Estimands and Estimation of COVID-19 Vaccine Effectiveness Under the Test-Negative Design
Bibliographic record
Abstract
The test-negative design is routinely used for the monitoring of seasonal flu vaccine effectiveness. More recently, it has become integral to the estimation of COVID-19 vaccine effectiveness, in particular for more severe disease outcomes. Because the design has many important advantages and is becoming a mainstay for monitoring postlicensure vaccine effectiveness, epidemiologists and biostatisticians may be interested in further understanding the effect measures being estimated in these studies and connections to causal effects. Logistic regression is typically applied to estimate the conditional risk ratio but relies on correct outcome model specification and may be biased in the presence of effect modification by a confounder. We give and justify an inverse probability of treatment weighting (IPTW) estimator for the marginal risk ratio, which is valid under effect modification. We use causal directed acyclic graphs, and counterfactual arguments under assumptions about no interference and partial interference to illustrate the connection between these statistical estimands and causal quantities. We conduct a simulation study to illustrate and confirm our derivations and to evaluate the performance of the estimators. We find that if the effectiveness of the vaccine varies across patient subgroups, the logistic regression can lead to misleading estimates, but the IPTW estimator can produce unbiased estimates. We also find that in the presence of partial interference both estimators can produce misleading estimates.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.006 | 0.111 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
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; a candidate call from one teacher head, not a consensus.
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".