The transition from phase II to phase III studies
Bibliographic record
Abstract
6514 Background: Phase II trials are performed to detect potential anti-tumor effects of a new treatment and should be used to decide whether to proceed to a phase 3 trial or not. However, many phase 2 trials never lead to a phase 3 trial despite encouraging results. Here we sought to determine how often (i) positive phase 2 trials have led to phase 3 trials, and (ii) how often phase 2 trials were designed to lead to a phase 3 trial. Methods: We reviewed 200 phase 2 trials, presented at ASCO meetings in 1995–1996, and 2006, selecting randomly 20 abstracts with encouraging results for 5 cancer sites (breast, lung, GI, GU, Gyn) in each time period. For those presented in 1995–1996, we searched systematically for subsequent randomized studies where one treatment arm was similar to that in the phase 2 study. For those presented in 2006, a questionnaire was sent to authors asking whether they recommend evaluating the regimen in a phase 3 trial, whether a phase 3 trial is planned and whether resources (budget, patients, drugs) are available to conduct a phase 3 trial. Results: Ten years after presenting phase 2 trials with positive results, only 13 regimens have been evaluated in a phase 3 trial. Of 100 investigators who presented a phase 2 trial in 2006, 42 returned the questionnaire, 36 confirmed that the results met criteria of efficacy and 25 thought the regimen should be evaluated in a phase 3 trial. Only 10 investigators plan to undertake a phase 3 trial, and 8 stated they had resources to do so. Reasons for not planning a phase 3 study included insufficient efficacy (7), insufficient access to patients (5) or financial support (5), lack of interest from colleagues (6), and lack of support from the company (8). Conclusions: Few (∼13%) phase 2 trials with promising activity are followed by phase 3 trials and this is not increasing with time. Reasons include lack of resources such as money, drugs and patients. Many of these limitations are known when planning the phase 2 study, implying that many phase 2 trials are not planned as precursors of phase 3 trials. Resources spent on such trials would be better applied to practice-changing phase 3 trials. No significant financial relationships to disclose.
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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 | 0.412 | 0.369 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.003 |
| Bibliometrics | 0.005 | 0.004 |
| Science and technology studies | 0.002 | 0.003 |
| Scholarly communication | 0.012 | 0.008 |
| Open science | 0.004 | 0.005 |
| Research integrity | 0.005 | 0.010 |
| Insufficient payload (model declined to judge) | 0.005 | 0.003 |
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".