Randomized phase II clinical trials can be an efficient means of evaluating several potential new treatments prior to a comparative phase III clinical trial.
Randomized clinical trials would gain from incorporating a concern for timing as well as dosing in all three stages of clinical trials (Phase I, II and III focusing on toxicity, efficacy and a comparison with the current best treatment, respectively) and could be cost-effectively preceded by 'Phase 0' trials so as to detect, sooner and with smaller sample sizes, desired or undesired effects that may otherwise be missed.
The author concludes that the randomized play-the-winner rule is appropriate for some clinical trials, but intense and thoughtful planning must take place in the design phase.
In our opinion, phase II randomized screening trials, when properly applied, can assure optimal use of limited phase III financial and patient resources.
Conversely, new approaches are needed to guide development of drug combinations since both standard phase II approaches and phase II-III randomized trials have a high risk of misleading. SummaryTraditional randomized clinical trials approaches are often inefficient, wasteful, and unreliable.
Although traditional phase II cancer trials are usually single arm, with tumor response as endpoint, and phase III trials are randomized and incorporate interim analyses with progression-free survival or other failure time as endpoint, this paper proposes a new approach that seamlessly expands a randomized phase II study of response rate into a randomized phase III study of time to failure.
