We Could Know Soon How Effective the Potential COVID Vaccines Are

The FDA’s emphasis on safety means a vaccine is months away, but we can learn before that how well they work against the virus.

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When will a COVID-19 vaccine be approved? That is the foremost question globally as the COVID-19 pandemic—entering its 10th month—shows no sign of easing on its own. To answer that question, we first need to know when sufficient evidence of the safety and effectiveness of the candidate vaccines will be available. The good news is that convincing signals of efficacy (or, alternatively, ineffectiveness) may come relatively soon.

COVID-19 vaccine efficacy assessments will be based on criteria released by the U.S. Food and Drug Administration (FDA) in June and the World Health Organization (WHO) in May. The FDA’s review will govern which vaccines are approved for use in the U.S.; the WHO’s guidance will inform the regulatory processes in many other countries around the world.

There are currently five vaccines targeted by the federal government’s Operation Warp Speed (OWS) program in, or nearing, Phase III clinical trials (see Figure 1). This the final step in the regulatory approval process and involves administering the vaccine, or a placebo, to tens of thousands of trial volunteers.

President Trump had signaled that he wanted one or more of the vaccines approved before the election in November. That has been ruled out by recent supplemental FDA guidance on the specific criteria needed to justify an emergency use authorization (EUA). To provide more time for potential adverse events to emerge, FDA is telling the sponsors of the vaccine candidates that it will not consider EUA applications until two months after half the trial participants have received the last dose of the candidate vaccine. In all cases, this will push EUA reviews until after November 3.

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  1. Avatar photo
    DougAz

    An okay walk through, still..

    As having led a PMA Class III product in one lifetime, you gentlemen make me a bit nervous with this communication.

    Small numbers, i.e. early signals, are both dangerous and unethical for any conclusions. Hope is not a scientific variable. "How well vaccines work against a virus" is always inclusive with Safety and Adverse Effects.

    Just realize, with 200,000,000 vaccines, a 1% adverse effects.....effect 2 Million people....likely for a life long adverse outcome.

    An adverse effect rate for this vaccine should be proven with 98% to 99% confidence level to be like no more than 1:10,000 (20,000) to 1:100,000 (2,000).

    Adverse effects would include: death; compromised immune systems; unknown effects to organs.

    We don't want to say about a Vaccine, the good news is you didn't get Covid-19. The bad news is you have to be on dialysis the rest of your life..

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    1. EPluribusUnum

      You are correct as far as you go but you don't go far enough. You have to compare the adverse effects of getting the vaccine, and the severity of those effects, against the costs of not vaccinating for some additional number of months or years. Most people don't suffer too badly from Covid-19, some die, and others recover but may suffer from significant long term damage to various organs. We also don't want to say to people that the good news is that you are not going to be on a dialysis but the bad news is that you are dead (or on O2 and in a wheelchair for the rest of your life.)

      Then there are economic effects that do need to be factored in. From a purely medical health perspective we would require people to wear masks nearly all the time, not just for Covid-19, limit automobile speeds to 10 mph, etc. Poverty would result which would redound in adverse health outcomes.

      It will take awhile to get a significant proportion of the population vaccinated, likely with multiple versions of vaccines. One thing that the FDA should do is to drastically up its game for reporting of adverse events. If one vaccine should prove then to have an inferior risk/reward ratio then use of that vaccine could be stopped.

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        DougAz

        Excellent points

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        1. EPluribusUnum

          Well, thank you sir.

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    2. Avatar photo
      Nick H

      All very true, but the article isn't saying anything about small sample sizes and safety. It's only discussing how large a sample has to be to get a good measure for efficacy. That sample size is limited by how many people in the trial get sick. The sample size for assessing safety and adverse effects is how many non-control patients are in the trial. Since the smallest of these studies is using 15,000 in the vaccine arm, they should all be able to get to a high confidence for the the 1:10,000 rate you mentioned.

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    Victor Clairmont

    As long as it works, hope to see a vaccine when it’s good to go. Thanks for the breakdown of the FDA guidelines and such.

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  3. Avatar photo
    Seth

    What are your thoughts on the FDA maybe not being willing to do an EUA in order to get better statistical data? Is this good or bad? https://www.statnews.com/2020/10/23/fda-shows-signs-of-cold-feet-over-emergency-authorization-of-covid-19-vaccines/

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    1. soapboxalpha

      Some of the best analysis I've seen on this subject is coming from Derek Lowe, a chemist in the pharmaceutical industry who runs the In The Pipeline blog (https://blogs.sciencemag.org/pipeline). He's got a recent post up that digs into a lot of the policy and ethical implications of Emergency Use Authorizations:

      https://blogs.sciencemag.org/pipeline/archives/2020/10/21/the-vaccine-tightrope

      After reading his post, I'd summarize the problem as follows. There are multiple companies running trials on multiple drug candidates. Those trials depend on having large numbers of people in the trial, some of home are given the drug being tested, some of them who are in a control group getting standard of care treatments. As long as no drugs are authorized for broad use, no problem -- all participants are only involved in a single trial, and nobody knows who is getting the vaccines vs getting the control (non-vaccine) treatment.

      All of that changes once the first drug is given a EUA. At that point, we won't know efficacy or side-effect details for all of the vaccines in all of the trials, but we'll have one approved vaccine that will presumably be under wide demand by the general public . . . and may be under wide demand by people who are already participating in other trials, or who were in the control group for the vaccine that just received the EUA. So . . . do we force participants in other trials to stay in those trials so that they generate valid data . . . even though some of those trial participants are in a control group and not getting a vaccine at all? Do we allow other trial participants to get the EUA vaccine and blow up the trial data? What if the first EUA vaccine is actually less effective or has more side effects than other candidates in the pipeline? These are hard questions, and need real thought...

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      1. EPluribusUnum

        All excellent questions. I believe that there there is a statistical answer to nearly all of them, trading off the possibility of a better vaccine against the costs of delaying a currently available vaccine of some statistical efficiency. (Then there is the added cost of economic shutdowns to be factored in.) Unlike with most vaccine trials in which there is usually only one vaccine in phase III trials at a time, the first vaccine past the finish line can not yet be declared the winner.

        With respect to "who were in the control group for the vaccine that just received the EUA" I believe that current protocols call for offering the treatment to the members of the control arm. It is one of the incentives to induce people to participate even though they may be getting a placebo.

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