Table 5 Case illustration (re-visited using 4-tiered approach)

Taking each of the objectives in turn, we re-express the progression criteria for the three objectives according to the 4-tiered approach, as follows:

(i) Recruitment uptake [expected n_s = 200]

• E ≤ 0.2 [P ≥ 0.05] -> RED (STOP)

• 0.2 < E < 0.35 -> AMBER (AMEND)//{A_c = 0.247 (i.e. 0.2 + 1.645√(0.2 × 0.8/200))}*

o 0.2 < E < 0.247 [P ≥ 0.05] -> AMBER_R (AMEND-major)

o 0.247 ≤ E < 0.35 [P < 0.05] -> AMBER_G (AMEND-minor)

• E ≥ 0.35 [P < 0.05] -> GREEN (GO)

Signals for n_s = 200:

0 to 40 (RED), > 40 to < 49.4 (AMBER_R), 49.4 to < 70 (AMBER_G) and 70 to 200 (GREEN) {i.e. 0.2 × 200 = 40, 0.247 × 200 = 49.4, 0.35 × 200 = 70}

(ii) Treatment fidelity [n_i = 34 (intervention arm only)]

• E ≤ 0.5 [P ≥ 0.05] -> RED (STOP)

• 0.5 < E < 0.75 -> AMBER (AMEND)//{A_C = 0.641 (i.e. 0.5 + 1.645√(0.5 × 0.5/34))—as shown in Table 1}*

o 0.5 < E < 0.641 [P ≥ 0.05] -> AMBER_R (AMEND-major)

o 0.641 ≤ E < 0.75 [P < 0.05] -> AMBER_G (AMEND-minor)

• E ≥ 0.75 [P < 0.05] -> GREEN (GO)

Signals for n_i = 34:

0 to 17 (RED), > 17 to < 21.79 (AMBER_R), 21.79 to < 25.5 (AMBER_G) and 25.5 to 34 (GREEN) {i.e. 0.5 × 34 = 17, 0.641 × 34 = 21.794, 0.75 × 34 = 25.5}

(iii) Follow up [n_r = 68 (intervention and control arms)]

• E ≤ 0.65 [P ≥ 0.05] -> RED (STOP)

• 0.65 < E < 0.85 -> AMBER (AMEND)//{A_c = 0.745 (i.e. 0.65 + 1.645x√(0.65 × 0.35/68))}*

o  0.65 < E < 0.745 [P ≥ 0.05] -> AMBER_R (AMEND-major)

o  0.745 ≤ E < 0.85 [P < 0.05] -> AMBER_G (AMEND-minor)

• E ≥ 0.85 [P < 0.05] -> GREEN (GO)

Signals for n_r = 68:

0 to 44.2 (RED), > 44.2 to < 50.66 (AMBER_R), 50.66 to < 57.8 (AMBER_G) and 57.8 to 70 (GREEN) {i.e. 0.65 × 68 = 44.2, 0.745 × 68 = 50.66, 0.85 × 68 = 57.8}

[Note: The continuity correction (-0.5 deduction) needs to be applied to the observed count from the study for each criterion prior to assessing into which signal band it falls]

In accordance with the multi-criteria aim, the decision to proceed would be based on the worst signal (as in Table 4)