Mine Durusu Tanriover1, Hamdi Levent Doğanay2, Serhat Unal3, Murat Akova4. 1. Department of Internal Medicine, Hacettepe University School of Medicine, Ankara 06230, Turkey; Hacettepe University Vaccine Institute, Ankara, Turkey. 2. Department of Gastroenterology, Turkish Republic Ministry of Health, Istanbul Provincial Health Directorate, University of Health Sciences Istanbul Umraniye Training and Research Hospital, Istanbul, Turkey. 3. Department of Infectious Diseases and Clinical Microbiology, Hacettepe University School of Medicine, Ankara 06230, Turkey; Hacettepe University Vaccine Institute, Ankara, Turkey. 4. Department of Infectious Diseases and Clinical Microbiology, Hacettepe University School of Medicine, Ankara 06230, Turkey; Hacettepe University Vaccine Institute, Ankara, Turkey. Electronic address: makova@hacettepe.edu.tr.
We thank Martina McMenamin and Benjamin Cowling for raising important issues on vaccine trials in the context of our Article. The work they refer to by Palacios and colleagues has not been published in a peer reviewed journal; thus we cannot comment on the accuracy or the comparability of its methods. The Indonesian trial data have been published, and although the main method of this study was similar to ours, the case definition of COVID-19 and the methods used for active surveillance were different. Only 1620 volunteers were included, but over a longer period of follow-up (approximately 2·5 months) precluding a direct comparison of the primary outcome. Nevertheless, the efficacy of CoronaVac against severe disease in this study was 100% because there were no critical cases or deaths attributable to COVID-19, which is undoubtedly similar to our results.Regarding post-vaccination neutralising antibody titres in the immunogenicity subset of our trial, the seroconversion rate was 89·7% in the vaccine group, of whom 92% had neutralising antibodies. This result might translate into 82·5% neutralising antibody positivity in these volunteers. The efficacy against symptomatic disease reported as 83·5% is compatible with this immunogenicity result. We performed active surveillance to detect COVID-19 in patients; however, because the primary outcome was symptomatic COVID-19, it is indeed possible that we missed asymptomatic patients. In fact, most of the COVID-19 vaccine trials target a similar outcome, focusing on efficacy to prevent symptomatic and severe disease rather than preventing infection. We were aware of the short follow-up period in our interim analysis and hence discussed this as a major limitation in the Article, stating that the study would not allow for commenting on the long-term protection.Real-world effectiveness data from pragmatic study designs will add value to phase 3 trials to see the performance of the vaccines in non-selected populations, as complementary rather than competing studies. For instance, Jara and colleagues reported the analysis of real-life data from Chile, including approximately 10·2 million people vaccinated with CoronaVac. The adjusted vaccine effectiveness among the fully immunised people was 65·9% (95% CI 65·2–66·6) for the prevention of COVID-19 and 87·5% (86·7–88·2) for the prevention of hospital admission.During a pandemic where only 2·3% of people in low-income countries had received at least one dose of a COVID-19 vaccine as of October, 2021, every single effort to make safe COVID-19 vaccines available is valuable. We believe that our data are an important contribution to the scientific literature in a world where we can no longer establish placebo-controlled randomised trials for COVID-19 vaccines for ethical reasons. The way forward to build confidence in vaccines is by reporting real-world data transparently.We declare no competing interests.