Adapting Health Technology Assessment agency standards for surrogate outcomes in early stage cancer trials: what needs to happen?
Bibliographic record
Abstract
INTRODUCTION: An avalanche of early stage cancer clinical trials is coming. The majority of these solely use surrogate outcomes that have not been validated against a target outcome of interest (e.g. overall survival). Current HTA guidance on surrogate outcome validation are not methodologically or practically conducive to this scenario. AREAS COVERED: We provide a high-level overview of methods, approaches, and conceptual thinking for making better use of limited evidence within early stage cancer HTA submissions. We outline regulatory and HTA issues and emphasize how evidence transitions from one to another, what major gaps currently exist, and how these may be bridged. We summarize current methodologies and practices, their pros and cons. We outline how complementary measurements strengthen evaluations and address fallacies and biases of conventional statistical methods for surrogate outcomes validation. The value of real-world data to support some of the necessary validity components is discussed. Lastly, we address the importance of the patient voice for better understanding which surrogate outcomes may appropriately inform HTA. EXPERT OPINION: Conventional surrogate outcome validation represents a fraught and sub-optimal framework for HTA purposes, particularly for early stage cancer. Tools for optimizing use of limited evidence exist. Education of stakeholders is highly needed.
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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 | 0.586 | 0.785 |
| Meta-epidemiology (narrow) | 0.002 | 0.002 |
| Meta-epidemiology (broad) | 0.005 | 0.007 |
| Bibliometrics | 0.006 | 0.009 |
| Science and technology studies | 0.002 | 0.009 |
| Scholarly communication | 0.017 | 0.015 |
| Open science | 0.008 | 0.008 |
| Research integrity | 0.012 | 0.030 |
| Insufficient payload (model declined to judge) | 0.008 | 0.005 |
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".