A study of 676 people vs. Several Thousand Studies: The Controversial Decision To Put Pfizer On Who Received AstraZeneca

Backed by the first results of the CombiVacs study of the Carlos III Health Institute (ISCIII), in addition to other international research, Health and the Autonomous Communities have agreed that people under the age of 60 who had the first dose of Astrazeneca receive a second dose of Pfizer.

However, the CombiVacs trial had an apparently very modest sample size (only 600 individuals) and was not double blind either, leading to some criticism from the scientific community that it is too risky to draw conclusions based on it, in addition to the fact that the positions of the European Medicines Agency (EMA) and the Spanish Medicines and Health Products Agency (AEMPS) continue to be to vaccinate with the same manufacturer.

Limitations of the CombiVacs

The CombiVacs trial involved 676 patients from different age groups and regions of Spain who have received a single dose of AstraZeneca, ranging from 18 to 59 years of age. The CombiVacs trial is also biased towards the results pursued by Health, that is, the control group (just over 200 people), was left with a single dose of AstraZeneca, so the effectiveness of giving a second one from Pfizer was not compared to giving a second one from AstraZeneca.

In the absence of the results being published in a scientific journal, the researchers have presented the information obtained so far, that has not convinced part of the scientific community.

For this reason, experts such as José Antonio Forcada, president of the Nursing and Vaccine Association (ANENVAC), an entity participating in the development of the national strategy, believes that “the most sensible thing” would have been to administer AstraZeneca to everyone. Opinion shared by the secretary of the Spanish Immunology Society, Carmen Cámara, and other experts.

The discrepancies, then, have not been slow to occur and Communities such as Madrid and Andalusia have been openly against mixing vaccines. There is also discussion that those who reject the second dose of Pfizer can inoculate AstraZeneca, despite rare cases of associated thrombi.

Do not panic

However, there are some considerations to be made regarding the limitations of the CombiVacs assay and the alarm that may arise from making decisions that are not based on the position of international scientific institutions such as the EMA. First of all, what mixing vaccines from different companies is not something new. This strategy, called “mixed or” heterologous “, is usually carried out on other occasions and with campaigns for other diseases.

In second place, conducting trials with few individuals is not uncommon when it comes to evaluating the mixture of vaccines that have already been studied. This is considered to be the safest type of clinical trial, as the treatment has already been under much research and has possibly been used in millions of people. It is not necessary to look for very large sample sizes, but rather representative sample sizes. A study with a larger but poorly represented sample size will be qualitatively worse than one with a more modest but well represented sample size. In other words: the sample size should not be an objective, but a consequence.

A 2014 study, for example, evaluating immunogenicity and safety of inactivated quadrivalent and trivalent influenza vaccines in children 18 to 47 months of age was carried out with a sample size of about 600 individuals. In this other adult study, just over 1,000 individuals were vaccinated to evaluate the safety and immunogenicity of an influenza vaccine. The same is true in this other study on the safety and immunogenicity of a recombinant meningococcal B vaccine when administered with routine vaccines to healthy infants in Taiwan. Or this one with 900 babies 3 to 5 months old.

Third, the preliminary results of another more robust trial, the British Com-Cov, already offers some data on the reactogenicity of combining vaccines, published in the journal The Lancet. According to the study, heterologous vaccine schedules induced greater systemic reactogenicity (low-grade fever, chills, tiredness, headaches, arthralgia, myalgia, and malaise) after the booster dose than counterpart vaccine schedules. In any case, the observed adverse effects have been mild and can be combated by administering paracetamol. The first immunogenicity results are expected in July.

At the moment, what is being considered is to verify that the immune response is similar or better when vaccines are mixed (it seems that it is) and that there are no serious side effects (it seems that it is not). The CombiVacs study may have flaws, but the sample size is not anomalous. Nor is it useful for studying extremely rare effects (which cannot be studied even in phase III).

Thus, many European countries have opted for these mixed vaccination programs, such as Germany, France, Sweden, Norway or Denmark. In the United Kingdom, the route was chosen to give those under 30 an alternative to AstraZeneca, then it was extended to all those under 40. Countries such as Italy, however, have continued to administer the second AstraZeneca without limitations.

The ISCIII study, therefore, seeks to be useful as complementary information at the international level because in the following months, if revaccination is necessary, it could be that “heterologous” guidelines are the only option due to a shortage of vaccines or other factors.

In other words, making decisions in this context requires not only scientific criteria, but others, in which the benefits and risks must be taken into account, but also social alarm or the economy. For this reason, there are countries that have opted for one or another strategy. The important thing is to clearly and transparently explain the reasons behind certain decisions, expose the pros and cons, and thus strengthen the confidence of the population.