Kritiku klinické studie vakcíny Comirnaty pro nejmladší děti jsme zaslali do Evropské lékové agentury

Eliška Sovová, Vladimír Čížek, Jana Králová, Jaroslav Janošek, Zuzana Krátká

V červenci 2022 byla ke schvalování odborné komisi v Evropské lékové agentuře předložena dokumentace ke klinické studii vakcíny proti Covid -19 pro děti ve věku 6 měsíců až 5 let . Před časem jsme zde zveřejnili naši analýzu dat  z této studie, která byla schválena odborníky FDA. Zjistili jsme mnoho závažných pochybení, a proto jsme se obrátili nejen na paní ředitelku SÚKLu s prosbou o pečlivé posouzení předložených dokumentů, ale oslovili jsme i ty, kteří k budou žádost Pfizer/ BioNTech o uvolnění vakcíny pro nejmenší posuzovat a případně schvalovat pro evropský trh.

Lékaři ze sdružení Iniciativa 21 a odborníci SMIS zaslali expertům v Evropské lékové agentuře (EMA) tento dokument:

Text dopisu, odeslaného 25. července 2022, publikujeme níže. Je signován 39 signatáři z řad lékařů, vědců a právníků. Podpořili ho také tři senátoři MUDr. Chalánková, MUDr. Dernerová a prof. MUDr. Žaloudík. 

Naši žádost dostali tito experti EMA: Koenraad Norga, Sabine Scherer, Alexis Nolte, Irene Rager, Ralph Bax, Georgy Genov, Spiridon Vamvakas, Francesca Day, Veronica Jekerle, Steffen Thirstrup, Emer Cooke, Brian Aylward.

Text dopisu:

Dear Madam, Dear Sir

In the name of our organization associating experts from the fields of medicine, science and law from the Czech Republic, we would hereby like to draw to your attention the problems of the study submitted recently to the FDA by Pfizer, which will, presumably, be soon submitted (if not submitted already) to EMA as well; namely, the subject of concern is the study supporting the request for approval of the use of the Comirnaty vaccine in the youngest children (6 months – 4 years of age). Unfortunately, the study shows significant shortcomings, while, most importantly, not clearly proving the vaccine efficacy.

After a thorough analysis of the study, we find the conclusion of the FDA meeting, i.e., unanimous approval of the application of the vaccine in this age group, highly dubious. We sincerely hope EMA would not mirror this failure. Among other things, we would like to emphasize the following facts (a more detailed analysis is provided in the attached material):

1) The efficacy of the vaccines against infection, hospitalization or death was not proved by the Pfizer study for any of the groups. The approximately 80% efficacy of the vaccine against infection declared in the Executive Summary is based just on a subgroup containing a small number of patients, which resulted in the confidence interval for this value ranging virtually from -370% to 100%; in other subgroups, the protective effect of the vaccine has not been demonstrated, either.

2) During the study, changes were made to the protocol to support the efficacy assessment of the 3rd dose (it should be noted that no positive vaccine effect was observed following 2 doses of the original protocol). This, in itself, would not have posed a major problem; however, as a result of these changes, an unprecedentedly high number of subjects were „unblinded,“ and the data presented as the main results come from only a small subset of patients.

3) Due to unblinding, it is very difficult to discern the actual length of follow-up of the safety profile after the Dose 3. For example, Tables 19 and 20 report a follow-up time after Dose 3 of less than 7 days for the majority of participants; on page 13, for example, for the 6-23 months group, only 461 subjects out of 1178 vaccinated are reported to have a follow-up time of more than 2 months (i.e. a minority, but presented as 60.8%). However, the median follow-up times after the Dose 3 stated in the report (e.g. page 23) are longer than one month (for both the blinded and combined populations), which is impossible given the fact that the majority of subjects were vaccinated with Dose 3 for less than one week.

4) The only endpoint showing certain beneficial effects of the vaccine was the production of antibodies. However, this criterion is very „soft“, among other things because the immunobridging included a comparison to a group of young adults whose immune system works very differently from the youngest children (regardless of the dichotomy in the official position that antibodies cannot be considered proof of protection from COVID-19 as no „safe“ level of antibodies can be established or of the fact that virus neutralization test was performed using the original Wu-han strain from which the vaccine was constructed while against the Omicron variant, the effectiveness is approximately 5-6 times lower).

5) COVID-19 is a far less dangerous disease for children under five than for the adult population, and severe course in this age group is rare, occurring most often in children with other underlying conditions. The death of a healthy child is exceedingly rare. To the best of our knowledge, we know of not a single fatality following reinfection with COVID-19 in a previously healthy child from this age group. It is likely that most children have already encountered the infection and acquired post-infection immunity. Administering the vaccine to these children may increase the risk of adverse events while providing no benefit (as demonstrated by the Pfizer study itself) to such children and hence, the risk associated with vaccine administration may significantly outweigh the benefit.

Therefore, we would like to kindly ask that EMA carefully and independently examines the results of the clinical trial with the above objections in mind and not mirror the FDA recommendations. We strongly believe that the objections raised in this letter and the attached analysis are relevant.  Many experts in the EMA are also mothers and fathers. We would like to kindly ask you to evaluate both the efficacy and the safety of this COVID-19 vaccine meticulously, in the same way as if it was a vaccine administered to your own children.

Thank you very much for your kind understanding and thorough evaluation of the submitted study.  We are well aware that you employ your own experts who are more than capable of evaluating any submitted study; however, we would like to point out that we stand at your disposal should you call on our expertise – we will be happy to help and are open to any discussion.

Yours sincerely (in alphabetical order)

Prof. MUDr. Jiri Benes, CSc., specialist in infectious diseases
Prof. MUDr. Jiri Beran, CSc., epidemiologist and vaccinologist
MUDr. Emil Berta, Ph.D., anaesthetist and ICU doctor
MUDr. Mgr. Jan Brodnicek, general practitioner and pneumologist
Mgr. Zuzana Candigliota, attorney-at-law
MUDr. Vladimir Cizek, angiologist, chairman of an ethics committee
MUDr. Alena Dernerova, pediatric neurologist, senator
Prof. RNDr. Gejza Dohnal, CSc., expert in applied statistics
MVDr. Vaclav Fejt, immunologist
RNDr. Tomas Furst, Ph.D., university teacher, data analyst
MUDr. Martin Gabrys, neurosurgeon
MUDr. Jana Gandalovicova, cardiologist
MUDr. Radan Gocal, specialist in internal medicine
MUDr. Jan Hnizdil, specialist in internal medicine and psychosomatics
MUDr. Jitka Chalankova, physician, senator
RNDr. Jaroslav Janosek, Ph.D., university teacher, editor of medical texts
Assoc. Prof. RNDr. Arnost Komarek, Ph.D., biostatistician
MVDr. Roman Kovarik, epidemiologist
MUDr. Mgr. Jana Kralova, general practitioner for children and adolescents
RNDr. Zuzana Kratka, Ph.D., clinical immunologist
Mgr. Vladimir Mrkvicka, attorney at law
JUDr. Tomas Nielsen, attorney at law
Assoc. Prof. RNDr. Marek Petras, Ph.D. vaccinologist and epidemiologist
Ing. Lenka Piherova, Ph.D., molecular biologist
MUDr. Lukas Pollert, physician, anesthetist
JUDr. Jindrich Rajchl, attorney-at-law
MUDr. Simon Reich, physician
Prof. MUDr. Eliska Sovova, Ph.D., MBA, cardiologist and sports physician
Mgr. Ondrej Svoboda, attorney-at-law
RNDr. Jiri Sinkora, immunologist
PhDr. Daniel Stach, psychologist
MUDr. Hana Stefanicova, cardiologist and sports physician
Mgr. Lenka Trkalova, attorney at law
MVDr. Jiri Urbanek, MBA, healthcare consultant
JUDr. Petr Vacek, attorney-at-law
JUDr. Vladana Vališová, LL.M., attorney at law
Mgr. Ondrej Vencalek, Ph.D., statistician
MUDr. Hana Zelena, Ph.D., virologist
Prof. MUDr. Jan Zaloudik, CSc., oncologist, senator