4 ms·

Looks interesting. Let us know in 3-5 years when the Phase III trials are done and there's an overall survival benefit beyond the standard of care at that time.

SV_BubbleTime 4y ago
3-5 years and previously completed phase three trials didn’t stop mRNA deployments. So, I have no idea if that is the new standard or not. Let’s hope it was a fluke, and that this on topic is a big deal.
- lumost 4y ago
  mRNA vaccines benefited from the statistical power of having a widespread pandemic. Trials could simply do a double blind test and check how often the treatment subjects got covid vs. control. With thousands of study participants and a fast moving virus statistical power is reached quickly. For cancers, the disease is slow moving and there are fewer patients seeking experimental treatment. Fewer still are willing to chance that they are part of a control group. The patients who do participate are likely taking multiple other treatments, limiting the statistical power of the trial.
  - loonster 4y ago
    You cannot use 10 women to grow a fetus in 1 month. Likewise, you cannot have a good understanding of the long term risks without having s study that runs longterm.
    - arcticbull 4y ago
      Luckily we've been studying mRNA vaccines for over 50 years, which gave us a very good understanding of the long-term effects. What we really needed to test for was short-term effects + efficacy. These are easy to determine when 1% of the population is infected at the time of your clinical trial. I can't stress how much the COVID mRNA deployment wasn't a "#yolo" moment like some folks still continue to insist. It was a product of years and years of meticulous research and development. This put us at the finish line, and all we had to do was get over it. We also got the J&J vaccine out in basically the same amount of time - because like the mRNA vaccines, the adenoviral vector vaccine platform had about 50 years of research and development behind it. To use your analogy, we started with 10 ladies each 8 months pregnant, and we got them over the line in a month. That doesn't mean the pregnancy took a month - just that we had a head start.
      - SV_BubbleTime 4y ago
        How many times did mRNA vaccines pass phase three trials in those 50 years? > We also got the J&J vaccine out in basically the same amount of time No skin off my back, but is that an example you want to use?
      - ch4s3 4y ago
        Not to be overly pedantic, but having the idea in the 1970s didn't count for much, because no one could get mRNA into human cells until around 1987. The first attempt at a vaccine was around maybe 1993. I mean, directionally your right but saying "we've been studying mRNA vaccines for over 50 years" isn't really correct.
    - lebuffon 4y ago
      Interesting that you used that phrase on HN. Not sure if you ever heard that Fred Brooks said software development is also like this: "It takes nine months to have a baby, no matter how many women you put on the the job" The Mythical Man Month We now return to our regularly scheduled program...
      - loonster 4y ago
        That is a much more eloquent way of putting it. I do wonder how old that phrase is.
    - throw__away7391 4y ago
      I am not a doctor nor a woman, but shouldn't the math on that work out to nine women? Also, I believe that even just one woman can grow a fetus in one month, no?
      - makeset 4y ago
        > shouldn't the math on that work out to nine women? The average term being a round 40 weeks, a pregnancy “month” is 4 weeks by convention.
        danachow 4y ago
        > The average term being a round 40 weeks, a pregnancy “month” is 4 weeks by convention. This convention is news to me - though the confusion is not. Months are plain old calendar months in pregnancy (ie about 4.3 weeks). https://www.verywellfamily.com/how-many-months-pregnant-am-i-2760090 https://www.verywellfamily.com/how-many-months-pregnant-am-i... 40 weeks is by convention from estimated last menstrual period, which is of course about 2 weeks prior to fertilization - so the actual gestastional period is closer to 38 weeks (that is closer to 9 months than 10 months).
    - lamontcg 4y ago
      Vaccines either produce side effects in 3-6 months or they don't. There's no hidden time bomb in all the people who were vaccinated last year. The FDA doesn't require long term safety studies for vaccines, and all the coronavirus vaccines have met the requirements. Nothing has been rushed. We have a good understanding of this because the side effects are entirely dominated by autoimmune conditions, and we understand from the field of rheumatology how those arise. We don't need to study pregnant women for another 5 years to see if any more babies pop out after the first one. Pregnancy is done in 9 months. Autoimmune side effects from vaccines happen in 3-6.
      - lamontcg 4y ago
        > This complex, specific and intricate process spans a number of months. Ultimately, though, in the absence of further stimulation by new copies of the spike protein, the immune response settles down, and effector cells—those directly and transiently involved in fighting the virus—decrease in frequency. Instead memory cells are established, poised to quickly ramp up production of antibodies, and even to replicate themselves, settling into their biological niches in our bodies until called upon once more if we happen to get infected. (This is what confers immunity to the coronavirus over the long run.) Antibody concentrations, some weeks after immunization, begin to reach their peak concentration in our blood, ultimately plateauing and beginning their slow decline. After this point, the risk of severe immunization-related complications doesn’t increase. Quite the opposite, in fact: it declines to virtually nothing after about three months. The six-month endpoint for these products is thus a rather conservative timeframe. Forget five or ten years: the way your immune system works does not allow for such long-term safety concerns. https://bostonreview.net/articles/the-long-term-safety-argument-over-covid-19-vaccines/ https://bostonreview.net/articles/the-long-term-safety-argum...
      - XorNot 4y ago
        It is wild how heavily downvoted this is. Everything in this comment is correct (I also note none of the downvotes could be bothered to present any rebuttal to the claims).
        blindmute 4y ago
    - mbreese 4y ago
      This is a phase I study. The point here is to establish safety. The study believes this treatment could have a benefit for patients, but they aren’t sure if there are unknown risks. This is to establish that there aren’t any unknown risks. The eligible patient population has already advanced on therapy (meaning the current standard of care hasn’t worked). Getting patients to any sort of long-term response is the goal here. If there are any long term risks, that would be considered a good outcome (because the patient is still alive to have long term effects). Any further (heritable genetic) risks are mitigated as the patients specifically are excluded if they are planning on having children in the near future.
  - mcswell 4y ago
    Do you really need a control group for this kind of study? The growth of cancer has been studied for well over a century, with millions of cases; what would a hundred more (to take a random number) tell you? (BTW, this is a real question, not a sarcasm!)
    - yourMadness 4y ago
      The control group is needed to measure process properties / systematic error. It does not need to be a placebo group. Previous data at the same hospital does not help because the regular medicine does not run according to study protocols.
- shadowgovt 4y ago
  It's not the new standard. Breast cancer is not contagious and has no chance of becoming a pandemic. The issue with a pandemic is every person infected is several more infectees in the future; geometric death effects instead of linear.
  - rory 4y ago
    At the risk of starting a flamewar... wasn't the difference actually just the pure volume of severe sickness and death? The clinical trials didn't even attempt to test viral spread, they tested prevention of symptoms. If suddenly 50% of the world population got breast cancer at once, I'm willing to bet we'd be fine rolling out new technologies faster than the typical standard, despite it being non-contagious.
    - ray__ 4y ago
      A major difference is that no two breast cancers are the same. You're probably correct in your second point due to the sheer demand, but developing a treatment for any cancer is not the same as developing a treatment for an infectious disease because there is no one-size-fits-all strategy. A situation like the one you describe with simultaneous onset of breast cancer in a large population would definitely facilitate research and help lead to a better standard of care, though.
Kalanos 4y ago
ok we will!
- deleted 4y ago
  [deleted]

SV_BubbleTime 4y ago

3-5 years and previously completed phase three trials didn’t stop mRNA deployments. So, I have no idea if that is the new standard or not. Let’s hope it was a fluke, and that this on topic is a big deal.

lumost 4y ago
mRNA vaccines benefited from the statistical power of having a widespread pandemic. Trials could simply do a double blind test and check how often the treatment subjects got covid vs. control. With thousands of study participants and a fast moving virus statistical power is reached quickly. For cancers, the disease is slow moving and there are fewer patients seeking experimental treatment. Fewer still are willing to chance that they are part of a control group. The patients who do participate are likely taking multiple other treatments, limiting the statistical power of the trial.
- loonster 4y ago
  You cannot use 10 women to grow a fetus in 1 month. Likewise, you cannot have a good understanding of the long term risks without having s study that runs longterm.
  - arcticbull 4y ago
    Luckily we've been studying mRNA vaccines for over 50 years, which gave us a very good understanding of the long-term effects. What we really needed to test for was short-term effects + efficacy. These are easy to determine when 1% of the population is infected at the time of your clinical trial. I can't stress how much the COVID mRNA deployment wasn't a "#yolo" moment like some folks still continue to insist. It was a product of years and years of meticulous research and development. This put us at the finish line, and all we had to do was get over it. We also got the J&J vaccine out in basically the same amount of time - because like the mRNA vaccines, the adenoviral vector vaccine platform had about 50 years of research and development behind it. To use your analogy, we started with 10 ladies each 8 months pregnant, and we got them over the line in a month. That doesn't mean the pregnancy took a month - just that we had a head start.
    - SV_BubbleTime 4y ago
      How many times did mRNA vaccines pass phase three trials in those 50 years? > We also got the J&J vaccine out in basically the same amount of time No skin off my back, but is that an example you want to use?
    - ch4s3 4y ago
      Not to be overly pedantic, but having the idea in the 1970s didn't count for much, because no one could get mRNA into human cells until around 1987. The first attempt at a vaccine was around maybe 1993. I mean, directionally your right but saying "we've been studying mRNA vaccines for over 50 years" isn't really correct.
  - lebuffon 4y ago
    Interesting that you used that phrase on HN. Not sure if you ever heard that Fred Brooks said software development is also like this: "It takes nine months to have a baby, no matter how many women you put on the the job" The Mythical Man Month We now return to our regularly scheduled program...
    - loonster 4y ago
      That is a much more eloquent way of putting it. I do wonder how old that phrase is.
  - throw__away7391 4y ago
    I am not a doctor nor a woman, but shouldn't the math on that work out to nine women? Also, I believe that even just one woman can grow a fetus in one month, no?
    - makeset 4y ago
      > shouldn't the math on that work out to nine women? The average term being a round 40 weeks, a pregnancy “month” is 4 weeks by convention.
      - danachow 4y ago
        > The average term being a round 40 weeks, a pregnancy “month” is 4 weeks by convention. This convention is news to me - though the confusion is not. Months are plain old calendar months in pregnancy (ie about 4.3 weeks). https://www.verywellfamily.com/how-many-months-pregnant-am-i-2760090 https://www.verywellfamily.com/how-many-months-pregnant-am-i... 40 weeks is by convention from estimated last menstrual period, which is of course about 2 weeks prior to fertilization - so the actual gestastional period is closer to 38 weeks (that is closer to 9 months than 10 months).
  - lamontcg 4y ago
    Vaccines either produce side effects in 3-6 months or they don't. There's no hidden time bomb in all the people who were vaccinated last year. The FDA doesn't require long term safety studies for vaccines, and all the coronavirus vaccines have met the requirements. Nothing has been rushed. We have a good understanding of this because the side effects are entirely dominated by autoimmune conditions, and we understand from the field of rheumatology how those arise. We don't need to study pregnant women for another 5 years to see if any more babies pop out after the first one. Pregnancy is done in 9 months. Autoimmune side effects from vaccines happen in 3-6.
    - lamontcg 4y ago
      > This complex, specific and intricate process spans a number of months. Ultimately, though, in the absence of further stimulation by new copies of the spike protein, the immune response settles down, and effector cells—those directly and transiently involved in fighting the virus—decrease in frequency. Instead memory cells are established, poised to quickly ramp up production of antibodies, and even to replicate themselves, settling into their biological niches in our bodies until called upon once more if we happen to get infected. (This is what confers immunity to the coronavirus over the long run.) Antibody concentrations, some weeks after immunization, begin to reach their peak concentration in our blood, ultimately plateauing and beginning their slow decline. After this point, the risk of severe immunization-related complications doesn’t increase. Quite the opposite, in fact: it declines to virtually nothing after about three months. The six-month endpoint for these products is thus a rather conservative timeframe. Forget five or ten years: the way your immune system works does not allow for such long-term safety concerns. https://bostonreview.net/articles/the-long-term-safety-argument-over-covid-19-vaccines/ https://bostonreview.net/articles/the-long-term-safety-argum...
    - XorNot 4y ago
      It is wild how heavily downvoted this is. Everything in this comment is correct (I also note none of the downvotes could be bothered to present any rebuttal to the claims).
      - blindmute 4y ago
  - mbreese 4y ago
    This is a phase I study. The point here is to establish safety. The study believes this treatment could have a benefit for patients, but they aren’t sure if there are unknown risks. This is to establish that there aren’t any unknown risks. The eligible patient population has already advanced on therapy (meaning the current standard of care hasn’t worked). Getting patients to any sort of long-term response is the goal here. If there are any long term risks, that would be considered a good outcome (because the patient is still alive to have long term effects). Any further (heritable genetic) risks are mitigated as the patients specifically are excluded if they are planning on having children in the near future.
- mcswell 4y ago
  Do you really need a control group for this kind of study? The growth of cancer has been studied for well over a century, with millions of cases; what would a hundred more (to take a random number) tell you? (BTW, this is a real question, not a sarcasm!)
  - yourMadness 4y ago
    The control group is needed to measure process properties / systematic error. It does not need to be a placebo group. Previous data at the same hospital does not help because the regular medicine does not run according to study protocols.
shadowgovt 4y ago
It's not the new standard. Breast cancer is not contagious and has no chance of becoming a pandemic. The issue with a pandemic is every person infected is several more infectees in the future; geometric death effects instead of linear.
- rory 4y ago
  At the risk of starting a flamewar... wasn't the difference actually just the pure volume of severe sickness and death? The clinical trials didn't even attempt to test viral spread, they tested prevention of symptoms. If suddenly 50% of the world population got breast cancer at once, I'm willing to bet we'd be fine rolling out new technologies faster than the typical standard, despite it being non-contagious.
  - ray__ 4y ago
    A major difference is that no two breast cancers are the same. You're probably correct in your second point due to the sheer demand, but developing a treatment for any cancer is not the same as developing a treatment for an infectious disease because there is no one-size-fits-all strategy. A situation like the one you describe with simultaneous onset of breast cancer in a large population would definitely facilitate research and help lead to a better standard of care, though.

Kalanos 4y ago

ok we will!

deleted 4y ago
[deleted]