Effects of Confounding Bias in COVID-19 and Influenza Vaccine Effectiveness Test-Negative Designs Due to Correlated Influenza and COVID-19 Vaccination Behaviors
Bibliographic record
Abstract
Abstract Background The test-negative design is commonly used to estimate influenza and COVID-19 vaccine effectiveness (VE). In these studies, correlated COVID-19 and influenza vaccine behaviors may introduce a confounding bias where controls are included with the other vaccine-preventable acute respiratory illness (ARI). We quantified the impact of this bias on VE estimates in studies where this bias is not addressed. Methods We simulated study populations under varying vaccination probabilities, COVID-19 VE, influenza VE, and proportions of controls included with the other vaccine-preventable ARI. Mean bias was calculated as the difference between true and estimated VE. Absolute mean bias in VE estimates was classified as low (<10%), moderate (10% to <20%), and high (≥20%). Results Where vaccination probabilities are positively correlated, COVID-19 and influenza VE test-negative studies with influenza and SARS-CoV-2 ARI controls, respectively, underestimate VE. For COVID-19 VE studies, mean bias was low for all scenarios where influenza represented ≤50% of controls. For influenza VE studies, mean bias was low for all scenarios where SARS-CoV-2 represented ≤10% of controls. Although bias was driven by the conditional probability of vaccination, low VE of the vaccine of interest and high VE of the confounding vaccine increase its magnitude. Conclusions Where a low percentage of controls are included with the other vaccine-preventable ARI, bias in COVID-19 and influenza VE estimates is low. However, influenza VE estimates are likely more susceptible to bias. Researchers should consider potential bias and its implications in their respective study settings to make informed methodological decisions in test-negative VE studies.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.364 | 0.477 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.009 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.004 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.003 | 0.003 |
| Research integrity | 0.003 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; the direct Gemma label and the distilled Codex classifier agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".