both AB’s and T Cells are important.....we think, I don’t think we really know tbh
COVID-19 Pandemic: Transmissions, Deaths, Treatments, Vaccines, Interventions and More...
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both AB’s and T Cells are important.....we think, I don’t think we really know tbh
Another treatment option showing promise...this time an inhaler.
https://www.theguardian.com/world/2...-inhaler-sng001-very-promising-say-scientists
https://www.theguardian.com/world/2...-inhaler-sng001-very-promising-say-scientists
Beat me too it.
https://www.bbc.com/news/uk-53469839
@numbers will be anxiously looking forward to breakdown of results from you.
They all seem to be heading into Phase III trials around the same time?
I mean no harm needed this to push back against an idiot
Yes, and it seems Moderna is least likely to work due to lack of T cell response. Though still a long way to go. No idea if any will work when challenged with the virus yet (for example the Oxford one was given to 8 monkeys back in late May or early June, and they all became infected when challenged).
What's the total number of people being selective, no wait, what's the % of people being selective? That latter one is a way more important stat.
Good news with Oxford vaccine- https://apple.news/A6GMn71BbRp2ll5BbhwnGmg
80% reduction in ICU patients is huge. Hopefully widely available soon.
Can someone who understands trial results explain the P value to me? Seems to be very clear results, but they are saying to temper reactions because the P value was close to not being statistically significant. Doesn’t make sense to me.
https://www.fiercebiotech.com/biotech/synairgen-shares-soar-300-covid-treatment-but-caveats-abound
A lot of vaccine trial info coming out today. Moderna and Pfizer jumping in the T Cell bandwagon and releasing more info on their trials today that their vaccine produced T Cell response too. Guess they didn’t want the Oxford vaccine taking a clear cut lead.
Also, some potentially bad info on the CanSino vaccine that it may not protect people who have gotten a certain type of cold virus in the past.
https://www.statnews.com/2020/07/20...icacy-of-oxford-astrazeneca-covid-19-vaccine/
Also, some potentially bad info on the CanSino vaccine that it may not protect people who have gotten a certain type of cold virus in the past.
https://www.statnews.com/2020/07/20...icacy-of-oxford-astrazeneca-covid-19-vaccine/
Only 9 deaths today-out of 9 million people.Full contact drills permitted for high school sports,but still no gyms.Even I'm speechless.
More on T Cell response from Pfizer. Looks like they they outperformed Moderna. Also got good T Cell response from a single dose (and not from the follow up dose that every vaccine needs so far).
https://www.fiercebiotech.com/biotech/pfizer-reports-strong-t-cell-response-to-covid-19-vaccine
https://www.fiercebiotech.com/biotech/pfizer-reports-strong-t-cell-response-to-covid-19-vaccine
I think it's safe to say when we get a good vaccine for this, even if tests show it works, there will be many who will refuse to take it.
I was working this morning - missed a lot, lol, with the Pfizer/BioNTech and Oxford/Astra-Zeneca vaccine papers coming out. Good news all around. Here's the Pfizer preprint paper (which is a separate study from the one which announced results a couple of weeks ago) and Derek Lowe's blog on what it means. He's a pretty skeptical guy and his take was, "let me say up front that I think they have some very encouraging results. It’s a good way to start the day."
https://www.medrxiv.org/content/10.1101/2020.07.17.20140533v1.full.pdf
https://blogs.sciencemag.org/pipeli...esults-antibodies-viral-mutations-and-t-cells
The Pfizer vaccine shows a pretty strong neutralizing antibody response that is fairly dose dependent and maybe just as importantly, shows neutralizing activity to more than a dozen viral strains created (in a pseudovirus), meaning the vaccine would likely be able to handle a wide range of mutations in the spike protein and its receptor-binding domain.
The Pfizer vaccine also shows a significantly better T-cell response than the Moderna vaccine, particularly for the CD8+ T-cells (excerpt from Lowe's blog, below) and the response (for both CD4+ and CD8+ T-cells) does not appear to be dose dependent. It's possible this will allow a lower dose vaccine, which would mean more doses available from the same manufacturing process. The safety and efficacy of the vaccine will be truly established in a 30,000-subject phase 2b/3 trial that is due to start by the end of July.
But as opposed to the Moderna candidate, there was also a robust CD8+ T-cell response (29/36 patients), which did not necessarily correlate with the antibody titers raised by the vaccine. Interestingly, neither of these T-cell effects were very dose-responsive. 6 out of 8 patients tested in the 1 µg dose cohort raised a T-cell response, and their CD4+ and CD8+ levels were almost the same as the 50 µg group! As a per cent of total circulating T cells, the levels seen after vaccination were significantly higher than those seen in the blood of convalescent patients, which could be a real difference. Recall that in the case of the 2003 SARS coronavirus, that antibodies disappeared from recovered patients, but that T-cell immunity has persisted for up to 17 years.
It will take several years to validate , produce and administer to the general population if ever. But you are correct there will be many who will not get it unless forced to by governmental agencies. There will be those who will drive the fear train as usual. Anti vaxxers and media will heighten the anxiety of many skeptics.
Thanks numbers. How easy (lead time?) would it be to scale these vaccines up if they are given the green light.
All of pharma would be in at that point, meaning profits aren’t a driver. You’ve gotta figure us at Merck, Novartis, Pfizer, GSK, BMS, SA, and AZ would all lead the charge and produce the vaccine.
since some of you have been posting about some of these theories in this thread and the old thread.
FDA vaccine guidance from a few weeks ago. Not sure if there is a paywall, so I will cut and paste:
COVID-19 Vaccine Should Demonstrate At Least 50% Effectiveness, US FDA Says
The Pink Sheet (Published: 30-Jun 2020 21:18, Received: 21:15:30)
Executive Summary: Guidance on COVID-19 vaccine development and licensure appears to set a precedent in specifying the clinical efficacy rate for a product approval; agency also takes accelerated approval off the table for now and says emergency use authorization may be granted only after safety and efficacy have been demonstrated.
The US Food and Drug Administration has set a bar for sponsors to meet in developing COVID-19 vaccines: an efficacy rate of at least 50%. The recommendation is intended to ensure resources are not wasted on a vaccine of limited value and to garner public confidence so people get vaccinated, thereby increasing the likelihood of achieving herd immunity.
The agency set the effectiveness bar in its guidance, "Development and Licensure of Vaccines to Prevent COVID-19," issued on 30 June.
"To ensure that a widely deployed COVID-19 vaccine is effective, the primary efficacy endpoint point estimate for a placebo-controlled trial should be at least 50%, and the statistical success criterion should be that the lower bound of the appropriately alpha-adjusted confidence interval around the primary efficacy endpoint point estimate is >30%," the guidance states. "A lower bound ≤30% but >0% may be acceptable as a statistical success criterion for a secondary efficacy endpoint, provided that secondary endpoint hypothesis testing is dependent on success on the primary endpoint."
"This was a bold move for FDA and the Office of Vaccines to state clearly where they are leaning." - Biologics Consulting's Norman Baylor
The recommendation appears to be the first time the FDA has proposed a clinical efficacy rate for a product. In guidances related to pandemic vaccines and seasonal inactivated vaccines, the agency has suggested efficacy thresholds based on immune responses, such as antibody titer development and seroconversion.
Norman Baylor, former director of the Office of Vaccines Research and Review in the FDA's Center for Biologics Evaluation and Research, said that in general the agency has not put out guidance with specific effectiveness values for vaccines.
"This was a bold move for FDA and the Office of Vaccines to state clearly where they are leaning," said Baylor, who is now president and CEO of Biologics Consulting. The document will expedite development because "all manufacturers know this is where the FDA is looking."
Arthur Caplan, professor of bioethics at NYU Langone Medical Center, said he has never seen the agency make such a recommendation. "It's usually not their role to pronounce a desired efficacy rate," he said.
Caplan said that even rolling out a 50% effectiveness rate is still not likely to produce herd immunity because some people will not be willing to get vaccinated unless it is closer to 85%. He added that there could also be manufacturing issues if the vaccine requires a booster shot.
National Institute of Allergy and Infectious Diseases director Anthony Fauci has indicated he would like to see an effectiveness rate higher than 50%. Axios reported that in an interview at the Aspen Ideas Festival, Fauci said he would settle for a "70, 75% effective vaccine" against COVID-19.
A Bid At Transparency
FDA commissioner Stephen Hahn noted the significance of the guidance at a 30 June hearing of the Senate Committee on Health, Education, Labor and Pensions. "We're making clear in our guidance what are the data we need that should be submitted to meet our regulatory standards of approval," he said. "This is particularly important as we know that some people are skeptical of vaccine development efforts."
Asked what he was doing to bolster public confidence in a vaccine, Hahn said one of the reasons the agency released the guidance is to provide regulatory clarity around what data are expected by the FDA. "We want to see certain parts of those data so that we can demonstrate to the world, to the nation, to the American people that we are following our rigorous standards with respect to safety and efficacy."
Recent surveys suggest concern that the fast speed at which a vaccine has been developed may deter uptake. ("Speed Of Coronavirus Vaccine Development May Hurt Public Confidence" "Pink Sheet" )
FDA 'Not Lowering The Bar For EUA'
The guidance also notes the requirements that must be met for the FDA to issue an emergency use authorization for a COVID-19 vaccine.
"Issuance of an EUA for a COVID-19 vaccine prior to the completion of large randomized clinical efficacy trials could reduce the ability to demonstrate effectiveness of the investigational vaccine in a clinical disease endpoint efficacy trial to support licensure, and such clinical disease endpoint efficacy trials may be needed to investigate the potential for vaccine-associated ERD [enhanced-respiratory disease]," the guidance states.
"Thus, for a vaccine for which there is adequate manufacturing information, issuance of an EUA may be appropriate once studies have demonstrated the safety and effectiveness of the vaccine but before the manufacturer has submitted and/or FDA has completed its formal review of the biologics license application."
The FDA said for investigational vaccines, an EUA assessment will be made on a case-by-case basis considering the target population, the product characteristics and the totality of the available scientific evidence relevant to the product.
Baylor said a lot of people were under the impression that a vaccine might be deployed quickly based on an EUA and antibody data, but the FDA is "not lowering the bar for EUA" as safety and effectiveness have to be demonstrated.
Accelerated Approval On Hold
The agency also indicated it was unlikely to grant accelerated approval for COVID-19 vaccines in the near term.
"Given the current state of knowledge about COVID-19, the most direct approach to demonstrate effectiveness for a COVID-19 vaccine candidate is based on clinical endpoint efficacy trials showing protection against disease," the guidance states. "Once additional understanding of SARS-CoV-2 immunology, and specifically vaccine immune responses that might be reasonably likely to predict protection against COVID-19, is acquired, accelerated approval of a COVID-19 vaccine ... may be considered if an applicant provides sufficient data and information to meet the applicable legal requirements."
For a COVID-19 vaccine, it may be possible to approve a product based on adequate and well-controlled clinical trials establishing an effect on a surrogate endpoint, such as immune response, that is reasonably likely to predict clinical benefit, the guidance states.
Conditions For Human Challenge Studies
The FDA also addressed the topic of human challenge studies, suggesting there may be circumstances in which they are appropriate.
"If it is no longer possible to demonstrate vaccine effectiveness by way of conducting clinical disease endpoint efficacy studies, the use of a controlled human infection model to obtain evidence to support vaccine efficacy may be considered," the guidance states. "However, many issues, including logistical, human subject protection, ethical and scientific issues, would need to be satisfactorily addressed."
A controlled human infection model is a human challenge study, in which subjects are administered a vaccine and then infected with the virus, instead of waiting for nature to infect people to see if the vaccine works. The guidance notes that at this time no controlled human infection models for SARS-CoV-2 have been established or characterized.
Caplan, who has been a leading advocate of human challenge studies for COVID-19 vaccines, said it is "startling" that the agency alluded to their potential use in the guidance.
Baylor said it makes sense for the FDA to address the challenge studies since they are being widely discussed and there are debates on whether and how they will be used. The guidance "puts a marker down," he said. "Right now, we aren't there," but it is good that the FDA made a statement on it.
Adaptive Design, Single Placebo
The guidance provides details on nonclinical data, clinical trial design, and chemistry, manufacturing and controls (CMC) for COVID-19 vaccines.
It notes that development programs might be expedited by adaptive and/or seamless clinical trial designs that allow for selection between vaccine candidates and dosing regimens for more rapid progression through the usual phases of clinical development.
Later phase trials, including efficacy trials, should be randomized, double-blinded, and placebo-controlled, the guidance states. An efficacy trial that evaluates multiple vaccine candidates against a single placebo group may be an acceptable approach to further increase efficiency provided that the trial is adequately designed with appropriate statistical methods to evaluate efficacy.
If the availability of a COVID-19 vaccine proven to be safe and effective precludes ethical inclusion of a placebo control group, that vaccine could serve as the control treatment in a study designed to evaluate efficacy with non-inferiority hypothesis testing, the FDA said.
The guidance also states that standardization of efficacy endpoints across clinical trials may facilitate comparative evaluation of vaccines for deployment programs, provided that such comparisons are not confounded by differences in trial design or study populations. The FDA recommends that either the primary endpoint or a secondary endpoint (with or without formal hypothesis testing) be defined as virologically confirmed SARS-CoV-2 infections with one more of several listed symptoms.
Trials need not screen for or exclude participants with a history or laboratory evidence of prior SARS-CoV-2 infection. However, those with acute COVID-19 or other acute infectious illness should be excluded. There should be adequate representation of the elderly and those with medical comorbidities, the guidance states, encouraging enrollment of populations most infected by the virus, specifically racial and ethnic minorities. It also advises sponsors to plan for pediatric assessments of safety and efficacy.
With regard to CMC, the FDA said complete details of the manufacturing process must be provided in the biologics license application, including data to support consistency of the manufacturing process. Final validation of formulation and filling operations may be completed after product approval, and postmarketing commitments to provide full shelf life data may be acceptable with appropriate justification, the guidance states.
The guidance is being implemented without prior comment. The agency announced in March that it would make COVID-19-related guidance documents available immediately. Comments on the vaccine guidance may be submitted at any time for agency consideration.
The guidance is to remain in effect for the duration of the COVID-19 public health emergency, which the Secretary of the Department of Health and Human Services declared on 31 January. Within 60 days following the termination of the public health emergency, the agency intends to revise and replace the document with an updated guidance that incorporates appropriate changes based on comments it receives and its experience with implementation.
COVID-19 Vaccine Should Demonstrate At Least 50% Effectiveness, US FDA Says
The Pink Sheet (Published: 30-Jun 2020 21:18, Received: 21:15:30)
Executive Summary: Guidance on COVID-19 vaccine development and licensure appears to set a precedent in specifying the clinical efficacy rate for a product approval; agency also takes accelerated approval off the table for now and says emergency use authorization may be granted only after safety and efficacy have been demonstrated.
The US Food and Drug Administration has set a bar for sponsors to meet in developing COVID-19 vaccines: an efficacy rate of at least 50%. The recommendation is intended to ensure resources are not wasted on a vaccine of limited value and to garner public confidence so people get vaccinated, thereby increasing the likelihood of achieving herd immunity.
The agency set the effectiveness bar in its guidance, "Development and Licensure of Vaccines to Prevent COVID-19," issued on 30 June.
"To ensure that a widely deployed COVID-19 vaccine is effective, the primary efficacy endpoint point estimate for a placebo-controlled trial should be at least 50%, and the statistical success criterion should be that the lower bound of the appropriately alpha-adjusted confidence interval around the primary efficacy endpoint point estimate is >30%," the guidance states. "A lower bound ≤30% but >0% may be acceptable as a statistical success criterion for a secondary efficacy endpoint, provided that secondary endpoint hypothesis testing is dependent on success on the primary endpoint."
"This was a bold move for FDA and the Office of Vaccines to state clearly where they are leaning." - Biologics Consulting's Norman Baylor
The recommendation appears to be the first time the FDA has proposed a clinical efficacy rate for a product. In guidances related to pandemic vaccines and seasonal inactivated vaccines, the agency has suggested efficacy thresholds based on immune responses, such as antibody titer development and seroconversion.
Norman Baylor, former director of the Office of Vaccines Research and Review in the FDA's Center for Biologics Evaluation and Research, said that in general the agency has not put out guidance with specific effectiveness values for vaccines.
"This was a bold move for FDA and the Office of Vaccines to state clearly where they are leaning," said Baylor, who is now president and CEO of Biologics Consulting. The document will expedite development because "all manufacturers know this is where the FDA is looking."
Arthur Caplan, professor of bioethics at NYU Langone Medical Center, said he has never seen the agency make such a recommendation. "It's usually not their role to pronounce a desired efficacy rate," he said.
Caplan said that even rolling out a 50% effectiveness rate is still not likely to produce herd immunity because some people will not be willing to get vaccinated unless it is closer to 85%. He added that there could also be manufacturing issues if the vaccine requires a booster shot.
National Institute of Allergy and Infectious Diseases director Anthony Fauci has indicated he would like to see an effectiveness rate higher than 50%. Axios reported that in an interview at the Aspen Ideas Festival, Fauci said he would settle for a "70, 75% effective vaccine" against COVID-19.
A Bid At Transparency
FDA commissioner Stephen Hahn noted the significance of the guidance at a 30 June hearing of the Senate Committee on Health, Education, Labor and Pensions. "We're making clear in our guidance what are the data we need that should be submitted to meet our regulatory standards of approval," he said. "This is particularly important as we know that some people are skeptical of vaccine development efforts."
Asked what he was doing to bolster public confidence in a vaccine, Hahn said one of the reasons the agency released the guidance is to provide regulatory clarity around what data are expected by the FDA. "We want to see certain parts of those data so that we can demonstrate to the world, to the nation, to the American people that we are following our rigorous standards with respect to safety and efficacy."
Recent surveys suggest concern that the fast speed at which a vaccine has been developed may deter uptake. ("Speed Of Coronavirus Vaccine Development May Hurt Public Confidence" "Pink Sheet" )
FDA 'Not Lowering The Bar For EUA'
The guidance also notes the requirements that must be met for the FDA to issue an emergency use authorization for a COVID-19 vaccine.
"Issuance of an EUA for a COVID-19 vaccine prior to the completion of large randomized clinical efficacy trials could reduce the ability to demonstrate effectiveness of the investigational vaccine in a clinical disease endpoint efficacy trial to support licensure, and such clinical disease endpoint efficacy trials may be needed to investigate the potential for vaccine-associated ERD [enhanced-respiratory disease]," the guidance states.
"Thus, for a vaccine for which there is adequate manufacturing information, issuance of an EUA may be appropriate once studies have demonstrated the safety and effectiveness of the vaccine but before the manufacturer has submitted and/or FDA has completed its formal review of the biologics license application."
The FDA said for investigational vaccines, an EUA assessment will be made on a case-by-case basis considering the target population, the product characteristics and the totality of the available scientific evidence relevant to the product.
Baylor said a lot of people were under the impression that a vaccine might be deployed quickly based on an EUA and antibody data, but the FDA is "not lowering the bar for EUA" as safety and effectiveness have to be demonstrated.
Accelerated Approval On Hold
The agency also indicated it was unlikely to grant accelerated approval for COVID-19 vaccines in the near term.
"Given the current state of knowledge about COVID-19, the most direct approach to demonstrate effectiveness for a COVID-19 vaccine candidate is based on clinical endpoint efficacy trials showing protection against disease," the guidance states. "Once additional understanding of SARS-CoV-2 immunology, and specifically vaccine immune responses that might be reasonably likely to predict protection against COVID-19, is acquired, accelerated approval of a COVID-19 vaccine ... may be considered if an applicant provides sufficient data and information to meet the applicable legal requirements."
For a COVID-19 vaccine, it may be possible to approve a product based on adequate and well-controlled clinical trials establishing an effect on a surrogate endpoint, such as immune response, that is reasonably likely to predict clinical benefit, the guidance states.
Conditions For Human Challenge Studies
The FDA also addressed the topic of human challenge studies, suggesting there may be circumstances in which they are appropriate.
"If it is no longer possible to demonstrate vaccine effectiveness by way of conducting clinical disease endpoint efficacy studies, the use of a controlled human infection model to obtain evidence to support vaccine efficacy may be considered," the guidance states. "However, many issues, including logistical, human subject protection, ethical and scientific issues, would need to be satisfactorily addressed."
A controlled human infection model is a human challenge study, in which subjects are administered a vaccine and then infected with the virus, instead of waiting for nature to infect people to see if the vaccine works. The guidance notes that at this time no controlled human infection models for SARS-CoV-2 have been established or characterized.
Caplan, who has been a leading advocate of human challenge studies for COVID-19 vaccines, said it is "startling" that the agency alluded to their potential use in the guidance.
Baylor said it makes sense for the FDA to address the challenge studies since they are being widely discussed and there are debates on whether and how they will be used. The guidance "puts a marker down," he said. "Right now, we aren't there," but it is good that the FDA made a statement on it.
Adaptive Design, Single Placebo
The guidance provides details on nonclinical data, clinical trial design, and chemistry, manufacturing and controls (CMC) for COVID-19 vaccines.
It notes that development programs might be expedited by adaptive and/or seamless clinical trial designs that allow for selection between vaccine candidates and dosing regimens for more rapid progression through the usual phases of clinical development.
Later phase trials, including efficacy trials, should be randomized, double-blinded, and placebo-controlled, the guidance states. An efficacy trial that evaluates multiple vaccine candidates against a single placebo group may be an acceptable approach to further increase efficiency provided that the trial is adequately designed with appropriate statistical methods to evaluate efficacy.
If the availability of a COVID-19 vaccine proven to be safe and effective precludes ethical inclusion of a placebo control group, that vaccine could serve as the control treatment in a study designed to evaluate efficacy with non-inferiority hypothesis testing, the FDA said.
The guidance also states that standardization of efficacy endpoints across clinical trials may facilitate comparative evaluation of vaccines for deployment programs, provided that such comparisons are not confounded by differences in trial design or study populations. The FDA recommends that either the primary endpoint or a secondary endpoint (with or without formal hypothesis testing) be defined as virologically confirmed SARS-CoV-2 infections with one more of several listed symptoms.
Trials need not screen for or exclude participants with a history or laboratory evidence of prior SARS-CoV-2 infection. However, those with acute COVID-19 or other acute infectious illness should be excluded. There should be adequate representation of the elderly and those with medical comorbidities, the guidance states, encouraging enrollment of populations most infected by the virus, specifically racial and ethnic minorities. It also advises sponsors to plan for pediatric assessments of safety and efficacy.
With regard to CMC, the FDA said complete details of the manufacturing process must be provided in the biologics license application, including data to support consistency of the manufacturing process. Final validation of formulation and filling operations may be completed after product approval, and postmarketing commitments to provide full shelf life data may be acceptable with appropriate justification, the guidance states.
The guidance is being implemented without prior comment. The agency announced in March that it would make COVID-19-related guidance documents available immediately. Comments on the vaccine guidance may be submitted at any time for agency consideration.
The guidance is to remain in effect for the duration of the COVID-19 public health emergency, which the Secretary of the Department of Health and Human Services declared on 31 January. Within 60 days following the termination of the public health emergency, the agency intends to revise and replace the document with an updated guidance that incorporates appropriate changes based on comments it receives and its experience with implementation.
Lots of good news today on the Oxford/Astra-Zeneca and Pfizer/BioNTech vaccines. Below are links to the actual preprint paper and Derek Lowe's take on it in his "In The Pipeline" blog in Science Translational Medicine - he's a medicinal chemist by training, who is pretty well-versed in everything related to pharma R&D of new drugs, and has been doing this blog for nearly 20 years. He's also a born skeptic (so not easily fooled by hype) and fiercely independent.
https://marlin-prod.literatumonline.com/pb-assets/Lancet/pdfs/S0140673620316044.pdf
https://blogs.sciencemag.org/pipeline/archives/2020/07/20/new-data-on-the-oxford-az-vaccine
Anyway, the data showed good response in neutralizing antibodies being raised and also showed fairly typical minor to moderate side effects (injection site pain, fatigue, chills and mild fever in some), as the Moderna and Pfizer vaccines have also shown (and are expected, as the vaccines are triggering an immune response in patients).
However, the paper didn't share much on the important T-cell response (the white blood cells that kill virus infected cells). The paper said: "Adenovirus-vectored vaccines are known to induce strong cellular immunity and ChAdOx1 nCoV-19 vaccination resulted in marked increases in SARS-CoV-2 spike-specific effector T-cell responses as early as day 7, peaking at day 14 and maintained up to day 56 as expected with adenoviral vectors." but the paper didn't show any of the data. Below is Lowe's bottom line take.
These results, overall, are fine – but I think that they would have been more impressive had they come out before the Moderna and Pfizer mRNA ones. As it is, I have trouble reconciling the big buildup from the British media (and, I have to add, from the editorial staff at The Lancet) with what’s actually presented here. I’m very glad that I don’t have to pick which vaccine to get based on the limited data we have (there are no efficacy numbers to compare, to pick the biggest gap in our knowledge!) But if I were forced to make such a choice, right now I’d take the Pfizer/BioNTech candidate. But let’s see how everyone performs where it counts.
Well the WHO didn't declare a global pandemic until March 11 and the Euro leaders went ballistic when Trump started the Euro restrictions on 3/12. Was anyone calling for them earlier publicly?
Pretty sure the formal declaration of it being a Pandemic was a formality at that time...it was a full blown pandemic before that.
Well I guess we can table this discussion since the mods felt justified in deleting my post that laid-out the real prep work going on at the Federal level behind the scenes. :ThumbsDown
At least in other news Schiano picked-up another big-time transfer recruit.:Chop banana:
Certainly looks promising on the surface, as it was a randomized, controlled clinical trial, but keep in mind, no paper has been published yet, so the data can't actually be reviewed by anyone, and the statistical significance of the clinical benefit is there, but just barely, likely because it was such a small trial (100 patients). Below is a nice write-up on exactly what that means.
https://www.biospace.com/article/uk-s-synairgen-reports-positive-covid-19-treatment/
It's worth noting that the p-value of the 79% figure was 0.046, which only provides a narrow margin for being statistically significant. P-value, or probability value, is a determination of statistical value. The smaller the p-value, the stronger the evidence is that the null hypothesis should be rejected. The null hypothesis is that there is no significant difference between specified populations, and any difference observed is related to sampling or experimental error. A p-value less than 0.05 is statistically significant; greater than 0.05, not statistically significant. Still, it is statistically significant, although barely.
Taking this a step further, the press release shares the following data, which I haven't seen in most of the articles for some reason, but is important. It's on the "odds ratio" confidence interval for the data. What it shows is that the 79% reduction in the odds of developing severe disease is, statistically a range of 3% to 96% reduction, meaning, yes major reduction is possible, but so is very minor reduction. Similar analysis for the odds ratio of being 2.19 times as likely to recover (HR = 2.19) - the 95% confidence interval for this is 1.03X to 4.69X as likely to recover, so it could be a major score or a very minor improvement.
This is the problem with very small trials. Personally, I wouldn't bet the farm on this drug until I saw results from larger trials, which are in the works, but the data are certainly good enough to warrant emergency use, in my opinion and fast-tracking of larger trials. I'd also be saying similar things if the p-value was just slightly above 0.05, i.e., despite that not being statistically significant, the results would've been considered very encouraging and would mean certainly a larger trial would be warranted to definitively determine efficacy and would mean consideration for emergency use.
The odds of developing severe disease (e.g. requiring ventilation or resulting in death) during the treatment period (day 1 to day 16) were significantly reduced by 79% for patients receiving SNG001 compared to patients who received placebo (OR 0.21 [95% CI 0.04-0.97]; p=0.046).
Patients who received SNG001 were more than twice as likely to recover (defined as ‘no limitation of activities’ or ‘no clinical or virological evidence of infection’) over the course of the treatment period compared to those receiving placebo (HR 2.19 [95% CI 1.03-4.69]; p=0.043).
https://www.globenewswire.com/news-...SNG001-in-hospitalised-COVID-19-patients.html
Seems like some folks were interested in more info on all of this. The first link, below, is on the null hypothesis, p-values and statistics in clinical trials and the 2nd link provides some history and commentary on where the p-value being less than 0.05 came from (1920's work by Dr. Fisher where 0.05 is right around where two standard deviations occurs around a normal population distribution mean) and the fact that it's a great guide, but not the end-all be-all in clinical science. The 3rd link is to a very simplified discussion of all this.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4571159/#:~:text=A high P value is,null hypothesis can be rejected.
https://www.ahajournals.org/doi/10.1161/STROKEAHA.114.006138
https://www.dummies.com/education/math/statistics/what-a-p-value-tells-you-about-statistical-data/
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And here's an update on CanSino's phase II vaccine trial in ~600 patients with a new paper and a just-issued blog from Derek Lowe's "In the Pipeline" (he's on fire today); both are linked below. This is also an adenovirus vector vaccine, like Oxford's, except this uses a human adenovirus with the SARS-CoV-2 spike protein sequence spliced in, while Oxford's uses a chimpanzee adenovirus as the vector.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31605-6/fulltext
https://blogs.sciencemag.org/pipeline/archives/2020/07/20/new-data-on-the-cansino-vaccine
Many have been concerned about the human adenovirus vector resulting in pre-existing immune system reactions to this vector and that looks to be occurring, which could limit the effectiveness of this vaccine. Lowe covers this nicely in the excerpt below.
Overall, then, this is a useful but limited publication. It tells us more about the CanSino vaccine’s profile, but it also raises some worries about just what everyone was already worried about: the pre-existing Ad5 immune response. This should come as no surprise to anyone, and the paper states clearly that this is their biggest concern going forward. In the Chinese population, about 50% of the population is in that category – in India it’s 80%, and in the US around 30%. The question is what differences one might see in the Phase II efficacy readouts. Remember, giving a booster shot with one of these viral-vector agents is quite problematic – after the first dose, the number of your patients who have neutralizing antibodies to the vector is now 100%. One the other hand giving one shot instead of two is potentially a big advantage – but only if that one shot is enough. Yet again, we’re going to have to let this shake out in Phase II. Maybe it won’t make a difference, but. . .given these concerns, if I were a betting man – perish the thought – this vaccine is not where I would be putting my money just now.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31605-6/fulltext
https://blogs.sciencemag.org/pipeline/archives/2020/07/20/new-data-on-the-cansino-vaccine
Many have been concerned about the human adenovirus vector resulting in pre-existing immune system reactions to this vector and that looks to be occurring, which could limit the effectiveness of this vaccine. Lowe covers this nicely in the excerpt below.
Overall, then, this is a useful but limited publication. It tells us more about the CanSino vaccine’s profile, but it also raises some worries about just what everyone was already worried about: the pre-existing Ad5 immune response. This should come as no surprise to anyone, and the paper states clearly that this is their biggest concern going forward. In the Chinese population, about 50% of the population is in that category – in India it’s 80%, and in the US around 30%. The question is what differences one might see in the Phase II efficacy readouts. Remember, giving a booster shot with one of these viral-vector agents is quite problematic – after the first dose, the number of your patients who have neutralizing antibodies to the vector is now 100%. One the other hand giving one shot instead of two is potentially a big advantage – but only if that one shot is enough. Yet again, we’re going to have to let this shake out in Phase II. Maybe it won’t make a difference, but. . .given these concerns, if I were a betting man – perish the thought – this vaccine is not where I would be putting my money just now.
Yep saw that also. We need a power ranking for the vaccines. CanSino and Moderna to the bottom. Pfizer and Oxford towards the top!
The one thing I just saw with the Oxford, only 10 people received the second, booster shot? I wonder why they didn’t put more emphasis on results with a second, booster shot.
Hahahaha. You Trumper's are as bad at lying as your hero! The US isn't even top 25 of deaths per 100k. You do know we all have Google and actually can fact check, no??. Oh yeah like Trump you don't care. Just keep lying. And the ban on travel was a complete fail!
https://coronavirus.jhu.edu/data/mortality
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Laughable--it's not even worth discussing this topic with someone dumb enough to compare the U.S. to Bermuda and believes reported numbers from the Chicoms, Putin and the ayatollahs in Iran. But maybe you can quantify how many more in the US would have been infected and died without the travel restrictions, or could have been saved if NY government officials didn't ignore the Harvard models. I won't hold my breath waiting for you though since I doubt anything like that is reported on CNN.
https://www.realclearpolitics.com/coronavirus/
Another great John Oliver show.
Absolutely amazing proof of what some people will believe.
Funny, you mention it a lot that you don't follow politics. Yeah right.
:Okay[roll]:flush:
You said the US was only behind Canada. And I stopped counting at 25. It could be outside the top 50. Just another lie by you!
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