Table 4.

Pros and Cons of Various Trial Design Strategies

Trial Design	Pros	Cons
Phase II followed by phase III, if phase II positive (phase II → III)	Only a 10% chance of accruing to the full phase III sample size when the experimental treatment is ineffective	Lengthiest trial design strategy for definitively demonstrating efficacy when the experimental treatment works
	Allows for a complete evaluation of the phase II data for starting a phase III trial, including consideration of other better experimental treatments that may have become available during the phase II accrual and evaluation	When the experimental treatment works, this design strategy is inefficient in that the phase II patients are not used in the phase III analysis
Phase II/III with no accrual suspension after phase II patients accrued	Only a 10% chance of accruing to the full phase III sample size when the experimental treatment is ineffective	Under no treatment effect, No. of accrued patients will be larger than the phase II → III design or the phase II/III design with accrual suspension
	Phase II patients used in phase III analysis	Phase II evaluation will be less thorough than in the phase II → III design or the phase II/III design with accrual suspension because of less complete follow-up for the phase II patients
Phase II/III with accrual suspension after phase II patients accrued	Only a 10% chance of accruing to the full phase III sample size when the experimental treatment is ineffective	When the experimental treatment works, it will take longer to get definitive results than with the phase II/III trial design with no accrual suspension
	Phase II patients used in phase III analysis	Possible delay in bringing accrual rates up to presuspenstion levels
Phase III (with interim inefficacy/futility monitoring)	Quickest trial design for definitively demonstrating efficacy when the experimental treatment works	Approximately 50% chance of accruing to the full sample size when the experimental treatment is ineffective