I am interested in statistical procedures and study designs used to determine the absence/acceptability of long-term sude effects of the anti-covid vaccines. Given that these vaccines were created and approved within a short period of time (less than a year), it seems that the studies using conventional survival analysis are of little value. I assume that one relies on the similarity with other, well-tested vaccines.

I have posted earlier a similar question in the biology community, and some suggested that the question has to do more with statistics (and medicine) than with biology.

After a medication/vaccine has been developed and tested in a lab, it has to pass a clinical study, which is essentially a series of statistical studies aiming to demonstrate that the medication is safe, produces desired effect, and does not have serious side effects. the data from these studies are tested against the threshold established by FDA (or equivalent authorities in other countries), and only then the medication is allowed for use on general public.

Note that the approval thresholds can vary depending on the nature of medication: e.g., cancer treatments have well-known side effects (think of the chemotherapy), which are tolerated for the sake of saving human lives. On the other had, vaccines used on healthy public should not have any significant side effects. The vaccines against SARS-CoV-2 might fall somewhere in between, due to the urgency of the current health crisis.

Phase II of clinical trial is most known in the popular culture - it is at this phase that the participants are separated into the test and the control groups, administered respectively the real medication and the placebo, which rises variosu moral dilemmas. Phase II is preceeded by a similarly designed Phase I, where the medication is tested on healthy people, to test its toxicity. Phase III is a finer study of the dozage, the side effects, etc., which is the subject of thre question.

Phase IV of the clinical studies begins after the approval and commercialization of the medication. My understanding is that Phase IV is essentially an epidemiological study, designed as a survival analysis for incidence of various adverse health conditions (or death), with the use of medication/vaccination appearing among the covariates. If this covariate is found to be (statistically) significant in terms of the incidence of the adverse side effects, the medicatuon/vaccine may be prohibited for further used/withdrawn from the market.

Contrary to a widespread belief, vaccines are not by themselves "safe" or "dangerous". Rather their safety is determined on a case-by-case basis, by the amount of the adverse effects they produce. Thus, the most comonly used vaccines, those that might be obligatory in some countries (e.g., 11 vaccines are obligatory in France) have been typically in use for decades, and judged safe on the basis of the wealth of the available data. However, even a safe vaccine can be judged too risky, if the risk of contracting the disease is very low - e.g., the use of the smallpox vaccine has been discontinued, since this disease is considered eradicated in most of the world, although it still exist in labs and isolated cases are occasionally reported. Another example is the tuberculesis vaccine, which carries a more substantial risk of side effects, and therefore used only on the contact cases or when traveling to risky regions. Among the vaccines that failed Phase IV trials and had to be withdrawn is Dengvaxia by Sanofi Pasteur.

A related problem is that of long-term vaccine efficacy - flu vaccine is known to be notoriously inefficient, due to the high variability of the influenza virus, whereas the tetanus vaccine has to be re-administered every few years.

Let us now get back to SARS-CoV-2 (covid, coronavirus). There is no doubt that it is not poisonous and that it is efficient against the virus. However their long-term side effects obviously could not be tested via Phase IV survival analysis methodology. On the one hand, the risk thresholds for these vaccines are lower, due to the worldwide health emergency (which is why they were authorized via emergency authorization, even before being vetted via peer review process as scientific publications). I so believe that the Phase III clinical trials include statistical procedures/safeguards that allow to assure the lack of serious side effects in the foreseable future. These statistical methods/designs are the point of my question.

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    $\begingroup$ It is not really about statistics but about medical research. For statistics you need data. Obviously, there is not long-term effects data for the vaccines, so statistics won't help. I guess you could try to extrapolate the results from other vaccines etc, but this would be more about using domain knowledge than statistics. $\endgroup$ – Tim Dec 29 '20 at 20:37
  • $\begingroup$ @Tim the question is about the statistical methods for extrapolating the data from other vaccines. But yes, it is about statistical procedures specific to medicine. $\endgroup$ – Vadim Dec 30 '20 at 8:22
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    $\begingroup$ @Vadim "extrapolating the data from other vaccines" that means there's no data from covid-19 vaccins. This should be clarified and the question is more like 'what are long-term side effects from vaccins?'. This is still not really statistics. Sure, you can have some data about this and that can be treated statistically (one could make some prediction for the probability of a long-term effect). But the core of the question is medicine and statistics hardly plays a role. $\endgroup$ – Sextus Empiricus Dec 30 '20 at 10:59
  • $\begingroup$ @SextusEmpiricus Perhaps, the title is misleading. The question is about the clinical studies methodology, which is basically applied statistics... to the extent that one can consider biostatistics as statistics. $\endgroup$ – Vadim Dec 30 '20 at 11:12
  • $\begingroup$ I believe that the idea about long-term vaccin safety a theoretical concept and not something based on experimental tests. You have this stuff like a Hoskin's effect or antibody-depenedent enhancement and who knows there is more but it is not based on direct evidence/data.... $\endgroup$ – Sextus Empiricus Dec 31 '20 at 0:33

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