Oxford/AZ publishes their results - Printable Version
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Oxford/AZ publishes their results - BostonCard - 12-08-2020
https://marlin-prod.literatumonline.com/pb-assets/Lancet/pdfs/S0140673620326611.pdf
It explains how some individuals came to receive a half-dose for their initial dose:
Quote:Two dosage groups were included in COV002: participants who received a low dose of the vaccine (2·2 × 10¹⁰ viral particles) as their first dose and were boosted with a standard dose (in the LD/SD group), and subse quent cohorts who were vaccinated with two standard-dose vaccines (SD/SD group). Initial dosing in COV002 was with a batch manufactured at a contract manufacturing organisation using chromatographic purification. During quality control of this second batch, differences were observed between the quantification methods (spectrophotometry and quantitative PCR [qPCR]) prioritised by different manufacturing sites. In consultation with the national regulator (Medicines and Healthcare products Regulatory Agency), we selected a dose of 5 × 10¹⁰ viral particles by spectrophotometer (2·2 × 10¹⁰ viral particles by qPCR), in order to be consistent with the use of spectrophotometry in the phase 1 study (COV001),5 and to ensure the dose was within a safe and immunogenic range according to measurements by both methods. A lower-than-antici-pated reactogenicity profile was noted in the trial, and unexpected interference of an excipient with the spec-trophotometry assay was identified. After review and approval by the regulator, it was concluded that the qPCR (low-dose) reading was more accurate and further doses were adjusted to the standard dose (5 × 10¹⁰ viral particles) using a qPCR assay. The protocol was amended on June 5, 2020,resulting in enrolment of two distinct groups with different dosing regimens with no pause in enrolment (version 6.0; appendix 2 p 330). A suite of assays has now been developed for characterisation of concentration (which confirmed the low and standard dosing), and future batches are all released with a specification dose of 3·5–6·5 × 10¹⁰ viral particles, and this was used for the booster doses in the efficacy analysis presented here.
One thing that I had been looking for is how well the vaccine prevents severe disease:
Quote:More than 21 days after their first dose, ten participants were hospitalised due to COVID-19 (defined as WHO clinical progression score ≥4), two of whom were assessed as having severe COVID-19 (WHO score ≥6), including one fatal case. All ten cases were in the control group (table 5).
So, with limited data (only 10 events), it does look like both the standard and low dose vaccines were effective in preventing serious COVID-19.
BC
RE: Oxford/AZ publishes their results - Goose - 12-08-2020
(12-08-2020, 11:20 AM)BostonCard Wrote: https://marlin-prod.literatumonline.com/pb-assets/Lancet/pdfs/S0140673620326611.pdfSo overall pretty good news. Seems they are going for the EUA with the data they have and do not think they will need another trial to get it. As I read the paper, efficacy was a little "muddled", but ranged from 62.5% to 90%, depending on the protocol. Not perfect, but useful. The total lack of severe disease in the treated group is encouraging even with small N.
It explains how some individuals came to receive a half-dose for their initial dose:
<snip>
One thing that I had been looking for is how well the vaccine prevents severe disease:
Quote:More than 21 days after their first dose, ten participants were hospitalised due to COVID-19 (defined as WHO clinical progression score ≥4), two of whom were assessed as having severe COVID-19 (WHO score ≥6), including one fatal case. All ten cases were in the control group (table 5).
So, with limited data (only 10 events), it does look like both the standard and low dose vaccines were effective in preventing serious COVID-19.
BC
RE: Oxford/AZ publishes their results - BostonCard - 12-08-2020
I believe they are planning another trial (or at least they were):
https://www.reuters.com/article/us-health-coronavirus-astrazeneca/astrazeneca-ceo-expects-to-run-new-global-trial-of-covid-19-vaccine-bloomberg-idUSKBN28620H
The question is whether what they have now is sufficient to get an EUA. I would guess so, based on the stated goalposts (>50% efficacy and lower bound of the CI > 30%), which they meet. Given that it offers the best chance to mass vaccinate quickly, I think it is probably worth moving forward with it. But I would like to see a three arm trial of half-dose versus full-dose versus placebo (or at least the half-dose versus placebo) to verify the ~90%.
https://www.wsj.com/articles/astrazeneca-covid-19-vaccine-trial-data-underscore-safety-range-of-efficacy-11607443250
AZ/Oxford will indeed submit the data.
BC
RE: Oxford/AZ publishes their results - Goose - 12-08-2020
(12-08-2020, 12:40 PM)BostonCard Wrote: I believe they are planning another trial (or at least they were):You raise an interesting question. The totality of their existing trials seems to justify an EUA, but for exactly what? From what I read, it would be the full dose both times, because there isn't as much data on the half followed by full? Yet the latter seems more promising (counter intuitive as that may be). A full study including a single dose as a fourth arm might be interesting. As was pointed out, the durability of immunity etc. is unknown for a single dose because everybody got a second.
https://www.reuters.com/article/us-health-coronavirus-astrazeneca/astrazeneca-ceo-expects-to-run-new-global-trial-of-covid-19-vaccine-bloomberg-idUSKBN28620H
The question is whether what they have now is sufficient to get an EUA. I would guess so, based on the stated goalposts (>50% efficacy and lower bound of the CI > 30%), which they meet. Given that it offers the best chance to mass vaccinate quickly, I think it is probably worth moving forward with it. But I would like to see a three arm trial of half-dose versus full-dose versus placebo (or at least the half-dose versus placebo) to verify the ~90%.
https://www.wsj.com/articles/astrazeneca-covid-19-vaccine-trial-data-underscore-safety-range-of-efficacy-11607443250
AZ/Oxford will indeed submit the data.
BC
RE: Oxford/AZ publishes their results - BostonCard - 12-08-2020
The hand-waiving argument I've seen for the half dose is that the full dose produces a vigorous response against the viral vector (the chimpanzee adenovirus) so that when the booster is injected, it is destroyed before it can ever enter cells and thus the spike proteins are never expressed and don't produce an immune response.
BC