Stakeholder-informed positivity thresholds for disease markers and risk scores: a methodological framework and an application in obstructive lung disease
Bibliographic record
Abstract
OBJECTIVES: A positivity threshold is often applied to markers or predicted risks to guide disease management. These thresholds are often decided exclusively by clinical experts despite being sensitive to the preferences of patients and general public as ultimate stakeholders. STUDY DESIGN AND SETTING: We propose an analytical framework for quantifying the net benefit (NB) of an evidence-based positivity threshold based on combining preference-sensitive (eg, how individuals weight benefits and harms of treatment) and preference-agnostic (eg, the magnitude of benefit and the risk of harm) parameters. We propose parsimonious choice experiments to elicit preference-sensitive parameters from stakeholders, and targeted evidence synthesis to quantify the value of preference-agnostic parameters. We apply this framework to maintenance of azithromycin therapy for chronic obstructive pulmonary disease using a discrete choice experiment to estimate preference weights for attribute level associated with treatment. We identify the positivity threshold on 12-month moderate or severe exacerbation risk that would maximize the NB of treatment in terms of severe exacerbations avoided. RESULTS: In the case study, the prevention of moderate and severe exacerbations (benefits) and the risk of hearing loss and gastrointestinal symptoms (harms) emerged as important attributes. Four hundred seventy seven respondents completed the discrete choice experiment survey. Relative to each percent risk of severe exacerbation, preference weights for each percent risk of moderate exacerbation, hearing loss, and gastrointestinal symptoms were 0.395 (95% confidence interval [CI] 0.338-0.456), 1.180 (95% CI 1.071-1.201), and 0.253 (95% CI 0.207-0.299), respectively. The optimal threshold that maximized NB was to treat patients with a 12-month risk of moderate or severe exacerbations ≥12%. CONCLUSION: The proposed methodology can be applied to many contexts where the objective is to devise positivity thresholds that need to incorporate stakeholder preferences. Applying this framework to chronic obstructive pulmonary disease pharmacotherapy resulted in a stakeholder-informed treatment threshold that was substantially lower than the implicit thresholds in contemporary guidelines.
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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 | 0.520 | 0.570 |
| Meta-epidemiology (narrow) | 0.004 | 0.002 |
| Meta-epidemiology (broad) | 0.005 | 0.009 |
| Bibliometrics | 0.007 | 0.006 |
| Science and technology studies | 0.002 | 0.013 |
| Scholarly communication | 0.007 | 0.007 |
| Open science | 0.005 | 0.010 |
| Research integrity | 0.007 | 0.008 |
| Insufficient payload (model declined to judge) | 0.005 | 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; 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".