Implementation of the ICH E9 (R1) addendum in vaccine efficacy studies: the hypothetical and principal stratum strategies
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Over the past decades, the primary interest in vaccine efficacy evaluation has mostly been on the effect observed in trial participants complying with the protocol requirements (per protocol analysis). The ICH E9 (R1) addendum provides a structured framework to formulate the clinical questions of interest and formalize them as estimands. In this paper, the estimand framework is retrospectively implemented in a human papillomavirus (HPV) phase 3 trial, where the vaccine efficacy was originally estimated on the per protocol set. We focus on two strategies for dealing with the presence of intercurrent events: the hypothetical and the principal stratum strategies. We address the interpretation of these two estimands, their estimation as well as articulation of the underlying identifiability assumptions. Finally, we leverage the results of the HPV application to formulate general considerations regarding the implementation of the ICH E9 (R1) addendum in vaccine efficacy studies.
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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 | 0.001 | 0.001 |
| 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 | 0.001 |
| 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 it