Bucci and others published correspondence in The Lancet May 12th 2021 reviewing this issue. They suggest that restricted access to data hampers trust in research.
They go on to continue suggesting that access to data that underpins study findings is imperative to check and confirm the findings claimed.
They also suggest that it is even more serious if there are apparent errors and numerical inconsistencies in the statistics and results presented. Unfortunately, they conclude that this appears to be what is happening in the case of the Sputnik V phase three trial.
Several experts have found problematic data in the published phase one and two results.
The authors have made multiple independent requests for access to the raw dataset, but these were never answered.
Despite publicly denying some problems, formal corrections were made to the article, thus addressing some concerns.
Notwithstanding, the previous issues and lack of transparency, the interim results from the phase three trial of the Sputnik V vaccine raises serious concerns.
Firstly, they have serious concerns regarding the availability of the data from which the investigators drew their conclusions. The investigators have stated that data will not be shared before the trial is completed. This will require, they say, approval by stakeholders including a so called security department.
The authors say that data sharing is one of the cornerstones of research integrity and should not be conditional and should follow the fair principles.
The second concern the author’s state is in regard to the trial protocol.
Unfortunately, the full study protocol has not been made publicly available, so the rationale behind any changes or the error rate adjustment is not known.
They note that the Sputnik V investigators mentioned three interim analyses which were added to the study on November 5th 2020 but these changes were not recorded in clinical trials.gov.
According to clinical trials.gov, the primary outcome was changed on September 17th 2020.
Initially the primary outcome was to be assessed after the first dose, but the evaluation was postponed to after the second dose. The presented primary results efficacy of 91-96% is dependent on this change but the reasons for the change have not been made public.
Moreover, the authors tell us that the latest clinical trials.gov record defines the primary outcomes inconsistently.
They also suggest that the definition of the primary outcome is unclear in the article where it says that when COVID-19 was suspected, participants were assessed with COVID-19 diagnostic protocols including PCR testing.
The authors tell us that there is a lack of crucial information here such as:
- The clinical parameters determining suspected COVID-19 cases.
- What diagnostic protocols were used?
- When the PCR testing was done?
- What specific methods were used?
- How many amplification cycles were used?
The authors suggest that in this way, cases of suspected COVID-19 as defined could have led to a bias in PCR testing used to assess the numbers of confirmed COVID-19 cases, which is crucial for efficacy determination.
A final point of concern about the study protocol relates to the enrolment and randomisation of patients.
According to the trial profile, 35,963 individuals were screened and 21,977 individuals were randomised.
The clinical trials.gov record mentions that 33,758 patients were enrolled. This last figure should be equal to either the number of participants screened or randomised.
Moreover, there is no information about what caused the exclusion of 13,986 participants as per the trial profile.
The third concern relates to the data reported and numerical results. The authors found the following data inconsistencies.
They found that at one point data for the vaccinated group on day 20 referred to more individuals than at day 10, as if there were other either information missing for 100 participants at day 10 or participants were enrolled after day 10.
Correction statements did not state the reason for this apparent number inconsistency.
The authors also found that the number of participants reported for the different vaccinated age cohorts did not add up to the reported total, 338 versus 342.
The authors conclude that with such inconsistencies, they question the accuracy of the reported data.
The authors also comment on a peculiar result of the major subgroup analysis of the primary outcome.
The vaccine efficacy was said to be high for all age groups and the reported percentages were:
- 91.9% in the 18-30 year old age group.
- 90% in the 31-40 year old age group.
- 91.3% in the 41-50 year old age group.
- 92.7% in the 51-60 year old age group.
- 91.8% in participants aged over 60 years.
The author’s looked at these figures and concluded a very low probability of observing a result such as this even if the actual vaccine effect was perfect.
The authors also found some highly coincidental results as reported figures for several groups were in fact the same.
The authors have urged the investigators and researchers to make publicly available all the data on which their analysis relies on.
They also suggests that access to the protocols, any amendments and individual patient records are paramount as much for clarification of the trial data and thus discussion of all issues.
LGP, the leading London doctors’ clinic commends the British Government on its vaccination programme and encourages all those eligible to be vaccinated.
Dr Paul Ettlinger
BM, DRCOG, FRCGP, FRIPH, DOccMed