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Record W4399630953 · doi:10.1287/msom.2023.0246

Adaptive Seamless Dose-Finding Trials

2024· article· en· W4399630953 on OpenAlex

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.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.

Bibliographic record

VenueManufacturing & Service Operations Management · 2024
Typearticle
Languageen
FieldMathematics
TopicStatistical Methods in Clinical Trials
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsRegretLeverage (statistics)Computer scienceMatching (statistics)Range (aeronautics)ToxicityMathematical optimizationMathematicsMachine learningMedicineStatistics

Abstract

fetched live from OpenAlex

Problem definition: We study early-stage dose-finding clinical trials with simultaneous consideration of efficacy and toxicity without parametric assumptions on the forms of the unknown dose-efficacy and dose-toxicity curves. We propose algorithms that adaptively allocate doses based on patient responses, in order to maximize the efficacy for the patients during the trial while minimizing the toxicity. Methodology/results: We leverage online learning to design the clinical trial and propose two algorithms. The first one follows dose-escalation principles and analyzes the efficacy and toxicity simultaneously. The second one uses bisection search to identify a safe dose range and then applies upper confidence bound algorithms within the safe range to identify efficacious doses. We show the matching upper and lower bounds for the regret of both algorithms. We find that observing the dose-escalation principle is costly, as the optimal regret of the first algorithm is in the order of [Formula: see text], worse than the optimal regret of the second algorithm, which is in the order of [Formula: see text]. We test our proposed algorithms with three benchmarks commonly used in practice on synthetic and real data sets, and the results show that they are competitive with or significantly outperform the benchmarks. Managerial implications: We provide a novel insight that following the dose-escalation principle inevitably leads to higher regret. The first proposed algorithm is suitable to use when little information about the dose-toxicity profile is available, whereas the second one is appealing when more information is available about the toxicity profile. Funding: This work was supported by the National Science Foundation [Grant 1651912]. Supplemental Material: The online appendix is available at https://doi.org/10.1287/msom.2023.0246 .

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.006
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesMeta-epidemiology (narrow), Insufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Theoretical or conceptual · Consensus signal: Theoretical or conceptual
GenreCandidate signal: Methods · Consensus signal: Methods
Teacher disagreement score0.153
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0060.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.001

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.

Opus teacher head0.603
GPT teacher head0.547
Teacher spread0.056 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it