Hilda Bastian, PhD Profile picture
Meta-science (PhD), writing, cartooning. Absolutely Maybe @PLOS & "Statistically Funny" blog on bias & clinical epidemiology. Occasionally @WIRED & @BMJ_Latest
Peter English #FBPE Profile picture Aviva Gabriel Profile picture Leslie Cook Profile picture 4 added to My Authors
25 Feb
ca 600,000 vaccinated with BNT-Pfizer vaccine in Israel, matched on demographic/clinical characteristics of 600,000 unvaccinated (median age 45) showed results similar to the phase 3 trial... 1/n nejm.org/doi/full/10.10…
...Similar pattern, for infection, symptomatic Covid-19, hospitalization, severe disease, death: 10,561 people infected, 57% of them developed symptoms; 369 in hospital, 229 severe Covid-19, 41 deaths...2/n
...7 days after 2nd dose: 92% efficacy against infection (CI: 88 to 95) - that's a strong result. Hospitalization: 87% (CI: 55 to 100) - wide confidence intervals, so not so certain. Remember, it's a group on the young side...3/n
Read 5 tweets
24 Feb
Away we go. J&J ENSEMBLE trial evaluation has landed - 8am again - thanks, FDA! ....1/n
fda.gov/advisory-commi…
...First up, yes, outcome measure was reasonably close to what we're used to. Here it is based on the FDA-harmonized definition (including mild disease) - & keep in mind this is with South Africa &c included: vaccine efficacy 67% (CI: 56-75) (CI is a measure of uncertainty)...2/n
...This is what that looks like. Keeping in mind it's a single shot - and 28 days after it is about similar to the time of 7 days after BNT-Pfizer's second shot (as they're 3 weeks apart). (ENSEMBLE-2 is underway to see a 2nd shot on day 57) ...3/n
Read 21 tweets
24 Feb
It's another ENSEMBLE-watch day! The FDA meets on 26th to discuss the evaluation of the J&J single-shot vaccine - 3rd vaccine for FDA - & they aim to publish report 2 days ahead, which they achieved for the last 2. So 🤞 all will be revealed in a few hours ... 1/n
...This is where reports will be posted: fda.gov/advisory-commi…

Trial protocol: jnj.com/coronavirus/en…

Press release with trial efficacy readout: jnj.com/johnson-johnso…

My thread on it:

Records on this vaccine: zotero.org/groups/2528572… ...2/n
...Things I'll be watching out for. By far the biggest set of "events" (people with symptomatic Covid-19) of any trial. So it'll be the strongest data yet on questions past that top line efficacy - efficacy in severe disease, for example, which others had too few to answer ...3/n
Read 7 tweets
22 Feb
Report from Scotland with great news on Covid vaccination reducing hospitalization rates. Not enough data released to be sure about much beyond that though, & number of vaccinated people hospitalized appears to be too small (happily!) to draw much beyond that though...1/2
..Some details about the study hps.scot.nhs.uk/a-to-z-of-topi… BBC says 58 people in hospital who were vaccinated a month before: % by vaccine & for over 80s, but that number seems too small to break it down it by vaccine & age. Overall, ca 90% lower. 🤞 bbc.com/news/health-56… 2/2
...Ah ... preprint tweeted by @jaclark73 - thanks! drive.google.com/file/d/162PJKb… Just hunting out the numbers now... 3/n
Read 18 tweets
19 Feb
This Oxford-AstraZeneca vaccine study from a preprint a couple of weeks ago is now published in the Lancet. At first look, there are some additions... 1/n thelancet.com/journals/lance…
...In the original thread, I'd had a question about hospital admissions, but ignore that if you re-read it: the wording is expanded a little in the paper, & it clears it up... 2/n
...The supplementary info includes listing of serious adverse events & unsolicited adverse events, but no data on solicited adverse events - all of that is new...3/n thelancet.com/cms/10.1016/S0…
Read 5 tweets
18 Feb
EMA (Euro drug regulator) assessment report for the Oxford-AstraZeneca vaccine is online. This one's 181 pages. Most of it's based on the original November data (as in the Lancet publication) but some includes is Ded 7 data (as in recent preprint): ema.europa.eu/en/medicines/h… ...1/n
...They had a major objection to the US manufacturing plant (it's also manufactured in the UK & Belgium - EMA is not assessing Covishield, the Indian version, at all). However, their concerns were resolved. Sounds like it was missing certification...2/n
...EMA wants additional data to validate quality of manufacture at all 3 sites is comparable. Since there's no assessment of Covishield here & WHO didn't do it, I assume this rests totally on the Indian regulator, which published no data (Indian trial still unpublished)...3/n
Read 21 tweets
16 Feb
TGA (Australian drug regulator) issued 2-year provisional approval for the Oxford-AstraZeneca vaccine, no age restrictions, with a cop-out on age - pushing the onus onto individual decisions. 4 to 12 week interval tga.gov.au/media-release/… ...1/n
...The Public Assessment Report released with the decision (49 pages) tga.gov.au/auspar/auspar-… It's for the AstraZeneca version: when CSL (local producer) is ready to supply, that won't need new clinical data... 2/n
...Reproductive safety study in mice is still underway - not recommended for pregnant women before then. Under clinical data, raised issue of follow-up injections possibly decreasing immunity... 3/n Image
Read 9 tweets
13 Feb
Preprint of the South African phase 1b/2 trial for the Oxford/AstraZeneca vaccine is online. Primary efficacy analysis is for 2,026 people who weren't infected with HIV (there was also a very small arm of people who were HIV+) medrxiv.org/content/10.110… ...1/n
...This shows you how the new variant spread in the 2 provinces the trial was conducted in...2/n Image
..As we already knew, the overall efficacy was 22%, but only 10% against the new variant, with a wide range of uncertainty: but enough for the trial's protocol for excluding efficacy. There were no severe illnesses in the vaccinated or placebo groups: a young, low risk group..3/n Image
Read 9 tweets
6 Feb
Unofficial unnamed AstraZeneca insider says they are doing the interim analysis for the US trial of the Oxford vaccine. AstraZeneca spokesperson says 4-6 weeks till data release. reuters.com/article/uk-hea… One is wrong? Or they'll release only when have FDA minimum follow-up?
..With results for AstraZeneca's large trial of the Oxford vaccine on the horizon ⬆️, some things I'm keeping in mind. It's a single, adequately powered, standardized, double-blind, fully placebo-controlled trial: the first for this vaccine. It's 2 doses, 4 weeks apart, so...2/8
...not designed to test the hypothesis that 8-week or 12-week interval increases efficacy. But as with other large vaccine trials, there'll be data relevant to onset of immunity to chew on. It's 2:1 randomization (twice as many in vax as placebo), final goal 150 events...3/8
Read 19 tweets
6 Feb
Sinovac's CoronaVac's phase 3 trial results: some data from Turkey in press release. Brazilian trial, much as Brazil announced: 50.65% vaccine efficacy for all symptomatic disease, 83.7% for people requiring medical care - & no severe or fatal disease..1/n businesswire.com/news/home/2021…
...Some extra context on the trial in Turkey. Essentially same result we heard before: 91.3% efficacy based on 29 people with symptomatic Covid-19 among 1,322 people. The confidence intervals on that when Turkey announced it: 71-97% ...2/n
...So no additional efficacy results; possible difference in healthcare workers. All 4 trials used vaccine from the same lot, which is good to know. No data from the other 2 trials (Indonesia & Chile), though. Records on this vaccine: zotero.org/groups/2528572…
Read 4 tweets
5 Feb
New preprint on the Oxford/AstraZeneca vaccine & B.1.1.7 ("UK" variant). Includes data on the people diagnosed with Covid-19 up to Jan 14 (so a month of extra data than their recent preprint on single dose)... 1/n papers.ssrn.com/sol3/papers.cf… (HT @joelving) ...1/n
...The vaccine reduced efficacy (more on that later). They were able to sequence the virus for 256 out of the 499 people sick with Covid-19...2/n
...The analysis is based on the UK phase 2/3 trial, where participants had regular swabs. So it includes the people they detected who had asymptomatic & symptomatic Covid-19....3/n
Read 14 tweets
2 Feb
New data for the Oxford/AstraZeneca vaccine, with extra month's worth of data, & combining 4 trials from phase 1 to 3, focusing on 1st dose: Indian phase 2/3 trial still not included. 332 events... 1/n papers.ssrn.com/sol3/papers.cf… (Preprint) (TY to the people who alerted me to it)
...Includes 2 phase 1/2 trials in UK & South Africa (2 in Japan & Kenya not included); phase 2/3 trial in the UK (phase 2/3 in India not included); & phase 3 in Brazil. A mixture of trials with & without primary efficacy endpoints. (US phase 3 trial still not this far)...2/n
...New analysis includes a range of non-standardized doses, including accidental low-dose group, with comparison mostly a meningococcal vaccine (Brazil, placebo 2nd shot). For the trials which were originally single shot trials, people were offered the 2nd: not all agreed...3/n
Read 21 tweets
2 Feb
Phase 3 trial for Sputnik V results landed!
To keep in mind: randomized 3 to 1 (not half in vax group, half placebo). It's a pair of vaccines, 1 shot of each, not same vax twice. Both are adenovirus vector vaccines - same category as Oxford & J&J... 1/n thelancet.com/journals/lance…
...We never saw a protocol for this one previously - and there isn't one released with this paper either... 2/n
...They measured their primary outcome from 21 days after the *first* vaccine (the shots are 21 days apart).

These people are at comparatively low risk of poor Covid-19 outcomes: 99% white; about 90% aged 60 or under; <1% at high risk of infection...3/n
Read 19 tweets
29 Jan
J&J ENSEMBLE data is here - what. a. day.

It works with a single, simple to distribute, shot, which is huge. And it's complicated.

Largest set of events yet: 468 people with symptomatic Covid-19 in 43,783

...1/n jnj.com/johnson-johnso…
...34% were over 60 (14,672 people). Diverse, from South Africa & the Americas. 41% had co-morbidities putting them at risk of severe Covid-19. Protection was consistent across age, race, & part of the world - even though 95% in SA were infected with the new "SA" variant...2/n
...First trial powered to answer the severe Covid-19 question: efficacy was 85% at 28 days after the injection (no event breakdown or confidence intervals). For moderate to severe, efficacy was 66%, varying a bit in the 3 regions (from 57% in SA to 72% in the US...3/n
Read 8 tweets
28 Jan
Interim readout from Novavax phase 3 from the 15k UK & 4.4k phase 2b from South Africa. High efficacy in the UK: 89.3% (95% CI: 75.2 – 95.4) - lowered a bit by the new variant...1/n ir.novavax.com/news-releases/… Image
...SA results heavily affected by new variant. Overall efficacy was 60% efficacy (95% CI: 19.9 – 80.1) for the bulk of people who were HIV- : very wide confidence intervals, because it's a small trial. With small HIV+ group included, (efficacy of 49.4%; 95% CI: 6.1 – 72.8) ...2/n
...Critically, the primary efficacy result, as for the other vaccines, is for people who hadn't had a previous SARS-CoV-2 infection. But 1/3 did. No data released for them, but previous infection may not protect against the new "SA" variant ...3/n Image
Read 8 tweets
26 Jan
Meanwhile, a few days ago the EMA published its EPAR (public assessment report) on the Moderna vax (HT @pajz_) ema.europa.eu/en/documents/a… It's 169 pages ...1/n
...There was "a major objection" to the US manufacturing sites, so they were withdrawn. Complete transfer for Europe to Swiss manufacturing due to conclude soon. (There have been Qs in the US about a batch there reuters.com/article/us-hea…)...2/n
...If you're interested in the chemical & biological aspects of this vaccine, there are pages for you to dig into - not an area I have any expertise in. Small amount of detail of reproductive toxicity study (in rats): no cause for concern....3/n
Read 10 tweets
25 Jan
It's on the agenda this week: possibly a decision on the Oxford/AstraZeneca vaccine from EMA's (Euro drug regulator) Human Medicine Committee? Applicants will be questioned at the meeting.

(EMA process steps explained here: ema.europa.eu/en/human-regul…)
Last night, I tweeted ⬆️ that the EMA (Euro drug regulator) meeting was considering the Oxford/AstraZeneca vaccine. I included a link to EMA processes, because the language on the agenda suggested there could be a problem: this is the explanation I mean in that link ....1/n
...German newspapers now reporting a claim the efficacy rate for people over 65 is only 8% & approval is indeed in question for that age group, at least (Paywalls: I can't read in full.) Rumor at this point, but a limit ...2/n bild.de/bild-plus/poli…, handelsblatt.com/politik/deutsc…
Read 15 tweets
24 Jan
TGA, Australia's drug regulator, has issued a 2-year provisional approval for Tozinameran (BNT/Pfizer vaccine) from age 16, & released its 42-page assessment report tga.gov.au/auspar/auspar-… ...1/n
...One of the conditions is TGA approval of at least 20 vials from each batch before release...2/n
..Study of reproductive safety in rats has been completed & found no signs of concern related to pregnancy. This wasn't completed when the FDA reported. No data is in this report though. Otherwise it's the same data basis...3/n
Read 5 tweets
22 Jan
For everyone else who's on ENSEMBLE-Watch - the big J&J trial for their Ad26.COV2.S vaccine - some background & context in case a press release lands soon. (On Wednesday, Stanford got the word to lock their data abc7news.com/johnson-and-va… so it is on!)...1/5
...It's a big trial - close to the size of the Pfizer trial for Tozinameran, substantially bigger than Moderna's - & the most international one. And co-primary endpoints are for moderate to severe Covid-19, including 1 at a month - which is longer than we've seen previously...2/5
...You can see the protocol for the trial here: jnj.com/coronavirus/co… (Note, it was originally for 60,000 but they got so many events it was cut back to 40)...3/5
Read 6 tweets
20 Jan
Sputnik V news: ANMAT, Argentina's drug regulator, has now extended authorization to people 60+ & released some data this time. Here's the listing of what they've received & analyzed (but it's not published) ... 1/n argentina.gob.ar/noticias/ampli…
...The new data on people 60+ they received: in 2,144 people, vaccine efficacy of 91.8% (95% CI 67.1% -98.3%). Almost all those people had antibodies by 28 days ...2/n
...ANMAT reports there's now data for 19,866 people who received both Sputnik V injections, with no serious adverse events (SAEs) judged to be vaccine-related. There were 47 SAEs in vax group vs 23 in placebo. Safety similar for older people in small safety study. 3/3
Read 4 tweets
17 Jan
After 10s of thousands of Brazilians participated in early trials of Covid vaccine, vaccination has at last begun there: Anvisa (drug regulator) approved Sinovac's CoronaVac & Serum Institute of India's Covishield (Oxford/AstraZeneca vaccine) ...1/n g1.globo.com/sp/sao-paulo/n…
...Before I get to the Anvisa documentation, important update on the alligator tracker: jacare-tracker.org It's tracking Brazilian as well as global vaccinations & it's now on Twitter too @jacaretracker ...2/n
...Anvisa's documentation is here & includes trial data as well as manufacturing standards reports: gov.br/anvisa/pt-br/a…

CoronaVac data for the Brazilian trial only. 12,123 people in the whole trial: 64.3% female, 4.9% 60 years or older. Median age: 37 (for Pfizer: 52)...3/n
Read 13 tweets