I've been seeing a lot of discussion around the dosage gaps recommended by government for the Astra/Oxford & Pfizer/BioNTech vaccines. My thoughts on the potential benefits & risks of such an approach, and the need for much greater transparency around these decisions. Thread.

The UK govt announced recently that both the Oxford & BioNTech vaccines would be now administered with a gap of between 4-12 weeks (so prioritise administration of first dose, given limited resources).

What is the basis of this?
The basis that's been discussed seems to be that
1) the first dose is likely to confer some degree of protection against disease, so better to roll this out as fast as possible, and
2) that for Oxford/Astra efficacy may be higher when the gap between doses is greater.
I discuss some of the technical details around the Oxford trial below for those interested in these. If you'd just like a summary of this, please skip to the summary tweet titled 'SUMMARY'.
What does published evidence show? The Astra/Oxford data are a bit messy because of protocol changes during the trial. This is because the trial was originally planned as a single dose trial, but a booster dose was added when developers realised that this would likely help.
This meant the 2nd dose was added months after the start of the trial. Because of the nature of the trial- younger people recruited into the trial first & older people recruited once it was decided that 2 doses should be used, younger participants were given the 2nd dose later.
To complicate matters there was an error early in the trial which meant that ~1,400 participants were given a low 1st dose by mistake. Given the first tranche of participants were <55 years, the low dose (1st dose)/standard dose (2nd dose) combination was only used in this group
So approximately 42% of participants <55 yrs had the lowdose/standard dose (LD/SD) combination, and all the older ones had the SD/SD combination. And the gap between doses was higher among <55 yr olds vs >55 yr olds, although I couldn't find the breakdown of this in the paper.
The efficacy results that are reported suggest an efficacy of ~60% in reducing disease for the SD/SD group, and ~90% for the LD/SD group. What is less clear is whether these differences are due to the lower first dose, younger participants, or longer gaps between doses.
So let's look at efficacy by age group and dose.
Vaccine efficacy among 18-55 yr olds SD/SD dosing was 59% vs LD/SD dosing at 90%.

Is this due to dosing, or differences in gaps between doses?
Differences in gaps don't appear to impact efficacy in this analysis.
Of course we can't evaluate this in ages >55 as they only had a short gap in dosing. So we don't have any data on longer gaps in >55 yr olds, at least in the data that are public.
I have seen reports that unpublished data support longer gaps between doses. But without seeing the data, I can't evaluate the basis for this. Presumably MHRA has evaluated the evidence before granting approval for the current dosage protocol.

https://t.co/9yaSAyHcKR
What about the efficacy after the first dose?
It looks like the first dose prevented all severe disease (although numbers were small) in the SARS-CoV-2 vaccine group compared to vaccine control after the first 21 days of vaccination, and <14 days after the 2nd dose.
SUMMARY: the Oxford/Astra trial examined dosing with gaps between 4-12 wks- although longer gaps appear to be limited mostly to younger participants. There was no difference reported in published data between these & efficacy from the 1st dose seems high for severe disease.
Given this, I can understand the plan for longer dosing gaps for this vaccine, although I do think that it's important that the unpublished data that support this are released for transparency & to build public trust which is essential at this point.
The application of the same principle to the Pfizer/BioNtech vaccine is more difficult to evaluate. This vaccine was studied with a strict protocol of 21 days between doses & the company has since issued a warning that they cannot ensure efficacy if protocol is changed
While the Pfizer trial shows reasonably high efficacy after the 1st dose of vaccine (~80%), the duration of this following 21 days is unclear. So there is a risk that this level may decline after this period, as we don't have direct data on this from trials.
However, there are also arguments for the approach the govt is taking, as outlined below. Essentially the thinking is that given the urgency, roll-out across double the numbers with 80% efficacy is better than rolling out half numbers with 95% efficacy.

https://t.co/966V4EYw13
The assumptions key to this argument are of course that:
1. Resources for roll-out are limited & fixed & we need to optimise how best to use them within limitations
2. There isn't significant decline in immunity after the 3 wk mark
3. Later dosing will not affect overall efficacy
I'm not a vaccinology expert so can't really comment on 2. and 3. From reading views from other experts, the general view seems to be that later dosing is unlikely to impact overall efficacy. What level of immunity lasts up to 12 weeks is less clear, I think.
I'm also not entirely clear about the impact of a longer period of partial immunity (if immunity declines following 3 wks) on viral adaptation. I know some experts have raised concerns about this. I think this is dependent on how much immunity declines prior to the 2nd dose.
Given a lot of this is conjecture, it's hard to know whether this is the right strategy for the Pfizer vaccine. I am naturally cautious about changing a protocol that's tried & tested to one where we don't have data on, particularly given the warnings issued by Pfizer.
I'm also concerned by the poor planning around this. Given these data were available for a while, it's not clear to me why this decision was made now, when hundreds of thousands have had their second appts booked in. Cancelling these is also time-consuming & undermines trust.
Irrespective of how and why the MHRA approved this, I think it's important to release the thinking & the data around it - to create transparency & build trust with the public, and with health-care workers. It's very clear that HCWs were not consulted in this, which led to chaos.
Such actions really risk undermining public trust, when it's already very low. We are counting on high vaccine uptake to be able to contain the pandemic - we can't afford to not take the public along on decisions such as this. Good communication & transparency is key.
Given the urgency of vaccine roll-out now, these are complex decisions. While there may be good scientific reasons for which these decisions have been made, it's important that these reasons are made clear & the public and HCWs are engaged in this decision-making process.
Just wanted to highlight one last point- it looks like the govt have released a document around this today.

A key part of the rationale appears to be a bottleneck in vaccine supply (rather than roll-out).

https://t.co/mccavkBGeb

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This is the exact problem with our government's thinking & response- despite this strategy of 'tolerating deaths' and half-way measures having spectacularly failed, it's quite amazing that our govt still hasn't learned anything, & continues to promote a policy of death. Thread


Had we adopted an elimination strategy early on, rather than one of tolerating a certain level of infection, we wouldn't be here now. The reason we're here is because the govt never committed to elimination.

We eased lockdown in May when infection levels were much higher than when other countries in Europe did this. The govt was warned about this, but did this to 'help the economy'. Not only did this lead us into the 2nd wave, the need for further lockdowns harmed the economy further

It's very clear from global evidence that we cannot 'tolerate a level of community transmission' and maintain 'R at or just below 1', which has been our governments policy for a long time. This isn't sustainable & very rapidly gets out of control, leading to exponential rises

Coupled with late action to contain these surges, not only does this lead to many more deaths, and much more morbidity with Long COVID, it also creates a fertile ground for viral mutations to accumulate with a greater risk of adaptation, which is exactly what happened in the UK
We've been falsely told 'schools are safe', 'don't drive community transmission', & teachers don't have a higher risk of infection repeatedly by govt & their advisors- to justify some of the most negligent policies in history. 🧵


data shows *both* primary & secondary school teachers are at double the risk of confirmed infection relative to comparable positivity in the general population. ONS household infection data also clearly show that children are important sources of transmission.

Yet, in the parliamentary select meeting today, witnesses like Jenny Harries repeated the same claims- that have been debunked by the ONS data, and the data released by the @educationgovuk today. How many lives have been lost to these lies? How many more people have long COVID?

has repeatedly pointed out errors & gaps in the ONS reporting of evidence around risk of infection among teachers- and it's taken *months* to get clarity on this. The released data are a result of months of campaigning by her, the @NEU and others.

Rather than being transparent about the risk of transmission in school settings & mitigating this, the govt (& many of its advisors) has engaged in dismissing & denying evidence that's been clear for a while. Evidence from the govt's own surveys. And global evidence.

Why?

More from Government

🧵⬇️1. Fb is LifeLog, LifeLog is Darpa, and DARPA is a Enterprise Run by CIA... Well... Past President... Big Tech, Big Pharma, MSM, HOLLYWOOD, DC...

Past Presidents....Zuckerberg, Gates...
All C_A... the Family business.... The company...


2. Past Presidents....Zuckerberg, Gates...
All C_A... the Family business.... The company...The Farm.... all C_A assets... most of them related by blood, business, or marriage...


3. "The individual is handicapped by coming face-to-face with a conspiracy so monstrous he cannot believe it exists. The American mind simply has not come to a realization of the evil which has been introduced into our midst." - J. Edgar Hoover


4. diff. names & faces.... Monsters that lurk in the Shadows. Swamp, Deep State, Establishment, Globalist Elite Cabal...

Shall we go back...How far back...


5. I know these monsters... it's when I try to explain them to others is when I run into a problem.This is why I'm better at retweeting and compiling. I never know where to start... Everytime I try to thread, i end up w/ a messy monstrous web.I'm better at helping others thread.
Labour Grandees are listed in Sir Keir Starmer's colleague Jeffrey Epstein's ''Little Black Book''; Blair, Mandelson and Alastair Campbell. COINCIDENTLY, Keir Starmer and some of the same people have connections to ANOTHER of the worlds most prolific peadophiles. #StarmerOut


Starmer failed to bring charges against Jimmy Savile for paedophilia. The decision was made despite the Crown Prosecution Service receiving substantial evidence of his crimes from witnesses and victims several years before Savile died in 2011. #StarmerOut
https://t.co/PNyX5uSAkw


With a past like hers, Margaret Hodge might show a bit more humility.
In the Eighties Hodge was aware of previous child sex abuse in the care homes for which she was responsible, and did nothing about it. #LabourLeaks #StarmerOut

As leader of Islington Council, a post she held from 1982-92, Margaret Hodge was aware of previous, horrendous child sex abuse in the care homes for which she was responsible, and did nothing about it. #LabourLeaks #StarmerOut #CSA

She was guilty of rather more than a casual failure of oversight. In an open letter to the BBC after it investigated a range of monstrous abuse (child prostitution, torture, alleged murders), Hodge libelled one of its victims as “seriously disturbed”. #LabourLeaks #StarmerOut
2017 https://t.co/kiqQoWR57e


https://t.co/W18nqFlLru


The GOP got rid of the SCOTUS filibuster so they could jam through three fringy right-wing Alito clones, including one right before the election, but sure thing, bud.

“Uh, actually, they got rid of the SCOTUS filibuster because Harry Reid did it first for something totally different! I am very smart!”

No. Knock it off.

Here’s the thing about the “But Harry Reid...” excuse:

1. McConnell was holding up Obama nominees, some *for literal years* without a vote.

2. Had he *not* done that, Trump would have inherited *even more* vacant seats.

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This is a pretty valiant attempt to defend the "Feminist Glaciology" article, which says conventional wisdom is wrong, and this is a solid piece of scholarship. I'll beg to differ, because I think Jeffery, here, is confusing scholarship with "saying things that seem right".


The article is, at heart, deeply weird, even essentialist. Here, for example, is the claim that proposing climate engineering is a "man" thing. Also a "man" thing: attempting to get distance from a topic, approaching it in a disinterested fashion.


Also a "man" thing—physical courage. (I guess, not quite: physical courage "co-constitutes" masculinist glaciology along with nationalism and colonialism.)


There's criticism of a New York Times article that talks about glaciology adventures, which makes a similar point.


At the heart of this chunk is the claim that glaciology excludes women because of a narrative of scientific objectivity and physical adventure. This is a strong claim! It's not enough to say, hey, sure, sounds good. Is it true?
शमशान में जब महर्षि दधीचि के मांसपिंड का दाह संस्कार हो रहा था तो उनकी पत्नी अपने पति का वियोग सहन नहीं कर पायी और पास में ही स्थित विशाल पीपल वृक्ष के कोटर में अपने तीन वर्ष के बालक को रख के स्वयं चिता पे बैठ कर सती हो गयी ।इस प्रकार ऋषी दधीचि और उनकी पत्नी की मुक्ति हो गयी।


परन्तु पीपल के कोटर में रखा बालक भूख प्यास से तड़पने लगा। जब कुछ नहीं मिला तो वो कोटर में पड़े पीपल के गोदों (फल) को खाकर बड़ा होने लगा। कालान्तर में पीपल के फलों और पत्तों को खाकर बालक का जीवन किसी प्रकार सुरक्षित रहा।

एक दिन देवर्षि नारद वहां से गुजर रहे थे ।नारद ने पीपल के कोटर में बालक को देख कर उसका परिचय मांगा -
नारद बोले - बालक तुम कौन हो?
बालक - यही तो मैं भी जानना चहता हूँ ।
नारद - तुम्हारे जनक कौन हैं?
बालक - यही तो मैं भी जानना चाहता हूँ ।

तब नारद ने आँखें बन्द कर ध्यान लगाया ।


तत्पश्चात आश्चर्यचकित हो कर बालक को बताया कि 'हे बालक! तुम महान दानी महर्षि दधीचि के पुत्र हो । तुम्हारे पिता की अस्थियों का वज्रास्त्र बनाकर ही देवताओं ने असुरों पर विजय पायी थी।तुम्हारे पिता की मृत्यु मात्र 31 वर्ष की वय में ही हो गयी थी'।

बालक - मेरे पिता की अकाल मृत्यु का क्या कारण था?
नारद - तुम्हारे पिता पर शनिदेव की महादशा थी।
बालक - मेरे उपर आयी विपत्ति का कारण क्या था?
नारद - शनिदेव की महादशा।
इतना बताकर देवर्षि नारद ने पीपल के पत्तों और गोदों को खाकर बड़े हुए उस बालक का नाम पिप्पलाद रखा और उसे दीक्षित किया।