Thanks for your reply. I actually agree with most of what your saying here so would like to clarify my point a bit. I agree with the ARR vs RRR discussion completely, I think this has been a huge issue the whole time. When I said I could see some benefit in very specific situations I wasn't talking about risk of getting the disease wh…
Thanks for your reply. I actually agree with most of what your saying here so would like to clarify my point a bit. I agree with the ARR vs RRR discussion completely, I think this has been a huge issue the whole time. When I said I could see some benefit in very specific situations I wasn't talking about risk of getting the disease which I believe is 100% for everyone. I also would have been interested to see public interest in these if they defined them as gene therapies and had to abide by the regulatory requirements of that class of drugs instead. Anyone that doubts these should be called gene therapy should see how the ICH/FDA defines this in their latest GT guidance which is ICH S12 released in September. That also interestingly says they recommend companies not only measure the delivery vehicle itself but also the expressed protein and track its distribution. Then they bizarrely state that the guidance doesn't apply to "prophylactic vaccines". Head scratcher there. In terms of ADE I agree on the informed consent and I was concerned about that myself but I'm a bit less concerned now as the signal for that doesn't appear the way it did in say Dengvaxia a few years ago. Additionally the MOA for Dengvaxia made perfect sense why we would see ADE. SARS-CoV-2 behaves differently than SARS-CoV and the information that I have to review doesn't show animal deaths upon exposure to the virus after vaccination. Sorry I can't post the materials here because I could lose my job but I reviewed Moderna, JnJ and Novavax (can't seem to find the Pfizer info). In terms of cancer risk there is a possibility but the problem with the study is they used the WT spike and not the altered spike used in the vax. Now does that discount the findings? No it does not and it doesn't prove safety either however in order to conclude that is happening we would need to study the actual antigen in question. Personally I think it's more likely that the transient immunosuppression caused by the vax is responsible for the rise in latent virus/cancer. That isn't to say though that I think efficacy is zero and risk/benefit tradeoff can be calculated. Based on the UK data if you normalize correctly (they don't in the report) you see *some* efficacy against hospitalization/death for a time. The problem I have with their methodology is they take cases and divide into the total pop (of vax or unvax) to get a rate per 100,000. This is incorrect as it overinflates the numbers as the populations are such different sizes, if you instead normalize to the number of positive tests the numbers look very different but show again some small efficacy. This goes back to the risk/benefit which can be calculated on an individual basis, in my case my risk of hospitalization is ~.000114% last I checked so even a 90% effective vaccine with this risk profile is unacceptable. However in the case of the family member I spoke of earlier their risk is orders of magnitude higher and a chance at a temporary reduction in their risk could be worth taking. Again I think this only applies to a small part of the population not the population in general and I'm not giving sweeping recommendations to anyone. The way I calculate risk is determine the risk reduction based on real world evidence (RWE) and multiply by risk of getting disease which I set at 1 (since I see it as 100%). Then I look at the known risk side of things and calculate those rates and it can make sense in some situations. The problem is in quantifying the known unknowns and the unknown unknowns so if the calculus is close I wouldn't do it. Personally, I believe early treatment is the best option however the vast majority of docs I've spoken with don't know how to do this and won't even try accepted therapies such as mAb's in patients that fit all the criteria even when I've handed them the info on how to get it and use it. It's a sad situation we find ourselves in to be honest.
Thanks for your reply. I actually agree with most of what your saying here so would like to clarify my point a bit. I agree with the ARR vs RRR discussion completely, I think this has been a huge issue the whole time. When I said I could see some benefit in very specific situations I wasn't talking about risk of getting the disease which I believe is 100% for everyone. I also would have been interested to see public interest in these if they defined them as gene therapies and had to abide by the regulatory requirements of that class of drugs instead. Anyone that doubts these should be called gene therapy should see how the ICH/FDA defines this in their latest GT guidance which is ICH S12 released in September. That also interestingly says they recommend companies not only measure the delivery vehicle itself but also the expressed protein and track its distribution. Then they bizarrely state that the guidance doesn't apply to "prophylactic vaccines". Head scratcher there. In terms of ADE I agree on the informed consent and I was concerned about that myself but I'm a bit less concerned now as the signal for that doesn't appear the way it did in say Dengvaxia a few years ago. Additionally the MOA for Dengvaxia made perfect sense why we would see ADE. SARS-CoV-2 behaves differently than SARS-CoV and the information that I have to review doesn't show animal deaths upon exposure to the virus after vaccination. Sorry I can't post the materials here because I could lose my job but I reviewed Moderna, JnJ and Novavax (can't seem to find the Pfizer info). In terms of cancer risk there is a possibility but the problem with the study is they used the WT spike and not the altered spike used in the vax. Now does that discount the findings? No it does not and it doesn't prove safety either however in order to conclude that is happening we would need to study the actual antigen in question. Personally I think it's more likely that the transient immunosuppression caused by the vax is responsible for the rise in latent virus/cancer. That isn't to say though that I think efficacy is zero and risk/benefit tradeoff can be calculated. Based on the UK data if you normalize correctly (they don't in the report) you see *some* efficacy against hospitalization/death for a time. The problem I have with their methodology is they take cases and divide into the total pop (of vax or unvax) to get a rate per 100,000. This is incorrect as it overinflates the numbers as the populations are such different sizes, if you instead normalize to the number of positive tests the numbers look very different but show again some small efficacy. This goes back to the risk/benefit which can be calculated on an individual basis, in my case my risk of hospitalization is ~.000114% last I checked so even a 90% effective vaccine with this risk profile is unacceptable. However in the case of the family member I spoke of earlier their risk is orders of magnitude higher and a chance at a temporary reduction in their risk could be worth taking. Again I think this only applies to a small part of the population not the population in general and I'm not giving sweeping recommendations to anyone. The way I calculate risk is determine the risk reduction based on real world evidence (RWE) and multiply by risk of getting disease which I set at 1 (since I see it as 100%). Then I look at the known risk side of things and calculate those rates and it can make sense in some situations. The problem is in quantifying the known unknowns and the unknown unknowns so if the calculus is close I wouldn't do it. Personally, I believe early treatment is the best option however the vast majority of docs I've spoken with don't know how to do this and won't even try accepted therapies such as mAb's in patients that fit all the criteria even when I've handed them the info on how to get it and use it. It's a sad situation we find ourselves in to be honest.