Moderna vaccine Phase I results - Printable Version
+- The CardBoard (https://thecardboard.org/board)
+-- Forum: Emergency (https://thecardboard.org/board/forum-11.html)
+--- Forum: Covid-19 (https://thecardboard.org/board/forum-12.html)
+--- Thread: Moderna vaccine Phase I results (/thread-19732.html)
+- The CardBoard (https://thecardboard.org/board)
+-- Forum: Emergency (https://thecardboard.org/board/forum-11.html)
+--- Forum: Covid-19 (https://thecardboard.org/board/forum-12.html)
+--- Thread: Moderna vaccine Phase I results (/thread-19732.html)
Pages:
1
2
RE: Moderna vaccine Phase I results - Mick - 05-23-2020
(05-23-2020, 10:32 AM)BostonCard Wrote: Yes, the Chief Medical Officer would have known of the early results and could have influenced the decision to release them (it probably would have been his call, though the communications group would have handled the details).
BC
Right, my point being that if the CMktgO sells her stock, it's probably just a coincidence; if the CMedO sells her stock, then it's potentially a big problem.
Along those lines, a friend of mine is very successful at timing his purchase and sale of stock around hiring and departure dates of CFOs.
RE: Moderna vaccine Phase I results - OutsiderFan - 05-24-2020
The myopic stupidity of Wall Street traders reacting to positive news about vaccine development is just downright embarrassing. It might make sense to drive up the price of a company who has positive vaccine news to report, but more than one company? Really?
The only way applying positive vaccine news to a broad market makes sense is if A) the vaccine has proven 80% effective in Phase 3 trials, and, if there is capacity to produce enough of it, and if there is ability to distribute it, and if enough people are getting it to make a difference stopping spread. That’s a long way from we had some positive vaccine news, and nothing that warrants anything but skepticism.
Just having a vaccine that works isn’t going to stop large swaths of the population from getting sick and dying, and even larger ones from not wanting to be around others enough to continue keeping economic activity that is suppose to drive company values, down.
RE: Moderna vaccine Phase I results - Goose - 05-24-2020
(05-24-2020, 04:30 AM)OutsiderFan Wrote: The only way applying positive vaccine news to a broad market makes sense is if A) the vaccine has proven 80% effective in Phase 3 trials, and, if there is capacity to produce enough of it, and if there is ability to distribute it, and if enough people are getting it to make a difference stopping spread. That’s a long way from we had some positive vaccine news, and nothing that warrants anything but skepticism.Unfortunately it has been a very long time since the ability to actually produce and sell a product at a profit has meant much on Wall Street. It is today mostly about guessing what stocks other people will pay outrageous sums for and buying those stocks. The "greater fool" theory is in full flower. At least it is not tulip bulbs.
RE: Moderna vaccine Phase I results - Snorlax94 - 07-14-2020
Results published
https://www.nejm.org/doi/full/10.1056/NEJMoa2022483?query=featured_home
LA Times article
https://www.latimes.com/science/story/2020-07-14/clinical-trial-results-indicate-moderna-vaccine-is-on-the-right-track
The results of the peer-reviewed study “are promising, and they support continued development of this vaccine,” Dr. Penny Heaton, chief executive of the Bill and Melinda Gates Medical Research Institute, wrote in [color=var(--primary-body-link-color)]an editorial[/color] for the journal. “However, we must bear in mind the complexity of vaccine development and the work still to be done before COVID-19 vaccines are widely available.”
RE: Moderna vaccine Phase I results - BostonCard - 07-14-2020
Quote:Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events.
That's not the safety profile of a vaccine that gets approved. At the very least, the 250 µg dose is toast, but even the 100 µg dose, 100% of the volunteers reported a systemic adverse event after the second dose (80% of the volunteers had a moderate adverse event). Even the lowest dose, more than 50% of volunteers had a systemic adverse event (25% moderate intensity). Even more had local symptoms.
The good news is that even the lowest dose produced immunogenicity. Moderna should have explored a lower dose, since the immunogenicity was pretty strong even at 25 µg. I think they are making a mistake in looking at 50 and 100 µg in the phase 2 trial (and planning for 100 µg in a phase 3). Yes, there is a question is how long immunity will last at the lower doses, but honestly I think the safety of the vaccine is going to be the problem.
BC
RE: Moderna vaccine Phase I results - burger - 07-15-2020
(07-14-2020, 10:46 PM)BostonCard Wrote:I haven't looked at the data, but I assume no one died or had a life-threatening response to the vaccine. I also assume that the study population was relatively healthy. Does a large number of adverse events in a trial mean that if you gave the vaccine to everyone, some people would die? I.e., are the symptoms seen in the trial the tip of the iceberg so to speak, and the actual response in the entire population would be a lot worse?Quote:Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events.
That's not the safety profile of a vaccine that gets approved. At the very least, the 250 µg dose is toast, but even the 100 µg dose, 100% of the volunteers reported a systemic adverse event after the second dose (80% of the volunteers had a moderate adverse event). Even the lowest dose, more than 50% of volunteers had a systemic adverse event (25% moderate intensity). Even more had local symptoms.
The good news is that even the lowest dose produced immunogenicity. Moderna should have explored a lower dose, since the immunogenicity was pretty strong even at 25 µg. I think they are making a mistake in looking at 50 and 100 µg in the phase 2 trial (and planning for 100 µg in a phase 3). Yes, there is a question is how long immunity will last at the lower doses, but honestly I think the safety of the vaccine is going to be the problem.
BC
Or is the problem just that headaches, etc. might reduce vaccine acceptance or create problems with loads of vaccinated people showing up at doctors' offices to get their symptoms checked?
RE: Moderna vaccine Phase I results - BostonCard - 07-15-2020
(07-15-2020, 09:26 AM)burger Wrote:(07-14-2020, 10:46 PM)BostonCard Wrote:I haven't looked at the data, but I assume no one died or had a life-threatening response to the vaccine. I also assume that the study population was relatively healthy. Does a large number of adverse events in a trial mean that if you gave the vaccine to everyone, some people would die? I.e., are the symptoms seen in the trial the tip of the iceberg so to speak, and the actual response in the entire population would be a lot worse?Quote:Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events.
That's not the safety profile of a vaccine that gets approved. At the very least, the 250 µg dose is toast, but even the 100 µg dose, 100% of the volunteers reported a systemic adverse event after the second dose (80% of the volunteers had a moderate adverse event). Even the lowest dose, more than 50% of volunteers had a systemic adverse event (25% moderate intensity). Even more had local symptoms.
The good news is that even the lowest dose produced immunogenicity. Moderna should have explored a lower dose, since the immunogenicity was pretty strong even at 25 µg. I think they are making a mistake in looking at 50 and 100 µg in the phase 2 trial (and planning for 100 µg in a phase 3). Yes, there is a question is how long immunity will last at the lower doses, but honestly I think the safety of the vaccine is going to be the problem.
BC
Or is the problem just that headaches, etc. might reduce vaccine acceptance or create problems with loads of vaccinated people showing up at doctors' offices to get their symptoms checked?
It doesn't always work that way, but the concern would be that if a large proportion of patients in a small study develop moderate adverse events, a small but non-zero proportion of patients in a larger study will develop more severe adverse events, and a few patients in a very large study (or once it goes to market) will develop life-threatening adverse events (or even die).
When the first H1N1 swine flu vaccine came out, it eventually had to be recalled because a small but significant increase in the risk of a very rare adverse event (Guillain-Barré Syndrome) which can cause paralysis. The increased risk over baseline was just 1.6 excess cases of Guillain-Barré syndrome per million people vaccinated, but for a person who is healthy, that is a devastating and unacceptable adverse event. A couple other vaccines that have had to be recalled because they caused rare side effects was the rotavirus vaccine (This additional risk is estimated to range from about 1 in 20,000 to 1 in 100,000 US infants who get rotavirus vaccine.). The other one (and this scares me about the COVID-19 vaccines) is dengue, which was severely restricted after potentially causing fatal ADE (antibody dependent enhancement, where the disease is actually worse in patients who are vaccinated) in 2 in 10,000 children.
BC
RE: Moderna vaccine Phase I results - lex24 - 07-15-2020
(07-15-2020, 12:17 PM)BostonCard Wrote:(07-15-2020, 09:26 AM)burger Wrote:(07-14-2020, 10:46 PM)BostonCard Wrote:I haven't looked at the data, but I assume no one died or had a life-threatening response to the vaccine. I also assume that the study population was relatively healthy. Does a large number of adverse events in a trial mean that if you gave the vaccine to everyone, some people would die? I.e., are the symptoms seen in the trial the tip of the iceberg so to speak, and the actual response in the entire population would be a lot worse?Quote:Solicited adverse events that occurred in more than half the participants included fatigue, chills, headache, myalgia, and pain at the injection site. Systemic adverse events were more common after the second vaccination, particularly with the highest dose, and three participants (21%) in the 250-μg dose group reported one or more severe adverse events.
That's not the safety profile of a vaccine that gets approved. At the very least, the 250 µg dose is toast, but even the 100 µg dose, 100% of the volunteers reported a systemic adverse event after the second dose (80% of the volunteers had a moderate adverse event). Even the lowest dose, more than 50% of volunteers had a systemic adverse event (25% moderate intensity). Even more had local symptoms.
The good news is that even the lowest dose produced immunogenicity. Moderna should have explored a lower dose, since the immunogenicity was pretty strong even at 25 µg. I think they are making a mistake in looking at 50 and 100 µg in the phase 2 trial (and planning for 100 µg in a phase 3). Yes, there is a question is how long immunity will last at the lower doses, but honestly I think the safety of the vaccine is going to be the problem.
BC
Or is the problem just that headaches, etc. might reduce vaccine acceptance or create problems with loads of vaccinated people showing up at doctors' offices to get their symptoms checked?
It doesn't always work that way, but the concern would be that if a large proportion of patients in a small study develop moderate adverse events, a small but non-zero proportion of patients in a larger study will develop more severe adverse events, and a few patients in a very large study (or once it goes to market) will develop life-threatening adverse events (or even die).
When the first H1N1 swine flu vaccine came out, it eventually had to be recalled because a small but significant increase in the risk of a very rare adverse event (Guillain-Barré Syndrome) which can cause paralysis. The increased risk over baseline was just 1.6 excess cases of Guillain-Barré syndrome per million people vaccinated, but for a person who is healthy, that is a devastating and unacceptable adverse event. A couple other vaccines that have had to be recalled because they caused rare side effects was the rotavirus vaccine (This additional risk is estimated to range from about 1 in 20,000 to 1 in 100,000 US infants who get rotavirus vaccine.). The other one (and this scares me about the COVID-19 vaccines) is dengue, which was severely restricted after potentially causing fatal ADE (antibody dependent enhancement, where the disease is actually worse in patients who are vaccinated) in 2 in 10,000 children.
BC
What is considered acceptable risk? If I understand you correctly (and I probably don’t) you are saying a vaccine that had an increased risk of a serious disease for 1.6 out of a million people is considered unacceptable. Is that true?
RE: Moderna vaccine Phase I results - BostonCard - 07-15-2020
(07-15-2020, 09:41 PM)lex24 Wrote: What is considered acceptable risk? If I understand you correctly (and I probably don’t) you are saying a vaccine that had an increased risk of a serious disease for 1.6 out of a million people is considered unacceptable. Is that true?
For a vaccine that is going into healthy people, the standard is very high. In the face of a widespread pandemic with a mortality rate of 0.5%, it may be lower, at least until the threat recedes a bit, but I expect the bar to be fairly high.
BC
RE: Moderna vaccine Phase I results - dabigv13 - 07-16-2020
I think I read that Moderna's phase three trials has 30,000 participants. Rare complications at a rate like 1 in a million will only be caught after this vaccine is released.
RE: Moderna vaccine Phase I results - BostonCard - 07-16-2020
(07-16-2020, 07:05 AM)dabigv13 Wrote: I think I read that Moderna's phase three trials has 30,000 participants. Rare complications at a rate like 1 in a million will only be caught after this vaccine is released.
Right, the rough guideline is that a clinical trial of 30,000 participants would only reliably exclude adverse events at a rate of 1 in 10,000 if you don't see them in the clinical trial (the so-called rule of three, which states that upper bound of the confidence interval for 0 events is roughly 3/n where n is the sample size).
BC