Moving the needle for oncology dose optimization: A call for action
Bibliographic record
Abstract
Moving the needle for oncology dose optimization: A call for actionProject Optimus is a major FDA initiative aimed at ensuring dose optimization in oncology drug development, moving away from the maximum tolerated dose paradigm and prospectively characterizing dose-response for efficacy and safety for patient-focused maximization of benefit vs. risk.[1][2][3] Mitigating toxicities and enhancing the overall benefit vs. risk of oncology therapies necessitates dose optimization with a commitment to evaluation of innovative dosing paradigms including individualized approaches, where appropriate.This requires the quantitative integration of pharmacological mechanisms of action, efficacy, and safety in the context of associated population variability.The problem of dose optimization in the context of the mechanism of action, cancer pathophysiology, and associated population variability sits neatly at the intersection of translational/ precision medicine and quantitative clinical pharmacology and is important to approach with a patient-focused mindset.Forums convened on the topic of oncology dose optimization largely engage scientific leaders primarily working on oncology research and development, and cancer medicine.These include workshops organized by Friends of Cancer Research (FOCR), 4 American Society of Clinical Oncology (ASCO), 5,6 American Association for Cancer Research (AACR), 7,8 and the International Society of Pharmacometrics (ISoP) 9 in partnership with the US Food and Drugs Administration (FDA).Of note, some of these efforts have yielded seminal publications 1,2,[10][11][12][13] and White Papers 14 offering initial recommendations, including the availability of a Draft FDA guidance on the topic.15 We posited that the American Society for Clinical Pharmacology and Therapeutics (ASCPT)-as a premier scientific and professional organization for clinical pharmacology and translational medicine-is optimally positioned to host a discussion of opportunities for our constituent disciplines (e.g., translational science, clinical pharmacology, pharmacometrics) to synergistically address this problem with a multidisciplinary approach.
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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 | 0.084 | 0.121 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.003 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.005 | 0.016 |
| Scholarly communication | 0.017 | 0.033 |
| Open science | 0.007 | 0.012 |
| Research integrity | 0.036 | 0.066 |
| Insufficient payload (model declined to judge) | 0.022 | 0.009 |
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 source (direct Gemma or distilled Codex), 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".