.
- calvinmorrison 6y ago
  How about "rushing" the vaccine to you know... end the pandemic? Or would you rather more people die "from covid" to hurt Trumps chances of winning?
  - RHSeeger 6y ago
    I'd rather more people die to Covid than find out 20 million people have failing livers and 5 million were born with birth defects because they rushed a vaccine without enough testing.
    - garmaine 6y ago
      COVID has already caused at least that many people to have measurable levels of internal organ damage.
      - umanwizard 6y ago
        Source?
  - MacsHeadroom 6y ago
    Vaccines shouldn't be rushed because that's how you kill people with vaccines. Phase 3 vaccine trials take 18-24 months for very good reasons.
  - apocalyptic0n3 6y ago
    The bigger issue is if they rush a drug that does long term harm to people, it could destroy the company. This is a drug that they will be giving out to 300+ million people in the US along. Screwing it up would result in a massive amounts of lawsuits that they may not recover from. They don't want to risk that just for some political capital with a person who may not be in power in a few months.
    - garmaine 6y ago
      The fix for that is easy: have the FDA authorization grant them immunity from vaccine safety or efficacy liability.
- rsynnott 6y ago
  I wouldn't have thought the companies involved are primarily thinking of that. The risk to the companies is that Trump going on about skipping trials will hurt public confidence in any vaccine that is finally released, even if such skipping never happens. This announcement may serve to reassure some people that the manufacturers are going to behave themselves even if the government is negligent. Also, probably, reassure some shareholders. The reputational risks involved in this trial-skipping stuff are horrific.
shajznnckfke 6y ago
The virus is pretty bad, right? Ought we be making a cost-benefit analysis where we compare the risks of side effects from the vaccine to the risks of the spread of the virus? In comparison to a vaccine like Gardisil, which surely prevents far fewer deaths than a covid-19 vaccine will, wouldn’t such an analysis actually indicate that the trials be rushed to some extent? I’m feeling anxious that the current political milieu has a few factors pushing against deployment of a vaccine: 1. Republicans have been downplaying the virus the whole time, so they don’t take the need for a vaccine seriously. 2. Democrats are justifiably afraid of Trump pushing out a vaccine to get a pre-election “win”. What I’m worried about: 1. Huge numbers of people dying every day from covid-19, with so many people out of work and struggling, with no end in sight other than a vaccine. What’s the worst-case scenario for undiscovered side-effects on a treatment that has already been tested on thousands of people for months, and how probable is that risk?
- marcosdumay 6y ago
  A bad vaccine is pretty bad, and can easily be much worse than the virus. That's why we test them.
- JMTQp8lwXL 6y ago
  No point shipping a vaccine early if it doesn't actually work. That could do more damage, people thinking it's safe to be around others maskless, when in fact the world population instead received an ineffective vaccine.
  - shajznnckfke 6y ago
    We already know that some of the vaccine candidates work (ie. immune response). I’m not arguing we should ship untested vaccines, but challenging how many months we need to wait after testing.
    - FreakyT 6y ago
      We know that they trigger an immune response, but that alone doesn't necessarily mean much. For example, an early SARS vaccine candidate triggered an immune response in tests, but that immune response in practice actually made SARS infections worse.[1] [1]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335060/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335060/
onetimemanytime 6y ago
>>I don’t feel reassured that those won’t be rushed. actually I am. Vaccine makers don't gain much by doing something risky (considering the negatives) so they'll check the ones seeking election at all costs.
- takeda 6y ago
  especially right now, a failure when so many are paying attention (and large part of population is now anti-vaxers) could actually ruin the company.
  - onetimemanytime 6y ago
    should have added that that the vaccine has very limited $$ potential (can't charge a gazillion for it due to bad PR and competition) and most makers have hundred billion brands that can be ruined by this. So they aren't going to risk their company for this. Lastly, suppose Acme Pharma released it against all common sense, all over the media scientists would talk against it, so lose-lose.
    - refurb 6y ago
      This! I have some experience with the big pharma companies and they are risk adverse, even when it comes to PR. They often have billions of dollars coming in from approved products, and they are often more worried about that existing revenue than any potential future revenue.
    - lbeltrame 6y ago
      However, these companies got a lot of money to ramp up production ahead of approval ("at-risk manufacturing") often by governments. If the vaccine is a fluke, they might be in trouble.
- Tarq0n 6y ago
  They probably could get some countries to indemnify them, they'd probably survive the damage to their reputation.
takeda 6y ago
I heard somewhere that we should be prepared for middle of next year. They don't want politics to influence the safety of it. Releasing a vaccine that would cause damage would be devastating for the company. I'm wondering how do they test it, do they inject volunteers with the vacine, and they tell them to go infect themselves with a virus that 1 time out of 100 will kill them and an unknown percentage disable them?
- darkerside 6y ago
  Not to mention people's health...
- deleted 6y ago
  [deleted]
- dmoy 6y ago
  > I'm wondering how do they test it, do they inject volunteers with the vacine, and they tell them to go infect themselves with a virus that 1 time out of 100 will kill them and an unknown percentage disable them? Obviously no They get a large set of people (tens of thousands), half placebo, and then check rates afterwards.
  - loeg 6y ago
    The larger the set the faster the results, but a large set is expensive. "Afterwards" is sort of a simplification. The study arms are compared regularly throughout in case the study needs to be ended one way or the other (Data and Safety Monitoring Committee). (If the vaccine is effective: great, we want to ramp up production and give it to everyone ASAP. If the vaccine is ineffective or has very bad side effects, we also want to conclude the study.)
- loeg 6y ago
  > I'm wondering how do they test it, do they inject volunteers with the vacine, and they tell them to go infect themselves with a virus that 1 time out of 100 will kill them and an unknown percentage disable them? No, and this is why Phase III trials take a long time, potentially a very long time if we actually get a handle on the virus with measures like masking and social distancing. Here's the protocol: 1. Volunteers get the vaccine (experimental arm) or a placebo (control arm). 2. They go about their lives. 3. Both study arms report any cases of COVID they develop. Also, any deleterious symptom (potential side effects). 4. If the vaccine arm has a statistically significant reduction in infection rates, and/or severity, everyone wins and the study is concluded. This process can take years if the background rate of infection is low enough.
refurb 6y ago
You can look up those details on clinicaltrials.gov. They will list the timeline for the primary endpoint. That doesn't include recruitment delays though. Here are the details for the Oxford/Astrazeneca vaccine.[1] It's a 1 year trial. From what I've seen, they vary in length, but have interim analyses scheduled on a regular basis (3-6 months). If they see a strong signal, they can seek approval based off that interim data. [1]https://clinicaltrials.gov/ct2/show/NCT04536051?term=ChAdOx1-nCov19&draw=2&rank=2 https://clinicaltrials.gov/ct2/show/NCT04536051?term=ChAdOx1...
loeg 6y ago
Potentially years.
mumblemumble 6y ago
According to FDA, phase III trials typically take 1-4 years. It's worth noting that, if there are any adverse effects that take a while to become apparent, the trial will need at least that long to be able to detect them. To my knowledge, severe vaccine reactions usually happen fairly soon, but a year before onset isn't necessarily unheard of for some vaccines. Also, that's just for vaccines that got approved; there may be some selection effects there. The bigger one I'm worried about is whether or not the vaccine will confer lasting immunity. If we rush a vaccine to market in six months, everybody gets it, and returns to their pre-pandemic lifestyles, then we'll be in for a nasty surprise on down the road if it turns out that it only confers immunity for a year. It seems to me like we need to consider the possibility that an imperfect vaccine is worse than no vaccine at all.
- RangerScience 6y ago
  If the vaccine only confers a few months of immunity, like the yearly flu vaccine, how long does it take to develop, produce and distribute the update?
  - hartator 6y ago
    I think the yearly flu vaccine give you lifetime immunity against the strains you are vaccinated against. However flu strains change every year. (Hopefully that won’t be the case for covid!)
    - mumblemumble 6y ago
      Officially, it gives you at least 6 months' worth of immunity, but, beyond that, there are no guarantees, and it generally fades over time. That's why the recommendation is to wait until shortly before the onset of flu season to get vaccinated: If you get vaccinated in July, there's no guarantee that the vaccination will carry you through the worst of a (northern hemisphere) flu season.
    - deleted 6y ago
      [deleted]
  - 6y ago

deelowe 6y ago

It's a moving target, so it's hard to say. Phase 3 trials depend entirely on the number of infected in the control group. Current estimates seem to indicate we may start seeing preliminary results in early Q4 with vaccines on target for an early 2021 date for implementation. These are the most aggressive schedules of course. Few are giving conservatives estimates right now, but I've seen June floated for more reasonable timelines.

dmarchand90 6y ago

My impression is that this was done to specifically counter Donald Trump rushing a vaccine prior to the election. I don't think it was really made to give any security beyond that

saiya-jin 6y ago
Any increase in testing time will give some, albeit hard to measure, improvement in safety of the vaccine. Or am I missing something?
- marcosdumay 6y ago
  Trump has made some very worrisome statements intended on either rushing a vaccine or placing the blame for the lack of it into whoever refuses to rush it. Then the FDA answered with a non-statement that said basically "there's no conspiracy, we are fully invested into doing our job". And, of course, that gave a clear signal that the FDA felt pressured and was reported worldwide with that bias. So, I read the GP saying that the manufacturers are telling the FDA "we know better than you" in an attempt to conserve their own credibility. Notice that this is a very bad message to pass into their own regulator, and worrisome for different reasons. But as long as it's only PR, it's not a real problem.
calvinmorrison 6y ago
How about "rushing" the vaccine to you know... end the pandemic? Or would you rather more people die "from covid" to hurt Trumps chances of winning?
- RHSeeger 6y ago
  I'd rather more people die to Covid than find out 20 million people have failing livers and 5 million were born with birth defects because they rushed a vaccine without enough testing.
  - garmaine 6y ago
    COVID has already caused at least that many people to have measurable levels of internal organ damage.
    - umanwizard 6y ago
      Source?
- MacsHeadroom 6y ago
  Vaccines shouldn't be rushed because that's how you kill people with vaccines. Phase 3 vaccine trials take 18-24 months for very good reasons.
- apocalyptic0n3 6y ago
  The bigger issue is if they rush a drug that does long term harm to people, it could destroy the company. This is a drug that they will be giving out to 300+ million people in the US along. Screwing it up would result in a massive amounts of lawsuits that they may not recover from. They don't want to risk that just for some political capital with a person who may not be in power in a few months.
  - garmaine 6y ago
    The fix for that is easy: have the FDA authorization grant them immunity from vaccine safety or efficacy liability.
rsynnott 6y ago
I wouldn't have thought the companies involved are primarily thinking of that. The risk to the companies is that Trump going on about skipping trials will hurt public confidence in any vaccine that is finally released, even if such skipping never happens. This announcement may serve to reassure some people that the manufacturers are going to behave themselves even if the government is negligent. Also, probably, reassure some shareholders. The reputational risks involved in this trial-skipping stuff are horrific.

shajznnckfke 6y ago

The virus is pretty bad, right? Ought we be making a cost-benefit analysis where we compare the risks of side effects from the vaccine to the risks of the spread of the virus? In comparison to a vaccine like Gardisil, which surely prevents far fewer deaths than a covid-19 vaccine will, wouldn’t such an analysis actually indicate that the trials be rushed to some extent? I’m feeling anxious that the current political milieu has a few factors pushing against deployment of a vaccine: 1. Republicans have been downplaying the virus the whole time, so they don’t take the need for a vaccine seriously. 2. Democrats are justifiably afraid of Trump pushing out a vaccine to get a pre-election “win”. What I’m worried about: 1. Huge numbers of people dying every day from covid-19, with so many people out of work and struggling, with no end in sight other than a vaccine. What’s the worst-case scenario for undiscovered side-effects on a treatment that has already been tested on thousands of people for months, and how probable is that risk?

marcosdumay 6y ago
A bad vaccine is pretty bad, and can easily be much worse than the virus. That's why we test them.
JMTQp8lwXL 6y ago
No point shipping a vaccine early if it doesn't actually work. That could do more damage, people thinking it's safe to be around others maskless, when in fact the world population instead received an ineffective vaccine.
- shajznnckfke 6y ago
  We already know that some of the vaccine candidates work (ie. immune response). I’m not arguing we should ship untested vaccines, but challenging how many months we need to wait after testing.
  - FreakyT 6y ago
    We know that they trigger an immune response, but that alone doesn't necessarily mean much. For example, an early SARS vaccine candidate triggered an immune response in tests, but that immune response in practice actually made SARS infections worse.[1] [1]: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335060/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3335060/

onetimemanytime 6y ago

>>I don’t feel reassured that those won’t be rushed. actually I am. Vaccine makers don't gain much by doing something risky (considering the negatives) so they'll check the ones seeking election at all costs.

takeda 6y ago
especially right now, a failure when so many are paying attention (and large part of population is now anti-vaxers) could actually ruin the company.
- onetimemanytime 6y ago
  should have added that that the vaccine has very limited $$ potential (can't charge a gazillion for it due to bad PR and competition) and most makers have hundred billion brands that can be ruined by this. So they aren't going to risk their company for this. Lastly, suppose Acme Pharma released it against all common sense, all over the media scientists would talk against it, so lose-lose.
  - refurb 6y ago
    This! I have some experience with the big pharma companies and they are risk adverse, even when it comes to PR. They often have billions of dollars coming in from approved products, and they are often more worried about that existing revenue than any potential future revenue.
  - lbeltrame 6y ago
    However, these companies got a lot of money to ramp up production ahead of approval ("at-risk manufacturing") often by governments. If the vaccine is a fluke, they might be in trouble.
Tarq0n 6y ago
They probably could get some countries to indemnify them, they'd probably survive the damage to their reputation.

takeda 6y ago

I heard somewhere that we should be prepared for middle of next year. They don't want politics to influence the safety of it. Releasing a vaccine that would cause damage would be devastating for the company. I'm wondering how do they test it, do they inject volunteers with the vacine, and they tell them to go infect themselves with a virus that 1 time out of 100 will kill them and an unknown percentage disable them?

darkerside 6y ago
Not to mention people's health...
deleted 6y ago
[deleted]
dmoy 6y ago
> I'm wondering how do they test it, do they inject volunteers with the vacine, and they tell them to go infect themselves with a virus that 1 time out of 100 will kill them and an unknown percentage disable them? Obviously no They get a large set of people (tens of thousands), half placebo, and then check rates afterwards.
- loeg 6y ago
  The larger the set the faster the results, but a large set is expensive. "Afterwards" is sort of a simplification. The study arms are compared regularly throughout in case the study needs to be ended one way or the other (Data and Safety Monitoring Committee). (If the vaccine is effective: great, we want to ramp up production and give it to everyone ASAP. If the vaccine is ineffective or has very bad side effects, we also want to conclude the study.)
loeg 6y ago
> I'm wondering how do they test it, do they inject volunteers with the vacine, and they tell them to go infect themselves with a virus that 1 time out of 100 will kill them and an unknown percentage disable them? No, and this is why Phase III trials take a long time, potentially a very long time if we actually get a handle on the virus with measures like masking and social distancing. Here's the protocol: 1. Volunteers get the vaccine (experimental arm) or a placebo (control arm). 2. They go about their lives. 3. Both study arms report any cases of COVID they develop. Also, any deleterious symptom (potential side effects). 4. If the vaccine arm has a statistically significant reduction in infection rates, and/or severity, everyone wins and the study is concluded. This process can take years if the background rate of infection is low enough.

refurb 6y ago

You can look up those details on clinicaltrials.gov. They will list the timeline for the primary endpoint. That doesn't include recruitment delays though. Here are the details for the Oxford/Astrazeneca vaccine.[1] It's a 1 year trial. From what I've seen, they vary in length, but have interim analyses scheduled on a regular basis (3-6 months). If they see a strong signal, they can seek approval based off that interim data. [1]https://clinicaltrials.gov/ct2/show/NCT04536051?term=ChAdOx1-nCov19&draw=2&rank=2 https://clinicaltrials.gov/ct2/show/NCT04536051?term=ChAdOx1...

loeg 6y ago

Potentially years.

mumblemumble 6y ago

According to FDA, phase III trials typically take 1-4 years. It's worth noting that, if there are any adverse effects that take a while to become apparent, the trial will need at least that long to be able to detect them. To my knowledge, severe vaccine reactions usually happen fairly soon, but a year before onset isn't necessarily unheard of for some vaccines. Also, that's just for vaccines that got approved; there may be some selection effects there. The bigger one I'm worried about is whether or not the vaccine will confer lasting immunity. If we rush a vaccine to market in six months, everybody gets it, and returns to their pre-pandemic lifestyles, then we'll be in for a nasty surprise on down the road if it turns out that it only confers immunity for a year. It seems to me like we need to consider the possibility that an imperfect vaccine is worse than no vaccine at all.

RangerScience 6y ago
If the vaccine only confers a few months of immunity, like the yearly flu vaccine, how long does it take to develop, produce and distribute the update?
- hartator 6y ago
  I think the yearly flu vaccine give you lifetime immunity against the strains you are vaccinated against. However flu strains change every year. (Hopefully that won’t be the case for covid!)
  - mumblemumble 6y ago
    Officially, it gives you at least 6 months' worth of immunity, but, beyond that, there are no guarantees, and it generally fades over time. That's why the recommendation is to wait until shortly before the onset of flu season to get vaccinated: If you get vaccinated in July, there's no guarantee that the vaccination will carry you through the worst of a (northern hemisphere) flu season.
  - deleted 6y ago
    [deleted]
- 6y ago