Two days ago, an analysis of real-world data from the UK was published as a pre-print (not yet peer-reviewed) detailing the effectiveness of Pfizer and AstraZeneca vaccines against two variants of the SARS-CoV-2 coronavirus: one, denoted as B.1.1.7, with its origins in Kent, UK, and the second, denoted as B.1.617.2, that was first detected in India.
Indian public policy has massive interest in this information since the broader B.1.617 variant is expected to, if it has not already, become the dominant strain of the disease within the population in India.
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Prior to this, the main data informing decisions were from AstraZeneca’s clinical trials to establish the safety and efficacy of its vaccine. The results were published on March 6, 2021. These new results validate the two-dose efficacy against the B.1.167.2, but indicate a lower efficacy for the one-dose regimen.
The ExpertDr Tushar Gore's focus area is pharmaceuticals. He studied at IIT-Bombay and the University of Minnesota, and has worked at McKinsey and Novo Nordisk. He is the former MD/CEO of Resonance Laboratories, a niche pharmaceuticals manufacturer.
Vaccine policy, underlying data
Indian guidelines for Covishield vaccination have evolved from a recommendation of a gap of 4-6 weeks in February, to 6-8 weeks in March, and finally to 12-16 weeks in May. These were based on the data from clinical trials conducted to prove the vaccine’s safety and efficacy, and are summarised below.
The two-dose efficacy (more than 14 days after the second dose) was 66.7%. There were no hospitalisations 22 days post the first dose compared to the non-vaccinated group which had 15. The single-dose efficacy (from day-22 to day-90 post-vaccination) was 76%. There were no hospitalisations in the period of 22 days from first dose up to 14 days from second dose. Efficacy data for interdose duration for some of the groups is:
2-dose efficacy with <6 week gap: 55.1%
2-dose efficacy with 12 weeks gap: 80%
In addition to proving safety, the trial’s purpose was to establish the efficacy of the two-dose regimen.
The trial found that a single-dose had a similar efficacy for up to 90 days to that of the two-dose regimen. Note that the average efficacy reported for single-dose (76%) is actually higher than that for the two-dose regimen. This seems odd, but a closer look at the confidence intervals shows that these intervals overlap and in such a situation, no definite conclusion can be drawn about the difference in these two numbers.
The second analysis showed that having a longer interval in between the doses did not negatively impact the ultimate efficacy. Here again, it appears that there is substantial difference between the efficacy of a regimen with >12 weeks and that with <6 weeks. Any specific conclusion cannot be drawn because of overlapping confidence intervals as well as non-uniformity in the composition of these sub-groups.
For example, the group that had an interval of <6 weeks had a higher proportion of older individuals.
In summary, the study clearly demonstrated the efficacy of the two-dose regimen. It suggested that increasing the gap between two doses could increase efficacy, and a single dose showed similar efficacy as two doses up to 90 days post-dose.
Goals and challenges
The goal of a vaccination program is to provide the strongest immunity that lasts the longest, and do so in the shortest amount of time (minimum doses, or, minimum spacing between multiple doses). These goals can be at odds, especially when a certain time duration is necessary to develop strong immunity, or if a longer gap between doses provides improved efficacy. Another challenge with a longer waiting period between doses is that individuals could be vulnerable during the waiting time with the protection of only one dose.
In India, the urgent need is to reduce cases of severe disease, and decrease burden on medical infrastructure. Data showed vaccinations are an effective tool to achieve this. Even a single dose showed some efficacy towards reducing severe disease.
Therefore, the approach to prioritise single-dose vaccination and provide some protection from severe disease to a wider population has the most potential to curb the burden on healthcare infrastructure.
Implications of new data
The new data are from a real-world study. In contrast to a clinical trial that collects data in the “future” by creating two groups — a vaccinated and an un-vaccinated — and tracks these to analyse the differences in infections between them, a real-world study collects “past” information. It analyses data for Covid-positive and -negative individuals. Marrying the vaccination details with the testing data enables comparison of vaccine effectiveness.
In the new study, 1,054 individuals were tested for the B.1.617.2 variant with 244 having received the AstraZeneca vaccine. The effectiveness of the AZ vaccine (two-dose regimen) versus this variant was 59.8%. In comparison, the effectiveness against the B.1.1.7 was 66.1%. Overlap in confidence intervals indicate not a significant difference between the two numbers. The effectiveness of a single dose was calculated as 32.9%. The duration over which this single-dose effectiveness is calculated is not detailed in the study.
The good news is that the two-dose regimen is effective against the new variant. The number cannot be directly compared with the efficacy reported in the clinical trial, but the additional information that it is similar to the B.1.1.7 variant indicates that the vaccine is effective versus multiple variants.
The efficacy of a single dose is an important parameter. As presented earlier, a high efficacy over a long timeframe will enable a vaccination programme to increase the gap between two doses and provide some protection to a broader population. The 32.9% effectiveness from this analysis appears low when compared to 76% reported in the clinical trial.
The crucial parameter for public policy, however, is the effectiveness against severe disease since this number will dictate the burden on the hospitals and medical infrastructure. This number has not been determined yet and will play an important role in future policy determination.
One action that can impact public policy is to not wait for others to furnish this data but harness our data to evaluate vaccine effectiveness in our own population. There is data for 180 million-plus already administered vaccine doses. The Aadhaar unique ID links the vaccine data, the PCR test data (and potentially further genomic data). Marrying the three data sets should provide the required information about vaccine effectiveness. Additional insights such as identification of “hot areas” could be used to tailor the vaccine deployment locally instead of through an overarching fixed inter-dose interval.
Serum Institute’s Covishield is India’s version of AZ vaccine. (AP Photo/Anupam Nath) 
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