The fast development of covid-19 vaccines has been a success story. But, when it comes to the Russian vaccines, this is a success with many failures, writes Vasiliy Vlassov

Seventy years ago, the Space Race was based on big, powerful countries using the same technology to compete with one another. The technology was not called “soft power” because it was part of the Cold War. But the first “Sputnik” and first man in space was a kind of soft power, attracting many to the ideas of communism for years after, until the USSR invaded Czechoslovakia in 1968. Now in 2021, the covid-19 vaccine race is based on countries competing with similar technologies. And again, the technological success has been used for propaganda: the most promising Russian vaccine received substantial budgetary support from the government, and has been named SPUTNIK-V, obviously to remind people of past successes. 

The parallels between the “Space Race” and the “Vaccine Race” are strong. While the USA moved towards space flight step by step via suborbital flights, the USSR sent Yuri Gagarin into space for a full orbital flight soon after a couple of dogs were used to test the safety. In 2020, the covid-19 vaccines have all been developed at speed and rushed through national drug regulatory processes. The testing of the vaccines has also been simplified for speed. Doubts were raised about the Russian vaccine when Vladimir Putin, the Russian president, announced that the vaccine had received emergency approval before phase I and II trial data were published. The prevailing propaganda is that Russia was the first country to register a vaccine. In fact, it was China who first registered a vaccine after releasing limited trial data, in a limited population. 

What are the concerns about this vaccine, and why it is important?

The Sputnik V vaccine was registered after the small phase 1 / 2 trial was conducted, which included only young healthy volunteers. Moreover, they were a select group of volunteers from the army. The sponsor of the vaccine and director of the research institute where the vaccine was developed, have rejected concerns about the study design, explaining that the study subjects were not draftees, but contract servicemen. The study was very small: only 20 subjects received the full two doses of the vaccine. The trial was apparently conducted without any pre-trial protocol and began even before the trial had been registered.  Russians were told that research institute staff and army staff had already received the vaccine, it was well tolerated and induced immunity. In April-May 2020 a number of people, who may describe themselves  as belonging to the Russian “elite”, were offered the vaccination and an unknown number of people were vaccinated.

The original protocol of the phase 1/2 trial has never been published. When the results were published  in The Lancet, it ignited many comments and some skepticism. [1] Enrico Bucci highlighted the unrealistic similarities between figures presenting the data. [2] The authors replied that the pattern is strange, but it is true. Many scientists, as well as our group at Russian society for evidence-based medicine (osdm.org), requested the raw data from the authors, but nobody has had any response from authors, as far as I know.  In January 2021, corrections to the numerical data were published in The Lancet. [4] This has led to even more questions and underscores the need to get access to the individual patient data.

On 9 November 2020, Pfizer and BioNTech reported the first interim efficacy analysis of their ongoing covid-19 vaccine trial.[5] The analysis was based on 94 cases of covid-19 and reported 90% efficacy. Two days later, Sputnik V vaccine developers announced their product was 92% effective, based on 20 cases. [6] It is noteworthy that an interim assessment of efficacy was not prespecified in the trial’s ClinicalTrials.gov registration entry (NCT04530396). Yet another interim report from the phase 3 trial appeared in The Lancet on 2 February 2021. [7] In this article, it states that the protocol was amended on 5 November 2020, but these changes appear not to have been registered in ClinicalTrials.gov. The protocol of the trial is not published. Like the first publication, the publication of the phase 3 study has also been met with criticisms and questions. The authors reported that the “study was organised and monitored by the Moscow branch of the Dutch contract research organisation Crocus Medical,” a company focused on the post-Soviet clinical trials market. [7]

The phase 3 study in The Lancet also came with a surprising data sharing statement: “[requests] will be reviewed and approved by the sponsor, security department, researcher, and staff on the basis of scientific merit and absence of competing interests. Once the proposal has been approved, data can be transferred through a secure online platform after the signing of a data access agreement and a confidentiality agreement.” To me, this seems like a good way to ensure the data are never shared and it eludes me why a journal would accept such a statement. Even the title of the article, “…an interim analysis of a randomized controlled phase 3 trial” surprises me given that, two months before publication, it was announced that randomization to the placebo group was stopped, and participants who had received placebo were unblinded. It means that the randomized trial as a comparative study is over.

Other vaccine candidates are being developed in Russia, but they have received little attention and have not received comparable large-scale state financial and marketing support. Two of them—CoviVac from Chumakov Federal Scientific Center for Research and EpiVacCorona from State Research Center of Virology and Biotechnology VECTOR—were recently registered, like Sputnik V, after limited trials. Reports on their efficacy and safety were not published for a long time. In March 2021 a report on the pre-clinical studies of the EpiVacCorona was published in the niche journal of the Rospotrebndzor. While the vaccination by this vaccine has already started, this only added to reasons to be skeptical. Developers of EpiVacCorona say that the antibodies to SARS-COV-2 after vaccination may not be found by usual methods, and special kits from Vector should be used. And the published patent lists a number of officials as patent holders, including director of the Russian national public health and consumer market service (Rospotrebnadzor).

Of course, many of the problems mentioned above, like unblinding of the placebo group and underreporting of side effects, apply to other covid-19 vaccines as well. Nor are the publications of those trials above serious criticism. But my focus here is on Russia, my home country, where excess mortality in 2020 has been one of the highest in the world, and where the quality of the reports and secrecy over trial data raise deep concerns about research integrity. 

There is enormous vaccine hesitancy in Russia. In some populations, 70-80% are not planning or unsure about getting a covid-19 vaccine. Perhaps in response, the Russian government has been offering the Sputnik V vaccine all around the world (despite low production levels).[9] And meanwhile, the vaccine has yet to be authorized by the European Medicines Agency, a process that has witnessed more than the normal share of regulatory fumbles. In one episode, after Sputnik’s sponsor announced it had applied to the European Medicine’s Agency (EMA), the EMA publicly said it hadn’t received the application. The EMA has since said that a review of Sputnik V has begun. 

In an effort to insert the Sputnik vaccine into as many markets as possible, the Russian government has chosen to not collaborate with the COVAX initiative. True to the Soviet tradition, Russia appears to be building its own line of global influence, offering up a lifesaving good—a vaccine. Unfortunately, the information about this particular vaccine is not sufficient, nor transparent enough.

Vasiliy Vlassov, Vice president, Society for Evidence Based Medicine, Moscow, Russia

Competing interests: none declared.

See also: Covid-19: Sputnik vaccine rockets, thanks to Lancet boost

References:

1. Logunov DY, Dolzhikova IV, Zubkova OV, et al. Safety and immunogenicity of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine in two formulations: two open, non-randomized phase 1/2 studies from Russia. The Lancet 2020; 396: 887-97. (accessed Feb 22, 2021)
2. Note of concern. Cattivi Sci. 2020; published online September 7. https://cattiviscienziati.com/2020/09/07/note-of-concern/ (accessed February 22, 2021). (accessed Feb 22, 2021)
3. Vlassov V, Rebrova O., Aksenov V. Behind the hype are design defects, low study quality, and questionable publication. (Originally published in Russian by «Troitsky Variant – Science» on November 16, 2020 http://osdm.org/english/2021/02/07/commentary-on-the-publication-of-phase-1-2-sputnik-v-trial/ (accessed Feb 22, 2021)
4. Department of Error. The Lancet 2021; January 9. 397: 98. DOI: 10.1016/S0140-6736(20)32721-5 (accessed Feb 22, 2021)
5. Pfizer and BioNTech Announce Vaccine Candidate Against COVID-19 Achieved Success in First Interim Analysis from Phase 3 Study. November 09, 2020. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-announce-vaccine-candidate-against. (accessed Feb 22, 2021)
6. [Efficacy of the Sputnik V vaccine against coronavirus is 92% in course of the first interim analysis of data from phase III clinical study in RF. November 09, 2020. https://sputnikvaccine.com/rus/newsroom/pressreleases/effektivnost-vaktsiny-sputnik-v-protiv-koronavirusa-sostavila-92-v-khode-pervogo-promezhutochnogo-an/. (accessed Feb 22, 2021)
7. Logunov DY, Dolzhikova IV, Shcheblyakov DV, et al. Safety and efficacy of an rAd26 and rAd5 vector-based heterologous prime-boost COVID-19 vaccine: an interim analysis of a randomized controlled phase 3 trial in Russia. The Lancet 2021; 0. DOI:10.1016/S0140-6736(21)00234-8. (accessed Feb 22, 2021)
8. Vlassov V, Rebrova O., Aksenov V. Commentary on the publication of preliminary results of the Sputnik-V vaccine phase 3 trial. February 05, 2021. http://osdm.org/english/2021/02/06/a-commentary-on-the-publication-of-preliminary-results-of-the-sputnik-v-vaccine-phase-3-trial/(accessed Feb 22, 2021)
9. Collis H. Martuscelli C. Russia’s ‘geopolitical’ vaccine: Is Sputnik too good to be true? Politico. February 17.2021. https://www.politico.eu/article/russia-sputnik-geopolitical-coronavirus-vaccine/. (accessed Feb 22, 2021).