Data discrepancies and substandard reporting of interim data of Sputnik V phase 3 trial – Authors' reply

Clear and transparent regulatory standards exist for provision of clinical trial data, including data reported in clinical study reports that are considered sufficient for regulatory review and approvals. The reporting of the interim analysis¹ in the phase 3 Sputnik V clinical trial fully complies with those standards. It is on this basis that Sputnik V has received registration in 51 countries, which confirms our full transparency and compliance with regulatory requirements.

The amendment was made to the protocol on Nov 5, 2020. The complete protocol, as amended (Section 10.4 Interim Analysis and Statistical Significance Level Applied), was submitted to The Lancet along with the rest of the documents for review.

Efficacy is assessed within 6 months after first dose (time of observation of study participants); however, the calculation of the primary outcome is based on the number of cases of COVID-19 in participants who received both doses (after second dose), as indicated in the protocol. This is consistent with the primary outcome of other studies.

The registration scheme for COVID-19 cases is described in the Article (p 674).¹ When COVID-19 was suspected, participants were assessed according to COVID-19 diagnostic protocols, including PCR testing at a central laboratory in Moscow, Russia. Severity of disease was established upon confirmation of the COVID-19 diagnosis by site investigators. A description of the assessment criteria for severity of COVID-19 is available in the appendix of the Article.¹ Thus, we have described the clinical parameters to determine COVID-19. PCR testing was done in hospitals using test systems registered in Russia.¹ It seems strange to ask about the number of amplification cycles when performing PCR on a registered test system.

Enrico Bucci and colleagues correctly note that 21 977 individuals were included in the study, as of Nov 24, 2020, as shown in figure 1 of the Article.¹ The ClinicalTrials.gov record states that as of Jan 20, 2021, the number of participants increased to 33 758. 13 986 individuals were indeed excluded; some of the volunteers were screened and had not yet been randomised at the time of the snapshot, and others were excluded according to the exclusion criteria or did not meet the inclusion criteria.

Numerical inconsistencies were simple typing errors that were formally corrected.

We provide data on the number of cases, sample sizes, efficiency values, confidence intervals, and significance level for each age group in the Article.¹ According to the above formula for calculating the efficiency and the method for calculating the confidence interval, readers can calculate and confirm that the efficiency values are the same as shown in table 2.¹ The homogeneity of the values only confirms the fact that, as described in the Article, the effectiveness of the vaccine does not differ between age groups. In this case, the main parameter by which one can judge the difference in effectiveness is the confidence interval, the differences in which are quite significant due to the different sample sizes and the number of COVID-19 cases at the time of analysis.

With regard to the data on the upper limit of the confidence interval in the placebo group in table S3 of the appendix, we confirm the data shown are correct.

It is important to note that the safety and immunogenicity of the Sputnik V vaccine has been confirmed by researchers in Argentina, where the vaccination with Sputnik V began. Preliminary data² show the vaccine has an appropriate safety profile, and the most common adverse events were pain at the injection site, fever, and muscle pain. A study of immunogenicity showed 16 titres of neutralising antibodies to SARS-CoV-2 after the first dose and 64 titres after the second dose, which correlates with the published results from vaccine clinical trial phase 1/2 and phase 3 in Russia.1, 3 Unfortunately, due to the use of different ELISA kits, it is not possible to compare the specific IgG concentrations in these studies. However, it should be noted that a specific humoral response was detected in all vaccinated participants.

An important detail in the report from Argentina⁴ is the observation that vaccination of people with a history of COVID-19 leads to a quick and significant increase in antibodies after a single dose of vaccine.

Thus, to date, the safety and immunogenicity of the Sputnik V vaccine has been confirmed in multiple studies.

© 2021 Tatyana Makeyeva/Reuters

We declare patents for an immunobiological expression vector, pharmaceutical agent, and its method of use to prevent COVID-19.