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Are Phase 1 Trials Therapeutic? Risk, Ethics, and Division of Labor

2012· article· en· W1564404634 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.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueBioethics · 2012
Typearticle
Languageen
FieldMedicine
TopicBiomedical Ethics and Regulation
Canadian institutionsMcGill UniversityUniversity of British Columbia
FundersCanadian Institutes of Health Research
KeywordsClinical trialArgument (complex analysis)NegotiationPhase (matter)MedicineEngineering ethicsPolitical scienceLawPathology

Abstract

fetched live from OpenAlex

Despite their crucial role in the translation of pre-clinical research into new clinical applications, phase 1 trials involving patients continue to prompt ethical debate. At the heart of the controversy is the question of whether risks of administering experimental drugs are therapeutically justified. We suggest that prior attempts to address this question have been muddled, in part because it cannot be answered adequately without first attending to the way labor is divided in managing risk in clinical trials. In what follows, we approach the question of therapeutic justification for phase 1 trials from the viewpoint of five different stakeholders: the drug regulatory authority, the IRB, the clinical investigator, the referring physician, and the patient. Our analysis shows that the question of therapeutic justification actually raises multiple questions corresponding to the roles and responsibilities of the different stakeholders involved. By attending to these contextual differences, we provide more coherent guidance for the ethical negotiation of risk in phase 1 trials involving patients. We close by discussing the implications of our argument for various perennial controversies in phase 1 trial practice.

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)0.010
metaresearch head score (Gemma)0.005
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.565
Threshold uncertainty score0.674

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0100.005
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0010.001
Insufficient payload (model declined to judge)0.0000.000

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.

Opus teacher head0.348
GPT teacher head0.500
Teacher spread0.152 · 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