7 ms·

Wonder what the trial exclusion criteria was...it’s not referenced in this article.

renewiltord 6y ago
Why wonder? Just use the primary source. Here's the Phase 1 https://clinicaltrials.gov/ct2/show/NCT04283461?term=NCT04283461&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04283461?term=NCT0428... Phase 2a and Phase 3 similarly listed.
mrjaeger 6y ago
Can read all of them in their published protocol at https://www.modernatx.com/sites/default/files/mRNA-1273-P301-Protocol.pdf https://www.modernatx.com/sites/default/files/mRNA-1273-P301... under section 5.2.
- tpmx 6y ago
  Relevant criteria for the question "does it it exclude old, fragile people with various common pre-existing conditions?" (not exhaustive, but indicative): Included: Pre-existing conditions are okay as long as they are in a stable condition (defined as no significant change in therapy etc for the 3 months before enrollment). Excluded: Immunosuppressive or immunodeficient state, asplenia, recurrent severe infections (HIV-positive participants with CD4 count ≥350 cells/mm 3 and an undetectable HIV viral load within the past year [low level variations from 50-500 viral copies which do not lead to changes in antiretroviral therapy [ART] are permitted]). Looks fair enough to an amateur like myself. Edit: Not sure how common a immunosuppressive or immunodeficient state is in a typical population. Perhaps it's common enough to be relevant?
  - disgruntledphd2 6y ago
    I think (from my parents and in-laws) that immunosuppression is normally associated with current cancer treatment. So, for example, it looks like this protocol would exclude people getting chemotherapy. Happy to be proven wrong on this by someone with more information.
    - JulianMorrison 6y ago
      Also transplant recipients take suppressants so their immune system doesn't reject the graft.
    - chimeracoder 6y ago
      > I think (from my parents and in-laws) that immunosuppression is normally associated with current cancer treatment. There are other reasons a person would be considered immunosuppressed, and plenty of non-chemotherapy drugs that have immunosuppressive effects. But yes, cancer is one of them. It would make no sense to include immunosuppressed people in the initial trials for a vaccine, the purpose of which is to determine whether a vaccine can induce an immune response.
      - disgruntledphd2 6y ago
        Yeah, agreed. My selfish concern is then whether or not the vaccine will work for them.
        chimeracoder 6y ago
        > My selfish concern is then whether or not the vaccine will work for them. We won't have hard data on that specific question for a very long time, but it's something your/their doctor would be better equipped to make an educated guess about, given the specifics of their situation ("immunosuppressed" can mean a range of things). In some cases, a vaccine might do nothing. In some, it might be actively dangerous. In some, it might have a weaker but still nonzero protective effect. But I wouldn't trust anything you read on HN that tries tell you anything more specific than that.
        tsimionescu 6y ago
        Unfortunately, vaccines can't really help immunocompromised people, as their immune system is simply unable to fight off any infection, regardless of whether it recognizes the infection or not (of course, this may be a matter of degrees). That is why, for example, people with advanced AIDS can die from essentially any pathogen.
  - Majromax 6y ago
    Immune suppressed/deficient patients are not good candidates for vaccines in the first place, since they would be unlikely to mount an effective immune response.
    - tpmx 6y ago
      I forgot that part. That's the reason why also young healthy people need to take the vaccine in order to stop the spread. It's a solidarity gesture.
      - maxerickson 6y ago
        A vaccine is likely to be safer for low risk people than a course of infection, it's not just helping slow the spread.
        sp332 6y ago
        I think tpmx's point is that the virus would also be less dangerous for them, so getting the vaccine has less chance of having a net benefit for the individual.
        tpmx 6y ago
        Yeah, it was, but I think the argument that the vaccine is a safer option for this crowd is also a pretty persuasive argument. I'm not exactly in this crowd (I'm 43) but given what I now know about the prevalence of scary long term covid-19 issues ("long haulers") in young people, I would take this vaccine in a heart beat "even" if I were young.
    - dotuser 6y ago
      That sounds backwards. Shouldn't those with weakened immune response be first in line for the vaccine? The vaccine would give them a boost. Those with strong immune response have a better chance of fighting off the virus.
      - 6y ago
  - nicholasjarnold 6y ago
    > Not sure how common a immunosuppressive or immunodeficient state is in a typical population. Pregnant women are considered immunosuppressed to a certain extent. I'm a software engineer and not a doctor though, so someone could perhaps shed more light on this.
  - cm2187 6y ago
    That could exclude people who are the most likely of dying of covid (a severe case of covid doesn't mean dying, for instance I heard an ICU specialist explaining that people who are seriously obese often require ICU treatment but rarely die from it, the people who die usually have serious co-morbidities and an already reduced life expectancy). But it's kind of secondary anyway. The main goal of the vaccine is to stop the virus from spreading in the population and getting a chance to reach vulnerable people. Even if it were to only protect people who wouldn't die of Covid in the first place, that's the vast majority of the population and enough to significantly reduce the chance of spreading. At the condition that these studies measure the right thing. If it merely stops the symptoms but doesn't stop the spread of the virus, that may be a problem.
  - lokar 6y ago
    Almost 40,000 people got an organ transplant in the US in 2019
    - reaperducer 6y ago
      And almost 140,000 people got COVID in the US yesterday.
  - yread 6y ago
    That's why it's so important that all the people who can get the vaccine get it - this is the herd immunity everyone is yammering about. If the healthy people are vaccinated the virus won't be able to spread to the people who can't get vaccinated.
- sandworm101 6y ago
  There is an additional question that opens the door to all sorts of hidden exclusions: Were study participants given medical advice prior to participation? If I ask my doctor whether it is a "good idea" for me to participate in an investigational study like this, there are all number of reasons he may advise against. Those reasons form a defacto hidden list of exclusions. Would a doctor advise a patient with diabetes, high blood pressure, or any other chronic illness, to participate in such a study?
  - amanaplanacanal 6y ago
    Why wouldn’t they? It’s not like the study intentionally infected people with the virus.
    - sandworm101 6y ago
      Because the default with chronically ill patients is no. There are also financial issues. If a patient is chronic then they are likely on ongoing treatments of some sort. If complication arise from the investigational medication then questions come up as to who will pay for what treatment. What if the complications lead to the patient having to abandon the ongoing chronic treatment? So the docs will lean towards no. And in the US there is the huge question of whether one's insurance even allows for such participation, but that is a question for one's lawyer rather than doctor. All such concerns can lead to the exclusion of certain populations, possibly the populations more relevant to the study.
  - yibg 6y ago
    Isn't this why the results are compared against the control group?
    - sandworm101 6y ago
      For a study to be valid and useful, the control group has to go through exactly the same criteria as the test group. Everyone is "blind" to whether they get the placebo or the real thing. So they all get the same interviews/tests and rejection criteria. Putting all the diabetics in the control/placebo group would make it pretty obvious who was and wasn't getting the real thing.
deleted 6y ago
[deleted]
mam2 6y ago
Yeah how would they find anyone careless enough aged more than 65 who would accept to 1/ take the vaccine 2/ expose himself to the virus to chekc his immunity. We will never know before trial
- mattkrause 6y ago
  None of these trials have used a "challenge" design where people were deliberately exposed to the virus. Instead, they vaccinate a ton of people and then let them go about their lives. Participants' risk of getting COVID shouldn't go up, unless participating in the trial induces them to behave more riskily.
  - tinus_hn 6y ago
    That wouldn’t be smart because they don’t get to know if they got the vaccine or the placebo.
    - mattkrause 6y ago
      No, definitely not! Still, risk homeostasis is (sometimes) a thing: people reportedly ski faster when wearing a helmet, drive closer with ABS, and stuff like that. I was just trying to pre-empt that argument. That said, if this were a factor, it would be small and would make the trial results most impressive, rather than less.
as_keyof_typeof 6y ago
I've also been wondering - are the trial participants purposefully exposed to the virus?
mssundaram 6y ago
Are the trial participants exposed to the virus purposefully or is the result that none of participants developed covid just from regular daily living?
- contravariant 6y ago
  There's a (blinded) control group so purely based on how deeply unethical it would be to purposefully expose them to the virus I'd wager they were 'natural' occurrences.
  - mssundaram 6y ago
    I understand how it could be unethical, though I'd be more confident in a study that had purposeful exposure - how can we say the vaccine really was the means of protection, and not just the current measures?
    - zeroimpl 6y ago
      That's precisely why there is a control group.
      - mssundaram 6y ago
        And that's what I mean, the control group may be avoiding exposure altogether.
        easde 6y ago
        The study compares how many people in the experimental group and control group develop symptomatic COVID-19. In this case 11 people in the experimental group developed COVID-19 versus 185 in the control group. Thus the vaccine is approximately 185 / (185 + 11) = 94% effective, assuming both groups behaved similarly. If the control group intentionally avoided exposure more than the experimental group, then the vaccine is even more effective than the study result. This is a blinded study though, so participants don't know which group they're in unless they go out of their way to find out (eg. taking an antibody test).

Why wonder? Just use the primary source. Here's the Phase 1 https://clinicaltrials.gov/ct2/show/NCT04283461?term=NCT04283461&draw=2&rank=1 https://clinicaltrials.gov/ct2/show/NCT04283461?term=NCT0428... Phase 2a and Phase 3 similarly listed.

mrjaeger 6y ago

Can read all of them in their published protocol at https://www.modernatx.com/sites/default/files/mRNA-1273-P301-Protocol.pdf https://www.modernatx.com/sites/default/files/mRNA-1273-P301... under section 5.2.

tpmx 6y ago
Relevant criteria for the question "does it it exclude old, fragile people with various common pre-existing conditions?" (not exhaustive, but indicative): Included: Pre-existing conditions are okay as long as they are in a stable condition (defined as no significant change in therapy etc for the 3 months before enrollment). Excluded: Immunosuppressive or immunodeficient state, asplenia, recurrent severe infections (HIV-positive participants with CD4 count ≥350 cells/mm 3 and an undetectable HIV viral load within the past year [low level variations from 50-500 viral copies which do not lead to changes in antiretroviral therapy [ART] are permitted]). Looks fair enough to an amateur like myself. Edit: Not sure how common a immunosuppressive or immunodeficient state is in a typical population. Perhaps it's common enough to be relevant?
- disgruntledphd2 6y ago
  I think (from my parents and in-laws) that immunosuppression is normally associated with current cancer treatment. So, for example, it looks like this protocol would exclude people getting chemotherapy. Happy to be proven wrong on this by someone with more information.
  - JulianMorrison 6y ago
    Also transplant recipients take suppressants so their immune system doesn't reject the graft.
  - chimeracoder 6y ago
    > I think (from my parents and in-laws) that immunosuppression is normally associated with current cancer treatment. There are other reasons a person would be considered immunosuppressed, and plenty of non-chemotherapy drugs that have immunosuppressive effects. But yes, cancer is one of them. It would make no sense to include immunosuppressed people in the initial trials for a vaccine, the purpose of which is to determine whether a vaccine can induce an immune response.
    - disgruntledphd2 6y ago
      Yeah, agreed. My selfish concern is then whether or not the vaccine will work for them.
      - chimeracoder 6y ago
        > My selfish concern is then whether or not the vaccine will work for them. We won't have hard data on that specific question for a very long time, but it's something your/their doctor would be better equipped to make an educated guess about, given the specifics of their situation ("immunosuppressed" can mean a range of things). In some cases, a vaccine might do nothing. In some, it might be actively dangerous. In some, it might have a weaker but still nonzero protective effect. But I wouldn't trust anything you read on HN that tries tell you anything more specific than that.
      - tsimionescu 6y ago
        Unfortunately, vaccines can't really help immunocompromised people, as their immune system is simply unable to fight off any infection, regardless of whether it recognizes the infection or not (of course, this may be a matter of degrees). That is why, for example, people with advanced AIDS can die from essentially any pathogen.
- Majromax 6y ago
  Immune suppressed/deficient patients are not good candidates for vaccines in the first place, since they would be unlikely to mount an effective immune response.
  - tpmx 6y ago
    I forgot that part. That's the reason why also young healthy people need to take the vaccine in order to stop the spread. It's a solidarity gesture.
    - maxerickson 6y ago
      A vaccine is likely to be safer for low risk people than a course of infection, it's not just helping slow the spread.
      - sp332 6y ago
        I think tpmx's point is that the virus would also be less dangerous for them, so getting the vaccine has less chance of having a net benefit for the individual.
        tpmx 6y ago
        Yeah, it was, but I think the argument that the vaccine is a safer option for this crowd is also a pretty persuasive argument. I'm not exactly in this crowd (I'm 43) but given what I now know about the prevalence of scary long term covid-19 issues ("long haulers") in young people, I would take this vaccine in a heart beat "even" if I were young.
  - dotuser 6y ago
    That sounds backwards. Shouldn't those with weakened immune response be first in line for the vaccine? The vaccine would give them a boost. Those with strong immune response have a better chance of fighting off the virus.
    - 6y ago
- nicholasjarnold 6y ago
  > Not sure how common a immunosuppressive or immunodeficient state is in a typical population. Pregnant women are considered immunosuppressed to a certain extent. I'm a software engineer and not a doctor though, so someone could perhaps shed more light on this.
- cm2187 6y ago
  That could exclude people who are the most likely of dying of covid (a severe case of covid doesn't mean dying, for instance I heard an ICU specialist explaining that people who are seriously obese often require ICU treatment but rarely die from it, the people who die usually have serious co-morbidities and an already reduced life expectancy). But it's kind of secondary anyway. The main goal of the vaccine is to stop the virus from spreading in the population and getting a chance to reach vulnerable people. Even if it were to only protect people who wouldn't die of Covid in the first place, that's the vast majority of the population and enough to significantly reduce the chance of spreading. At the condition that these studies measure the right thing. If it merely stops the symptoms but doesn't stop the spread of the virus, that may be a problem.
- lokar 6y ago
  Almost 40,000 people got an organ transplant in the US in 2019
  - reaperducer 6y ago
    And almost 140,000 people got COVID in the US yesterday.
- yread 6y ago
  That's why it's so important that all the people who can get the vaccine get it - this is the herd immunity everyone is yammering about. If the healthy people are vaccinated the virus won't be able to spread to the people who can't get vaccinated.
sandworm101 6y ago
There is an additional question that opens the door to all sorts of hidden exclusions: Were study participants given medical advice prior to participation? If I ask my doctor whether it is a "good idea" for me to participate in an investigational study like this, there are all number of reasons he may advise against. Those reasons form a defacto hidden list of exclusions. Would a doctor advise a patient with diabetes, high blood pressure, or any other chronic illness, to participate in such a study?
- amanaplanacanal 6y ago
  Why wouldn’t they? It’s not like the study intentionally infected people with the virus.
  - sandworm101 6y ago
    Because the default with chronically ill patients is no. There are also financial issues. If a patient is chronic then they are likely on ongoing treatments of some sort. If complication arise from the investigational medication then questions come up as to who will pay for what treatment. What if the complications lead to the patient having to abandon the ongoing chronic treatment? So the docs will lean towards no. And in the US there is the huge question of whether one's insurance even allows for such participation, but that is a question for one's lawyer rather than doctor. All such concerns can lead to the exclusion of certain populations, possibly the populations more relevant to the study.
- yibg 6y ago
  Isn't this why the results are compared against the control group?
  - sandworm101 6y ago
    For a study to be valid and useful, the control group has to go through exactly the same criteria as the test group. Everyone is "blind" to whether they get the placebo or the real thing. So they all get the same interviews/tests and rejection criteria. Putting all the diabetics in the control/placebo group would make it pretty obvious who was and wasn't getting the real thing.

deleted 6y ago

[deleted]

mam2 6y ago

Yeah how would they find anyone careless enough aged more than 65 who would accept to 1/ take the vaccine 2/ expose himself to the virus to chekc his immunity. We will never know before trial

mattkrause 6y ago
None of these trials have used a "challenge" design where people were deliberately exposed to the virus. Instead, they vaccinate a ton of people and then let them go about their lives. Participants' risk of getting COVID shouldn't go up, unless participating in the trial induces them to behave more riskily.
- tinus_hn 6y ago
  That wouldn’t be smart because they don’t get to know if they got the vaccine or the placebo.
  - mattkrause 6y ago
    No, definitely not! Still, risk homeostasis is (sometimes) a thing: people reportedly ski faster when wearing a helmet, drive closer with ABS, and stuff like that. I was just trying to pre-empt that argument. That said, if this were a factor, it would be small and would make the trial results most impressive, rather than less.

as_keyof_typeof 6y ago

I've also been wondering - are the trial participants purposefully exposed to the virus?

mssundaram 6y ago

Are the trial participants exposed to the virus purposefully or is the result that none of participants developed covid just from regular daily living?

contravariant 6y ago
There's a (blinded) control group so purely based on how deeply unethical it would be to purposefully expose them to the virus I'd wager they were 'natural' occurrences.
- mssundaram 6y ago
  I understand how it could be unethical, though I'd be more confident in a study that had purposeful exposure - how can we say the vaccine really was the means of protection, and not just the current measures?
  - zeroimpl 6y ago
    That's precisely why there is a control group.
    - mssundaram 6y ago
      And that's what I mean, the control group may be avoiding exposure altogether.
      - easde 6y ago
        The study compares how many people in the experimental group and control group develop symptomatic COVID-19. In this case 11 people in the experimental group developed COVID-19 versus 185 in the control group. Thus the vaccine is approximately 185 / (185 + 11) = 94% effective, assuming both groups behaved similarly. If the control group intentionally avoided exposure more than the experimental group, then the vaccine is even more effective than the study result. This is a blinded study though, so participants don't know which group they're in unless they go out of their way to find out (eg. taking an antibody test).