What is known (and what is not known) about Covid vaccines. Enrico Bucci’s post
Where are we with the Covid vaccines? The post by Enrico Bucci, Ph.D. in Biochemistry and Molecular Biology, adjunct professor at Temple University in Philadelphia, author of the book "Bad Scientists"
The post by Enrico Bucci, Ph.D. in Biochemistry and Molecular Biology, adjunct professor at Temple University in Philadelphia, author of the book "Bad Scientists", taken from his Facebook profile with the author's authorization
Vaccines have always been a highly polarizing topic, but in this period this is accentuated by the contrast between corporate and political communications, on the one hand, and methodological references that are misunderstood by people as indicative of a lack of clarity, concealment and possible fraud from 'other.
Before venturing into the next discussions, which will go into depth on what has been published, I would like to recall here some selected points.
1. The communications of the companies of efficacy percentages are lot numbers (as I wrote) or sports bar numbers (as Guido Rasi said), both for technical reasons (because they are based on samples that are too small and therefore accompanied by an interval of very large uncertainty) and for concrete reasons (because no number has been provided to the regulatory authorities, such as the EMA, to be able to make a calculation). They must therefore be understood for what they are: optimistic messages to investors and competitors, when they come from companies, and to voters / citizens, when they come from politicians.
2. We have good reason to believe that many of the vaccine candidates in development are effective. This is because, on small but significant samples, their immunogenicity – that is, the ability to induce neutralizing antibodies and the ability to activate the cellular immune response, which probably has a longer duration – is a fact established with sufficient robustness in studies ( published) of phase 1/2.
3. Without believing in precise numbers, what the companies have communicated for phase 3 leads us to believe that a certain degree of protection is conferred, even if it is not possible to know further details; this on the simple basis of the consideration that completely false numbers would lead to such a reverse, after the regulatory examination, as to discourage such a gamble. A lie of this kind is possible, but it does not appear probable; in any case we wait.
4. What effectiveness are we talking about, with regard to the most advanced vaccine candidates? In many of the Phase 3 clinical trials, the primary endpoint – that is, the target specified as the primary efficacy assessment – is the ability to decrease the number of symptomatic virus positive individuals. If a vaccine candidate achieves this goal, strictly speaking, there is no evidence that it can prevent infection. Since the decrease in positive symptomatic subjects does not imply that the virus is eradicated in the vaccinated, but only that the symptoms decrease, this primary objective does not allow to evaluate whether the viral circulation is reduced or not. For that it will be necessary to wait for the periodic PCR data that some phase 3 studies foresee equally, even if not as a primary endpoint; and in particular it will be necessary to wait for the review of the regulatory agencies, which will re-examine the data from the beginning.
5. The data on immunogenicity in the elderly, judging from what has been published, are good. On the contrary, many studies are designed excluding the so-called fragile subjects (with particularly risky pathologies, with polypathologies, with a combination of advanced age and previous pathologies). This means that we will have the data for these people much later. Here too, there is a rationale: since we should have a control group for this type of subjects, individuals who are very fragile to the virus should be left exposed to the infection after placebo treatment, to specifically measure the vaccine efficacy in those groups. It was decided, in my opinion rightly, not to proceed on this path, trusting that the protection possibly conferred by the vaccine to the entire population and the safety measured also apply to these subjects.
6. The duration of the immune protection conferred by the vaccine is, on the basis of the evidence we have today, greater than several months. We do not know what the overall duration will be, but we have indirect data deriving from cases of natural reinfection, which, over the course of almost a year, seem very rare, and in the case of SARS-1 are equally very rare over the many years. In any case, the argument of those who would like to wait for years of experimentation to determine the duration of the immune protection conferred is obviously wrong, given that precisely to determine that duration it is necessary (as well as ethical) to vaccinate the population.
7. The safety of all vaccine candidates looks good at the moment. The serious adverse events that occurred, and that are reported in some phase 1/2 studies and in a phase 2/3 study, were all not attributable to the vaccine candidate tested. However, the ability of a clinical trial to identify potential adverse effects depends on the size of the population sample studied and the duration of the study. Due to their size, current studies are such as to be able to identify even rare adverse events (although not all studies are equally effective from this point of view); for the observation time, it is crucial to establish whether, as soon as the measure of efficacy is reached, the placebo group should also be vaccinated. When this occurs, the ability to specifically attribute adverse events to vaccines is lost; however, it is difficult to have proof that a vaccine works, and to leave tens of thousands of people in the placebo group exposed to the virus, just to identify any adverse effects. So this difficult decision must be taken by judging with an ethical and statistical yardstick (to define the maximum statistical threshold of rare events that we want to accept) always by the regulatory agencies. Of course, we can't keep vaccine “discoveries” for very many people for years, just to know if rare adverse events may occur.
I hope these seven points can help guide you in the ongoing public discussion. I'll be looking into more recent studies on some vaccines in the near future, starting with the most advanced study published – the Astra Zeneca Phase 2/3 trial.
This is a machine translation from Italian language of a post published on Start Magazine at the URL https://www.startmag.it/sanita/che-cosa-si-sa-e-cosa-non-si-sa-dei-vaccini-anti-covid-il-post-di-enrico-bucci/ on Mon, 30 Nov 2020 10:14:34 +0000.