Error propagation in simulated treatment comparisons for multiple myeloma: Results from a simulation.
Bibliographic record
Abstract
e20523 Background: Comparing the effectiveness of multiple myeloma treatments presents a challenge due to the limited number of head-to-head trials with which to conduct indirect treatment comparisons. This is particularly true when subgroup analysis is of interest. In comparative effectiveness research Simulated Treatment Comparisons (STCs) are becoming increasingly common in the absence of head-to-head trials. STCs use estimates from limited IPD to adjust for covariate imbalance between trials, however the uncertainty from these estimates is generally ignored when estimating relative treatment effects. This study demonstrates the need to account for this uncertainty when conducting STCs for indications such as multiple myeloma. We introduce an STC method that accounts for the uncertainty due to covariate adjustment, and demonstrate its effectiveness via simulation. Methods: We simulated two single arm studies (N = 300 for both), each containing age and overall survival. We assume study 1 has individual patient data available, and study 2 only has aggregate age data and a digitized Kaplan-Meier curve. We compute a covariate adjustment term based on the mean age difference between the studies and the age coefficients from fitting a parametric survival model to the observed study 1 IPD. We then estimate the variance of this adjustment term via bootstrapping and incorporate this uncertainty into a Bayesian STC model which estimates the relative treatment effect for the two study datasets converted to a digitized Kaplan-Meier format. Results: The proportion of 95% credible intervals (CrI) that captured the true treatment effect was 86.8% without error propagation, whereas 92.0% of CrI’s captured the true treatment with error propagation. 94.9% of CrI’s contained the true treatment effect when using survival regression with the complete IPD. Conclusions: Failing to account for uncertainty from the covariate adjustment when conducting simulated treatment comparisons generally leads to underestimating the uncertainty of the relative treatment effect. This method better captures the uncertainty introduced when conducting an STC and has the potential to yield more reliable estimates of the comparative effectiveness of multiple myeloma treatments.
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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 | 0.007 | 0.584 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| 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 | 0.001 | 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 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".