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Alternate Endpoints for Screening Phase II Studies

2009· review· en· 85 citations· W2130626169 on OpenAlex· 10.1158/1078-0432.ccr-08-2034

Why is this work in the frame?

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

Canadian affiliationAn author listed a Canadian institution. This is the only route the usual frame has.

Full frame distilled prediction

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.

Candidate categories
Meta-epidemiology (narrow), Research integrity
Consensus categories
none
Domain
Candidate signal: noneConsensus signal: none
Study design
Candidate signal: Not applicableConsensus signal: none
Genre
Candidate signal: ReviewConsensus signal: Review
Teacher disagreement score
0.947
Threshold uncertainty score
1.000
Validation status
machine_predicted_unvalidated · codex-gemma-dda1882f352a

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0060.007
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0040.001
Bibliometrics0.0000.001
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0010.001
Research integrity0.0010.003
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

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.

Opus teacher head0.831
GPT teacher head0.738
Teacher spread
0.093 · how far apart the two teachers sit on this one work
Validation status
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Abstract

Phase II trials are screening trials that seek to identify agents with sufficient activity to continue development and those for which further evaluation should be halted. Although definitive phase III trials use progression-free or overall survival to confirm clinical benefit, earlier endpoints are preferable for phase II trials. Traditionally, tumor shrinkage of a predetermined degree (response) has been used as a surrogate of eventual survival benefit based on the observation that high response rates (RR), and particularly complete responses, in the phase II setting resulted in survival benefit in subsequent phase III trials. Recently, some molecularly targeted agents have shown survival and clinical benefit despite very modest RRs in early clinical trials. These observations provide a major conundrum, with concerns of inappropriate termination of development for active agents with low RRs being balanced by concerns of inactive agents being taken to late-phase development with resultant increases in the failure rate of phase III trials. Numerous alternate or complementary endpoints have been explored, incorporating multinomial endpoints (including progression and response), progression-free survival, biomarkers, and, more recently, evaluation of tumor size as a continuous variable. In this review, we discuss the current status of phase II endpoints and present retrospective analyses of two international gastrointestinal cancer studies showing the potential utility of one novel approach. Alternate endpoints, although promising, require additional evaluation and prospective validation before their use as a primary endpoint for phase II trials.

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.

The record

Venue
Clinical Cancer Research
Topic
Genetic factors in colorectal cancer
Field
Medicine
Canadian institutions
Princess Margaret Cancer CentreOntario Institute for Cancer Research
Funders
not available
Keywords
Surrogate endpointClinical trialClinical endpointMedicineOncologyPhases of clinical researchClinical study designEndpoint DeterminationInternal medicineProgression-free survivalIntensive care medicineOverall survival
Has abstract in OpenAlex
yes