Table 1.

Characteristics of phase II and phase III treatment and diagnostic studies.

	Treatment study		Diagnostic study
	Early phase II	Late phase II / Phase III	Comparative accuracy studies	RCT
Objective	Dose-finding, administration form, preliminary efficacy, safety	Primary: efficacy; Secondary: safety	Accuracy: sensitivity, specificity, positive and negative predictive values	Patient benefit/ outcome such as survival
Design	Single-arm studies, food-drug interaction crossover trial	RCT	Paired	RCT
Blinding	Kept when study is randomized	To the fullest possible extent	Temporarily of results	Rarely possible
Input for sample size planning	Phase I studies of respective clinical project, literature	Phase II studies of respective clinical project, literature	Pilot study, possibly literature	Combining results from accuracy studies with expected benefit from improved diagnoses [2], literature
Use of interim analyses	No	Yes, with external, study-independent Data Monitoring Committees	Yes, internal assessment of interim results	Yes, internal assessment of interim results
Purpose of interim analyses	Not applicable	Primary: early stopping due to fertility or futility; Secondary: adjustment of sample size	Primary: adjustment of sample size due to lacking/ limited a priori information for sample size planning; Secondary: early stopping due to futility	Primary: early stopping due to fertility or futility; Secondary: adjustment of sample size