The Oxford Vaccine’s True Efficacy Remains Uncertain

The preliminary results provided reason for optimism, but left many questions unanswered.

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The vaccine candidate sponsored by the University of Oxford and AstraZeneca has shown promise in preventing COVID-19 in Phase III clinical trials, but the evidence is not yet convincing enough to put it in the same category as competitors from Pfizer-BioNTech and Moderna. Consequently, it is likely that the Food and Drug Administration (FDA) will insist on more and better data before granting regulatory approval.

The preliminary results from the Oxford-AstraZeneca Phase III trial provided cause for optimism, but left many questions unanswered. While reporting an overall vaccine efficacy rate of 70 percent—a rate that exceeds the minimum 50 percent threshold set by the World Health Organization (WHO) and FDA for approving COVID-19 vaccines—the trial sponsors further announced that the efficacy of their vaccine was 90 percent for a limited subset of participants who received a half dose and then a full dose one month apart. 

Just under 1 in 4 participants in the vaccine arm of the trial received the half-dose/full-dose regimen, which was the result of a manufacturing error and not a part of the original trial protocol. The rest, 3 out 4 trial volunteers in the vaccine arm, received two full doses one month apart. 

For participants who received the full-dose/full-dose regimen, the observed vaccine efficacy rate was 62 percent, or 28 percentage points below the half-dose/full-dose regimen. Because so many more participants received two full doses rather than a half dose followed by a full dose, the average efficacy rate when combined across the two dosing regimens was closer to the efficacy rate found among those receiving the full-dose/full-dose regimen. 

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  1. Avatar photo
    BrandonAlleman

    Predicted pardon Bingo cards please.

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  2. Brett

    How is efficacy measured?

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      Nick H

      As I understand it, in a general way it's just a measure of how many people in the trial who got sick were given the placebo vs those that got sick after getting the vaccine. So if 100 people in the trial got COVID-19 and 70% of those had received the placebo, the efficacy would be 70%. There's more to it than that, but this should give you a rough estimate.

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      1. Brett

        I'm asking because no one is intentionally exposed, right? So that being the case, how does one know it was not just luck? I understand that if you have almost no cases that is meaningful but if 10-30 percent of people getting the vaccine still get the disease based on ordinary daily life I don't know how that can be considered meaningfully different than the status quo which seems to be on the order of 10-30 percent of the population having acquired the disease going about their ordinary daily life.

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        1. Avatar photo
          Connie

          I am a participant in the Phase III trial of Moderna’s mRNA-1273. They wanted people who had a high risk of getting COVID. I was a flight attendant (before I got involuntarily furloughed), and that is why they included me in the trial.

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          Tom B.

          Once you have enough people in your trial and it runs for long enough, the statistics on infection rate become very meaningful. If you tested 10 people (double blind, placebo, etc. etc.), luck could explain a big difference in infection rate. If you test 1,000 people, that's much less likely. If you test 100,000 people, even LESS likely. At some point the law of large numbers takes over, and you can be incredibly confident that differences in infection rate and severity you see are from the vaccine. There is no *need* to intentionally infect volunteers with COVID after vaccination.

          However, such trials take *time* and *numbers* (of people vaccinated and of COVID cases). In order to speed up the process, you can do human challenge trials, where you intentionally expose people (volunteers) to COVID after vaccination and see the results. Last I knew, the UK was planning at least one challenge trial, and the WHO was considering some to help speed research.

          I will point out, though, that challenge trials are not NECESSARY to know that a vaccine is effective. They're essentially a time-saving measure. And they come with some potentially serious ethical concerns.

          It seemed like you also had a question of "if the vaccine is only 70% effective, how is it useful?" Even if a vaccine is only 70% effective, it can drive the reproduction number (R0 or Rt) of COVID under 1 if enough of the population is vaccinated (the default for COVID is higher than 1, and last I knew estimated between 3 and 6, substantially higher than the flu and similar to smallpox). If the effective reproduction number is less than 1 after enough people are vaccinated, COVID will not effectively spread through the population, and the pandemic will tail off.

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          1. Brett

            Thank you that makes sense in theory. I could see how that would work well if it was, say, 99 percent effective. Then with thousands of people youd see the "normal" infection rate among those who got placebo and something less than normal among the vaccinated. If for example we tested vaccinated people and saw positivity rates of 1 percent that would convince me it was very effective. But I still don't understand how the math of that works out on that concept of 70-90 percent efficacy means those who took the vaccine only test positive 10-30 percent of the time when we consistently see 5-15 percent of people infected in any large sample of unvaccinated people being tested. I assume the positivity rates among the vaccinated must be much lower than 10 percent to call it 90 percent effective but I wonder if that's right and if anyone has seen numbers illustrating that's what happened in these trials.

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  3. rob

    This is quite disappointing. If this is just a lower rate then the other two vaccines but still more effective than the average flu shot and it can help get more people vaccinated quicker and I still feel it should be pushed forward.

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  4. Joe1776

    Sorry this is slightly off topic but I don’t understand why our cdc decided to prioritize all health workers even young ones over high risk people to get the vaccine first. There is apparently no data it prevents the transmission of the virus.

    Most of the studies I read say vaccinate high risk groups first if you want to save lives.

    https://www.medrxiv.org/content/10.1101/2020.08.14.20175257v2.full-text

    https://www.medrxiv.org/content/10.1101/2020.09.08.20190629v1


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    1. Avatar photo
      Tom B.

      First, that's an oversimplification of the conclusions from the (non-peer reviewed) study you linked.

      Second, healthcare workers are prioritized because they are considered "critical infrastructure workforce" (see https://www.cdc.gov/vaccines/imz-managers/downloads/COVID-19-Vaccination-Program-Interim_Playbook.pdf page 15).

      "As defined by USA Patriot Act of 2001 (42 U.S.C. 5195c(e)), critical infrastructure includes any “systems and assets, whether physical or virtual, so vital to the United States that the incapacity or destruction of such systems and assets would have a debilitating impact on security, national economic security, national public health or safety, or any combination of those matters.”" (https://www.cisa.gov/identifying-critical-infrastructure-during-covid-19)

      In other words, healthcare workers are being vaccinated first because if they cannot work (due to COVID), it has a debilitating impact on national public health (at a minimum).

      Immediately after health care workers (and other critical infrastructure workers), the next set to be vaccinated are adults with high risk and / or the elderly. This is essentially exactly what your linked manuscript suggests doing for a case with low vaccine supply, which is the scenario the CDC predicts for Phase 1 rollout of the vaccine (figure on page 12 of the CDC pdf linked above).

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      1. Joe1776

        "First, that's an oversimplification of the conclusions from the (non-peer reviewed) study you linked."

        No it is not oversimplification it is the conclusion. And it is not one study it is 2 articles. They may not be peer reviewed but they are written by experts in their field and you offer nothing to contradict it but the patriot act and you analysis involves no science.

        Our public health is best served by giving the vaccines to those who are most at risk from dying from it. Not giving it to young healthy people who get it and are far less likely from dying.

        Why not use facts and science to decide how we will save the most lives?

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      2. Joe1776

        The health care workers are not dying off anything close to the elderly and those with other risk factors. If the health care workers are elderly or vulnerable they can get the vaccine too. I just don’t understand why perfectly healthy people under say 35 should get the vaccine to avoid missing a week of work when that vaccine could have saved someone’s life.

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          PaulH

          You can't just say "science" and claim it supports your policy preference. As Tom B points serious people have considered these issues and come to different conclusions. Indeed, it appears that they have decided that it is important that healthcare workers remain healthy so that they are able to treat patients with the disease. We know that overloaded health systems have inferior results. So having healthcare workers sidelined for several weeks because of the disease (even if they ultimately survive) may well have negative consequences on mortality in hospital systems.

          That is a fact and science based argument. Reasonably people can disagree with it, but you can't just claim that only you are considering facts and science.

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          1. Joe1776

            Serious people at the cdc told WHO we didn’t want their tests early on as we would make our own. That was a disaster. Serious people told us not to wear masks. We should understand why they are making these decisions. The information from this, committee seems to suggest they were not solely concerned with saving lives.

            If your policy is saving lives then tall the articles say give the vaccine to the most vulnerable. These are mathematical models used in the articles I posted. If you have better science showing that giving a 30 year old pharmacist the vaccine will save more lives then post it. Don’t assume serious people in our government won’t make serious error of judgment they will.

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      Idontdocute

      If you don’t take care of the healthcare workers first, you will not have healthcare workers staying at your facilities. My system is now offering a finders fee for bringing a bedside nurse into the staff of $10,000...finder’s fee...not working. Those vents aren’t going to run themselves.

      While you are looking up studies, here is what we may soon be asking us to help with next because we obviously don’t have enough piling on our souls from Halloween and Thanksgiving and bars. Next is Christmas and New Year plus two or three weeks, maybe followed by cold calculated triage to finish crushing us.

      https://academic.oup.com/phe/article/13/2/157/5900805

      Go ahead and tell us that we now need to get in a line behind the rope because we, we, need to start working to statistically save more lives and stop caring about ourselves quite so much.

      At least we wash our hands and wear our masks. Sometimes two masks with the cheap one over the N95.

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      1. Joe1776

        You seem to think health care staff are in short demand only because of COVID. Older ones may be and I am fine with at risk health care workers getting the vaccine. But I don’t think many people under 40 are suddenly going to want to work at your facility because they get a free vaccine shot if a 10k finders fee isn’t working.

        My area was one of the top hotspots in the nation and the hospitals are not overwhelmed.

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    3. Avatar photo
      Matmos

      There are difficult trade-offs. Our hospitals are overwhelmed and your chances of getting covid as a healthcare worker are much higher because of the levels of virus you are exposed to. We need healthcare workers in the hospitals saving the lives of patients. For every healthcare worker less we can expect more sick folks to die.

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      1. Ingenero.lux

        Plus while there is no data this does inhibit the spread of the virus, there’s also no data it doesn’t. Meaning it may, which when combined with the above, the risks they are purposefully taking to save the lives of others, and the relative ease of vaccination (front line healthcare workers, very easy to vaccinate quickly) gives plenty of reason to prioritize healthcare workers.

        High risk groups are right after, and this push is consistent with some of the recommendations - some because people are still debating the ethics of any and every recommendation, including vaccinating the US before second and third world countries having a worse time of it rather than having us wait until their issues with COVID have decreased to our levels, or many other questions. I’m conflicted on what is most ethical, which is the biggest point - there are hard questions with no right answer, just attempts to figure out what’s best.

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          PaulH

          Yes, to be perfectly clear, whether or not it inhibits the spread just hasn't been studied.

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          1. Joe1776

            But I do think they have some idea if people with the vaccine still get the virus and the symptoms are just more mild. If that is the case they would still transmit the disease although the transmission window may be shorter. The problem is it seems people transmit this before they even have symptoms.

            I'm not sure if the vaccines are more a preventitive or a sort of pretreatment for Covid.

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    4. Laura Crowder

      Because even young health care workers are in the High Risk group.

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      1. Joe1776

        It is sad that we still confuse risk of being sick like a flu and risk of dying. I think this shows a lack of compassion for elderly people. If a young health care worker gets sick they may miss work for a week or two but the elderly who have other risk factors die.

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          Idontdocute

          I tell you what, Joe..do you own a set of scrubs? You know what, I will bet you that you haven’t even looked up the average age of American nurses. If you had done either of these, you wouldn’t be saying this. I am 62, not some cute little young thing that you have in mind from, where, movies? How in God’s green earth could you believe that hospitals could unsuccessfully offer $10,000 finder bonuses to educated informed professionals who have an exponentially better understanding of the risks they personally would face and believe they are afraid of a week long low risk “flu”?

          So, exactly who are you accusing of lacking compassion that is causing this sadness in your soul?

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          1. Joe1776

            I know plenty of people in health care. And not all nurses are 62. I am just saying instead of denying the vaccine to someone who is 78 years old and has diabetes and a history of heart disease why not give that person the vaccine you would otherwise give to a 30 year old pharmacist. Or a 25 year old cna.

            Different areas have shortages of nurses. Several of my friends are nurses. They are in their 30s and 40s and they would like to be able to let an elderly person have their vaccine because they know and treat covid for people their age. Unfortunately they suspect they will be forced to get the vaccine in order to keep working. So it will be a limitation on people working in health care not an encouragment.

            I am not against allowing special rules for people in health care to get priority. If someone is over 50 or has some other condition that would keep them from working. But giving (and likely forcing) everyone under 35 even if they are perfectly healthy to have the vaccine and denying it to people who are elderly and could die from this is not compassionate or smart.

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    Bill Nelson

    Given that this is a pandemic, there should be an expectation that some level of uncertainty must be acceptable. And a case can be made for approval of some amount of a vaccine after stage 2 trials. Serious problems call for allowing greater risk acceptance.

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    1. Ingenero.lux

      We’re beginning to get to a very difficult stage in this - rubber meets the road. We weren’t sure any vaccine candidate would work or work well, now we have at least three that meet the minimum threshold for acceptability - the question is what we do now. In absence of statistically sound data for the higher efficacy for the Oxford/Astra Zenica vaccine (the dataset for 90% being too small to reach acceptability), I’m sure there’s a question of what to do and how to prioritize. Does the government try half/full dose regimes and hope it’s not a statistical fluke? Full/full dose regimes and hope people won’t reject the vaccine hoping for the mRNA versions? Wait for more data on this vaccine and focus on the vaccines with higher proven efficacy, accepting less vaccination immediately for potentially better results later but maybe not because the statistics could prove accurate?

      I think this ultimately comes down to both the technical aspect of the vaccines and a very complicated logistical question involving speed of distribution, trade offs, manufacturing capacity or overlap, and so on, questions we (here) don’t really have the answer to. Fortunately the COO of Operation Warp Speed (I’m a SciFi geek and even I think that’s a ridiculous name) is an Army General who spent his career in logistics, because this really is a hard one to solve without that background. Figuring out the correct way to square this circle is an immense responsibility, hopefully he and his team work this out as efficiently as possible.

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      1. P Satter

        Operation Warp Speed sounds like a typical military name, denoting their urgency to develop a vaccine. But unfortunately it's also simultaneously a worrisome name for the elderly who will need to decide to take it. "Are you going to take the vaccine?" an elderly neighbor asked me. When I answered in the affirmative, she asked "But don't you think they hurried it through too fast and it might be dangerous?'

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      DougAz

      I don't think any of the opinion authors from AEI have any science or technical background, let alone in risk analysis

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        Bill Nelson

        So I looked up the first author. Recent graduate, econ and math. Also on the swimming team. So I believe the math part is covered. AEI scholars and researchers are competent. You may disagree with their analysis but you need to show why.

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          DougAz

          Fair point Bill.

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