Testing behaviour may bias observational studies of vaccine effectiveness

Abstract

BACKGROUND: Recent observational studies suggest that vaccines may have little effect in preventing infection with the Omicron variant of severe acute respiratory syndrome coronavirus 2. However, the observed effects may be confounded by patient factors, preventive behaviours, or differences in testing behaviour. To assess potential confounding, we examined differences in testing behaviour between unvaccinated and vaccinated populations. METHODS: We recruited 1,526 Australian adults for an online randomized study about coronavirus disease 2019 (COVID-19) testing in late 2021, collecting self-reported vaccination status and three measures of COVID-19 testing behaviour: testing in past month or ever and test intention if they woke with a sore throat. We examined the association between testing intentions and vaccination status in the trial’s baseline data. RESULTS: Of the 1,526 participants (mean age 31 y), 22% had a COVID-19 test in the past month and 61% ever; 17% were unvaccinated, 11% were partially vaccinated (one dose), and 71% were fully vaccinated (two or more doses). Fully vaccinated participants were twice as likely as those who were unvaccinated (relative risk [RR] 2.2, 95% CI 1.8 to 2.8, p < 0.001) to report positive COVID testing intentions. Partially vaccinated participants had less positive intentions than fully vaccinated participants (RR 0.68, 95% CI 0.52 to 0.89, p < 0.001) but higher intentions than unvaccinated participants (RR 1.5, 95% CI 1.4 to 1.6, p = 0.002). DISCUSSION: Vaccination predicted greater COVID-19 testing intentions and would substantially bias observed vaccine effectiveness. To account for differential testing behaviours, test-negative designs are currently the preferred option, but their assumptions need more thorough examination.

Waning effectiveness of BNT162b2 and ChAdOx1 covid-19 vaccines over six months since second dose: OpenSAFELY cohort study using linked electronic health records

“…This limitation should not affect results for the ≥65 subgroup, most of whom are retired, or comparisons between BNT162b2 and ChAdOx1. Thirdly, consistent with an Australian survey, 33 we found that unvaccinated people had tested less frequently than vaccinated people during the prevaccine rollout period when widespread testing was available (table 1) and were considerably less likely to be tested during follow-up (supplementary table S7). Fourthly, differential depletion of susceptible people in the unvaccinated groups over time may lead to attenuation of hazard ratios even when true vaccine effectiveness does not change.…”

“…This implementation of OpenSAFELY is hosted within the TPP environment, which is accredited to the ISO 27001 information security standard and is NHS IG Toolkit compliant. 33 Data sharing: Data management and analyses were conducted in Python version 3.8.10 and R version 4.0.2. All data were linked, stored, and analysed securely within the OpenSAFELY platform (https://opensafely.org/).…”

COVID-19 vaccination effectiveness rates by week and sources of bias: a retrospective cohort study

“…Vaccination directly influenced the attitude of patients towards their symptoms, causing a delay in seeking care and a higher symptom severity threshold needed to seek care or get tested. On contrary, vaccinated patients in other studies had higher rates of testing compared with unvaccinated 20 38. This indicates that patients’ attitude towards risk of infection and testing may vary geographically and over time.…”

Effectiveness of BNT162b2 and CoronaVac COVID-19 vaccination against asymptomatic and symptomatic infection of SARS-CoV-2 omicron BA.2 in Hong Kong: a prospective cohort study

“…Moreover, previous observational vaccine effectiveness studies that do not have a prescribed similar testing schedule might be biased by the potential differential testing frequencies and behaviours among people with different vaccination status. 10 , 11 Previous vaccine effectiveness studies against omicron infections have focused mainly on various mRNA vaccine candidates, including BNT162b2 (Pfizer–BioNTech) and the mRNA-1273 (Moderna) vaccine, or adenoviral vector vaccines, such as ChAdOx1 nCoV-19 (AstraZeneca), 4 , 5 , 7 , 8 , 9 , 12 and, to our knowledge, the effectiveness of inactivated vaccine (eg CoronaVac [Sinovac]) against omicron infections has yet to be investigated. Although previous studies have reported the effectiveness of BNT162b2 among children and adolescents, 9 , 12 the comparative effectiveness of BNT162b2 and CoronaVac vaccines among different age groups remains unclear.…”