Table 1 Distribution of the type of adaptive designs (ADs) implemented in confirmatory trials and their frequency stratified by sector

Sample size re-estimation (SSR)

7(23 %)

7(41 %)

Blinded SSR allowing for increase only

4

4

1

2

11

-

Blinded SSR allowing for increase or decrease

2

1

1

2

3

-

Unblinded SSR allowing for increase only

2

5

1

2

10

-

Unblinded SSR allowing for increase or decrease

2

5

1

-

-

-

Unblinded SSR based on promising zone concept

2

-

2

3

10

-

Standard two-arm Group Sequential Design (GSD)

7(23 %)

8(47 %)

Stopping early for futility only

2

7

1

3

26

-

Stopping early for efficacy only

1

.

1

-

-

-

Stopping early for efficacy or futility

4

6

-

3

8

1

Stopping early for safety only

4

2

2

2

5

1

Stopping early for safety or futility

2

2

-

1

5

-

Stopping early for non-inferiority only

-

-

-

1

-

1

Futility analysis (outside GSD framework)

8(27 %)

5(29 %)

Based on conditional power

5

7

1

3

3

2

Based on predictive power

2

1

1

1

-

1

Based on confidence interval of the interim effect

3

3

1

-

-

-

Operational seamless 2/3 design

7(23 %)

6(35 %)

Dropping futile treatment arms in phase 2 only

5

5

1

3

3

1

Selecting only one promising treatment in phase 2 only

1

-

1

3

2

1

Selecting multiple promising treatments in phase 2 only

-

-

-

2

3

1

Other

2

-

2

-

-

-

Inferential seamless 2/3 design

2(7 %)

3(18 %)

Dropping futile treatment arms in phase 2 only

2

1

1

1

2

-

Addition or dropping futile treatment arms in phase 2 only

1

.

1

-

-

-

Strictly phase 3 multi-arm multi-stage design

2(7 %)

2(17 %)

Stopping trial for efficacy or futility or dropping futile treatment arms

1

1

-

-

-

-

Information-based GSD

-

-

-

4(24 %)

3

2

Standard GSD with SSR

-

-

-

1(6 %)

-

1

Patient enrichment or subgroup selection

2 (7 %)

.

2

2(12 %)

-

2

Response adaptive randomisation

2(7 %)

2

-

2(12 %)

2

1