No, actually the article was about small sample size, and the Covid vaccine trials had very large sample sizes, but perhaps not large enough. Pfizer overestimated the number of people in the placebo group who would get Covid. This is not surprising given that the studies took place when society was still taking precautions, and the sampl…
No, actually the article was about small sample size, and the Covid vaccine trials had very large sample sizes, but perhaps not large enough. Pfizer overestimated the number of people in the placebo group who would get Covid. This is not surprising given that the studies took place when society was still taking precautions, and the sample was volunteer (not random) and thus likely biased towards the cautious and risk avoidant. (Remember, the study was blinded, so everybody likely took precautions). Given the underestimation in the placebo group, the results would likely have been even better if nobody took any precautions during the study. (Ethics precluded this). The clinical trials were limited by their short duration, and the only outcome measured was infection. The more important data has been collected during subsequent waves of infection in which the vaccines, especially when boosted, showed good efficacy against the most important outcome, death, especially among those in high risk groups. The 2nd link is one such study, and there are many others, but I chose this one because it was not funded by Pharma. One criticism often leveled at the Covid vaccine clinical trials was that only RRR was reported, and not ARR. (A topic which Dr. Mandrola addressed last week). I always like to see both, and usually go more by the ARR combined with safety data. But as the article in the first link below explains, RRR has an important function when making public health decisions in a pandemic. Also, overall ARR is not meaningful when outcomes vary greatly by subgroup, as is the case with Covid. One then needs to look at the ARR of each subgroup. So even though I hear you about Big Pharma, there are plenty of other sources of data to demonstrate that the risk-benefit ratio is good for the vaccines, especially in high risk populations.
Some criticise vaccine studies (such as the one you quote here) because they do not measure the reduction in "all cause mortality" but rather concentrate only on mortality due to the disease. Is this a valid concern?
Vaccine trials aren't the only RCT's that fail to measure all cause mortality. Whether that makes sense probably depends on a number of things, including the length of the trial (i.e., a few months vs. a few years). See first link below for more info. on that. As for the Covid vaccines, subsequent research found that non-Covid deaths were lower in those who were vaccinated. (2nd link). But that was most likely due to selection bias, which can happen when participants are not randomly selected from the general population (i.e., health user bias). After correcting for this as much as they could, at least they did not find any excess deaths among the vaccinated.
So it seems to me that if one determined the standardised mortality in a population and decided on a clinically significant mortality reduction (say 5%) we could determine the size of a random sample of this population which should be given the vax. In this way we could show that the anti-vax narrative is false. I worry that if we fail to do these studies people will become reluctant and the only way you will get them to comply is to mandate.
I don't think there is the political will to fund such a study, nor would pharma want to spend the money. I also don't think devout anti-vaxers are convinced by data or logic. I don't think the Supreme Court would ever uphold mandates for all, especially now that the data shows the vaccine does not prevent transmission. At this point, the only studies likely to be funded are retrospective, not RCT's, and/or antibody titers in animals for newer versions, like what's currently done for the flu vaccines when modified.
You betcha! I just wish I had better answers for you! :) Hopefully public trust in science will be restored, and more people will read Substacks such as this one to help them discern when to trust pharma, and when to call them on the carpet. My preference would be to find a better way to fund drug trials. I hope Prasad and/or Mandrola have some creative ideas to share on that topic!
I’m a masters degreed addiction therapist who was taught to read EVERY bit of EVERY article by a great internist - we would critically examine journals together for decades.
No, actually the article was about small sample size, and the Covid vaccine trials had very large sample sizes, but perhaps not large enough. Pfizer overestimated the number of people in the placebo group who would get Covid. This is not surprising given that the studies took place when society was still taking precautions, and the sample was volunteer (not random) and thus likely biased towards the cautious and risk avoidant. (Remember, the study was blinded, so everybody likely took precautions). Given the underestimation in the placebo group, the results would likely have been even better if nobody took any precautions during the study. (Ethics precluded this). The clinical trials were limited by their short duration, and the only outcome measured was infection. The more important data has been collected during subsequent waves of infection in which the vaccines, especially when boosted, showed good efficacy against the most important outcome, death, especially among those in high risk groups. The 2nd link is one such study, and there are many others, but I chose this one because it was not funded by Pharma. One criticism often leveled at the Covid vaccine clinical trials was that only RRR was reported, and not ARR. (A topic which Dr. Mandrola addressed last week). I always like to see both, and usually go more by the ARR combined with safety data. But as the article in the first link below explains, RRR has an important function when making public health decisions in a pandemic. Also, overall ARR is not meaningful when outcomes vary greatly by subgroup, as is the case with Covid. One then needs to look at the ARR of each subgroup. So even though I hear you about Big Pharma, there are plenty of other sources of data to demonstrate that the risk-benefit ratio is good for the vaccines, especially in high risk populations.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9115787/
https://www.sciencedirect.com/science/article/pii/S1201971222005938
Damned lies and statistics then!
Some criticise vaccine studies (such as the one you quote here) because they do not measure the reduction in "all cause mortality" but rather concentrate only on mortality due to the disease. Is this a valid concern?
Vaccine trials aren't the only RCT's that fail to measure all cause mortality. Whether that makes sense probably depends on a number of things, including the length of the trial (i.e., a few months vs. a few years). See first link below for more info. on that. As for the Covid vaccines, subsequent research found that non-Covid deaths were lower in those who were vaccinated. (2nd link). But that was most likely due to selection bias, which can happen when participants are not randomly selected from the general population (i.e., health user bias). After correcting for this as much as they could, at least they did not find any excess deaths among the vaccinated.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024667/
https://www.sciencedirect.com/science/article/pii/S0264410X22015614
So it seems to me that if one determined the standardised mortality in a population and decided on a clinically significant mortality reduction (say 5%) we could determine the size of a random sample of this population which should be given the vax. In this way we could show that the anti-vax narrative is false. I worry that if we fail to do these studies people will become reluctant and the only way you will get them to comply is to mandate.
I don't think there is the political will to fund such a study, nor would pharma want to spend the money. I also don't think devout anti-vaxers are convinced by data or logic. I don't think the Supreme Court would ever uphold mandates for all, especially now that the data shows the vaccine does not prevent transmission. At this point, the only studies likely to be funded are retrospective, not RCT's, and/or antibody titers in animals for newer versions, like what's currently done for the flu vaccines when modified.
Thanks for taking the time to answer my question. You have been very helpful.
You betcha! I just wish I had better answers for you! :) Hopefully public trust in science will be restored, and more people will read Substacks such as this one to help them discern when to trust pharma, and when to call them on the carpet. My preference would be to find a better way to fund drug trials. I hope Prasad and/or Mandrola have some creative ideas to share on that topic!
Thank you for an easy to follow explanation.
You're welcome, and I'm happy to hear it was easily understood. Sometimes I'm not sure! :)
I’m a masters degreed addiction therapist who was taught to read EVERY bit of EVERY article by a great internist - we would critically examine journals together for decades.