The role of the estimand framework in the analysis of patient-reported outcomes in single-arm trials: a case study in oncology
Bibliographic record
Abstract
BACKGROUND: Patient-reported outcomes (PROs) play an increasing role in the evaluation of oncology treatments. At the same time, single-arm trials are commonly included in regulatory approval submissions. Because of the high risk of biases, results from single-arm trials require careful interpretation. This benefits from a clearly defined estimand, or target of estimation. In this case study, we demonstrated how the ICH E9 (R1) estimand framework can be implemented in SATs with PRO endpoints. METHODS: For the global quality of life outcome in a real single-arm lung cancer trial, a range of possible estimands was defined. We focused on the choice of the variable of interest and strategies to deal with intercurrent events (death, treatment discontinuation and disease progression). Statistical methods were described for each estimand and the corresponding results on the trial data were shown. RESULTS: Each intercurrent event handling strategy resulted in its own estimated mean global quality of life over time, with a specific interpretation, suitable for a corresponding clinical research aim. In the setting of this case study, a 'while alive' strategy for death and a 'treatment policy' strategy for non-terminal intercurrent events were deemed aligned with a descriptive research aim to inform clinicians and patients about expected quality of life after the start of treatment. CONCLUSIONS: The results show that decisions made in the estimand framework are not trivial. Trial results and their interpretation strongly depend on the chosen estimand. The estimand framework provides a structure to match a research question with a clear target of estimation, supporting specific clinical decisions. Adherence to this framework can help improve the quality of data collection, analysis and reporting of PROs in SATs, impacting decision making in clinical practice.
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How this classification was reachedexpand
Direct model labels (unvalidated)
Per-model category and study-design labels from the labeling rounds. They are machine output, unvalidated, and the disagreement between models ships as data. No study design here is MEDLINE-validated yet.
| Model arm | Categories | Study design | Confidence |
|---|---|---|---|
| gemma | Metaresearch Domain: Methods · Genre: Methods About the Canadian research system: no · About a Canadian topic: no | Not applicable | low |
| gpt | no category Domain: not available · Genre: Methods About the Canadian research system: no · About a Canadian topic: no | Other design | low |
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 | 0.099 | 0.280 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.005 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.002 |
| 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, unvalidatedLabeled directly by 2 models reading the full record.
The models disagree on parts of this classification; every voice is preserved in the section at the end of the page.
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".